NEUROCHEMICAL CORRELATES OF DEMENTIA SEVERITY IN ALZHEIMERS-DISEASE -RELATIVE IMPORTANCE OF THE CHOLINERGIC DEFICITS

Cholinergic markers, neuropeptides, and amines and their metabolites w ere sampled from identical specimens across 10 neocortical regions in a large sample of Alzheimer's disease (AD) cases and controls. Levels of choline acetyltransferase, acetylcholinesterase, somatostatin, cort icotropin-releasing factor, serotonin, and 5-hydroxyindoleacetic acid were significantly reduced in AD versus controls. After data reduction , the most descriptive neurochemical indices were used to examine the relationship of neurochemical measures and dementia severity within th e AD sample, controlling for age effects. Dementia severity ratings we re based on antemortem assessments (46.9% of AD sample) and postmortem chart review (53.1% of the AD sample). Choline acetyltransferase acti vity was highly correlated with clinical dementia ratings across the n eocortex of the AD cases. Somatostatin and corticotropin-releasing fac tor levels were correlated with dementia severity only when control ca ses were included in the analyses. None of the amines, their metabolit es, or the neuropeptides quantified related significantly to dementia severity in the AD cohort. These data (a) confirm the strong associati on of cholinergic deficits with functional impairment in AD and show t hat this association is independent of age and (b) suggest that of all the neurochemical species quantified, the cholinergic indices may be unique in their association with dementia severity.