Lecture notes Gerontology, Groningen

Lecture: Introduction to gerontology

What is gerontology?

Gerontology is the study of social, biological and psychological aspects of aging. So, aging is the main focus of this course. This course also takes a neuropsychological approach. It shows a relation between (healthy) aging and changes in the brain. The signs and symptoms of common dementia syndromes, their neurobiological underpinnings and the consequences for the patients and their families will be discussed. Not only dementia but also other neurodegenerative diseases and other diseases related to aging are explained in this course.

Healthy aging

In our everyday lives, we talk about healthy aging a lot. For example by the media or at your university. This is also shown by the drawing: “Staircase of old age” (Trap des ouderdoms): We start at a point in the bottom (when we are born), then we all climb up. The text underneath the drawing says: we all go up and down. Some go down very softly, others with a bang. With this the painters mean that some are confronted with many diseases, others with none while getting older.

As years go by, the distribution of ages is changing. Distribution of ages in 1950 was equal for males and females. There were less people of a higher age and many babies. In 1990 the baby boom generation becomes visible. There is an increase in the number of adults. Also the number of 70 year olds and older is increased by then. Last year (2014) it becomes visible that the baby boom generation is getting older (between 50-60 ), there is an increase of older people and a big drop of births. A future prediction is that there will still be less births and more people getting older. This situation is mainly for developed countries. Less developed countries are more comparable to the triangle situation in 1950. But also in the less developed countries the distribution of ages is changing. But since aging is sometimes accompanied by diseases, problems occur. Because now, we have to start dealing with more people with diseases. In more developed countries there are way more older people, but also in less developed countries there is an increase in older people. Life expectancy at birth also grows all over the world (although faster in the developed countries). Number of children per woman is on a decrease, all over the world.

What is aging?

Aging has many definitions. Chronological age as a definition of aging is mostly used. Chronological age means the time since you were born. But also age as a biological age exists. This means where do you stand relative to the years you will still live. Ofcourse this can only be speculative, because you don’t know when you die. Next to these two there is functional age: this means your competence in carrying out tasks. The better you are at carrying out tasks, the younger your functional age. The fourth definition is psychological age, by which is meant how well a person can adapt to changing environment. The better the adapting, the lower the psychological age. The last one is social age. This includes beliefs held by us about how individuals in a particular age should act, dress etcetera. But, when are you old? Chronological age: 65. But this line is arbitrary: we just defined it this way. We say someone is young old when he/she is between 65-74, old old between 75-84 and oldest old after 85. Someone’s getting old in their functional age when they arrive the third age (between retirement and start of age imposed limitations, can be at any age) and fourth age (when you will have cognitive and physical impairments with everyday functioning).

There are also many different perspectives on aging process. Normative aging means what is normal or wat is average for everybody in the population. Successful aging is about what would be an ideal outcome. Positive aging means having found happiness and wellbeing, also when confronted with physical and psychological changes of aging.

Theories of aging

There are two models of theories of aging. These two models have strong influence. The first is Selective Optimization with Compensation model of aging. This model says we engage in adaptation to our environment through our entire lives. We can learn and change and use our additional energy/tasks we have. We start with certain conditions (antecedent conditions): these are developed in a certain way. Then we experience a reduction in general reserve capacity of our energy. We then engage in different processes based on changing and adapting and this brings is a specific outcome. These processes tell us how to deal with the conditions we experience. There are three strategies in this model: selection, optimization and compensation. Selection means concentrating on domains in which we will likely still perform good. Optimization means focussing on the behaviours that maximize quality of life and not only quantity. Compensation means substitute new strategies when losing others.

The second model is the ecological model of aging. This model is about our competences and interaction (or adaptation to) with environment. Especially the pressure and challenges brought by our environments. Interaction between these two also changes with age. There is an optimal zone (maximum performance potential), where you feel good. Also a zone where you can just deal with it (marginally zone) and a zone where you can’t deal with it (maladaptive behaviour). Competence can be physical, sensory, cognitive and social capabilities. Zones can be different for all of them. For example, a person with high competence will often adapt in a better way when exposed to environmental pressure.

Aging

Why do we get older? What determines how long we life? We all have biological changes, like physical appearance. They develop when we get older and it ends with death. Aging is very gradual and it adds up (cumulative). We have a peak in early adulthood and decline after early adulthood. There is a huge difference in rate of decline between individuals. Most older adults are neither helpless or dependent. Are biological changes a consequence of aging or of disease? Aging without disease is quite rare. Most of us get a disease in their lifetime. The likelihood of many diseases is increased with aging. Aging affects the consequences of a disease. Disease and aging interacts.

Some terms are related to age. Morbidity refers to illness and disease. Mortality refers to death. These two are related. Morbidity can result in mortality. Death is usually preceded by morbidity, but it doesn’t to be. Life span is upper limit of time that humans can live. The maximum species can live is 120 years. This hasn’t changed over time. But more people will live up to the max. Much more females will get this old. Life expectancy means that people in a particular birth cohort are expected to live this long. This has increased over time. Affected by many factors like nutrition, medical care and hygiene. The number of people who will approach the maximum life span will increase.

Theories of biology of aging

Some say: biological aging occurs in an organism without outside factors. Others say: biological aging is influenced by our environments, how we cope with them and our daily habits. Primary aging is an unavoidable biological processes that affects all species (cumulative). But there are huge individual differences between species and organisms. You can’t stop primary aging. Secondary aging is experienced by most but doesn’t have to be by everyone and is caused by hostile environmental influences (lack of exercise, smoking, disease). Programmed theories are related to primary aging. Aging is under the control of genetics. You can’t change it. Three of these are explained. The first is time clock theory. In a human infant cells double 50 times. In a mouse they only double 10-15 times. So aging or life span is related to how often your cells divide. Life span is genetically determined by a time clock. Infants (have a longer life span) double their cells way more than adults. Down syndrome/progeria: less dividing of cells. Telomeres is a protective cap at the end of our chromosomes. They become shorter as we grow older and as cells divide more. Second theory is immune theory. Everybody has a immune system that protects us. Immune system is programmed to stay for a certain amount of time, after this it declines. We have a limited amount of antibodies. Then they will attack and destroy normal bodies (cancer). Last programme theory discussed is evolutionary theory. Species are programmed to bear and rear youngsters. After they did that, they have fulfilled what they had to do. Depending on levels of energy we have we continue after we have raised our children. The more we have used of these levels, the more prone we are to diseases.

Stochastic theories are related to secondary aging. Random damage to our bodies occurs as we age and accumulates. The idea behind this theory is that even identical twins have different rates of aging. If only genetics would cause aging, this is not possible. The first stochastic theory is error theory: many errors occurring in our cells. Resulting in many faulty molecules. This is a result from our metabolic processes due to exposure to environmental factors, like radiation. Cells can repair some of it, but not all of them. This leads to damage. Second theory is wear and tear theory. As soon as we begin our lives we all have a fixed level of energy (physiological) is we use it early, aging begins early. Can we slow it down? People who have a severe physical job might lose their energy earlier. But this is not shown in research! The last stochastic theory is stress theory. There are two systems involved in stress responses. First is sympathetic nervous system. If we experience stress, our pupils dilate. Or an increase of heart rate occurs. Second one is hypothalamic-pituitary adrenal axis. This is a complex system which secretes cortisol when we experience stress. Stress theory says that stress triggers physiological activation resulting in a secretion of stress related hormones. In younger organism stress systems quickly return to normal levels, in older organisms this doesn’t happen. They experience a prolonged exposure to glucocorticoids.

Individual differences

Quality of air, diet, exercise, education and work history all have an impact on aging. People with a higher education get later in their life diseases than people with low level of education. Level of stress, health care, marital status and social relationships also play roles. In studies with rats they showed that rats with 50 percent less caloric intake live longer and have less change of cancer. Rats who constricted to this all their lives have the longest longevity. People with reduced caloric have lower insulin levels. What’s the influence of marital status? It is said that married people are more likely to have healthy habits because of social control. This phenomenon is stronger for men than for women. Because women in general probably are more concerned with health. But marriage is not all positive. Breakups and divorces can have very negative effect on your health. Single from midlife doesn’t result in greater mortality risks. Can we stop aging process? Media does a lot of antiaging marketing. Superfood? Antiaging crème? But there is no scientific evidence that these will help. Changing lifestyle is more promising: stop smoking (decreases risk for cancer and heart disease), cutting down intake of sugar and fat, exercise and positive feeling of physical capability and adequate medical care, intellectual stimulation and social contacts.

Physical changes

Age-related physical changes are changes in appearance of skin and hair. Skin becomes drier and you get wrinkles. Hair becomes thinner and grey. In women facial wrinkles and grey hair needs to be avoided. In men these are found characteristic. Physical sings of aging in women are unattractive, not in men. Muscle mass decrease with age. Older adults need longer time to recover. Our energy that we have in our muscles decreases with age. Age related degeneration of joints occurs, most common arthritis. This is pain and loss of movement caused by degeneration of joints. Risk factors: increasing age, obesity, heredity, low socioeconomic status and being a female. Also loss of bone density in the vertebrae is common. Men can lose an inch in height, women up to two inches. Also osteoporosis is seen a lot: extreme loss of bone mass and deterioration of bone tissue. This leads to breaking bones more easily. Risk factors for osteoporosis are increasing age, family history, female, smoking, calcium and vitamin D intake and inactive lifestyle. Problems is respiratory and cardiovascular systems occur. For example, atherosclerosis. This means that fatty substance occur in the vessels which block the vessels. Hypertension, aneurysm and stroke also more common in older people.

Causes of mortality in the Netherlands

Most people die of heart disease. Then cancer. After that respiratory disease. Psychiatric disorders, digestive system related diseases and last non-natural deaths are also in the top 10. The first three issues are all related to aging.

Health care for older adults

What is important? Older adults usually have no cure for their diseases, so they just have to live with it. It is important to maintain good quality in life, even living with all the impairments. There are many support mechanisms for the older ones: housecleaner, meals on wheels, grocery shopping by someone else. Basic activities of daily living (going to toilet, dressing, eating, bathing) are needed to maintain independence. The goal of health care is to update these needs so people can maintain their independence. Percentage of daily living activities limitations are might higher among those aged 85+ . Instrumental activities of daily living are more complex activities required for carrying out the business of daily life (shopping, managing money, housekeeping, using telephone). These are assessed to see which kind of care these older people need. Chronic disease can often be managing by strict medication regime. Old old people do usually not restrict to this regime. Older adults often have more than one chronic disease.

Lecture: What happens when we get older?

Healthy aging and the brain

What happens to our brain when we get older? In this lecture we are not looking at diseases, but at the normal aging process. We have different ways to study the aging brain. One of them is post-mortem brain research. We can examine the brain at different levels, even to a cellular level. But we have limited sample sizes. The number of brains donated to research is increasing but still not enough people give their brain to research. In past few years we started using a lot of neuroimaging techniques. Computerized tomography (CT) is used in clinical practice a lot. Also we use Magnetic Resonance Imaging very often. The spatial resolution is much better in MRI than it is in CT-scans. MRI and CT-scans are used to look at the structure of the brain. When we want to look at the functions of the brain we can also use FMRI and Positron emission tomography. We are also able to see neurotransmitters in PET-scans. In order to make PET-scans researchers inject people with radioactive fluid which can be trace it in the brain. This fluid usually connects itself to a neurotransmitter, which become then visible on the scan.

Changes in the human brain

The weight of our brain goes up when are born, when we get older it decreases. It decreases up to 10% by the tenth decade. Males have a heavier brain than females. The difference between the brain weight relative to your body weight between males and females is not so big. Brain weight relative to body stays more stable in individuals aged 20 years and older. We can also see differences when we look at the volume of the brain. The cerebral cortex starts declining already in younger adults. But the decline is much stronger in older people. There are very strong differences between different regions in the brain. Some people show very steep decline, others have a more stable volume.

Structure of the brain

Grey matter

Brain regions that reduce in volume with age are caudate nucleus, cerebellum, hippocampus and lateral prefrontal cortex. Over time these areas of the brain have a decline in volume. Other regions do not show this decline. This is seen in the primary visual cortex and entorhinal cortex (memory). Also age related atrophy of grey matter differs: the frontal lobes show the steepest rates of decline. After that the parietal lobes show the steepest decline. Decline becomes worse with increasing age. For example, there is a decline of 0.86 % of volume per year in the whole sample, but a 1,85 percent decline of volume is found after the age of 70. No gender differences are found for this.

White matter

White matter changes are found everywhere in the brain. Just like grey matter, the greatest white matter loss is seen in frontal regions. The decline is even more extensive in the white matter(connections in the brain) than the grey matter. An anterior to posterior gradient is found, meaning that the greatest decline is seen in the frontal region. The decline starts at the frontal part of the brain and moves to the back.

What happens to the cerebrospinal fluid and cavities? Between 20 and 50 years of age the brain occupies 90% of the cranial cavity. After this age the brain progressively occupies less space. As a consequence of this there is an increase in cerebrospinal fluid. Because of the loss of volume there is a widening of the sulci.

Functional changes in the brain

Neurotransmitters

Communication between different neurons is done by neurotransmitters. Dopamine is the most often studied neurotransmitter. Dopamine has two forms of receptors. D1 and D2. If you get older there is a loss of D1 and D2 receptor binding. A decrease of 7-10 percent in this is found. Also the dopamine transporter (helps transmitting the message) declines 4 – 8 percent per decade. Also here a anterior-posterior gradient is found, so the frontal lobes are affected first.

Younger and older adults recruit different areas when they are doing the same task. This refers to compensation and adaptation, seen at a behavioural and brain level. Two important patterns are: 1. Posterior-Anterior shit in Aging (PASA). Older people show a decrease of activation in the posterior part. In the frontal brain the people show an increase of activation, seen in areas for attention, problem solving, memory function, perception. If you age a stronger involvement of higher order cognitive processes is found. 2. Hemispheric Asymmetry Reduction in older adults (HAROLD). This principle is looking at memory, perception, inhibitory control. Usually in young people one hemisphere is involved in a task. In older people usually both hemispheres are used. This is because of additional areas of the brain are used to compensate the reduction of the brain. Symmetry between hemispheres declines when people age.

There are two explanations for these processes are found. The first is compensation. Bilateral activity is associated with successful cognitive performance. This bilateral activity is found in more high performing people. The second one is dedifferentiation. An age related difficulty to specialize areas for different tasks is found. When you get older there is a dedifferentiation in the brain, causing that you can still perform in the same level. Most evidence is available for the compensation explanation. Rossi et al. (2004) have applied rTMS to left or right side of the brain (which makes this side stop functioning in the normal way). Their research results showed that in young adults retrieval was more affected and in older people less affected while applying rTMS to one side of the brain. This is because for older people both left and right hemisphere are involved in tasks like this, so they can compensate for the loss of functioning in one hemisphere.

Effect on cognitive functionioning

There are significant correlations between structure of the brain and cognitive functioning. Different functions of the brain show different results. People experience a decline in speed of processing as they get older. Also a big decline in working memory is found. Long term memory also declines. But, short-term memory is relatively stable. There is some decline, but not that steep as the other memory forms. Verbal knowledge (vocabulary knowledge) can perhaps even increase. To summarize: In general an age related decline is found, except for verbal knowledge.

There are no differences between cultures looking at non-verbal neuropsychological tests. If we look at verbal neuropsychological tests, we see big differences. This also has an effect on the age related decline.

Cognitive functions

Many studies are done looking at memory, executive functions, attention, visual perception, language etc. If we look at attention, visual perception and recognition memory a decrease of activation in occipital areas, accompanied by frontal increases is seen. This is supported by the PASA-model. Working memory, language, memory encoding and retrieval show evidence for the HAROLD model. PASA and HAROLD affect cognitive functions in different ways. Many people have studied aging and over time many different theories have been proposed. Here the 5 most important theories are discussed:

Sensory deficit theory

We have many age related deficits in sensory processing. Older people show for example problems in hearing and seeing. There are strong relations between differences in sensory processing and age related cognitive decline. The sensory cortex is affect by aging, aging causes a decline in activation. This is a bottom-up process. On the other side, the association cortex shows compensation, a top down process. Sensory cortex has a big influence on sensory processing, association cortex in cognitive functioning. Sensory and cognitive functioning also influence eatchother. So, top down processes can compensate for bottom up processes.

Resources deficit theory

Aging is associated with a reduction in the amount of attentional resources. We have difficulties with demanding cognitive tasks, because they ask a lot from our attention. Deficits are smaller when your environment shows support (for example a reminder on your desk). When attentional resources are reduced in younger people, the same pattern in shown. This is also shown in neuroimaging studies. Attention relies strongly on the prefrontal cortex. Older adults show decreased activation in the PFC part important for attention tasks. Older adults tend to show a more bilateral activation.

Speed deficit theory

Time required by early operations reduces the time available for later operations. This shows a limited time mechanism. So the more time the early operation takes, the less is left for the second. Also the products of early operations are lost or irrelevant by the time once later operations are completed (earlier are not relevant anymore when later mechanisms kick in) This shows a simultaneity mechanism. This is supported by the fact that processing speed is in big decline. The mechanisms behind this phenomenon are white matter detoriation and an increase of neural network supporting cognitive performance. In a normal brain, myelin sheath support information processing trough the brain. If these sheaths become thinner, information processing slows down. That’s what causing the white matter detoriation. Both the PASA model and HAROLD model say that more and other areas of the brain are recruited to perform same task. This is also a cause of the decline in processing speed.

Inhibition deficit theory

Age-related cognitive decline is due to decline in inhibitory control of working memory. When inhibitory control declines, we can’t focus any more to relevant information. This results in mental clutter and an impaired working memory. This is supported by the fact that older adults say that they remember irrelevant information better. We also see differences between regions that exert inhibition (anterior) and regions that are affected by inhibition (posterior). Also older adults show weaker activity for inhibition than younger adults and greater activity in regions that are supposed to be disinhibited.

Scaffolding theory of aging and cognition (STAC)

Age related cognitive decline might be explained by a combination of mechanisms. Speed deficit, sensory, working memory and inhibition deficit might all play a role. This theory combines all of these. It is a theory that stands for the possibility of both deficient and preserved performance on cognitive tasks. The brain must adapt to challenging neural challenges including atrophy. Scaffolding represents a compensatory strategy allowing older people to maintain a high level of activity and performance. This model is often used but it is not specific to old age, it is specific to the life span. When there is aging we have neural challenges (decline of white matter, cortex thinner, dopamine depletion, shrinkage). We also see changes in a functional level: increased functional activity. Decreased visual and sensory cortex activation and specifity is seen. Also decreased hippocampal activation (decreased memory function) is seen. These two are related. In reaction to these two we have compensatory scaffolding (posterior anterior shift and HAROLD allow you to compensate) and scaffolding enhancement. The latter means we can support our performance by training, and new learning exercise leading to the scaffolding going on in your brain. This scaffolding occurs in the prefrontal cortex. Aging brain is less efficient in scaffolding because of disease and pathology. This might entirely limit the scaffolding. Causes of cognitive aging are multifactorial. In one person decline can be steep, in others not. This is due to the amount of scaffolding a person performs. Scaffolding is promoted by cognitive activity (external challenge: reading, exercise)

Individual differences

Research has shown that decline in brain structure is not directly related to the severity of cognitive decline. Cognitive reserve is defined as the individual differences in cognitive processes and neural networks that allow that some people are better in adapting to changes in brain structures than others. Two people with the same head trauma can respond totally different to the same level of damage. We can measure cognitive reserve with intelligence (crystallized), level of education, work level, literacy, integrity of social relations. High level of all these leads to high level of responding to damage. People who perform on a high level in cognitive performance, remain relatively stable to decline in their brain until the point when there’s too much cognitive decline. People with low cognitive deserve can’t deal this long with the decline, and start declining more early relative to decline in brain structures. This is also seen in neurodegenerative diseases studies.

But when is behaviour abnormal or is it just healthy aging? Three factors play a major role in cognition. The first one is age, cognitive performance relative to one’s age. Also the level of education should be kept in mind. Gender also plays a role. Some tasks are better performed by men, others by women. For example, recognition of emotion is done better for anger, fear and sadness by women. So always compare people with the same age, same gender and same level of education. That’s why normative samples are developed in NPO’s. Statistical definition: performance is abnormal when a person obtains a score below or above two standard deviations between the mean of their normative group.

Differential diagnosis

This is the determination of which of several diseases might be responsible for the produced symptoms. This is common practise in neurology and psychology. Based on comparing symptoms to the normal we can differentiate between different diagnosis. For example: a patient with forgetfulness, loss of overview and inability to use phone and pc and less social active. Can be someone with a burnout, healthy aging, mild cognitive impairments or Alzheimer’s dementia. If it is a certain diagnose, what kind of impairments do I expect to see in the patient? Examination of these expected impairments shows which diagnose can be confirmed. To prevent errors we use differential diagnosis.

Lecture: Alzheimer’s Disease

Mild Cognitive Impairment & Alzheimer’s Disease

A brief introduction to dementia

Dementia stems from Latin and the meaning of the word is madness. Nowadays it’s defined as a chronic disease of the brain characteristic by a progressive and global detoriation in intellect, including memory, learning, orientation, language and comprehension. A devastating consequence of dementia is loss of independent living skills (social and work related). All around the world 35.6 million people have dementia. Above age 65 the prevalence of dementia is 5% . After 65 the prevalence doubles every 5 year, going up to 20-40 % above 85 years. The biggest risk factor for developing dementia is age. There are exceptions to this: 2-10% of people having dementia is younger than 65. Women are more effected by dementia than men because they have a higher life expectancy. Dementia is less seen in less developed countries. In developed countries people become older so they have a higher risk for dementia.
Currently much research is done at dementia, but still no treatment to cure or stop progression of dementia is found. The only thing we available is symptomatic treatment, a form of partially effective treatment. Symptomatic treatment only relieves symptoms.
There are many subtypes of dementia and many brain pathologies causing dementia. Alzheimer , vascular and frontotemporal dementia are part of the cortical dementias. Huntington, Lewy Bodies and Parkinson’s dementia are part of the subcortical dementias.

Alzheimer’s Disease

Alzheimer’s Disease is in 1901 for the first time described by Alzheimer. The story was about a 51 year old woman, Auguste D, who showed a sudden change in behaviour. Her symptoms were described by her man: panic, terror, suspicion of her man having an affair, couldn’t cope, admitted to hospital, weakening of memory, sleeplessness, restlessness, unable to perform mental of physical work, and she was never free of fear.
Now it is described as a degenerative brain disorder including intellectual and behavioural detoriation, dominated by memory impairments. Also visuospatial impairment, language impairment and preserved social skills are found. The disease starts usually after 65. Life span after diagnosis is usually around 10 years but can also be 20. Motor and primary sensory disturbances are either not present or start late with their presentation.
DSM 5 criteria for Alzheimer’s disease include: 1) Insidious onset and gradual progression of impairment in 1 or more cognitive domains (slow onset, getting worse over time) 2) Clear evidence of decline in memory and learning and at least in one other domain (for example executive functioning) 3) No evidence of mixed etiology (cerebrovascular disease can’t be present for example)

Alzheimer is the most common form of dementia. The second most common one is vascular dementia accompanied by Alzheimer. There are many patients with mixed pathology. Alzheimer can be assessed with the Mini- mental state examination (MMSE). The MMSE assesses orientation (what day it is), registration (repeat the named objects) , attention and calculation, recall, language (naming things, writing a sentence) and a visual constructive part. All these together make one score. Even ten years after dementia diagnosis there is still a gradual decline going on in scores on MMSE. There is also a major difference in rate of regression between individuals (some so fast, some very slow).

Brain

The brain of Alzheimer’s patients becomes much smaller as the disease continues. Due to the fact that the grey matter is shrinking. The arteries are located more on top as the disease progresses. This is a direct consequence of neurodegeneration. Very severe degeneration is found in the Medio temporal lobe. This is the area where the hippocampus, related to memory, is. There are also changes on the level of neurotransmitters: imaging studies show reduced neocortical and amygdaloidal AChE (acetylcholinesterase) activity. This means that Alzheimer is related to dying back of choleric neurons.
On a cellular level plaques and tangles are seen in brain. Post mortem plaque formation is detected. This process begins with the misfolding of amyloid proteins. This leads to neurofibrillary tangles. A consequence of plaques and tangles is synaptic disruption. This means that neurons aren’t able to communicate so well anymore. This is also again related to neurodegeneration. The synaptic disruption spreads over the brain, with more and more areas becoming involved in this process.

People can be relieved because of getting a diagnosis for their progressing memory problems. But it is also devastating to get this diagnose because there is no cure for dementia, no chance at getting better.

Disease of memory

Dementia is also called disease of memory, because of the progressive memory impairment as a big part of the disease. In the mild stages, memory problems are inconsistent but more than normal forgetfulness. Some days one remembering is without flaws, other days things are forgotten like names, phone numbers, misplacement of personal belongings. Also missing appointments and forgetting to remember events is representative. At mild stages, housekeeping and activities of daily living are usually maintained if support can be given by caretakers of partner. Also cues of clues or multiple choices can help them remembering (because of recognizing). In moderate stage people are affected in daily living. Persistent forgetting is characterized by repetitive asking the same question and awareness is a bit gone. Patients cannot store any new information for more than a few minutes or maintain a coherent stream of though. Increased reliance on spouse is seen. In a severe stage even the most overlearned facts are lost. Patients can’t even recognize family members, which is of course very hard for their family.
Memory loss is related to degeneration of the hippocampus and the entorhinal cortex. Holes can be found in the brain at brain pictures. Long term memory model is divided in episodic, semantic, procedural and emotional memory. Declarative memory (episodic and semantic) is impaired first. Remote (autobiographic) memory is relatively preserved in the beginning. New episodes cannot be remembered anymore. This process is usually assessed by Word list (Rey Auditory Verbal learning Test)in which 15 words presented. Evaluation of encoding, consolidation and retrieval can be done with this test. In a healthy old person, the number of words one can remember over time should increase. Alzheimer’s patients can remember some words, but their learning curve is much more flat than in healthy elderly. They have difficulty learning new information. The implicit memory is initially spared (things we do automatic).

Working memory

Our working memory works with two systems. The phonological loop (inner voice) and the visuospatial sketch pad (inner eyes). In the middle we have a central executive which makes these two understandable. Digit Span test, forward and backward, can be done to test this. In early stages of Alzheimer’s dementia working memory is relatively spared ( for a short period memory is present) In the moderate stage working memory becomes also affected. Learning of new info is by then immediately affected, remote and working memory is still relatively spared. In severe stages all types of memory are affected.

Visuospatial and perceptual functions

Visuospatial and perceptual impairment for Alzheimer’s patients means getting lost and being disorientated. Also dressing disturbance (apraxia), the inability to dress properly or find sleeves for example, is present sometimes. Impaired contrast and figure ground discrimination is found, for example missing the toilet while urinating. Also visual agnosia can be present: a patient cannot recognize normal objects, familiar faces, or discriminate between animals. This is associated with visual association cortex impairment. From a clinical point of view this is not apparent before memory and attentional disturbances are fully established. Visuospatial and perceptual functions are assessed by Complex Figure of Rey or in Clock drawing.

Language

Aphasia is a acquired disturbance secondary to brain damage. It’s an important feature of Alzheimer. In the starting phase word finding difficulties are seen, speech becomes less spontaneous and speech becomes empty (replacing words which can’t be remembered with words with no meaning). Also some comprehension deteriorates. In the moderate stage the auditory comprehension deteriorates. Languages in severe stage patients becomes dysprosodic, some develop reiterative speech (echolalia, palilalia). In the final stage patients become mute (no speaking of language anymore). We do not know if they are still able to understand language. But output and input of writing are affected at a certain point in time. This is a gradual process.
Apraxia is found too. Assessment for apraxia is done with giving commands to follow sequences, for example: pretend to comb your hair or pretend to brush your teeth. Apraxia is rare though, usually it only occurs in later stages.

Attention

Attention has different subcomponents: selective attention, sustained attention and divided attention. With Alzheimer’s patients sustained attention is preserved in the early stages. Patients eventually become distracted very fast. Executive functioning includes planning, inhibition, working memory, initiative taking and more. These functions are mainly needed in non-routine situations: impairments for reacting in these situations are already present in early stages of the disease. Still memory impairments are most pronounced but executive functioning problems are a very important part of Alzheimer’s too. Assessment for this can be done with the Trail test. Impairments in executive functioning are often the impairments that underlie problems with activities of daily living.

Other features

In severe stages all of the functions named above are impaired. Language and praxis are a little bit less impaired than the others but still affected in a very bad way. Significant individual differences are found again.
Neuropsychiatric features are also core features of Alzheimer’s. Some patients are confronted earlier with neuropsychiatric features than others. Once they arise, some evolve again, some disappear and some stay the same. The behavioural detoriation may be triggered by some acute stressor, for example moving from home to a nursing home. Patients with Alzheimer’s dementia become totally lost because of this. Patients with Alzheimer’s dementia range from showing apathy to showing agitation or even eating disorders.
Personality and social behaviour are relatively preserved. Subtle changes like emotional detachment or indifference can occur. A patient functions from a social view relatively well. Other people underestimate the impairments they have because of this. This makes diagnoses harder to establish.
Patients with apathy show less motivation to do stuff. This ranges from mild passivity and loss of interest to aboulic immobilization. Apathy is the most common neuropsychiatric feature and can also be misdiagnosed as a dementia. Apathy is strongly associated with anosognosia. Anosognosia is a deficit of self-awareness. Because of suffering from anosognosia patients have an attitude like: I do not know and I do not care (showing in poor hygiene or inappropriate dressing). A patient suffering from Alzheimer’s disease with apathy is more dependent and has a higher likelihood to get other neuropsychiatric diseases than patients without the apathy feature.

Delusions and hallucinations are also found in Alzheimer’s patients. Delusions are more common and are usually persecutory, involving fears of personal harm, theft and spousal infidelity. Hallucinations are usually visual. They predict more rapid functional and cognitive decline. Also depression often coexist, not as a response. Depression and Alzheimer’s dementia are caused by changes going on in the brain and have a symptom overlap. It could be that depression precedes the development with Alzheimer’s disease (retrospectively looking)
Aggression and agitation is also a common feature, usually provoked by confusion due to impairments or delusions. Also the depression in a patient that is too impaired to express distress can show it through aggression. Sleep disturbances and pain can also be a cause, just as infections and drug interactions. Finally, environmental changes can be the cause of aggression too.

Mild Cognitive Impairment (MCI)

MCI is characterized by subjective and objective cognitive symptoms. These symptoms should be greater than expected for one’s age and education level, but the patient must still be able to function fairly well. Patients with MCI complain about the impairments (subjective) but show no daily life impairments. MCI is seen as a sort of transitional stage between normal aging and dementia.
Diagnostic criteria for MCI include: 1) Being concerned about change in cognitive functioning (of himself or by informant) 2) Impairment in one or more cognitive domains 3) Preservation of independence in functioning (this is what is distinguishes from dementia) 4) No dementia present
Subtypes of MCI are amnesic, non-amnesic, single domain and multiple domains. Amnesic means with memory impairment evident. Non-amnesic means with impairment present in other cognitive domain. Single domain means cognitive impairment in one domain. Multiple domain MCI means cognitive impairment in more than one domain. Different subtypes have different etiologies.
Possible etiologies can be: early stage of neurodegenerative disease, early stage of cerebrovascular disease, psychiatric (depression) or traumatic (head injury). These are the most likely etiologies, but there are others too. Like medication side effects, metabolic factors or infection. Different subtypes of MCI also have different prognosis. Amnesic MCI usually progress to Alzheimer. Non-amnesic MCI usually progress into other type of dementia (subcortical). But, they can also progress to normal level. Or they can stabilize over time, so no further decline is found.

Prevalence

The prevalence of MCI is 19 % up to 75 and older. It is 29% for the age of 85 or older. It is also found that 10-19% of MCI patients develops Alzheimer. So MCI is a risk factor for Alzheimer. The majority of MCI-patients progress to a dementia after 6 years (65-80%). Patients who do not develop Alzheimer have a cause that is reversible (e.g. metabolic factors or medication use). It is always important to have a differential diagnosis: normal cognitive aging (aging brings with cognitive decline), dementia, depression, delirium, metabolic factors, and medication use should be kept in mind too. Objective assessment with depression patients is showing impairments in memory, executive function, attention, psychomotor speed. But these can be reversible with treatment.
Delirium is a very acute clinical condition with disturbed consciousness and cognitive dysfunction. Sometimes followed by psychotic features.
DSM 5 criteria for delirium include: 1) Disturbance in attention and awareness 2) Develops over a very short period of time, represent a change from normal 3) Additional disturbance in cognition 4) Cannot be explained by neurocognitive disorder 5) Evidence form history, laboratory and physical examination that is not a consequence of other medical condition.
The prevalence of delirium is 1-2% in the population. But these numbers increase when age increases, older adults have a prevalence of 12-24% ( developing a delirium). This happens often after an operation. In the intensive care the prevalence of developing a delirium after operation is actually 70-87%. Delirium also causes cognitive impairments, but reversible. These patients can have a full recovery.

Influence of age and Gender

MCI is more common in men than in women. Fewer years of education is also associated with a higher risk. Multiple and single domain amnestic MCI have more risk in developing Alzheimer’s disease. But not all patients with Alzheimer are diagnosed with MCI first.

Lecture: Dementia

Vascular dementia

Vascular dementia was first described in 1894 (even before Alzheimer) by a man called Otto Binswanger. He described an association between atherosclerosis, a reduction in cerebral perfusion, and cognitive decline in older adults. It has been given different labels throughout the years.
Old labels include senile dementia and multi infarct dementia (multiple diffuse strokes, resulting in a dementia). Multi infarct strokes are not the only cause of vascular dementia.
Nowadays this disease is called vascular dementia. The term vascular dementia implements that vascular pathologies are present aside from the stroke, such as subcortical microvascular disease present. Or vascular cognitive impairment can be the case. Vascular dementia ranges on a spectrum from vascular cognitive impairment without dementia to vascular dementia. This spectrum is used very often nowadays.
Vascular dementia is the second or third most common type of dementia, but there are differences between countries in the world. In China and Japan 50% of people with dementia have vascular dementia. In North America is the Alzheimer’s disease is twice as much diagnosed as vascular dementia. In Europe 10-30% of all dementia cases is vascular dementia.
The DSM 5 criteria for vascular dementia are: 1) the criteria are met for major or mild neurocognitive disorder 2) the clinical features are consistent with a vascular etiology, as suggested by either of these: onset of cognitive deficits is temporally related to one or more cerebrovascular events or evidence for decline is prominent in complex attention and frontal-executive function. 3) There must be evidence that there is present of cerebrovascular disease from history, physical examination and / or neuroimaging considered sufficient to account for the neurocognitive deficits. 4) The symptoms should not be better explained by any other brain disease or systemic disorder (differential diagnosis needed)
The criteria for major or mild neurocognitive disorder (1) are a) evidence of significant cognitive decline from a previous level of performance in one or more cognitive domains based on: concert of the individual, informant or clinical or based on more formal assessment (NPO’s) b) the cognitive deficits interfere with independence and everyday activities in the minimum requiring assistance in instrumental activities of daily living c) Delirium should be excluded. d) not better explained by any other disorder)

Neuropathology

There is no definitive set of pathological criteria for vascular dementia, unlike Alzheimer’s Disease. The underlying pathology can be expansive. Result of this is a diffuse pattern of brain injury, so vascular dementia is seen in many different types of presentations. Patients can’t be compared because of different symptoms and pathologies. A consequence of this is that it is difficult to define a gold standard, so there is no golden standard present yet. We diagnose vascular dementia mainly based on what we know on neuroimaging or events usually described and based on neuropsychological assessment. There are some key neuropathological features, leading to vascular dementia. These key features are the presence of small or large vessel disease, white matter lesions, infarcts, and lacunes. Also the absence of confounding pathologies, excluding other diseases (for example finding lewy bodies or amyloid plagues) is an indication of vascular dementia.

White matter lesions

White matter lesions are varied and diffuse. Two types can be found. The first, white matter hyper intensity, is usually present in older adults. This can be recognized as lighter grey spots on neuroimaging and is caused by a disrupture of the white matter of the brain. The other type is diffuse demyelination (degeneration of myelin). Diffuse demyelination can be seen as white spots on neuroimaging. A stroke can also occur in the white matter. Strokes can be recognized as red spots in the white matter on neuroimaging. Lacunes are very small perivascular cavities located very deep in the brain. Lacunes are recognized as degeneration in the cavities that surround vascular system. It is important to remember that stroke and lacunes can also occur in the grey matter.
Stroke
There are different types of strokes. An Ischaemic stroke is an occlusion of a major cerebral blood vessel or series of small cerebral blood vessels (blockage). An ischaemic stroke can be due to an embolism or can also be due to atherosclerosis. In atherosclerosis thickening of the vascular wall takes place and at a certain point this wall is so thick blood cannot come true anymore. A fatty substance in the arteries can be seen looking at the brain when atherosclerosis is diagnosed.
A haemorrhagic stroke is the rupture of a large or small cerebral blood vessel. A lot of blood flows into the brain so the brain gets pressed in a corner leading to tissue damage. This can occur cortical or subcortical.
A stroke is usually a large vessel stroke (also called large vessel disease), in this case one or more arteries supplying blood to the brain are ruptured or experience blockage. The effects of this are relatively focal. Also a small vessel stroke (also called small vessel disease or lacunar stroke) can take place, meaning a blockage of the cerebral micro vessels. This is very strong related to hypertension. In these cases there are usually many small strokes on top of eatchother in different parts of the brain, affecting other parts in the brain, leading to a relatively diffuse effect.
The small vessel strokes are more often associated with vascular dementia. Both forms of stroke can occur too. The type of stroke has different prognosis for vascular dementia. Small strokes give no immediate effect because of small events occurring after eatchother. So usually in these cases vascular dementia has a slow onset and a gradual decline. With large strokes an immediate onset of cognitive impairments occurs. So vascular dementia resulting from this has an abrupt onset and a stepwise decline, relatively stable for a while and declines further after this.

Clinical manifestation

Heterogeneity is the case in vascular dementia. Not one person is alike, different areas are affected and different strokes occur. The neuropsychological manifestation is driven by the extent of focal and diffuse vascular lesions. Middle cerebral artery provides the side of the brain with blood. Anterior cerebral artery provides the front of the brain with blood and the posterior cerebral artery provides the back. Rupture of these arteries results in total different problems. When rupture of the middle cerebral artery occurs, typically hemiplegia, aphasia and hemianesthesia (loss of sensory feeling in one part of your brain) are found. When rupture takes place in the anterior cerebral arteries paraplegia (loss of control lower part body), abulia, executive dysfunctions and personality changes are found. Rupture in the posterior cerebral arteries can lead to homonymous hemianopia (visual perception problems), alexia with or without agraphia, visual agnosia, Balint syndrome and/or prosopagnosia.
Patients can have impairments in different domains, learning and memory, executive functions, attention, language, visuoperceptual functions and psychomotor skills. There is some evidence for a typical pattern in vascular dementia patients: impairment in attention and executive functions are most salient. Impaired performance on can thus be seen in planning, set shifting etcetera. Patients with Alzheimer’s Disease and vascular dementia show comparable performance across most domains, the differences can be found in performance on attention and executive functions tasks. Alzheimer’s patients are usually relatively spared in these domains, as vascular dementia patients are usually relatively are spared in memory in the beginning.
Also language can be impaired with in patients with vascular dementia. Naming difficulties usually worsen with progress of the disease. Impairments in visuoperceptual skills occur as well. And the consequences of psychomotor dysfunctions are that patients can become very slow in the things that they do.

Neuropsychiatric disturbances

Neuropsychiatric disturbances can be part or result of the disease. Depression, apathy and anxiety are present most of the time. These can all be present in Alzheimer’s patients too, but patients with vascular dementia are usually more depressed because they are more aware of their disease. They still have insight in the disease, while Alzheimer’s Disease patients have not. Depression can be primary to pathological changes, but it usually secondary because of realising what is going on and the impairments these patients experience. Many patients are diagnosed with purely Alzheimer’s disease or purely vascular dementia, but there are also patients who have both diagnoses. Post mortem is found that the pathology seen in Alzheimer’s patients (plaques and tangles in the brain) is relatively common in patients with vascular dementia. If this is the case, the name mixed dementia is given. Patients with mixed dementia also have some pathology in the brain of vascular dementia, strokes occur too. Because of this the decline in behavioural changes occurs earlier than with patients with Alzheimer’s disease only. Also clinical pure Alzheimer’s disease patients are post-mortem associated with vascular disease, so it is not only the other way around. There are two hypotheses for the question if Alzheimer’s disease and vascular dementia interact or if they are just around at the same time. Hypothesis 1 states that two independent pathologies co-occur. Hypothesis 2 states that vascular changes stimulate the formations of Alzheimer’s pathology (plagues and tangles). Both options might be the case.

Risk factors

The change at getting vascular dementia increases when more risk factors are present. Age is a risk factor, because the prevalence of other risk factors increases as people age (diabetes, hypertension, cerebrovasculature fragility). Genetics is another risk factor for one rare hereditary form of micro vessel disease: Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukocephalopathy (CADASIL). When having CADASIL, deep and periventricular white matter changes and Transient Ischemic Attacks(very small, but many on top of eatchother can lead to problems) and strokes can occur. Other forms of vascular dementia not related to genetics.
Diabetes and hypertension are the biggest factors, followed by obesity and smoking. Another risk factor is having a cardiovascular disease, like cardiac arrhythmia or myocardial infarcts. These diseases reduce your cerebral blood flow. Finally heart failure is associated with reduced blood flow to body and brain.

Frontotemporal dementia

Frontotemporal dementia is also called frontotemporal lobe degeneration. It was formerly called Pick’s disease because it was first described by Arnold Pick in 1892. Frontotemporal dementia is a progressive neurodegenerative disease. Underneath the age of 60 frontotemporal dementia is the most common type of dementia. The mean age of onset is between 52 and 56 years. Frontotemporal dementia is more common underneath 60 years than Alzheimer’s disease. The prevalence in age group 45-64 is 12 in 100.000 individuals. In the brain very severe degeneration of the front part of the brain can be seen, so atrophy in frontal temporal lobes takes place. Also a hypometabolism in the medial and later prefrontal cortex can be seen in frontotemporal dementia patients. It was named Pick’s disease before because of the inclusion of Pick bodies. These result in a rupture of the communication between neurons in the frontal and temporal areas in the brain. Studies found that 29-45% of the patients with frontotemporal dementia have a positive family history. In case of this is first degree family the risk is 3:5 times higher and a stronger genetic component is found.
There are different subtypes: a behavioural/dysexecutive variant and the primary progressive aphasias (a. semantic dementia b. progressive non-fluent aphasia)

The Dsm 5 criteria for frontotemporal dementia are: 1) the criteria are met for neurocognitive disorder. 2) insidious onset and gradual progression. 3) for the behavioural variant: 3 or more of these should be found: behavioural disinhibition, apathy or inertia, loss of sympathy or empathy, stereotyped or compulsive behaviour, hyper orality and dietary changes. Prominent decline in social cognition. For the language variant: prominent decline in language abilities: speech production, word finding, object naming, grammar or word comprehension. 4) relative sparing of memory in the beginning 5) not due to other disease

Behavioural variant

The behavioural variant is the most common type. The progress to death in this subtype is very fast. The mean survival time is around 9 years. For Alzheimer’s disease the mean is 11.8 years and for the semantic variant also around 12 years. The most prominent features in the beginning are an insidious onset of personality change and behavioural abnormalities. Patients have poor insight, deny the existence of illness, show a lack of concern, have a loss of personal awareness, loss of social awareness and blunting of affect. This subtype is are very hard to diagnose in the beginning because these features can be part of many other diseases. The frontal lobe is initially specifically affected. Other behavioural changes include increased submissiveness, showing a lack of empathy (leading to troubles within families), more self-centred behaviour, emotionally cold, decreased concern about family and friends, inappropriate sexual comments and gestures. Also features of obsessive compulsive disorder (repetitive cleaning, organizing objects into groups, hoarding, counting) can be seen in some patients leading to diagnosing OCD per error. Behaviour is very impulsive.
The frontal cortex is affected. Many different subcomponents of the brain are located in the frontal cortex. When the orbitofrontal cortex is damaged, disinhibition, poor impulse control (clinically: restlessness, irritated, aggressive, violent outburst, excessive sentimentality), antisocial behaviour, stereotyped behaviour and decreased agreement is seen. When the dorsolateral frontal cortex,
medial frontal cortex and anterior cingulate cortex are affected apathy is usually the result (which may be mistaken for depression) But depression is uncommon in the behavioural variant of frontotemporal dementia.
When predominantly the right hemisphere is affected, patients show dramatic changes in attitudes, beliefs or religious sentiment (may become religious at once) and the most severe behavioural changes. Also dietary changes can be seen, like craving for sweets and decreased satiety leading to weigh gain. Finally some features of the Kluver Bucy syndrome can occur, for example patients putting weird things in their mouth. In the more advanced disease (behavioural variant) also a language dysfunction develops.
In neuropsychological assessment can be found that impairments of executive functions and social cognitions are the most common features in behavioural variant. Memory and visuospatial functions are relatively spared.

Semantic Dementia

Semantic dementia is the language variant. Semantic dementia points to a progressive loss in knowledge about people, facts and words or semantic knowledge. Patients start misusing words or are unable to recognize objects. A loss of memory for words, loss of word meaning and result is common for patients with progressive fluent aphasia. They are still progressive (fluent) in their speech. Semantic paraphasias are frequently present. Substitute phrases (like ‘thing’ or ‘stuff’) are often used leading to empty language. Patients are aware of these deficits because they hear themselves talking. They are unaware of their comprehension difficulties. Repetition, prosody (emotional tone), syntax and verb generation are preserved. Temporal lobe is initially specifically affected.

Assessment

Patients with semantic dementia are most impaired on category fluency tests (name as many cars possible in one minute). Naming tasks are hard. Generation of verbal definitions of words and pictures are impaired. In the early stage patients misidentify things and show a loss of subordinate knowledge. In the moderate and severe stage a loss of more than superordinate knowledge is seen, their specificity is gone. In the final stages behavioural problems occur on top of the language problems. Patients are disinhibited, compulsive, and show emotion comprehension impairments. These behaviours are more present in the right hemisphere damaged patients. In early stages is recent memory still relatively intact. Many autobiographical memories are lost. This is the other way around in Alzheimer’s Disease.

Progressive Non-fluent Aphasia

Patients with progressive non-fluent aphasia present with changes in fluency, pronunciation and word finding difficulties. Language difficulties showed are agrammatism (might use omission or use words incorrectly, or phonemic paraphasias) stuttering, impaired repetition (in contrast to semantic dementia), alexia and agraphia. Behavioural changes are not present until later stages of the disease. Executive functions including working memory are often impaired. Episodic, semantic memory and visuospatial relatively preserved.

Lecture: Lewy body diseases & Parkinson’s disease

Lewy body diseases

The name Lewy body diseases is a cluster of several diseases. Three diseases are included in this cluster, namely Parkinson’s disease without dementia, Parkinson’s disease with dementia and dementia with Lewy bodies. Parkinson’s disease with dementia and dementia with Lewy bodies are part of the Lewy body dementias. All three diseases are characterized by Lewy bodies. A Lewy body is a neuronal occlusion consisting of the following proteins: ubiquitin and alpha-synuclein. These are typically found in subcortical nuclei (especially in the substantia nigra). Between individuals with Lewy body diseases can be huge differences in where the Lewy bodies are located in the brain. In some parts of the brain Lewy bodies cause dementia, in other parts they cause Lewy bodies dementia. Pathology differs very strongly from Alzheimer’s Disease.

Parkinson’s disease

Parkinson’s disease was first described by James Parkinson in 1817. He wrote an essay on the shaking palsy, as a disease of the central nervous system. Characteristic features of this disease are: tremor, lessened muscle power, looking as if they are bent forward, they have a tendency to start walking faster and faster when they eventually start walking. The prevalence in 55-65 year olds is 0.3 per 1000. In the age group of 85 and older, prevalence is 4.4 per 1000. So again, old age is a risk factor, but young people can be affected as well (few people already in age group 30-40). Quite a lot of the patients has an onset before 50. The youngest case reported was 11 years old.
Parkinson’s disease is a progressive neurodegenerative disease which becomes worse over time. It has an insidious onset. Parkinson’s disease is caused by death of neurodegeneration of dopaminergic neurons in the substantia nigra. Dopamine is the neurotransmitter needed for communication between different neurons in the brain. Substantia nigra is black tissue, in Parkinson’s patients this black tissue disappears causing Parkinson. Dopamine levels decrease.
Parkinson’s disease can only be seen in the brain post mortem. But F-Dopa pet scan (when patients are injected with F-Dopa, a radioactive substance) enables us to study the dopamine levels in the brain. The higher the score on this scan, the more dopamine is still present in the brain. The uptake of the radioactive substance F-Dopa is much slower in Parkinson.
Fronto striatal circuits are affected by substantia nigra. Different parts of your frontal cortex (medial, dorsolateral, orbitofrontal) are strongly related to the striatum. Caudate nucleus and nucleus accumbens project to the frontal lobes. If something goes wrong in this stage, it effects the whole system. In Parkinson’s patients cells of substantia nigra degenerate leading to a decreased amount of dopamine. This decreased amount of dopamine leads to a decreased activity striatum which then leads to decreased activity in the frontal cortex.

Motor and neuropsychiatric symptoms

Parkinson’s disease is characterized by different motor symptoms. Tremor in rest (usually left/right arm), rigidity (something you can only feel, stiffness in the muscles), bradykinesia (slow in movement), postural instability (easily out of balance, fall a lot). These lead to the following clinical appearance: difficulties arising from chair, difficulties walking: slow, shorts steps, difficulties turning in bed (normal people do this automatic, no longer possible now), difficulties of keeping balance, frequent falls, monotone speech, drooling (because they lose ability to automatically swallow)
But Parkinson’s disease is not only a motor disease. It is a combination of a neurological disease and psychiatric disease. Four neuropsychiatric symptoms are usually present: depression (in 50% of patients), hallucinations (in 50%), cognitive decline (in 84%) and dementia (in 84%)
Neuropsychiatric symptoms associated with Parkinson’s disease are depression, apathy and anhedonia. These are usually not a response to the disease but are caused by the neurological changes. Clear visual hallucinations (humans or animals) are often reported. This is often a precursor for dementia. Also impulse control disorder is frequently reported, caused by the treatment patients receive (increasing dopamine in the brain or deep brain stimulation, nuclei stimulation).

Cognitive impairments

In patients who visit a neurologist for the first time is found that 24 percent already has cognitive impairments. Cognitive impairments also progress over time (like motor symptoms). Mild cognitive impairment in the context of Parkinson’s disease or Parkinson’s disease dementia. Affected domains are: psychomotor speed (slow in thinking), language (not similar to aphasia, difficulties complex sentence structure, mild), memory, visuospatial skills, mostly attention and executive functions. That executive functioning and attention are mostly affected is not surprising, because of the frontal cortex impairments caused by the damaged fronto striatal circuits. As the disease progresses, patients can develop dementia (50%). If they develop this they experience a degeneration of attention and psychomotor speed. Risk factors are age, visuoconstructive dysfunctions, and impaired semantic verbal fluency (name as many animals as possible)
The diagnostic criteria for Parkinson’s disease dementia are: a) The disturbance occurs in the setting of established Parkinson’s disease. b) Insidious onset and gradual progression. c) Not attributable to another medical condition or mental disorder. d) This disease has a negative influence on functioning in daily life. e) cognitive impairments are present in at least 2 of these domains: memory, attention, executive, visuospatial. Presence of agitation, visual hallucinations, excessive daytime sleepiness, depression, anxiety, apathy make the diagnose more likely.
Compared to Alzheimer’s disease we see that more in more cortical disorder as Alzheimer’s disease aphasia, apraxia, agnosia are common but these are not common in Parkinson’s disease (subcortical dementia). Also the memory impairments are different. In Parkinson’s disease patients experience troubles with retrieving. In Alzheimer’s disease patients experience problems with storing new information. Patients with Parkinson’s disease perform relatively well on a recognition task. External cues have a positive effect in Parkinson’s disease patients, but not in Alzheimer’s disease patients.
Visuospatial problems are more often present in Parkinson’s disease patients. In contrast to Alzheimer’s disease little cortical atrophy is found. More fronto-parietal hypometabolism is seen in Parkinson’s disease patients.

Dementia with Lewy Bodies

Clinical and pathological features of dementia with Lewy Bodies show overlap with the features of Parkinson’s disease, but key features distinguish these diseases. Parkinson’s disease dementia is diagnosed in patients who develop cognitive problems 12 months or longer after development of motor symptoms (so the motor symptoms first). In patients with dementia with Lewy Bodies dementia occurs before the motor impairments. The cognitive impairments first progress over time and then the motor impairments occur.
The DSM 5 criteria for dementia with Lewy Bodies are: a) criteria are met for major or mild neurocognitive disorder b) insidious onset and gradual progression c)meets a combination of core diagnostic features and suggestive diagnostic features (2 core or 1 suggestive and 1 core). These core features are: fluctuating cognitions with variations in attention and alertness, recurrent hallucinations visual which are well formed and detailed, spontaneous features of parkinsonism, onset after cognitive decline. The suggestive features are: rapid eye movement sleep disorder and severe neuroleptic sensitivity. d) not better explained by any other disorder.
The prevalence of dementia with Lewy bodies is 10-25% of all dementias, 112 per 100000 persons. It is the second to third most common cause of dementia (depends on sample looked at). The central feature of dementia with Lewy Bodies is a progressive cognitive decline interfering with daily functioning. Impairments in memory, visuospatial, attention and executive dysfunction are found.
When comparing to Alzheimer’s disease patients, patients with dementia with Lewy Bodies show more severe deficits in attention, verbal fluency, visuospatial ability, executive, psychomotor speed. Their performance on Mini Mental state examination is relatively preserved. In Alzheimer’s disease more deficits in memory are reported. Memory fails at the retrieval stage in patients with Lewy body dementia, leading to intact performance on recognition tasks. Confrontation naming tasks are preserved. The rate of cognitive decline is slightly faster in patients with dementia with Lewy Bodies than with Alzheimer’s disease. The survival rate for patients with dementia with Lewy bodies is between 6-9 years and for patients with Alzheimer’s disease between 8 and 11 years.
The core feature of dementia with Lewy bodies is the fluctuation in cognition and alertness. This is a very prominent symptom, occurring very early in the disease. These fluctuations can occur minutes to hours or days to weeks. Depth of fluctuations range from impairments in concentration to episodes of wakeful unresponsiveness to episodes of daytime sleepiness. These fluctuations are likely due to damage to the alerting and arousal systems in the brainstem. Identification of this problem is difficult, so always ask caregiver about information. If you have a suspect of fast fluctuations, use same test more than once during an assessment. Second core feature is parkinsonism: 45-100 percent of patients experience these symptoms. These motor symptoms mirror symptoms with Parkinson’s disease. There are some differences: rest tremor is less common. Rigidity and bradykinesia are present in both. Postural stability, hypomimia and gait difficulties are more present in dementia with Lewy Bodies. The Thirty core feature is neuropsychiatric symptoms: 80% of patients has visual hallucinations, usually early in the disease. Very colourful, vivid, three-dimensional images of mute people or animals are seen. Patients have some degree of insight, somehow realise that the hallucinations are not real, but this decreases as the disease progresses. This is not very upsetting for patient but it is upsetting for caregiver. Hallucinations are either associated with paranoid delusions (theft or persecution) or delusional beliefs that loves ones are replaced by imposters (Capgrass syndrome). Apathy, anxiety and depression can occur. These neuropsychiatric symptoms tend to persist and stay part of the disease.
Suggestive features of dementia with Lewy bodies are sleep disorders. Mainly Rem Sleep Behaviour Disorder. Normally when we sleep our muscles relax, this does not occur when having Rem Sleep Behaviour Disorder. Vigorous movement in sleep is reported, as if patients are acting out their dreams. Patients do not recall these movements during their sleep but partner usually remembers this. Partner can also be hit per accidence. Rem sleep Behaviour disorder is associated with dementia in general, but more common associated with Lewy body disease than with Alzheimer’s disease or frontotemporal dementia (90% LWB). Rem sleep behaviour disorder is also a risk factor for dementia with Lewy Bodies (proceeds). Another suggestive feature is severe neuroleptic sensitivity. Neuroleptic medicines are used to treat psychoses. These neuroleptics have many side effects (drowsiness, falls, parkinsonism). Side effects can occur in anyone but they are more prominent in patients with dementia with Lewy Bodies.
Occipital hypometabolism can be seen in the brain. Also a reduced dopaminergic transmission: no differences between Parkinson’s disease (dementia) and dementia with Lewy bodies. Dementia with Lewy bodies and Parkinson’s disease dementia have a strong overlap with regard to pathology and symptoms. This overlap gets more apparent in the later stages of disease. Only can be distinguished in early stage.

Huntington’s Disease

Huntington’s disease is also a subcortical disease. It is described by George Huntington (1872) for the first time. He called it insanity and impairment of the mind. Huntington’s disease is a rare disorder, the estimated number of patients in the Netherlands is 1200-1500 patients. Every year 60 new patients are diagnosed. Huntington’s disease is a progressive, hereditary disease with insidious onset, with motor /cognitive and neuropsychiatric symptoms. In 1993 was found that Huntington is caused by a CAG repeat on the short arm of chromosome 4. CAG has tree DNA bases: cytosine, adenine and guanine. Healthy individuals have less than 36 repeats of CAG. When 36-39 repeats are found, symptoms are mild and people can stay relatively healthy until old age. Above 40 CAG-repeats Huntington’s disease usually arises. Huntington’s disease is an autosomal dominant disease. Every son or daughter of a gene carrier has 50 percent of being affected by Huntington’s disease gene. Age of onset is mean 40, but there is a huge range from infancy until 90 years. The more CAG repeats you have, the lower the age of onset. Someone can be diagnosed based on presence of motor symptoms, positive family history and DNA testing. Huntington gene leads to changed functioning of huntingtin protein, leading to neurodegeneration of the brain. Early stages: degeneration of striatum, resulting in a dysfunction of the fronto-striatal circuits (just like in Parkinson’s disease). So, In Huntington’s disease the frontal cortex is affected. Also changes in the dopaminergic neurotransmitter system occur because of impairments in the striatum.
In Huntington’s disease there is a decreased dopamine receptor binding, not decreased amount of dopamine. In the later stages of Huntington’s disease more global atrophy of the brain can be seen. The ventricle becomes bigger. Huntington’s disease is not strictly a movement disorder. Cognitive decline can be an early symptom. In 8.4% of patients cognition impairment was the first symptom and in 15% a combination of motor and cognitive impairments.
Motor symptoms are dyskinesia (chorea: uncontrollable movement, dance like), hyperkinesia (decreased number of spontaneous movement), bradykinesia, dystonia (sustained muscle contractions), rigidity, dysarthria (speech is difficult to understand, speech becomes less clear because of pronunciation problems), problems with eye movements, problems with swallowing, problems with keeping balance. Chorea is the most striking symptom.

Cognitive impairments

The progressive decline in Huntington’s disease differs between patients. Usually the cognitive impairments are relatively mild until later stages or very fast progression with an evident dementia. Psychomotor speed, attention, memory, executive functions problems are particularly present. Far from the onset of disease 40% of studies already finds impairments, in the early stages of the disease almost all studies find impairments of executive functions. Patients show impairments in self-control: they do not recognize and correct errors. Inhibition, planning of tasks, taking initiative and selective attention are impaired. Memory problems are reported as problems in encoding and retrieval of information, working memory. Psychomotor speed impairments, slowness of thinking (assed by trail making test) and slowness in acting, are not caused by motor symptoms. Patients can have either motor or mental slowness or both. Language impairments are mainly found in later stages of the disease, not speech itself but the pronunciation is impaired. Social cognition is impaired because of impairments of frontal cortex: recognition of emotions is affected. In later stages even impairment in theory of mind is found. Intellectual functioning in later stages also becomes affected, nonverbal tasks are more severely affected than verbal tasks. Bradyfrenia has a negative influence on tasks with a speed component.
The odd thing is that these patients rarely complain while their motor impairments are so severe. This might have to do with impairments in executive functioning. Also might be because of a psychological protection mechanism: causing patients to be not aware. Or physiological mechanism: patient are not sensory aware of chorea movements. It is not clear yet which of these is true.

Neuropsychiatric symptoms

Patients show changes in their affect, character and behaviour. There are large individual differences, however. Affective disorders can be present, like depression (primary consequence of the pathophysiological changes). Also suicide risk is much higher compared to the general population. Often anxiety is reported (being insecure about the future). Apathy can be present mainly in middle or late stage in disease, related to stage of disease and executive impairments. Agitation is often one of the first symptoms of the disease. This can also result in verbal or physical aggression, which is very hard to deal with for caregivers. Disinhibition is present, patients show no self-control related to eating, drinking, speaking or sexuality. Result: some patients get addicted to alcohol, drugs or gambling. Also compulsive behaviour can occur. Psychoses can occur, but less common neuropsychiatric disease.

Lecture: Mobility

Mobility and Dementia

Anselm Fuermaier

Mobility

Clinical neuropsychologists are very often approached with the question if older people with neurological conditions should be able to drive in a vehicle. This is nowadays an important question because of the current societal changes. The proportion older people will be doubled by 2075. The fastest growing age group is 85+. In this age group normal cerebral and cognitive decline takes place, but also pathological cerebral and cognitive decline. This decline has consequences for daily functioning, this can for example be seen in mobility. With the concept mobility all kinds of transports are meant, but the most important part is driving in a car. People are very used to be able to drive in a car.
Mobility is very important for patients for different reasons: to travel and for the feelings of independence and to booster self-esteem. These feelings are still very important for older people. Besides these advantages, mobility also brings exercise benefits (being out of the house) and social involvement in the local community. Potential travel, knowing that they can travel if something happens, even if they don’t do it, is a crucial reason to feel safe for most of the patients. Many studies show that out of home activities attribute to physical health and psychological wellbeing.
Older people still drive: of the age group 80-84, 51 percent still drives. From age group 85-90 only 15 percent remains. So a big drop occurs in between these five years.

Research Methods

While assessing if older people are still able to drive safely, driving outcome and driving performance are considered. Assessors are looking at individual characteristics in association with driving performance and driving outcomes. Driving outcomes can for example be a crash. Driving performance can be high risk behaviour (e.g. running a red light). We need different methods to assess this association.

Assess driving

• In a behind the wheel examination individuals are examined on the road. Advantages of this method are: measurement on the road, it is a direct method and results are quantifiable. Disadvantages are: this method is not standardised so individuals are not really comparable (differences can occur in when/where a person is driving, is it raining etcetera). This method cannot control if a person is facing challenging circumstances or not. Also a subjective rating is applied.

• Instrumented vehicle: in this method instruments are linked to vehicle inputs (e.g. cameras). Advantages of this method are: it is easy quantifiable, more objective, and takes place in the car. Disadvantages of this method are that this method is very expensive, not so easy to implement all the time, a certainly clipped car is needed, and patients sometimes show problems adapting to a new car.

• Driving simulator virtual reality is a very practical method. Advantages of this method are: the situation can be exactly controlled (for example make the weather very bad), the researcher can decide about challenging situations, it is a very safe presentation, great variation in elaboration of implementation, and concise conclusions can be stated. There is some criticism at this method though, because some say translation from simulated driving to real world is not possible. People can for example be more risky because they know it is not for real, feels like gaming.

• Crash statistics are very easy to collect and have very strong clinical relevance. Negative consequences are that these statistics are collected after the effect and cannot predict or prevent anything. Crashes are very infrequent events and only if they are reported to authorities they will count in this assessment, so researchers are depended on authorities (who don’t always have the same interests).

• Self-report questionnaires (e.g. about driving history) are very easy to asses and large databases can be made because they can be distributed online in a short period of time to very much people. A downside is that not everybody is able to assess their own performance, so bias can be found in the data (over/underestimation).
  Several types of methods are needed for different kinds of questions. Each method has his own advantages and disadvantages. The closer to reality the testing method, the less controlled the method is. Cognitive tests show medium correlations with driving performance, but the closer the assessment is to reality the closer the results are related to driving performance. How to rate on the road performance is a very hard decision. That’s why objective scales of on road behaviour differ.

Comparing diseases and driving performance

In this section the results of driving assessment from healthy older drivers and drivers with neurological conditions are compared. The used neurological conditions are Alzheimer’s Disease, Parkinson’s Disease and Mild Cognitive Impairment (MCI). The variables tested for are crash rates, driving errors and cognition.
Healthy older drivers do not have more crashes, majority has even lower rates. The rate of crashes increases when driving exposure decreases. So, older peoples who drive less are involved with more crashes (subpopulation). Older drivers are more likely to be involved with: intersections, stop signs, and turning against oncoming traffic. Older people show a dangerous breaking profile: they drive close to a stop sign and then stop very fast (so people from behind might hit them). Older drivers fail to evaluate the speed of oncoming cars. Drivers above 90 even fail to see oncoming vehicles.
Cognitive functions can predict driving performance from tests. Results on On the road tests can be predicted with: memory, visual perception, constructional praxis and executive functions. Results from assessment in an instrumented car can be predicted by how easily distracted one is and visual spatial skills. For assessment in the simulator the trail making test is the best predictor for safe/unsafe/restricted driving. Cognitive functions are associated with driving performance predictions, but there is high variability in results. So a conclusion for the individual person can’t be made.

Alzheimer’s disease

Alzheimer’s patients do not have an increased risk of a crash. They do commit more driving errors. Also the severity of dementia is associated with rates of BTW (Behind the Wheel) exam failure. Many drivers with Alzheimer’s Disease are able to safely maintain routine driving over several years (driving their own route) but their ability to adapt to novel situations is declined (trouble occurs in new unexpected situations). But errors not necessarily lead to crashes. Alzheimer’s patients will pass in their own situation a Behind the Wheel exam, but can fail the simulator test. Here the importance of using more methods is shown.
Cognitive functions that predict crashes, errors and the sudden braking profile are executive functions (assessed by Trail Making Test) and visuospatial abilities. The Trail Making Test is very old, very short and easy to conduct. The Trail Making Test is also easy to analyse. That’s why it is used so much. The TMT is very sensitive (so it finds differences between control and patients easily). But it is hard to say what this test actually measures. Again, very heterogeneous results are found.

Parkinson’s Disease

Parkinson’s patients do not perform more crash risk errors. Most of them pass on the road driving situations. But they are more likely to perform certain errors, not high crash risk errors, but more minor errors (changing lanes, failing to check a blind spot, backing out of space, indecisiveness at intersections, reduces usage of side and rear-view minor). In a driving simulator these errors can be detected. When using the driving simulator it is possible to make a prediction for the future driving behaviour. It is very important to make a recommendation about their impairments in the future.
Cognitive functions predict error counts in a BTW exam (behind the wheel), while comparing the drivers valuated as safe, unsafe or marginal safe and comparing Parkinson’s Disease drivers passing and failing simulation ride. But it’s again a difficult question how to define passing or failing. Neurological assessment again is important here. Executive, visuospatial functions and visual attention (anything involved with attention) are most predictive for performance.

Patients with Mild Cognitive Impairment (MCI)

Drivers with MCI are not more unsafe than healthy drivers, but their driving is somehow not optimal. Executive dysfunctions may underlie different driving performance. Research is behind on this topic, but it is important that research will be done in the future because people with MCI can develop Alzheimer’s Disease later on, and predictions are needed for their future behavior. A problem with this research is that many people with MCI are not detected or not diagnosed.

So, many older drivers drive very safely in their own environment, but they might have problems driving in new or challenging situations. They are not able to adapt in these new situations. A higher proportion of older drivers are more likely to commit some types of error, but these errors do not have to lead to higher crash rates. There is a clear association between cognition and driving, but its heard to make the statistical significant outcome’s to clinical meaningful outcomes. We need to consider risk factors as: history of crashes/errors, reduced driving mileage, self-reported avoidance, and if aggressive personality characteristics observed.

Assessment of Fitness to Drive

We need evidence based assessment of fitness to drive. The aim of this is to compose a battery/assessment method to accurately fitness to drive in older people. History of illness, off-road assessment and on-road assessment needs to be assessed for this battery. Depression in dementia can be very similar to dementia or comorbid to dementia. This underlies cognitive problems. Also assess individual characteristics (marital status, gender, how important is mobility for this person). These personal variables are crucial to make good conclusion, because people can be very dependent on mobility (physical or psychological).
In off road assessment these cognitive functions are assessed: divided attention, short term memory, mental flexibility. After off road assessment, on road assessment (with driving specialist) is done. Be careful, a patient can also occur nervous, cautious and initially slow because of importance of mobility for this person. Driving tendencies are assessed. But, cognitive impairment is not equal to driving impairment! A multimethod assessment approach is needed to make a decision.
To test cognition: general mental status (eg. MMSE), attention (working memory, attention switching), memory functioning (learning, recall), executive functions (Trail making test, fluency), and visuospatial skills are assessed.
Risk factors for crash rates are: age, medical condition, medication treatment, history of crashes/citation, reduced driving mileage, avoidance patterns, and personality characteristics: aggressive traits. Equal important is the awareness of the patient’s own functional ability. If somebody is aware of problems, they might be able to compensate for their dysfunctions.

Decision making

Decision making about if the patient is still able to drive safely can be done in different ways. Usually dichotomization is used. Dichotomization means yes or no (nothing in between). Everything above the cut-off score is categorized as fit. Every score beneath the cut off score is categorized unfit. But errors can occur. How many do you classify as unfit? To answer this question sensitivity and specifity are important. Sensitivity is the number of people classified as unfit to drive divided through all the people who are unfit to drive. Sensitivity should be very high. Specifity is those that are classified as fit to drive divided through all people that are fit to drive). When someone is categorized as unfit, this can have big consequences. Usually depression rates much higher. Another concept associated is the predictive power. Positive predictive power: how many of older people classified as unfit to drive are actually unfit? Negative predictive power: how many of older people classified as fit to drive are actually fit?
But there are also other possibilities of defining cut-offs, for example trichotomization. Three options are possible: fail, uncertain or pass. But then again the question rises, what should we do when we someone is categorized uncertain? Another possibility to define cut-offs is serial dichotomization. After three passed test someone is safe to drive, but a patient fails one of the tests he or she is unsafe to drive. Serial trichotomization is the last option: When categorized uncertain two times, new test for fail or pass to make a final conclusion.
Next to the cut-off score, norms have to be considered. With this is meant how good is this person compared to people from the same age group?

FItCI; Fitness to drive with cognitive impairment: study

Need for individual assessment of fitness to drive, because a lot people with Alzheimer fail the fitness to drive test, but also a lot pass. The solution of the study is that patient’s should be tested an on road test by Dutch licensing authority. Clinical interviews (driving questionnaires, clinical dementia rating, driving behaviour and experience), neuropsychological tests (attention, executive functions, visuospatial and traffic-related tests) and driving simulator (intersections, swerving, steering, priority regulations, merging) were used in this study. Surprisingly, neuropsychological tests found to be best predictive source of information. A combined approach gives an 97.4% accuracy. Neuropsychological tests also had the highest specifity and sensitivity.

Interventions

Believe in technology might actually not improve behaviour, but detoriate behaviour.
Information from technologic devices has to be presented to driver, which increases the workload for drivers. Also, the devices should not take away responsibility from the driver (they still have to stay focused and active). Other types of intervention might be considered.
Cognitive interventions
Training of cognitive functions which are fundamental of driving. Older people are trained to increase speed of processing, improvement of visual attention and processing speed (first on computer then in more real life studies). This is very promising to drive safely for a longer period! Some questions are still open, at which age/function most beneficial? Is it preventing to decline or improving performance? Which mode of delivery?
Educational interventions
Are aimed to identify potential problems, develop solutions, facilitate family discussion related to quit driving (people are more happy when they decide for themselves that they want to stop driving than they have to) They work by giving the patient a driving decision workbook, educational training sessions, and knowledge to enhance your safety (KEYS). These improve performance in daily life. In older people they bring greater awareness, self-regulation, and reduced driving. The long term outcome is questioned, though.

Clinical interventions

These take in account that reduced mobility can result in depression, social isolation, threats to self-concept and loss of independence. Its based on the Social Cognitive Theory (Bandura) and focuses on self-efficacy (feelings of control over self and environment). In older people its promising to reduce negative effects of driving cessation.

If all these not work alternatives for mobility can be considered. Acceptable and accessible public transport for older adults are slow motorized driving (8-50 km): e- bikes, scooter, mobility scooter or a micro car. This can extend their quality of life. But are these really safe? And under which conditions? More research is needed to answer these questions.

Lecture: Decision making & caregivers

Decision making & caregivers

Caregivers

The caregivers of patients with neurological and psychiatric disorders can be nurses and doctors. But this lecture is about the family members of the patients. Most of the time the partners or children of the patient take the role of caregiver. Today we talk specifically about the caregivers of older people. Caregivers might have different problems to deal with. For example, that they want to respect the independence of the patient and help them at the same time or how they have to respond to the patients.

Dementia

As told before, cognitive symptoms of patients with dementia are: memory loss, executive dysfunctions problems and agnosia. Also psychiatric and behavioral problems arise: apathy, hallucinations, depression, aggression, restlessness can manifest. The duration can be a few years to over a decade. There have been many hypotheses about caregivers of patients with dementia.

• Wear and tear hypothesis: Over time the caregivers functioning steadily declines as a result of prolonged stress.

• Adaption hypothesis: Caregivers adapt to the demand of caregiving over time and their physical and mental health stabilizes or improves

• Trait hypothesis: In spite of the progressing dementia, caregivers function well because of individual characteristics.

Most evidence is found for the adaption hypothesis. But, several factors about caregivers have to be taken into account. First, caregiver predictors which include the personality of the caregiver and caregiver strategies. Second, patient behavior (memory loss, agitation) and third: caregiver consequences (stress, quality of relationship).

Dementia is a progressive disease. Many people think that disease starts in a mild form with all the symptoms and these progress over time, with the dysfunctions getting only worse over time. But that’s not dementia. At some point one develops memory loss, at another time aggression. So new symptoms occur later in the disease progression, they are not all present in the beginning and get worse over time. This pattern differs between patients. Caregivers need to adapt constantly for this pattern based on the changing behaviour of the person they take care of.

Problems in daily life

Caregivers have to remind their patients to appointments, medication and other things. Also language difficulties can cause problems in the relation of caregiver and patient. Financial difficulties may be a problem because the patient can make mistakes, but also that care and healthcare costs a lot of money. Even in their basic healthcare they might need some help. Cooking dinner or making coffee might, for example, need help from the caregiver. On top of that, a caregiver has to think about the future. Decisions about nursing home and the death have to be made. These topics are very hard for caregivers to deal with.

Caregiver burden means the multidimensional response to physical, psychological, emotional, social and financial stressors associated with the caregiver experience. This burden cannot be strictly tied to the severity of dementia or length of time someone has provided care. So burden is not a constant thing, it changes over time.

Progress in the disease

The early stages of Alzheimer’s disease are often characterized by memory disturbances, personality change. A diagnose might be given. In the beginning a diagnose might bring some relief. But soon many questions and concerns arise. In the middle stages the problems becomes worse and new problems might start (anger, agitation, depression). Depression can also occur in the caregiver. In the late stages of dementia we often see nursing home placement, because the care needed becomes too much for the caregiver alone. The nursing home placement doesn’t have to result in a decrease of burden because of financial strains, loss of companionship and concerns about quality of nursing home care.

Caregiver predictors

There are gender differences in caregiver burden. Female caregivers experience more depression, anxiety and psychiatric problems. Women also spend more time on caregiving. On top of that, women have more caregiver burden and role conflict. Women have social activities, work, children and have to take care of parent now. Therefore, women are more likely to become so-called ‘super caregivers’, and want to do many tasks simultaneously whereas men more focus on one task.

Three important things have to be taken into account. First, there is great variation among individuals in the nature and impact of caregiving. Second, gender differences are more pronounced among adult children than among spouses. And last, men are certainly not immune to caregivers problems.

Burden depends on the relation to patient. Spouse caregivers experience more stress and depression. They are usually caregivers for a longer amount of time and are not able to leave patient. They have a greater likelihood of having health problems themselves. Adult (children of the patient) caregivers are more likely struggling with a role problem and conflicts might arise with other siblings about the care of the parents. Spouse is always next to the patient, while a child-caregiver also has a life outside of the problems.

Coping skills make a huge different. Coping means how we deal with problems. Problem-focused coping is the form of coping which includes making effort to change the stressful event. Emotional focused coping is done when internal strategies are used to manage ones emotions. Active problem solving is associated with better wellbeing. Differences might also occur because of differences in personality. Some caregivers are more likely to perceive a situation as stressful. Very optimistic individuals might be less effected with the burden. Neurotic individuals and individuals with high anger levels might be most effected.

On top of these factors, some other factors can also be important. Social support is often very beneficial. Also the health behaviour is important. Physical activity, not smoking, and limited alcohol consumption have a positive effect on caregiver burden. Even companion animals might have a positive effect on caregiver burden.

Caregiver consequences

Some studies looked at relation between caregiver burden and blood pressure. Stressful situations lead to a higher blood pressure. Caregivers show more difficulties maintaining a stable blood pressure. Also, high burden show increased activity in the hypothaliamic-pituitairy adrenal axis (result of stress response). So an increased level of cortisol is the consequence. When increased for a longer period of time, this increased level of cortisol has negative impact. Caregivers might then have a poor antibody response. High levels of caregivers burden (distress, depression) can also cause increased risk of cardiovascular disease. Caregivers bring more visits to the doctor, use more medication, are more often in the hospital, have more days of illness, and show more chronic illnesses. It is even an independent risk factor for mortality.

But, in all these: large individual variation is found.

Are dementia caregivers unique?

Dementia caregivers vs caregivers of patients with cancer and diabetes.

The majority of caregivers are taking care of parents (49%), 18% of friends and little groups are taking care of spouse and others. The same picture is shown in caregivers of patients with cancer and dementia. Also the activities of daily living that need support aren’t so much different in patients with cancer or dementia. Again the same pattern is shown in needed help with instrumental activities of daily living. In diabetes 65% of caregivers take care of their parents. In daily living activities less help is needed but in the instrumental activities no major differences are shown. So, most caregivers take care of their parents, this is irrespective of type of disease. Patients with dementia and cancer need more support with activities of daily living than patients with diabetes.

Caregiver burden is thus present in many different diseases. Caregiving also has positive aspects. Caregivers feel needed, feel good about themselves. Caregiving can enhances spirituality, self-efficacy and personal growth. Caregivers might feel a strengthened relationship with others (with the patient or with another helping person). Caregivers who find this positive elements are less depressed and burdened. They have personalities which focus on gains instead of losses. End result is based on negative and positive consequences. This result can change throughout the patients illness.

Decision making

Decision making is very important in our daily lives. In older adulthood independent living, financial management and treatment consent, testamentary capacity, research consent, sexual consent, voting and driving decisions have to be made. This lecture is about treatment consent (medical decision making) and financial decision making. On these two we have most knowledge. Still there is a lot unknown information. Financial decision making includes the ability to independently manage ones financial affairs in a manner consistent with self-interest and personal values. To make proper decisions these qualities are needed: the ability to describe financial concepts (declarative knowledge), procedural knowledge (how to pay a bill), and judgment (which insurance is best for my situation). In daily life, you can think about shopping for groceries, buying or selling a house, having (problems with) a car, buying a TV. Financial decision making can be very simple, but also complex decisions have to be made. Financial decision making can be assessed with the Financial Capacity Instrument (FCI). The FCI assesses 9 domains. 1.) Basic monetary skills. 2) Financial conceptual knowledge 3.) cash transactions 4.) Check book management (bit outdated now) 5.) bank statement management 6.) financial judgement (can one detect risk of phishing and other fraud) 7.) bill payment. 8.) knowledge of personal assets/ estate arrangements (savings, investment). 9.) investment decision king. Based on this a total score is made and compared to a cut off score. Other kinds of assessments include: Real life situation (semi structured interview). Can patients identify the problem in the given situation? Does the patient understand which options are available? Reasoning, the pros and cons of a decision, is assessed. Can someone appreciate the value of the decisions? And can someone express their choice?

Impairments in financial decision making are not already present in all individuals with MCI. Some patients also have more experience with financial decision making than others. Patients with dementia need more help and even more patients say they cannot do it at all. Patients in the mild stage early on already have a broad range of impaired financial skills. This skill declines with the progress in a year both in simple and complex domains. In normal ageing only minimum changes are seen in financial decision making. In dementia patients help is needed.

Areas in the brain associated with financial decision making are the medial frontal cortex, precuneus, angular gyrus, hippocampus and the dorsolateral frontal cortex. The volume of these areas is declined in patients with dementia. Decline of the medial frontal cortex shows impairment in financial decision making, but research has only looked at the structure of the brain. Not at the activity in the brain. These conclusions are also based on only one study. More research is needed. Important cognitive functions needed for financial decision making are arithmetic skills (needed for basic transactions), visuomotor sequencing, memory functions and executive functioning. Financial decision making is thus multidimensional because of the different cognitive functions involved.

Medical decision making

Older adults are confronted with diseases, but should they still take treatment or not? They are certainly positive effects of the treatment but these treatments also can have negative side effects. Electrodes for Parkinson’s patients might, for example, lead to addiction, behavioural changes, or infections.

Medical decision making refers to patient’s capacity (cognitive and emotional) to accept a proposed treatment, refuse treatment or select among other treatment alternatives. Assessment of medical decision making is done by confronting the patient with an example situation. Neuropsychologists look at understanding of the patient (do they understand all the options, situation). These assessments are also about reasoning: to what extent can the person arrive at a certain decision? And appreciation: what would certain treatment mean for me? A patients must be able to evaluate certain options and express a choice. MCI patients show no impairments in expressing and make better choices than persons with Alzheimer’s Disease. But in progressed dementia, many problems are shown in this assessment. Understanding, reasoning and appreciating are impaired. Expressing problems arise in the language problems variant. The same general pattern as the financial decision making is found. Memory, executive functioning, and attention are needed for medical decision making. Medical decision making might also have legal, ethical and clinical consequences. Decision making can be done by a legal representative (if I’m not able to make this decision myself, my daughter can make this decision). Clinicians have to be careful with the decision if patient can make his own decisions? With mild impairments it is very hard to say where to draw the line. This is one of the reasons why we need more assessment tools.