Neuroscience Clerkship

ALZHEIMER'S DISEASE

Above: Typical gross pathologic picture of Alzheimer's Disease - marked atrophy and "hydrocephalus ex vacuo".
 

• Age. Rare before 40; some cases reported as young as 30; prevalence doubles every 5 years after age 65. Its incidence in persons over 85 approaches 50 percent.

• Genetics. Family history increases risk 4 X, pattern, usually autosomal dominant: mutations identified: presenilin 1 and 2; amyloid precursor protein; E4 allele of apolipoprotein E.

• Female - as high as 2:1 vs males

• Down's syndrome

• Low Education level

• Head trauma (can accelerate onset by 5-7 yrs)

• Vascular disease

• Memory impairment (1st and most prominent symptom)

• Anosagnosia

A common rule of thumb: if the patient complains of memory loss, they usually do not have AD; if a family member brings the patient to the doctor and complains that the patient is developing memory loss, they often will be found to have AD.

• Aphasia (especially anomia)

• Apraxia

• Depression (up to 30%)

• Delusions and hallucinations (up to 30%)

• Personality changes

• Behavioral disturbances including:

Verbal and physical aggression

Wandering

Agitation

Binge eating

Inappropriate sexual behavior

Uncooperativeness

Attempts at self inflicted harm

Physical Examination

Generally normal except for cognitive impairments

Note: AD does not affect vision, muscle strength, coordination, sensation, reflexes and walking at the time of diagnosis

Labs/Imaging

Testing is needed to exclude other causes of dementia. However Alzheimer's remains a diagnosis of exclusion. Nevertheless, CT/MRI may show white matter lesions and brain atrophy. EEG shows a loss of alpha activity and increase in theta and delta activity.

Pathology

Gross brain pathology shows generalized atrophy.

On microscopic analysis, AD is characterized by two main lesions, senile plaques (also called neuritic plaques or Alzheimer plaques) and neurofibrillary tangles. Senile plaques have a central core of fibrillary amyloid material.

Prognosis

Although motor skills are initially preserved and plateaus occasionally occur, there is usually an eventual steady progression over 5 - 10 years from that as described above to a bedridden, mute, incontinent, and unresponsive state. Death is usually due to bronchopneumonia.

There is no cure for AD.

Disorientation may be reduced by providing a quiet, familiar, well lit environment with labels on doors and other objects throughout the living space.

Neuroleptics and short acting benzodiazepines may be used for acute behavioral disturbances.

Anticholinesterases (Donepezil (Aricept), Rivastigmine (Exelon), and Galantamine (Reminyl) are prescribed for early AD to stabilize or slow memory loss.

Memantine (Namenda®) has been recently approved by the FDA to treat moderate-to-severe symptoms of Alzheimer’s disease. It can be used alone or in combination with other medications. Memantine is an anti-glutamate agent. Clinical studies have shown that it can improve memory and function and prolong the ability of Alzheimer’s patients to perform some tasks independently.