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Int J Geriatr Psychiatry. 2019 Dec;34(12):1833-1844. doi: 10.1002/gps.5199. Epub 2019 Aug 22.

Cognitive resilience among APOE ε4 carriers in the oldest old.

Author information

Department of Social Sciences and Health Policy, Division of Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, NC.
Department of Biostatistics and Data Science, Division of Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, NC.
Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
Department of Internal Medicine, Section on Geriatrics and Gerontology, Wake Forest School of Medicine, Winston-Salem, NC.
Department of Neurology, Wake Forest School of Medicine, Winston-Salem, NC.
Department of Family Medicine and Public Health, University of California San Diego School of Medicine, La Jolla, CA.
Geriatric Research Education and Clinical Centers (GRECC), Veterans Affairs Tennessee Valley Healthcare System, Vanderbilt University Medical Center, Nashville, TN.
Department of Epidemiology and Population Health, Albert Einstein College of Medicine, New York City, NY.
Department of Preventive Medicine, University of Tennessee Health Science Center, Memphis, TN.
Department of Psychiatry and Behavioral Medicine, Wake Forest School of Medicine, Winston-Salem, NC.
Laboratory of Behavioral Neuroscience, National Institute on Aging, Baltimore, MD.



Relatively few APOE ε4+ carriers survive to old age (age 80+) without cognitive impairment (CI); thus, little is known about distinguishing characteristics of resilient APOE ε4+ carriers. Herein, we describe the sociodemographic characteristics of a large sample of resilient APOE ε4+ women from the Women's Health Initiative Memory Study (WHIMS) and compare them to noncarriers and APOE ε4+ women who developed CI before age 80.


Women were recruited for clinical trials evaluating postmenopausal hormone therapy and incidence of dementia. During posttrial follow-up, cognitive status was adjudicated annually. Among 5716 women, we compared groups by APOE ε4 status using logistic regression, covarying for treatment, demographics, lifestyle, cardiovascular and physical function, well-being, and self-rated general health.


Among 557 APOE ε4+ women, those who survived to age 80+ without CI had higher baseline self-rated general health (odds ratio [OR]: 1.02; 95% confidence interval [CI], 1.01-1.04) and cognitive scores (OR: 1.18; 95% CI, 1.12-1.25) than those who did not reach age 80 without CI. Baseline high total cholesterol and low-density lipoprotein (LDL) levels were similar across APOE ε4+ groups but were higher compared with APOE ε4- women. Among women who survived to 80+ without CI, more APOE ε4+ women had a history of high total cholesterol (P = .003) and LDL cholesterol (OR: 1.01; 95% CI, 1.00-1.01). There were no differences in hypertension, diabetes, or other vascular risk factors in APOE ε4+ women compared with noncarriers.


Results highlight the importance of baseline cognitive function and general health for late-life cognition among ε4+ women.


APOE ε; cognitive resilience; mild cognitive impairment; oldest old; probable dementia


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