The degenerative changes in the brain that occur in ALzheimer's disease affect cholinergic neurons selectively. This discovery has inspired efforts to treat patients with medications that may improve cholinergic neurotransmission. Although two such medications, lecithin and physostigmine, have not produced marked improvement when given individually, there is reason to believe that they may be beneficial in combination. This hypothesis is now being tested. Discovery of the cholinergic deficit in Alzheimer's disease also opened the possibility of antemortem diagnosis through detection of altered levels in cerebrospinal fluid (CSF) of markers for cholinergic activity in the brain. Acetylcholinesterase, the enzyme that degrades acetylcholine, is particularly promising as a cholinergic marker because its activity in CSF is easily measured and has been shown to be influenced by neuronal activity. Anomia, the inability to name objects, is a frequent early symptom of Alzheimer's disease. It may be associated with diffuse distribution of Alzheimer's degeneration in the brain, or with focally intense degeneration in the dominant temporal lobe. Three disorders have been suggested to explain anomia in patients with dementia: impaired visual recognition, impaired semantic memory (the store of knowledge involved in using language), and impaired word retrieval. Each of these impairments, individually or in combination with the others, could account for the anomia in Alzheimer's disease. The central hypothesis of this proposal is that anomia in Alzheimer's disease is caused by a cholinergic deficiency. This hypothesis will be tested by mearurement of naming ability in patients with Alzheimer's disease both before and during a trial of therapy with lecithin and physostigmine. The proposed research will also include study of cognitive abilities related to naming, and measurement of acetylcholinesterase activity in CSF. These concurrent studies will detect features that characterize patients who improve with treatment, and will also be useful in the differential diagnosis and subclassification of Alzheimer's disease.
