Association Between Apolipoprotein E₄ and Cognitive Decline in Elderly Adults

Abstract

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 E 4 versus those without E 4 had poorer memory performance (mean score difference À 0.20 (95% confidence interval (CI) 5 À 0.31 to À 0.09) for immediate recall and À 0.32 (95% CI 5 À 0.48 to À 0.16) for delayed recall and slower information processing (difference in Stroop, 2.79 seconds, (95% CI 5 1.20-4.28); Letter-Digit score, À 0.36, (95% CI 5 À 0.77-0.05). Subjects with apolipoprotein E 4 showed a greater decline in immediate ( À 0.22, 95% CI 5 À 0.33 to À 0.11) and delayed ( À 0.30, 95% CI 5 À 0.46 to À 0.15) memory scores but no significant change in speed of information processing (Stroop, P 5.17; Letter-Digit, P 5.06). Memory scores decreased 2.5% from baseline in those without E 4 , 4.3% in E 4 heterozygotes (P 5.01 for immediate and P 5.03 for delayed, vs no E 4 ) and 8.9% to 13.8% in E 4 homozygotes (P 5.04 for immediate and P 5.004 for delayed, vs heterozygotes). Apolipoprotein E 4 was associated with greater decline in instrumental activities of daily living (Po.001). Cognitive decline was not associated with lipoprotein levels. CONCLUSION: Findings in PROSPER indicate that E 4 is associated with more-rapid cognitive decline and may, therefore, predispose to dementia. J Am Geriatr Soc 55:1777-1785, 2007. Key words: memory; dementia; trial; statin A major challenge in the quest to promote healthy aging is to uncover the determinants of cognitive decline in the general population and the risk factors that lead to the development of frank dementia. Although age is the main predictor of cognitive function, investigators have also reported that a history of hypertension, diabetes mellitus, stroke, depression, and lack of physical activity are factors. [1][2][3][4][5][6] The apolipoprotein E phenotype (apolipoprotein E is coded by a gene (e) that exhibits allelic variants e 2 , e 3 , and e 4 ) has been linked consistently and strongly to the appearance of Alzheimer's disease and to some aspects of cognitive decline in elderly cohorts. 1,2,[5][6][7][8][9] Inheritance of E 4 (the product of e 4 ) especially in the homozygous form, has been associated in cross-sectional studies with risk of Alzheimer's disease and poorer global cognitive function, episodic memory, and executive function, although the magnitude of the effect is modest. 10,11 Longitudinal data also show good evidence of an association between E 4 and risk of Alzheimer's diseas...

Apolipoprotein ɛ4 and neuropsychological performance in Alzheimer's disease and vascular dementia

“…This has been demonstrated previously in a large cohort of patients (n = 5804) taking part in the PROSPER study [23]. Again, most of the participants were free of dementia (89.3% of 4 present and 92.8% of 4 absent participants had MMSE scores >24 at their final assessment).…”

APOE E4 status predicts age-related cognitive decline in the ninth decade: longitudinal follow-up of the Lothian Birth Cohort 1921

“…Whereas the APOE2 protein may exert a protective effect from Alzheimer's disease, 4 the APOE4 isoform has been related to reduced neuronal survival and cognitive impairment. 5,6 Although individuals carrying at least one copy of the APOE E4 allele have an increased risk of developing Alzheimer's disease, it is less clear whether the APOE genotype may also be involved in non-pathological cognitive ageing: several studies indicate that possession of the APOE E4 allele relates to increased cognitive decline during normal ageing, [7][8][9][10][11][12][13][14] but other studies do not find evidence for such an association. [15][16][17][18] Various explanations for these conflicting results may be put forward.…”

ApoE genotype and abnormal auditory cortical potentials in healthy older females

“…The 2 allele has the lowest risk of AD, followed by 3, with the greatest AD risk with 4 (∼3 times higher than normal risk) (Poirier et al, 1993). Possession of the 4 allele is also associated with memory decline in healthy normal aging (Packard et al, 2007). Moreover, the extent of the memory disorder is greater in ApoE 4 carriers with amnestic mild cognitive impairment or AD compared to non-carriers with these disorders (Fleisher et al, 2005;van der Vlies et al, 2007).…”