Association Between Apolipoprotein E4 and Cognitive Decline in Elderly Adults
Article first published online: 29 OCT 2007
Journal of the American Geriatrics Society
Volume 55, Issue 11, pages 1777–1785, November 2007
How to Cite
Packard, C. J., Westendorp, R. G.J., Stott, D. J., Caslake, M. J., Murray, H. M., Shepherd, J., Blauw, G. J., Murphy, M. B., Bollen, E. L.E.M., Buckley, B. M., Cobbe, S. M., Ford, I., Gaw, A., Hyland, M., Jukema, J. W., Kamper, A. M., Macfarlane, P. W., Jolles, J., Perry, I. J., Sweeney, B. J., Twomey, C. and for the Prospective Study of Pravastatin in the Elderly at Risk Group (2007), Association Between Apolipoprotein E4 and Cognitive Decline in Elderly Adults. Journal of the American Geriatrics Society, 55: 1777–1785. doi: 10.1111/j.1532-5415.2007.01415.x
- Issue published online: 29 OCT 2007
- Article first published online: 29 OCT 2007
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<.001). Cognitive decline was not associated with lipoprotein levels.
CONCLUSION: Findings in PROSPER indicate that E4 is associated with more-rapid cognitive decline and may, therefore, predispose to dementia.