Cholinergic deficits contribute to behavioral disturbance in patients withdementia

Background: Noncognitive behavioral changes such as depression, aggressive behavior, psychosis, and overactivity occur frequently in patients with dem entia, in addition to cognitive impairment, and often determine the need fo r institutionalization. The biochemical basis of such changes is poorly und erstood. Clinical trial data indicate that cholinomimetics improve noncogni tive behaviors. This study investigated the relationship between markers of the cholinergic and dopaminergic neurotransmitter systems and noncognitive behavioral symptoms assessed during the course of dementing illness. Metho d: Brains from 46 patients with dementia (36 with AD and 10 with mixed or o ther dementias using Consortium to Establish a Registry for AD criteria) we re examined together with 32 normal controls. The patients with dementia ha d been evaluated every 4 months, often over several years, for cognitive pe rformance (Mini-Mental State Examination) and behavior (Present Behavioral Examination). Concentrations of dopamine (DA) and major metabolites, cholin e acetyltransferase activity (ChAT), and density (Bmax) of DA D1 receptors in frontal and temporal cortex were studied by radioligand binding protocol s. None of the patients was receiving cholinomimetic drugs. Results: ChAT a ctivity, but no other neurochemical markers, was reduced in AD compared wit h controls. Loss of ChAT activity correlated with cognitive impairment. Low ered ChAT activity also correlated with increasing overactivity in patients with dementia in both frontal and temporal cortex whereas ChAT:DA and ChAT :D1 ratios in temporal cortex correlated negatively with aggressive behavio r. Conclusions: Disturbance of the cholinergic system may underlie both cog nitive and some noncognitive behavioral changes in dementia, providing a ba sis for rational therapy.