Ella is 88 years old and was living at home until very recently. Her children, who visited her regularly, noticed she was becoming more forgetful. At first, she mislaid objects, and then she began to forget her doctor's appointments. With time, her personality changed and she became withdrawn. At home she would forget to turn off the stove or leave the kettle on until it boiled dry. After seeking advice from a gerontologist and social worker, Ella's children placed her in a nursing home with a unit equipped for patients with Alzheimer disease. What is dementia? Why is Alzheimer disease based on a "diagnosis of exclusion"? What are the macroscopic and microscopic features of the brain that are typical in Alzheimer disease?



One of Ella's children brought her a new pair of slippers to wear in the nursing home. A minute after she received them, Ella could not remember the exchange and asked what they were doing on her bed. What part of the brain has largely been affected to produce this behavior, and what is the pathophysiology involved?

Dementia involves the deterioration of intellect to the extent that it interferes with occupational or social activity. Any disorder that damages the areas of the brain involved with memory and learning can result in dementia. Problem solving, memory, judgment, abstract thought, language, perception, and motor skills may all be affected in the presence of dementia.

Macroscopically, there is loss of neurons with cortical atrophy, particularly in the parietal and temporal lobes. The gyri narrow and the sulci deepen as tissue atrophies. The ventricles are also affected and enlarge as the brain mass declines.
Microscopically, neuritic plaques and neurofibrillary tangles characterize Alzheimer disease. Neuritic plaques (or senile plaques) consist of degenerating nerve terminals that form clusters around a neurotoxic amyloid β-peptide nucleus. The plaques are largely found in the neocortex, hippocampus, and isocortex. Neurofibrillary tangles develop in the cytoplasm of neurons. The tangles are composed of fibrous proteins and hyperphosphorylated tau proteins wrapped tightly in a helical fashion. They are resistant to enzymatic breakdown and compromise the function of the neuron they inhabit.

The hippocampus is central to the encoding and consolidation of short-term memory and retrieval of long-term memory. It is also responsible for the processing of information. In Alzheimer disease, the hippocampus is particularly vulnerable to the development of neuritic plaques and neurofibrillary tangles. The production of choline acetyltransferase (an enzyme responsible for the synthesis of acetylcholine) declines as a result. When acetylcholine is deficient, the formation and processing of memory by the hippocampus are compromised.

 

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