title: Cholinergic deficits contribute to behavioral disturbance in patients with dementia.
abstract: BACKGROUND
  Noncognitive behavioral changes such as depression, aggressive behavior, psychosis, and overactivity occur frequently in patients with dementia, in addition to cognitive impairment, and often determine the need for institutionalization. The biochemical basis of such changes is poorly understood. Clinical trial data indicate that cholinomimetics improve noncognitive 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.
  
  
  METHODS
  Brains from 46 patients with dementia (36 with AD and 10 with mixed or other dementias using Consortium to Establish a Registry for AD criteria) were examined together with 32 normal controls. The patients with dementia had been evaluated every 4 months, often over several years, for cognitive performance (Mini-Mental State Examination) and behavior (Present Behavioral Examination). Concentrations of dopamine (DA) and major metabolites, choline acetyltransferase activity (ChAT), and density (Bmax) of DA D1 receptors in frontal and temporal cortex were studied by radioligand binding protocols. None of the patients was receiving cholinomimetic drugs.
  
  
  RESULTS
  ChAT activity, but no other neurochemical markers, was reduced in AD compared with controls. Loss of ChAT activity correlated with cognitive impairment. Lowered 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 behavior.
  
  
  CONCLUSIONS
  Disturbance of the cholinergic system may underlie both cognitive and some noncognitive behavioral changes in dementia, providing a basis for rational therapy.-1467
authors.affiliation: Dementia Research Laboratory, Centre for Neuroscience Research, GKT School of Biomedical Sciences, King's College London, UK.
authors.forename: S L
authors.initials: SL
authors.lastname: Minger
authors.forename: M M
authors.initials: MM
authors.lastname: Esiri
authors.forename: B
authors.initials: B
authors.lastname: McDonald
authors.forename: J
authors.initials: J
authors.lastname: Keene
authors.forename: J
authors.initials: J
authors.lastname: Carter
authors.forename: T
authors.initials: T
authors.lastname: Hope
authors.forename: P T
authors.initials: PT
authors.lastname: Francis
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000201:enzymology* / Q000473:pathology / Q000523:psychology*; D002795:Choline O-Acetyltransferase / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D001523:Mental Disorders / Q000201:enzymology* / Q000473:pathology / Q000523:psychology*; D011569:Psychiatric Status Rating Scales; D011869:Radioligand Assay; D017447:Receptors, Dopamine D1 / Q000378:metabolism
chemical_list: D017447:Receptors, Dopamine D1; D002795:Choline O-Acetyltransferase