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Examining the Complicated Relationship Between Depressive Symptoms and Cognitive Impairment in Preclinical Alzheimer Disease

Javaherian, Kavon, BS*; Newman, Brianne M., MD; Weng, Hua, PhD‡,§; Hassenstab, Jason, PhD∥,¶; Xiong, Chengjie, PhD‡,∥; Coble, Dean, PhD; Fagan, Anne M., PhD∥,¶; Benzinger, Tammie, MD, PhD¶,#; Morris, John C., MD∥,¶

Alzheimer Disease & Associated Disorders: January-March 2019 - Volume 33 - Issue 1 - p 15–20
doi: 10.1097/WAD.0000000000000284
Original Articles

Introduction: The relationships between Alzheimer disease (AD), cognitive performance, and depression are poorly understood. It is unclear whether depressive features are a prodrome of AD. In addition, some studies of aging exclude depressed individuals, which may inappropriately limit generalizability. The aim of the present study was to determine whether depressive symptoms affect cognitive function in the context of preclinical AD.

Methods: Cross-sectional multivariate analysis of participants in a longitudinal study of aging (n=356) that evaluates the influence of depressive symptoms on cognitive function in cognitively normal adults.

Results: There is no relationship between the presence of depressive symptoms and cognitive function in those with either no evidence of preclinical AD or biomarker evidence of early-stage preclinical AD. However, in later stages of preclinical AD, the presence of depressive symptoms demonstrated interactive effects, including in episodic memory (0.96; 95% confidence interval, 0.31-1.62) and global cognitive function (0.46; 95% confidence interval, 0.028-0.89).

Conclusions: The presence of depressive symptoms may be a late prodrome of AD. In addition, studies investigating cognitive function in older adults may not need to exclude participants with depressive symptomology, but may still consider depressive symptoms as a potential confounder in the context of more extensive neuronal injury.

*Washington University School of Medicine

Division of Biostatistics

Department of Neurology, Washington University School of Medicine

Department of Psychiatry and Behavioral Neuroscience, Saint Louis University School of Medicine

Department of Neurology, Knight Alzheimer’s Disease Research Center

#Division of Diagnostic Radiology, Mallinckrodt Institute of Radiology, Washington University, St. Louis, MO

§Evidera, Waltham, MA

K.J., B.M.N., J.H., and J.C.M.: were involved with designing the study and writing and editing the manuscript. K.J., D.C., and C.X.: had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. A.M.F. and T.B.: were involved with determining use of biomarkers and imaging data. J.H.: assisted with psychometric testing data and the creation of cognitive domains.

Supported by National Institute on Aging grants P50 AG05681, P01 AG03991, and P01 AG026276, as well as the following funds: The Charles and Joanne Knight Alzheimer’s Disease Research Center Support Fund, The David and Betty Farrell Medical Research Fund, The Daniel J Brennan Alzheimer’s Research Fund, The Thomas E. Brew Foundation Fund, and The Fred Simmons and Olga Mohan Alzheimer’s Research Support Fund. Image acquisition and processing were funded by the following grants: 1P30NS098577, R01 EB009352, and UL1TR000448.

The authors declare no conflicts of interest.

Reprints: John C. Morris, MD, Knight Alzheimer’s Disease Research Center, Washington University School of Medicine, 4488 Forest Park Avenue, Suite 130, St. Louis, MO 63108 (e-mail:

Received May 29, 2018

Accepted October 1, 2018

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