Alzheimer Disease and Other Dementias
Definition of dementia (according to DSM-IV): “Multiple cognitive deficits that are sufficiently severe to cause impairment in occupational or social functioning.” Must involve memory plus other cognitive domains; must show decline from premorbid function; exclude delirium. See also Chapter 1.
Degenerative Diseases
Alzheimer Disease (AD)
Clinical Syndrome
First symptom: memory impaired for newly acquired information; memory for remote events less impaired. Later: impaired language, abstract reasoning, executive functions; delusions, other psychotic behavior; major depression; agitation, hallucinations.
Rigidity, bradykinesia, shuffling gait, postural instability common.
Progressive, terminates in complete incapacity, then death in 4 to 16 years.
EEG: generalized slowing. MRI: diffuse atrophy, particularly frontotemporal. PET: temporoparietal hypometabolism.
Epidemiology
Prevalence: <1% before age 65; 5% to 10% at age 65; 30% to 40% after 85.
Lifetime risk double in siblings of patients. The ε4 polymorphism of apolipoprotein E gene (chromosome 19) increases risk. Autosomal inheritance in 5% with mutation in one of three genes (synuclein, presenilins).
Other risk factors: traumatic head injury, lower educational achievement, parental age at time of birth, smoking, Down syndrome in first-degree relative.
Pathology and Biochemistry
Diffuse atrophy of cerebral cortex, especially frontal, parietal, temporal.
Senile neuritic plaques: core of extracellular amyloid surrounded by enlarged axonal endings.
Neurofibrillary tangles: fibrillary intracytoplasmic structures within neurons, containing paired helical filaments, tau protein.
50% to 90% reduction of activity of choline acetyltransferase (CAT); decreased synthesis of acetylcholine, in cerebral cortex and hippocampus. Loss of CAT correlates with severity cognitive loss.
Diagnosis
Mental status examination, neuropsychologic testing most helpful. Brain imaging (CT or MRI) to exclude other causes of dementia.
Treatment
Anticholinesterases: tacrine (use limited by hepatotoxicity), donepezil, rivastigmine, galantamine. Small benefit on cognitive performance; unclear effect on functional capacity.
Psychotropic drugs for agitation, delusions, psychosis, depression in AD.
Frontotemporal Dementia
Pick disease: progressive dementia, personality change, speech disturbance, inattentiveness; sometimes parkinsonian signs. Rare; some familial. Frontotemporal atrophy; round intraneuronal inclusions (Pick bodies) contain tau protein; ubiquitinated inclusions (Table 107.1).Related posts:
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