Do lesions involving the cortical cholinergic pathways help or hinder efficacy of donepezil in patients with Alzheimer's disease?
OBJECTIVE
To investigate the influences of vascular lesions detected by MRI, lesions involving the cortical cholinergic pathways and hippocampal thickness on therapeutic responsiveness to donepezil in patients with Alzheimer's disease (AD).


METHODS
The study cohort contained 67 patients with probable AD. We used the revised Hasegawa Dementia Rating (HDS-R) and the Clock Drawing Test (CDT) to evaluate drug efficacy for 24 months. The Cholinergic Pathways Hyperintensities Scale (CHIPS), a newly developed visual scale, was used to semiquantify lesions on the cholinergic pathways.


RESULTS
Over the 24-month period, the results of the CDT showed more apparent and constant association with white matter hyperintensities (WMH) and lesions on the cholinergic pathways than the HDS-R. WMH may enhance, while lesions on the cholinergic pathways may attenuate sensitivity to donepezil treatment when judged by the CDT. No apparent association between the thicknesses of hippocampi with baseline cognition or therapeutic responsiveness to donepezil was found.


CONCLUSIONS
Donepezil may be more efficacious when further executive dysfunction caused by WMH is added to AD dementia and less so when cholinergic reserves are further impinged upon by lesions involving the cortical cholinergic pathways.
Fukui
Toshiya
T
Division of Neurology, Department of Internal Medicine, Showa University Northern Yokohama Hospital, Yokohama, Japan. tfukui@med.showa-u.ac.jp
Hieda
Soutaro
S
Bocti
Christian
C
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000175:diagnosis / Q000188:drug therapy* / Q000473:pathology*; D002540:Cerebral Cortex / Q000187:drug effects* / Q000473:pathology*; D002799:Cholinergic Fibers / Q000187:drug effects* / Q000473:pathology*; D002800:Cholinesterase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use*; D015331:Cohort Studies; D000077265:Donepezil; D005260:Female; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology; D006801:Humans; D007189:Indans / Q000627:therapeutic use*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009434:Neural Pathways / Q000187:drug effects* / Q000473:pathology*; D009483:Neuropsychological Tests; D010880:Piperidines / Q000627:therapeutic use*; D016896:Treatment Outcome
D002800:Cholinesterase Inhibitors; D007189:Indans; D010880:Piperidines; D000077265:Donepezil