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The association of APOE genotype and cognitive decline in interaction with risk factors in a 65-69 year old community sample.

ABSTRACT: BACKGROUND: While the evidence of an association between the apolipoprotein E (APOE) *E4 allele and Alzheimer's disease is very strong, the effect of the *E4 allele on cognitive decline in the general population is more equivocal. A cross-sectional study on the lifespan effects of the *E4 allele 1 failed to find any effect of the *E4 allele on cognitive performance at ages 20-24, 40-44 or 60-64 years. METHODS: In this four year follow-up study, we reexamine the effect of *E4 in the sample of 2,021 individuals, now aged 65-69 years. RESULTS: Performance on the Mini-Mental State Examination (MMSE) was significantly poorer for *E4 homozygotes than heterozygotes or non-carriers. The effects of the *E4 genotype on cognitive decline over four years were found on the MMSE and Symbol-Digit Modalities test but only when controlling for risk factors such as head injury and education. Analyses were repeated with the exclusion of participants diagnosed with a mild cognitive disorder, with little change. CONCLUSION: It is possible that *E4 carriers become vulnerable to greater cognitive decline in the presence of other risk factors at 65-69 years of age.

SUBMITTER: Christensen H

PROVIDER: S-EPMC2488328 | biostudies-literature | 2008

REPOSITORIES: biostudies-literature

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The association of APOE genotype and cognitive decline in interaction with risk factors in a 65-69 year old community sample.

Christensen Helen H Batterham Philip J PJ Mackinnon Andrew J AJ Jorm Anthony F AF Mack Holly A HA Mather Karen A KA Anstey Kaarin J KJ Sachdev Perminder S PS Easteal Simon S

BMC geriatrics 20080714

<h4>Background</h4>While the evidence of an association between the apolipoprotein E (APOE) *E4 allele and Alzheimer's disease is very strong, the effect of the *E4 allele on cognitive decline in the general population is more equivocal. A cross-sectional study on the lifespan effects of the *E4 allele 1 failed to find any effect of the *E4 allele on cognitive performance at ages 20-24, 40-44 or 60-64 years.<h4>Methods</h4>In this four year follow-up study, we reexamine the effect of *E4 in the ...[more]

PMID: 18620605

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Project description:There are few intervention studies that demonstrated linking social participation to lower risk of cognitive decline. We examined prospectively the protective effect of a community intervention program promoting social participation on the incidence of cognitive disability.The baseline was established in a survey of community-dwelling older people aged 65 years old or more in July 2006 (2793 respondents, response rate 48.5%). The setting was Taketoyo town in Japan, where municipal authorities launched an intervention that was based on the establishment of community-based centers called "salons," where the town's senior residents could congregate and participate in social activities, ranging from arts and crafts, games, and interactive activities with preschool children. Three salons were established in May 2010, and a total of 10 salons were in operation by 2013. We recorded the frequency of salon participation among survey respondents till 2013 and conducted two follow-up surveys (in 2010 and 2013) to collect information about health status and behaviors. The onset of cognitive disability was followed from May 2007 to January 2014. We used the marginal structural models to evaluate the effect of program.The range of prevalence of cognitive disability was from 0.2% to 2.5% during the observation period. The proportion of respondents who participates to salons increased over time to about 11.7%. The frequency of salon participation was protectively associated with cognitive decline, even after adjusting for time-dependent covariates and attrition (odds ratio = 0.73, 95% confidence interval: 0.54-0.99).Our study suggests that operating community salons that encourage social interactions, light physical activity, and cognitive activities among older participants may be effective for preventing cognitive decline. In future studies, we need to understand what sorts of activities (e.g., those involving light physical activity vs. purely intellectual activities) are most effective in maintaining cognitive function.

Project description:ObjectiveTo exam the association of cognitive decline with APOE ε4 allele carriage and dietary protein intake and investigate whether there is a gene-diet (GxD) interaction of APOE ε4 allele carriage and dietary protein intake on cognitive decline in a nationwide cohort of older adults.MethodsA cohort study of participants from Chinese Longitudinal Healthy Longevity Survey was conducted from 2008 to 2014. A total of 3029 participants (mean age of 77.0 years, SD = 9.0; 49.3% were women) was enrolled. We genotyped APOE ε4 allele for each participant and calculated the diversity of dietary protein intake (DDPI) by summing up the frequency of intake of the 6 protein-rich foods (meats, fish, eggs, nuts, dairy products, and bean products). We assessed cognitive function using the Mini-Mental State Examination (MMSE). We used ordinal regression model to estimate the independent and joint effects of APOE ε4 carrier and dietary protein intake on cognitive decline, adjusting for potential confounders of age, sex, education, socio-economic status, lifestyles, BMI, and cardiometabolic conditions.ResultsThere was significant association between carrying APOE ε4 allele and faster cognitive decline (Odds ratio: 1.19, 95% CI = 1.00-1.42), independent of potential confounders. While the associations of DDPI and the intake of 6 protein-rich foods with cognitive decline did not reach any statistical significance. We observed significant interactions of APOE ε4 with DDPI and fish intake, at multiple correction-adjusted Ps < 0.05. In those who were APOE ε4 carriers rather than non-carriers, both high DDPI (OR = 0.54, 95% CI: 0.34-0.88) and daily fish intake (OR = 0.43, 95% CI: 0.22-0.78) were significantly associated with slower cognitive decline, respectively. We also found that frequent intake of fish benefits women more than men regarding the mitigating of cognitive decline among APOE ε4 allele carriers (P for interaction = 0.016).ConclusionsThe results of this study support the hypothesis that diversified protein food intake in addition to frequent fish intake may reduce the detrimental effect of APOE ε4 on cognitive health.

Project description:ObjectiveAn Alzheimer's disease (AD) diagnosis is preceded by a long period of cognitive decline. We previously demonstrated increased risk of decline among individuals possessing one or more APOE ?4 alleles together with a family history of AD. The objective of this study is to investigate the possibility that such an increased risk might be due to AD risk genes with small effects in combination with APOE.MethodsParticipants in the Health and Retirement Study (HRS) over the age of 65, who contributed DNA, and had two or more evaluations with an abbreviated version of the modified Telephone Interview for Cognitive Status (TICS-m) were eligible for the study (n = 7451). A genetic risk score (g-score) was derived using AD risk genes' meta-analyses data, assigning risk according to the number of risk alleles and summed over all the risk genes. Trajectories of cognitive function were modeled in four groups of Caucasian participants with and without one or more APOE ?4 alleles and either a high or low g-score: APOE ?4-/low g-score; APOE ?4-/high g-score; APOE ?4+/low g-score; and APOE ?4+/high g-score. Post hoc analyses evaluated interactions between individual genes and APOE.ResultsIndividuals in the APOE ?4+/high g-score group exhibited the greatest cognitive decline over time (p<.0001). This risk appeared to be greater than the sum of the effects of either high g-score or APOE ?4 alone. When gene interactions were individually tested with APOE, a statistically significant interaction with CD33 was discovered (p = 0.04) although the interaction was no longer significant when adjusted for multiple comparisons.ConclusionsIndividuals with multiple AD risk genes in addition to having one or more APOE ?4 alleles are at greater risk of cognitive decline than individuals with either APOE ?4 or a high genetic risk score. Among those with one or more APOE ?4 alleles, having one or more copies of the CD33 C (risk) allele may further increase the risk of cognitive decline.

Dataset Information

The association of APOE genotype and cognitive decline in interaction with risk factors in a 65-69 year old community sample.

Publications

The association of APOE genotype and cognitive decline in interaction with risk factors in a 65-69 year old community sample.

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