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Pinpointing the Cause of Non-Alzheimer Dementia

Pinpointing the Cause of Non-Alzheimer Dementia

Many physicians, including psychiatrists, may shy away from seeing elderly patients with symptoms of dementia because they imagine that there are a large number of alternative diagnoses and that differential diagnosis is complicated. In fact, however, the number of possible diagnoses in most situations is relatively small and the diagnosis of dementia in older patients is certainly feasible in primary care psychiatry.

In order to diagnose specific causes of dementia, the physician must first be certain that dementia is the syndrome that best describes the patient's symptoms. Although depression, delirium, psychosis, aphasia, and mild cognitive impairment share some features with dementia, each is a distinct syndrome with its own differential diagnosis. It is important to consider all of these syndromes when evaluating a patient with suspected dementia.

Alzheimer disease (AD) is the most common dementia; it constitutes 60% to 80% of all dementias. AD begins insidiously and typically evolves over years. Its core cognitive symptom is short-term memory loss, but other abnormalities of judgment, abstract reasoning, spatial orientation, word finding, and personality are common.

The clinical diagnosis of AD is based on the presence of a cognitive disorder in which short-term memory loss is predominant. As of 2006, there are no routinely used biomarkers for AD. Cerebrospinal fluid markers, such as reduced levels of amyloid beta peptide or increased levels of tau peptide, have modest accuracy, but because of the lack of an evidence base in autopsy-confirmed cases, the markers are of uncertain clinical value. The use of Pittsburgh compound-B (PIB) in positron emission tomography holds considerable promise as a means of establishing whether a patient has the amyloid beta peptide pathology of AD.1 Validation of PIB imaging in dementia is currently being investigated in Alzheimer centers worldwide. How ever, it is unlikely that PIB imaging will be available for general clinical use for a few years.

Vascular dementia and Lewy body disease are the next most common forms of dementia. They are about equally prevalent, each accounting for roughly 15% of all diagnosed dementias (Figure). Beyond AD, vascular dementia, and Lewy body disease, the other dementias are much less common. These and other dementias are de scribed in more detail below.

Vascular dementia
The effects of cerebrovascular disease on cerebral function cause vascular dementia.2 The incidence and prevalence of vascular dementia mirror AD in that this condition becomes increasingly common with advanced age. A number of cerebrovascular mechanisms can lead to a cerebral injury, including large-vessel infarctions, multiple lacunar infarctions, extensive subcortical and periventricular white matter disease, and microvascular changes. These tissue injuries are usually due to atherosclerotic disease or amyloid angiopathy. Autoimmune mechanisms are a far less likely cause of vascular dementia.

The full range of the clinical ex pression of vascular dementia is not completely understood. The most well-known syndrome is that in which cognitive impairment occurs within 3 months of a clinically recognized stroke and there is evidence of infarcts in cognitively relevant cerebral regions. Usually, there are neurologic signs or symptoms that are consistent with a cerebrovascular cause, such as hemiparesis or hemianopia.

Sometimes, a patient who presents with a cognitive disorder that clearly follows stroke may have a nondiagnostic imaging study. A more challenging clinical situation arises in patients who have no clear-cut clinical history of stroke but who have imaging studies showing multiple bilateral large- or small-vessel infarcts. In each of these instances, there is almost certainly a pathologically relevant cerebrovascular process.

There is currently no specific cog nitive profile of vascular dementia. However, if there were a typical clinically recognized syndrome of vascular dementia, it would be that of a person with profound executive and attentional deficits and slightly less impaired short-term memory. Patients with vascular dementia are often apathetic and lack initiative, although these features are not specific to the syndrome.

There is increasing awareness of the etiologic overlap of AD and vascular dementia. Both share risk factors such as hypertension, diabetes, and hyperhomocysteinemia. The neuropathologic overlap of the 2 syndromes is also con siderable. Many patients with otherwise typical Alzheimer pathology also have cerebrovascular disease. Similarly, many patients with significant amounts of cerebrovascular pathology also have some Alzheimer pathology.

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