Differential Diagnosis of Depression and Dementia - Bieliauskas & Drag - 2013 - Article

Studies have shown that depression in older adults has a prevalence rate between 3 and 14% in that population. One in 15 older adults may experience major depression over the course of one year. This late life depression is associated with negative outcomes, like disability, functional impairment, increased medical symptoms and increased use of health care services. Depression also has economic costs. Because of unexplained somatic complaints and functional impairments, older adults with depression use more medical services. One study showed that depressed older adults incurred 50% higher medical costs than non-depressed people of the same age. Most of these costs went to diagnostic visits, emergency room visits, pharmacy costs and primary care visits. A small part went to mental health care. Late-life depression can place a big burden on patients, the health-care system and caregivers. It is therefore important to assess the illness adequately and to treat the disorder.

Pseudodementia

Late-life depression can be accompanied by cognitive impairments. These changes look a lot like those associated with dementia. In the history, a psychiatric illness that mimicked dementia symptoms was referred to as pseudodementia. The cognitive symptoms of pseudodementia were assumed to be related to transient mood symptoms. Because of this, they were thought of as reversible with adequate psychiatric treatment. Because of this, the term reversible dementia was also used to describe depression-induced cognitive impairments. Wells was one of the first clinicians to popularize the term reversible dementia. He observed his patients with pseudodementia and saw that they had complaints of memory loss that were not apparent to their examiner. They also highlighted their failures and talked much about their disability. However, they functioned well and better than they said they can. This is different from patients with dementia, because patients with dementia often lack insight into the extent of their dysfunction and they tend to minimize their symptoms because of that. He also noted that patients with pseudodementia often responded ‘don’t know’ to close-ended questions, while they were able to provide detailed responses on open-ended questions. Patients with depression-related deficits also have recent and remote memory deficits. Wells also said that demented individuals often try to rely on calendars and notes, but depressed individuals do not attempt to compensate for their difficulties.

Pseudodementia was initially popular among clinicians, but now clinicians debate about the use of this term and the term is not really used anymore in current practice. The term was important, because it encouraged clinicians to evaluate every patient carefully and to look at alternate causes of cognitive decline other than dementia. However, this term has drawbacks. It implies a mutually exclusive process and this may lead the clinician to focus on whether someone is demented or depressed and the possibility that both conditions could be present is excluded. This term also implies complete reversibility. Research has found that in some older adults with depression and cognitive impairment, executive functioning did improve after an antidepressant treatment, but it failed to reach normal levels of performance. Other studies have also found that the treatment of depression may initially lead to improvements in dementia-related symptoms, follow-up shows that true reversibility of dementia is uncommon.

Depression as symptom of dementia

Although late-life depression can reflect a psychiatric disorder, it is more often the case that depressive symptoms are early manifestations of an underlying progressive dementing illness. High rates of depression and psychiatric symptoms are found across various neurodegenerative disorders, like vascular dementia, Parkinson’s disease and Alzheimer’s disease. Studies found that half of all individuals with cognitive impairment or diagnosed with dementia exhibited at least one psychiatric symptom. People with cognitive impairment or mild dementia most often have depression as a psychiatric symptom. In many studies, depressive symptoms appear to be highly prevalent in individuals with dementia. Depression can’t be solely attributed to a reaction to the disease itself. There is also no strong support for an association between severity of dementia and depression. Symptoms of depression can be equally prevalent across disease stages. There is a high comorbidity between depression and dementia and research has shown that depressive symptoms may be an early sign or risk factor for subsequent dementia or impairment. One study found that people baseline depression were more likely to develop dementia compared to non-depressed counterparts and they are also more likely to develop dementia earlier. It may be that depression is a risk factor for dementia, but it is also likely that depression is a behavioural manifestation of the dementia process itself. More research is needed into this subject.

Clinical assessment

Neuropsychologists play a big role in the assessment and treatment of dementia and depression. Many clinicians, like psychologists and neurologists often refer older adults for neuropsychological evaluation to better clarify a patient’s cognitive and psychiatric complaints. Neuropsychological evaluation can help diagnosis, management and treatment of the symptoms better.

It is important for the neuropsychological evaluation of a patient with depressive symptoms to gain qualitative and quantitative understanding of the symptoms. However, it is often difficult to assess depression in older adults. This can result from the fact that symptoms of depression are sometimes confounded by the effects of age and medical disorders. A loss of interest in activities and changed in appetite, libido and weight are common to medical illnesses, effects of aging and depression. For example, somebody may have a decline in social activities, but that should not mean that this person is depressed. He or she might no longer be able to drive and doesn’t have friends or relatives nearby. Also, a preference to stay home might be fatigue because of medical conditions rather than symptoms of depression. Older adults may also be more likely to underestimate their depressive symptoms. Older adults may have lower functional expectations for themselves, because of their increasing age and they may therefore dismiss their depressive symptoms due to the ageing process or declining health. Also, older adults are less likely to report dysphoric mood than younger people. Older people rather present vague symptoms, like fatigue or trouble sleeping. Given the fact that older adults are less likely to report dysphoric mood, clinicians need to look to subtle indicators of depression. These subtle indicators can be social isolation, headaches, changes in appetite, fatigue or delayed recovery from medical procedures. A careful evaluation must be performed. This basically suggests that all older adults who complain of cognitive problems should be screened for depression.

There are psychometric instruments that have been developed to screen for depression. Some of these are the Hamilton Depression Rating Scale (HDRS) and the Geriatric Depression Scale (GDS). The last scale specifically targets symptoms common to depression in older adults. There are also rating scales that have been developed specifically for use in patients with dementia. There are rule-out diagnoses to consider when a patient present with reported changes in both mood and cognitive functioning. Some disorders should be considered, like depression, bipolar disorder and anxiety. Symptoms as depression, apathy and irritability are also common across many of the dementia subtypes, like Alzheimer’s disease and Lewy body dementia. Changes in mood can also be associated with strokes. Many medications used to treat medical illness in older adults can cause depression-like symptoms. Beta-blockers and other drugs can affect both cognitive and mood functioning. Clinicians should also consider that depression may be a secondary reaction to a chronic medical illness. Digestive disorders and heart disease are also associated with an increased rate of depression symptoms. This is probably the case because people perceive a lack of control over medical symptoms.

Difference between dementia and depression

The psychiatric and cognitive symptoms associated with dementia can differ from those associated with a primary depression. Depression is usually associated with a more acute onset of symptoms (days or weeks), while the impairments associated with dementia can progress over years. This means that a gradual onset and progression of mood and cognitive symptoms will more likely reflect a dementing process and an acute onset is typically associated with depression. Also, depression often goes together with subjective cognitive complaints. Older people with depression are more likely to complain more about their cognitive difficulties than individuals with dementia. These complains may be out of proportion to the person’s actual level of functioning. A patient may complain of severe memory deficits, but still independently manage his or her finances. A lack of insight into symptoms is common in dementia and these people will more likely minimize their cognitive difficulties.

The presence of apathetic symptoms can be important when differentiating between dementia and depression. Apathy can be seen as a loss of motivation and is manifested as a lack of interest, low social engagement and an empty emotional response. Apathy can be a principal symptom of depression, but it can also reflect an independent syndrome and as distinct from the dysphoric symptoms of depression. Apathy is often seen as indifference and dysprhoric symptoms are often seen as guilt, sadness, hopelessness and self-criticism. Apathy is a feature in many neurodegenerative disorders, like Parkinson’s disease and Alzheimer’s disease. Apathy symptoms are more prevalent than dysphoric symptoms in people with Alzheimer’s disease. This means that apathy may be an early marker of preclinical Alzheimer’s disease and dysphoric mood may be more indicative of a depressive disorder.

There are also other depressive symptoms that are associated with dementia. Depressive profiles can differ between primary depression and dementia and because of this, a new set of diagnostic criteria has been proposed. The new criteria require the presence of three symptoms and these symptoms are similar to the symptoms in major depressive disorder. Social isolation and irritability are added to these. Decreased positive affect or a depressed mood is required. These symptoms don’t have to be present every day (like they are in primary depression). Clinicians should also take the age of onset of depressive symptoms into consideration. There are difference between early-onset and late-onset depression, so these might be distinct entities. Late-onset depression has a first onset between 45 and 60 years of age. Pathogenic brain contributions are different for these two different onsets. Some researchers suggest that there are cognitive difficulties associated with an initial onset of depression and that these are based on neurological disease. Some studies have found that high-intensity lesions and atrophy have a connection to late-onset depression. Others have found a correlation between findings on neuroimaging and cognitive changes with depression. Loss of interest has also been found to be greater in late-onset depression. So, depression with a late age of onset is more likely to be associated with neuropathology or the early stages of dementia. When it comes to sleep patterns, depression and dementia can also differ. Alzheimer’s Disease is associated with poor sleep and with frequent night awakenings. The onset sleep is also later and goes together with difficulty awakening in the morning. Older adults with depression have difficulty falling asleep, wake up early in the morning and have an impaired sleep continuity. So people with depression have difficulty staying asleep in the morning, while people with Alzheimer’s disease have difficulty waking up in the morning. Increased REM sleep is more characteristic of depression than dementia and this might help distinguish depression from dementia. However, clinicians don’t have this sleep information ready available. They first have to request a formal sleep study.

Neuropsychological profiles

Neuropsychological testing is important and may help distinguish dementia from depression. The cognitive changes in dementia are more severe than those in depression. So there is a difference in severity, but there are also qualitative differences. Cognitive symptoms associated with dementia are progressive, but cognitive deficits related to depression should stabilize or improve with good management of the psychiatric symptoms. So there need to be repeated neuropsychological evaluations. Other differences are those in effortful processing. Cognitive changes in depression lead to difficulties on tasks that require a high degree of cognitive resources, but performances on tasks that are more automatic require less effort the complete. The deficits in dementia result in the impairments that are independent of the degree of effortful processing. This hypothesis might be useful, but it may be overly generalized and has not been supported fully by research.

Late-life depression is associated with cognitive deficits in the domain of attention, memory and executive functioning. Especially the executive functioning difficulties are most prominent in depression. These difficulties can mediate the cognitive difficulties found in other domains, like memory. Alzheimer’s disease is characterized by a prominent memory deficit. Depression and dementia can both impact performance on immediate and delayed memory tasks, but delayed retrieval tasks can differentiate between the two. Alzheimer’s disease goes together with fast forgetting of information and this results in poor delayed recall and recognition performance. Alzheimer’s Disease affects the hippocampus and this area is critical to memory encoding and storage. Depressed people may have difficulties with delayed recall, but their performance can improve when they are given cues. Research has shown that old people with depression perform poorly on list learning tasks, but when they were given semantic cues, their memory improved to normal levels. These cued recall tasks did not improve the memory of people with dementia and so these tasks can be used to distinguish Alzheimer’s Disease from depression.

Recognition tasks can also help distinguish between dementia and depression. Recognition tasks minimize the need for strategic and effortful retrieval and depressed people show adequate performance on these tasks, while patients with Alzheimer’s Disease do not. Serial position effects can also be informative. People with Alzheimer’s Disease show poorer overall recall on word lists compared to depressed people. Alzheimer’s Disease individuals recalled words from the end of the list better than the words from the beginning of the list. This is consistent with difficulty retaining information in memory over time. Depressed people recalled words from the beginning and end of the list better than words from the middle of the list. This poor middle-list performance distinguishes depressed people from healthy ones. There are also some other differences between these two. Patients with Alzheimer’s disease have more difficulty performing dual tasks than patients with a depression. Dementia is also more associated with impairments on task of naming, visuopercentual processing and ideomotor praxis (inability to mimic hand gestures) than depression is. So, dementia and depression can differ in quantity and quality of cognitive deficits. Alzheimer’s Disease is typified by a prominent memory disturbance and also with deficits in praxis and language. Depression shows a frontal mediated pattern deficit, that leads to executive functioning deficits which can have its effects on other cognitive domains, because of the lack of initiation or strategic processing.