Association Between Apolipoprotein E4 and Cognitive Decline in Elderly Adults

• Published in: Journal of the American Geriatrics Society (JAGS) 2007-11, Vol.55 (11), p.1777-1785
• Main Authors: Packard, Chris J., Westendorp, Rudi G.J., Stott, David J., Caslake, Muriel J., Murray, Heather M., Shepherd, James, Blauw, Gerard J., Murphy, Michael B., Bollen, Edward L.E.M., Buckley, Brendan M., Cobbe, Stuart M., Ford, Ian, Gaw, Allan, Hyland, Michael, Jukema, J. Wouter, Kamper, Adriaan M., Macfarlane, Peter W., Jolles, Jellemer, Perry, Ivan J., Sweeney, Brian J., Twomey, Cillian
• Format: Article
• Language: English
• Subjects: Activities of Daily Living - classification; Aged; Aged, 80 and over; Alzheimer Disease - blood; Alzheimer Disease - diagnosis; Alzheimer Disease - genetics; Anticholesteremic Agents - therapeutic use; Apolipoprotein E4 - genetics; Biological and medical sciences; Cholesterol - blood; Cholesterol, HDL - blood; Cholesterol, LDL - blood; Cognition & reasoning; Cognition Disorders - blood; Cognition Disorders - genetics; Cohort Studies; Cross-Sectional Studies; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; dementia; Dementia, Vascular - blood; Dementia, Vascular - diagnosis; Dementia, Vascular - genetics; Female; Follow-Up Studies; General aspects; Genetic Carrier Screening; Homozygote; Humans; Ireland; Male; Medical disorders; Medical sciences; memory; Mental Status Schedule; Miscellaneous; Netherlands; Neurology; Neuropsychological Tests; Older people; Phenotype; Pravastatin - therapeutic use; Proteins; Public health. Hygiene; Public health. Hygiene-occupational medicine; Risk Factors; Scotland; statin; Statistics as Topic; trial; Triglycerides - blood
• ISSN: 0002-8614; 1532-5415
• DOI: 10.1111/j.1532-5415.2007.01415.x

OBJECTIVE: To determine the influence of apolipoprotein E on cognitive decline in a cohort of elderly men and women. DESIGN: Prospective study. SETTING: Scotland, Ireland, and the Netherlands. PARTICIPANTS: Five thousand eight hundred four subjects aged 70 to 82 from the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER). MEASUREMENTS: Subjects were assessed at baseline and over a mean 3.2‐year (range 0.7–4.2) follow‐up for memory (Picture‐Word Recall), speed of information processing (Stroop and Letter‐Digit Coding), global cognitive function (Mini‐Mental State Examination), and activities of daily living. RESULTS: At baseline, subjects with apolipoprotein E4 versus those without E4 had poorer memory performance (mean score difference −0.20 (95% confidence interval (CI)=−0.31 to −0.09) for immediate recall and −0.32 (95% CI=−0.48 to −0.16) for delayed recall and slower information processing (difference in Stroop, 2.79 seconds, (95% CI=1.20–4.28); Letter‐Digit score, −0.36, (95% CI=−0.77–0.05). Subjects with apolipoprotein E4 showed a greater decline in immediate (−0.22, 95% CI=−0.33 to −0.11) and delayed (−0.30, 95% CI=−0.46 to −0.15) memory scores but no significant change in speed of information processing (Stroop, P=.17; Letter‐Digit, P=.06). Memory scores decreased 2.5% from baseline in those without E4, 4.3% in E4 heterozygotes (P=.01 for immediate and P=.03 for delayed, vs no E4) and 8.9% to 13.8% in E4 homozygotes (P=.04 for immediate and P=.004 for delayed, vs heterozygotes). Apolipoprotein E4 was associated with greater decline in instrumental activities of daily living (P