title: Changes in cognitive functions of patients with dementia of the Alzheimer type following long-term administration of donepezil hydrochloride: relating to changes attributable to differences in apolipoprotein E phenotype.
abstract: OBJECTIVE
  We conducted a study of changes in cognitive functions by long-term monitoring of dementia of Alzheimer type (DAT) patients to investigate the relationship between the progression of DAT symptoms and the presence of apolipoprotein (ApoE)4.
  
  
  METHODS
  The subjects consisted of 40 DAT patients who had been treated with donepezil for 3 years or more. The Mini-Mental State Examination (MMSE) and Alzheimer's Disease Assessment Scale - Cognitive Subscale Japanese version (ADAS-Jcog), were conducted annually. The patients were categorized into ApoE4(+) and ApoE4(-) groups. Changes in initial cognitive function assessment score (0 years) were then studied longitudinally at each stage of the observation period (1, 2, 3 years) (Wilcoxon's signed-rank test). Moreover, the scores at each time period were compared cross-sectionally between the two groups (Mann-Whitney U-test).
  
  
  RESULTS
  Significant decreases in MMSE scores were observed at the three time periods in both groups (P < 0.01) in the cross-sectional study. In the longitudinal study, the ApoE4(+) group demonstrated a lower trend (P < 0.1) after 1 year only. Significantly poorer ADAS-Jcog scores were observed in the ApoE4(+) group at the 3-year point both in the longitudinal and in the cross-sectional study (P < 0.05). For ADAS-Jcog sub-items, in the longitudinal study, orientation was demonstrated to be significantly poorer in the ApoE4(+) group in the third year (P < 0.05).
  
  
  CONCLUSIONS
  ApoE4 was suggested to not only be a risk factor for disease onset, but also a risk factor for exacerbation of symptoms with respect to long-term prognosis.
authors.affiliation: Department of Geriatric Medicine, Hachioji Medical Center, Tokyo Medical University, Tokyo, Japan. kitikiti@hi-ho.ne.jp
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Kanaya
authors.forename: Shine
authors.initials: S
authors.lastname: Abe
authors.forename: Minoru
authors.initials: M
authors.lastname: Sakai
authors.forename: Hiroko
authors.initials: H
authors.lastname: Fujii
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Iwamoto
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D001057:Apolipoproteins E / Q000235:genetics / Q000378:metabolism*; D010054:Brief Psychiatric Rating Scale; D003071:Cognition; D003430:Cross-Sectional Studies; D018450:Disease Progression; D000077265:Donepezil; D006801:Humans; D007189:Indans / Q000627:therapeutic use*; D008137:Longitudinal Studies; D008297:Male; D009483:Neuropsychological Tests; D018697:Nootropic Agents / Q000627:therapeutic use*; D010641:Phenotype; D010880:Piperidines / Q000627:therapeutic use*; D011379:Prognosis; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D001057:Apolipoproteins E; D007189:Indans; D018697:Nootropic Agents; D010880:Piperidines; D000077265:Donepezil