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The Influence of Chronic Stress on Dementia-related Diagnostic Change in Older Adults

Peavy, Guerry M. PhD*; Jacobson, Mark W. PhD†,‡; Salmon, David P. PhD*; Gamst, Anthony C. PhD*,§; Patterson, Thomas L. PhD†,‡; Goldman, Sherry MA†,‡; Mills, Paul J. PhD; Khandrika, Srikrishna PhD; Galasko, Douglas MD*,†

Alzheimer Disease & Associated Disorders: July–September 2012 - Volume 26 - Issue 3 - p 260–266
doi: 10.1097/WAD.0b013e3182389a9c
Original Articles

Increased susceptibility of the aging brain to both chronic stress and incipient dementia-related neuropathology may accelerate cognitive decline. We investigated associations between chronic stress and diagnostic change in 62 individuals (mean age, 78.7 y) participating in an Alzheimer disease research center longitudinal study. The subjects, diagnosed at baseline as cognitively normal (CN) or with mild cognitive impairment (MCI), were followed for an average of 2.5 years. Senior neurologists, blind to detailed measures of stress and cognition, assigned diagnoses annually. Logistic regression analyses assessed the accuracy with which measures of stress (event-based ratings, cortisol levels) predicted the conversion to MCI and dementia. Eleven individuals with MCI at baseline received a dementia diagnosis during follow-up. Sixteen converted from cognitively normal to MCI. Prolonged, highly stressful experiences were associated with conversion from MCI to dementia. The cortisol awakening response, with age and education, was associated with a diagnostic change to MCI. Cortisol measures were not associated with the progression from MCI to dementia, and there was no association between stressful experiences and the change to MCI. Mechanisms associated with the transition from normal cognition to MCI may differ from those associated with a diagnostic change to dementia. These findings could facilitate the identification of interventional strategies to reduce the risk of decline at different stages of susceptibility.

*Department of Neurosciences

Department of Psychiatry

§Department of Family and Preventive Medicine

Department of Medicine (Clinical Research Center), University of California

Veterans Administration Medical Center, San Diego, CA

Supported by the National Institute of Mental Health (5R01MH063782) and the Alzheimer’s Association (IIRG-02-4051). This study was also supported by the UCSD Shiley-Marcos Alzheimer’s Disease Research Center (P50 AG005131), a Grant from the State of California (Alzheimer Research Centers of California), and the UCSD Clinical Research Center Laboratory (MO1 RR 000827).

The authors declare no conflicts of interest.

Reprints: Guerry M. Peavy, PhD, UCSD Shiley-Marcos Alzheimer’s Disease Research Center, 8950 Villa La Jolla Dr Ste C-129, La Jolla, CA 92037 (e-mail: gpeavy@ucsd.edu).

Received February 18, 2011

Accepted September 17, 2011

© 2012 Lippincott Williams & Wilkins, Inc.