Formerly, when virtually all forms of dementia were untreatable, there was little advantage to either the patient or the family in ascertaining the cause of the cerebral disease. There are now adequate treatments for a number of diseases and conditions that cause cognitive decline, putting a premium on proper diagnosis.
The currently potentially treatable forms of dementia are those caused by normal-pressure hydrocephalus; chronic subdural hematoma; the dementia of HIV paraneoplastic and related autoimmune encephalitis; nutritional deficiencies (thiamine—Wernicke-Korsakoff syndrome, Marchiafava-Bignami disease, pellagra, vitamin B12 deficiency); chronic intoxication (e.g., alcohol, sedatives); multiple cerebral infarctions; certain endocrine and metabolic disorders (myxedema, Hashimoto encephalopathy), neurosyphilis and other chronic meningitides, Cushing disease, chronic hepatic encephalopathy; frontal and temporal lobe tumors; vascular dementia, cerebral vasculitis; sarcoidosis; progressive multifocal leukoencephalopathy (PML), Whipple disease; multiple sclerosis; and sometimes neglected, the pseudodementia of depression. Exclusion of most of these diseases is readily accomplished by careful history, sequential clinical evaluations, and testing of blood and CSF, CT, MRI, and neuropsychologic testing. We have incorporated the results of metabolic brain imaging (both FDG-PET and amyloid-ligand imaging) as well as CSF amyloid-tau ratio into practice when feasible.
In exceptional situations, brain biopsy may be justified in the diagnosis of dementia, almost limited to rapidly progressive cases. A perspective, albeit from a sample in the past that cannot be generalized to practice, has been given by Warren and colleagues of 90 consecutive brain biopsies performed between 1989 and 2003 for the evaluation of dementia. More than half provided a diagnosis, mostly Alzheimer, Creutzfeldt-Jakob disease, and inflammatory disorders. However, reasonable assurances must be given to the neurosurgeon that prion disease is unlikely.
A special problem in differential diagnosis is the distinction between a late-life depression and a dementia, especially when some degree of both is present. Observation over several weeks or more, and the patient’s demeanor, makes the distinction clearer. Multiinfarct dementia may be difficult to separate from Alzheimer dementia, as discussed further on. The dementia of normal-pressure hydrocephalus may also be confused with Alzheimer dementia (see Chap. 29). The problem of distinguishing Alzheimer disease from a more “benign” form of memory decline associated with aging comes up frequently in practice, as discussed further on. These treatable conditions are discussed in Chaps. 20, 29, and 33, and the important topic of depression is addressed in Chap. 48.
Often we have been confident on clinical grounds that a patient had Alzheimer disease, only to have revealed at autopsy that progressive supranuclear palsy, Lewy-body disease, Pick disease, another non-Alzheimer degeneration of the frontal lobes, or cortical-basal-ganglionic degeneration was the cause. All are discussed later in this chapter.
There is no evidence that any of the formerly proposed therapies for Alzheimer disease—cerebral vasodilators, stimulants, l-dopa, massive doses of vitamins B, C, and E, gingko biloba, hyperbaric oxygen, intravenous immunoglobulin, and many others—have any salutary effect. Trials of oral physostigmine, choline, and lecithin have yielded mostly negative or uninterpretable results.