188 ALZHEIMER’S DISEASE AND OTHER DEMENTIAS
Harrison’s Manual of Medicine
ALZHEIMER’S DISEASE AND OTHER DEMENTIAS
Alzheimer’s Disease (AD)
Other Causes of Dementia
Dementia is a deterioration in cognitive ability. Memory loss is most common, but other mental faculties affected may include attention, judgment, comprehension, orientation, learning, calculation, problem solving, mood, and behavior. Agitation or withdrawal, hallucinations, delusions, insomnia, and loss of inhibitions are also common. Dementia is chronic, whereas delirium is an acute condition associated with fluctuating altered consciousness (agitation or lethargy); often accompanied by fever, tachycardia, or tremor.
DIAGNOSIS The mini-mental status examination is a useful screening test for dementia (Table 188-1). A score of <24 points (out of 30) indicates a need for more detailed cognitive and physical assessment.
Table 188-1 The Mini-Mental Status Examination
DIFFERENTIAL DIAGNOSIS Dementia has many causes (Table 188-2); it is essential to exclude treatable etiologies. Pseudodementia (depression) can be difficult to distinguish from dementia, but memory is usually intact on careful testing. Prior bouts of depression suggest pseudodementia. Some clinical clues suggest a treatable disorder—early, prominent gait disturbance; urinary incontinence (normal-pressure hydrocephalus); resting tremor, bradykinesia (Parkinson’s disease); neuropathy (vitamin B12 deficiency); bradycardia; delayed relaxation of stretch reflexes (hypothyroidism); early-onset seizures (neoplasm); insomnia, anxiety, psychiatric disturbance, seizures (drug intoxication or withdrawal); rapid progression with ataxia, rigidity, myoclonus (Creutzfeldt- Jakob disease); fever, meningismus (chronic infection); confusion, ophthalmoparesis, ataxia, followed by severe anterograde and retrograde amnesia (Wernicke-Korsakoff syndrome).
Table 188-2 Differential Diagnosis of Dementia
Approach to the Patient
An approach to the workup of dementia is outlined in Table 188-3. Brain MRI or CT identifies multi-infarct dementia, brain tumors, subdural hematoma, and normal-pressure hydrocephalus. Several laboratory tests (thyroid function, vitamin B12, CBC, electrolytes, VDRL) indicated in all pts; additional tests (e.g., HIV, liver and renal function, LP, toxic screen, angiogram, or brain biopsy) determined by the clinical situation. EEG indicated if seizures or Creutzfeldt- Jakob disease suspected; EEG is normal in pseudodementia.
Table 188-3 Evaluation of the Demented Patient
ALZHEIMER’S DISEASE (AD)
Most common cause of dementia; affects 3–4 million persons in the U.S. Cost >$50 billion dollars/year.
CLINICAL MANIFESTATIONS Pts present with subtle recent memory loss then develop slowly progressive dementia. Memory loss is often not recognized initially—in part due to preservation of social graces until later phases; impaired activities of daily living (keeping track of finances, appointments) draw attention of friends/family. Disorientation, poor judgment, poor concentration, aphasia, apraxia, and alexia increasingly occur as the disease progresses. Pts may be frustrated or unaware of deficit. Death from malnutrition or secondary infection. Typical duration 8–10 years.
PATHOGENESIS Risk factors for AD are old age, positive family history. Pathology: neuritic plaques composed of Ab amyloid and other proteins; neurofibrillary tangles composed of abnormally phosphorylated tau protein. The apolipoprotein E (apo E) gene (chromosome 21) has a role in pathogenesis; the e4 allele appears to modify age of onset of AD and is associated with sporadic and late-onset familial cases of AD. Apo E testing is not indicated as a predictive test at this time. Rare genetic causes of AD are Down’s syndrome (trisomy 21), amyloid precursor protein (APP) gene mutations (chromosome 21), mutations in presenilin I (chromosome 14) and presenilin II (chromosome 1) genes.
There is no definitive treatment for AD; management of behavioral/neurologic problems in conjunction with family and caregivers is essential. Depression is common in early stages and may respond to antidepressants (SSRIs, tricyclics). Mild sedation may help insomnia. Agitation controlled with low- dose haloperidol (0.5–2 mg). Notebooks and posted daily reminders can function as memory aids in early stages. Kitchens, bathrooms, and bedrooms need evaluation for safety. Pts must eventually stop driving. Caregiver burnout is common; nursing home placement may be necessary. Local and national support groups (Alzheimer’s Disease and Related Disorders Association) are valuable resources.
Drug therapy is limited. Centrally acting cholinesterase inhibitors approved for mild-moderate AD presumably function by increasing cerebral levels of acetylcholine. Donepezil (Aricept), 5–10 mg/d PO, has the advantages of few side effects and is given in a single daily dosage. Clinical trials show improved caregiver ratings of pt function and a decreased rate in decline of cognitive test scores. Estrogen may be helpful as a preventive measure in postmenopausal women. The value of vitamin E is uncertain.
OTHER CAUSES OF DEMENTIA
VASCULAR DEMENTIA Typically follows multiple strokelike episodes (multi-infarct dementia) or rarely develops in a slow progressive fashion (diffuse white matter or Binswanger’s disease). Unlike AD, focal neurologic signs (e.g., hemiparesis) are usually present at presentation.
FRONTOTEMPORAL DEMENTIA Responsible for 10% of all cases of dementia. Patients often irritable, disinhibited; better performance than AD on tests of construction, copying, and calculation. May be sporadic or inherited; some familial cases due to intronic mutations of tau gene on chromosome 17.
DIFFUSE LEWY BODY DISEASE Dementia with rigidity and other parkinsonian features. Lewy bodies are intraneuronal cytoplasmic inclusions.
NORMAL-PRESSURE HYDROCEPHALUS (NPH) Presents as a gait disorder (ataxic or apractic), dementia, and urinary incontinence; gait improves in 30–50% of pts following ventricular shunting; dementia and incontinence do not improve.
HUNTINGTON’S DISEASE Presents as chorea and altered behavior. Typical onset fourth to fifth decade but can present at almost any age. Autosomal dominant inheritance; the abnormal gene has expanded trinucleotide repeat resulting in a protein (huntingtin) with an expanded polyglutamine tract; function of huntingtin is unknown. Diagnosis confirmed with genetic testing coupled with genetic counseling. Symptomatic treatment of movements and behaviors; SSRIs may help depression.
For a more detailed discussion, see Bird TD: Memory Loss and Dementia, Chap. 26, p. 148; and Alzheimer’s Disease and Other Primary Dementias, Chap. 362, p. 2391, HPIM-15.