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Donepezil delays progression to AD in MCI subjects with depressive symptoms


Lu, P. H., Edland, S. D., Teng, E., Tingus, K., Petersen, R. C., Cummings, J. L.


Neurology, Volume: 72, No.: 24, Pages.: 2115-2121

Year of Publication



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.;

Bibtex Citation

@article{Lu_2009, doi = {10.1212/wnl.0b013e3181aa52d3}, url = {}, year = 2009, month = {jun}, publisher = {Ovid Technologies (Wolters Kluwer Health)}, volume = {72}, number = {24}, pages = {2115--2121}, author = {P. H. Lu and S. D. Edland and E. Teng and K. Tingus and R. C. Petersen and J. L. Cummings}, title = {Donepezil delays progression to {AD} in {MCI} subjects with depressive symptoms}, journal = {Neurology} }


administration & dosage, aged, aged, 80 and over, alzheimer disease, antioxidants, brain, cholinesterase inhibitors, cognition disorders, complications, depression, depressive disorder, disease progression, donezepil, double-blind method, drug effects, drug therapy, drug therapy combination, e, female, humans, indans, male, mci, metabolism, middle aged, neuropsychological tests, physiopathology, piperidines, placebos, prevention & control, psychology, severity of illness index, time factors, tocopherols, treatment outcome, vitamin

Countries of Study


Types of Dementia

Alzheimer’s Disease, Mild Cognitive Impairment (MCI)

Types of Study

Randomised Controlled Trial

Type of Outcomes


Type of Interventions

Pharmaceutical Interventions, Risk Factor Modification

Risk Factor Modifications

At risk population

Pharmaceutical Interventions

Anti-Alzheimer medications, e.g.: donezepil, galantamine, rivastigmine, memantime, Herbal remedies, vitamins, dietary supplements