Assessment of Alzheimer’s Disease - Loewenstein - 2013 - Article

Alzheimer’s Disease is a horrible illness and costs many countries a lot of money annually. The greatest risk factor for Alzheimer’s Disease is age and because of the growing ageing population, this disease can reach huge proportions. Alzheimer’s Disease was discovered fifty years ago, but not until now have we known the causes of the disorder. The neuropathology of Alzheimer’s Disease are senile plaques and neurofibrillary tangles in the brain. However, this can only be seen when a person is death. Researchers think that plaque formation in these patients begins with the abnormal misfolding of a protein called beta amyloid (A-beta). This protein causes toxic amyloid fibrils twenty to thirty years before clinical symptoms of Alzheimer’s Disease are manifested. These proteins continue to get worse, especially in the frontal lobes, the posterior and anterior cingulate, striatum and precuneas. Eventually, no phosphor group can’t be added to the protein tau anymore and this will result in neurofibrillary degeneration. This is seen as neurofibrillary tangles. This, in turn, will lead to neurodegenerations of structures like the hippocampus and to synaptic disruptions. These changes can be seen on neuroimaging machines, like MRI.

There is an early neurodegeneration in medial temporal lobes and so the first clinical manifestation of Alzheimer’s Disease is seen as the disruption of short-term memories. Further on in the disease, there are more pronounced memory difficulties, like misplacing things, repeating conversations, forgetting appointments and the worsening ability to recall recent events. A patients may also begin to have trouble with finding words, getting lost while driving or having trouble with judgment. This is caused by the worsening of cortical regions, like the frontal, temporal and parietal lobes. After a while, a patient becomes less able to manage his/her business and he or she loses the ability to perform activities of daily living. The progression of the illness is variable. It can be from several years to as many as 20 years, but eventually it will lead to total disability and death. The clinical diagnosis of Alzheimer’s Disease has a couple of criteria. The criteria are:

1. Memory impairment and an impairment in at least one other cognitive domain

2. Impairment in social and occupational function

3. No other possible causes of the dementia syndrome

A clinical diagnosis can only be rendered when all other possible causes for the dementia have been rules out. It seems that the diagnosis of Alzheimer’s Disease is one of exclusion. Neuropsychological assessment is needed to confirm the presence and degree of cognitive deficits. Gradual onset of memory decline and progressive course are called probable Alzheimer’s Disease, atypical presentations when other etiologies may affect cognitive impairment are called possible Alzheimer’s Disease. The accuracy of the clinical criteria for probable Alzheimer’s Disease exceeds 85%, but a final diagnosis of the disorder can only be made when examining the density of plaques and tangles upon autopsy. Recently, there has been a revision in the proposed guidelines for the diagnosis Alzheimer’s Disease. The diagnosis of probable Alzheimer’s Disease now includes non-amnesic presentation of the illness (executive, language and visuospatial). There is also an addition of biomarkers which strengthen the certainty of diagnoses, like low AB42 in the cerebrospinal fluid, disproportionate atrophy in the basal, medial and lateral temporal lobe on MRI and elevation of tau proteins. Nowadays, Alzheimer’s Disease is no longer a diagnosis of exclusion. For the diagnosis of Alzheimer’s Disease it is also important to establish the presence or absence of cognitive impairment. When a person is moderately or severely impaired, the clinician will find enough information to arrive at a clinical impression. However, sometimes the cognitive deficits can be quite mild and difficult to detect by experienced clinicians. People who have a high cognitive reserve can employ other brain resources to mask certain deficits. The current treatments for Alzheimer’s Disease do not treat the underlying pathology of Alzheimer’s Disease. However, some recent studies suggest that treatments will be most effective in the earliest stages of Alzheimer’s Disease, before multiple systems degenerate.

Mild cognitive impairment

Research has found that the clinical manifestation of Alzheimer’s Disease occurs well before the manifestation of a dementia syndrome and a clinical diagnosis of the disorder. Mild cognitive impairment is an intermediate state between a normal cognitive state and a dementia. As mentioned in the chapter about mild cognitive impairment, the criteria for a mild cognitive impairment are a subjective memory complaint by the patient or somebody who knows him/her very well, intact intellectual function, objective evidence of memory impairment and no sufficient cognitive impairment to cause impairment in social or occupational function. In clinical settings, the rate of progression from mild cognitive impairment to dementia was 10-15% per year. However, in community settings, the progression to dementia among subjects with MCI is less. This means that mild cognitive impairment does not have to be confined to only an amnesic impairment, but it can also be defined by non-memory impairments. There are different types of mild cognitive impairment, that have been discussed in a previous chapter. The degree of impairment on both non-memory and amnesic measures is associated with the likelihood that individuals with mild cognitive impairment will progress to dementia instead of reverting to a normal state. Some studies have found that there is a difference in progression to dementia between people with amnesic and non-amnesic mild cognitive impairment, while other studies have found there is not so much different (both have a progression of approximately 52-56%). Some studies have found that impairment in more than one domain was most predictive in progression to dementia. The greatest likelihood of progression to dementia was in the multiple memory impairment group.

The clinical interview

A big part of a neuropsychological assessment is a detailed clinical interview with the patient and a collateral informant who is familiar with the patient’s daily life. It is most effective to interview the patient and the caregiver separately. This way, they can speak freely. Many informant are reluctant to share information about certain deteriorations in front of their relatives. It is important to initially gather information about the current cognitive difficulties that are experienced by the patient. It is also helpful to figure out whether the primary symptoms reported are primary those associated with memory or whether they are also represented by executive, language or attention disturbances. Memory impairment is an important feature of the disease, but individuals may initially present with language deficits or problems with executive function. Sometimes a person has cognitive resources to compensate for the initial deficits. However, the neurodegenerative process will continue until it progresses to a point where no successful compensation is possible. The first deficits will often be characterized by a language disturbance, like the inability to retrieve words. When the predominant symptoms in younger patients are language and executive dysfuntion, the clinician must consider the possibility of a frontotemporal dementia versus Alzheimer’s Disease. If there are predominant concerns with executive disturbances, cognitive slowing and attention disturbances, diffuse Lewy body disease must be considered.

It must also be determined if there has been a sudden onset of the symptoms or whether the cognitive disorder has a slowly progressive course, with gradual worsening of symptoms. In the first case, a non- Alzheimer’s Disease disorder can be considered, in the second case, Alzheimer’s Disease can be considered. The interview allows the clinician to determine the nature and extent of cognitive decline. The clinical interview gives the examiner the opportunity to determine the extent to which observed deficits interfere with occupational function. It also gives the opportunity to determine the effects of anxiety, depression and medical conditions on function.

Neuropsychological assessment

Neuropsychological batteries assess different aspects of neuropsychological function and the most sophisticated batteries assess executive function, learning memory, language and visuospatial skills. It is also good to have measures of processing speed and attention. When a clinician want to evaluate an individual for the presence of early dementia, he or she will probably give a measure of a list learning task. The advantage of this is that it provides an assessment of learning over several trials, which can evaluate the effects of proactive and retroactive inference and they provide measures of delayed recall. Recognition memory should also be assessed. These components are important in the evaluation of Alzheimer’s Disease. Difficulties with delayed recall are features of Alzheimer’s Disease, but not all Alzheimer’s Disease exhibit these features. It depends on the circumstances of evaluation for the choice of memory test. Most test are about reduced, delayed or cued recall.

There are also assessment of non-memory functions. The assessment of language function includes and evaluation of receptive and expressive language skills. There are different tests for word retrieval skills, like the Boston Naming Test. There are questions of semantic fluency and letter fluency. Elements of executive function tests are the ability to solve problems, plan, shift between cognitive sets and engage in concept formation. One of the measures for executive dysfunction is the Winsconsin Card Sorting Test. This is not a test for repeated testing. Sometimes it is important to distinguish between a perceptual disturbance from the inability to construct figures based on the perception, tests as the Hooper Visual Organization Test and Judgment of Line Orientation.

The neuropsychological tests should be administered to any older adult in which it is important to establish the absence or presence of cognitive deficits. Different patterns of neuropsychological deficits may help the clinician in diagnostic formulation and help the clinician to monitor progression and response to treatment. Sometimes there are cases that will remain difficult to diagnose, even with the most sensitive neuropsychological assessment. The clinician may conduct serial assessments in 6-9 months to track progression.