Donepezil delays progression to AD in MCI subjects with depressive symptoms.
OBJECTIVE
To determine whether the presence of depression predicts higher rate of progression to Alzheimer disease (AD) in patients with amnestic mild cognitive impairment (aMCI) and whether donepezil treatment beneficially affect this relationship.


METHODS
The study sample was composed of 756 participants with aMCI from the 3-year, double-blind, placebo-controlled Alzheimer's Disease Cooperative Study drug trial of donepezil and vitamin E. Beck Depression Inventory (BDI) was used to assess depressive symptoms at baseline and participants were followed either to the end of study or to the primary endpoint of progression to probable or possible AD.


RESULTS
Cox proportional hazards regression, adjusted for age at baseline, gender, apolipoprotein genotype, and NYU paragraph delayed recall score, showed that higher BDI scores were associated with progression to AD (p = 0.03). The sample was stratified into depressed (BDI score > or =10; n = 208) and nondepressed (BDI <10; n = 548) groups. Kaplan-Meier analysis showed that among the depressed subjects, the proportion progressing to AD was lower for the donepezil group than the combined vitamin E and placebo groups at 1.7 years (p = 0.023), at 2.2 years (p = 0.025), and remained marginally lower at 2.7 years (p = 0.070). The survival curves among the three treatment groups did not differ within the nondepressed participants.


CONCLUSIONS
Results suggest that depression is predictive of progression from amnestic mild cognitive impairment (aMCI) to Alzheimer disease (AD) and treatment with donepezil delayed progression to AD among depressed subjects with aMCI. Donepezil appears to modulate the increased risk of AD conferred by the presence of depressive symptoms.
Lu
P H
PH
Departments of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA. plu@mednet.ucla.edu
Edland
S D
SD
Teng
E
E
Tingus
K
K
Petersen
R C
RC
Cummings
J L
JL
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000517:prevention & control / Q000523:psychology; D000975:Antioxidants / Q000008:administration & dosage; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage; D003072:Cognition Disorders / Q000150:complications* / Q000188:drug therapy* / Q000523:psychology; D003866:Depressive Disorder / Q000150:complications* / Q000503:physiopathology; D018450:Disease Progression; D000077265:Donepezil; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007189:Indans / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D010880:Piperidines / Q000008:administration & dosage*; D010919:Placebos; D012720:Severity of Illness Index; D013997:Time Factors; D024505:Tocopherols / Q000008:administration & dosage; D016896:Treatment Outcome
D000975:Antioxidants; D002800:Cholinesterase Inhibitors; D007189:Indans; D010880:Piperidines; D010919:Placebos; D000077265:Donepezil; D024505:Tocopherols