Dementia

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Differential Diagnosis: Dementia has many causes (Table 185-1 Differential Diagnosis of Dementia). It is essential to exclude treatable etiologies; the most common potentially reversible diagnoses are depression, hydrocephalus, and alcohol dependence. The major degenerative dementias can usually be distinguished by distinctive symptoms, signs, and neuroimaging features (Table 185-2 Clinical Differentiation of the Major Dementias).

History: A subacute onset of confusion may represent delirium and should trigger the search for intoxication, infection, or metabolic derangement (Chap. 18 Confusion, Stupor, and Coma). An elderly person with slowly progressive memory loss over several years is likely to have Alzheimer's disease (AD). A change in personality, disinhibition, gain of weight, or compulsive eating suggests frontotemporal dementia (FTD), not AD; apathy, loss of executive function, progressive abnormalities in speech, or relative sparing of memory or visuospatial abilities also suggests FTD. Dementia with Lewy bodies (DLB) is suggested by the early presence of visual hallucinations, parkinsonism, tendency to delirium, sensitivity to psychoactive medications, or a REM behavior disorder (RBD, the loss of skeletal muscle paralysis during dreaming).

A history of stroke suggests vascular dementia, which may also occur with hypertension, atrial fibrillation, peripheral vascular disease, and diabetes. Rapid progression of dementia with myoclonus suggests a prion disease such as Creutzfeldt-Jakob disease (CJD). A rapidly progressive dementia with psychiatric symptoms and seizures suggests paraneoplastic encephalitis associated with NMDA receptor antibodies; affected pts are often young women with ovarian teratoma (Chap. 79 Neurologic Paraneoplastic Syndromes). Gait disturbance is prominent with vascular dementia, Parkinson's disease, DLB, or normal-pressure hydrocephalus. Multiple sex partners or IV drug use should trigger search for an infection, especially HIV or syphilis. A history of head trauma could indicate chronic subdural hematoma, chronic traumatic encephalopathy, or normal-pressure hydrocephalus. Alcoholism may suggest malnutrition and thiamine deficiency. A history of gastric surgery may result in loss of intrinsic factor and vitamin B₁₂ deficiency. A careful review of medications, especially of sedatives and tranquilizers, may raise the issue of drug intoxication. A family history of dementia is found in Huntington's disease and in familial forms of AD, FTD, DLB, or prion disorders. Insomnia or weight loss is often seen with depression-related cognitive impairments, which can also be caused by the recent death of a loved one.

Examination: It is essential to document the dementia, look for other signs of nervous system involvement, and search for clues of a systemic disease that might be responsible for the cognitive disorder. Typical AD does not affect motor systems until late in the course. In contrast, FTD pts often develop axial rigidity, supranuclear gaze palsy, or features of amyotrophic lateral sclerosis. In DLB, initial symptoms may be the new onset of a parkinsonian syndrome (resting tremor, cogwheel rigidity, bradykinesia, and festinating gait). Unexplained falls, axial rigidity, dysphagia, and gaze deficits suggest progressive supranuclear palsy (PSP).

Focal neurologic deficits may occur in vascular dementia or brain tumor. Dementia with a myelopathy and peripheral neuropathy suggests vitamin B₁₂ deficiency. A peripheral neuropathy could also indicate an underlying vitamin deficiency or heavy metal intoxication. Dry cool skin, hair loss, and bradycardia suggest hypothyroidism. Confusion associated with repetitive stereotyped movements may indicate ongoing seizure activity. Hearing impairment or visual loss may produce confusion and disorientation misinterpreted as dementia. Such sensory deficits are common in the elderly.

Choice of Diagnostic Studies: A reversible or treatable cause must not be missed, yet no single etiology is common; thus a screen must employ multiple tests, each of which has a low yield. Table 185-3 Evaluation of the Pt with Dementia lists most screening tests for dementia. Guidelines recommend the routine measurement of a complete blood count, electrolytes, renal and thyroid function, a vitamin B₁₂ level, and a neuroimaging study (CT or MRI). Lumbar puncture need not be done routinely but is indicated if infection or inflammation is a consideration; CSF levels of tau protein and amyloid β₄₂ show differing patterns with the various dementias although their sensitivity and specificity are not yet sufficiently high to warrant routine use. An EEG is rarely helpful except to suggest a prion disease or an underlying nonconvulsive seizure disorder. The role of functional-metabolic imaging in the diagnosis of dementia is still under study; amyloid imaging has shown promise for the diagnosis of AD; currently the main clinical value is to exclude AD as the likely cause of dementia in pts who have negative scans. Brain biopsy may be indicated to diagnose vasculitis, potentially treatable neoplasms, or unusual infections.