The Relationship Between Midlife and Late Life Alcohol Consumption, APOE e4 and the Decline in Learning and Memory Among Older Adults

Downer, Brian; Zanjani, Faika; Fardo, David W.

doi:10.1093/alcalc/agt144

Cited by 31 publications

(37 citation statements)

References 44 publications

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“…AD-like) cluster, a difference that is more significant than for clusters produced by LCMM approaches on this dataset. [32] and body mass [33]. The inconsistency of these studies may be explained by cohort differences and/or the strong methodological challenges of the study of cognitive decline [7].…”

Section: Discussionmentioning

confidence: 99%

Heterogeneity of cognitive decline in dementia: a failed attempt to take into account variable time-zero severity

Kiddle

Parodi

Johnston

et al. 2016

Preprint

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NOTE: The biases seen in simulations of Temporal Clustering appear to be even worse in real applications. While this was a novel and interesting approach, ultimately this work has been discontinued. I feel the biases are due to propagated error in estimating individual level offsets based on a single noisy measure, amplified by the fact that high MMSE scores change very slowly and therefore many estimates are from near an asymptote on the left hand of the model. We continue to work in this area, with other approaches showing significantly more promise.Understanding heterogeneity in Alzheimer's disease (AD) progression is critically important for the optimal design of trials, allowing participants to be recruited who are correctly diagnosed and who are likely to undergo cognitive decline. Current knowledge about heterogeneity is limited by the paucity of long-term follow-up data and methodological challenges.Of the latter, a key problem is how to choose the most appropriate 'time zero' to use in longitudinal models, a choice which affects results. Rather than a pre-specified 'time zero' we propose a novel methodology -Temporal Clustering -that defines a new 'time zero' using individual offsets inferred from the data. We applied this to longitudinal Mini-Mental State Examination (MMSE), where this approach ensures that individuals have similar estimated MMSE scores at this new 'time zero'. Simulations showed that it could accurately predict cluster membership after the application of a filter. Next we applied it to a cohort of 2412 individuals, with large variability in MMSE score at first visit. Temporal Clustering was used to split individuals into two clusters. The group showing faster decline had higher average levels of AD risk factors: cerebrospinal fluid tau and APOE 4. Cluster membership predicted by Temporal Clustering was less affected by individuals' cognitive ability at first visit than was the case for clusters found using Latent Class Mixture Models. Further application and development of this method will help researchers to identify risk factors affecting 3 cognitive decline.

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Section: Discussionmentioning

confidence: 99%

Heterogeneity of cognitive decline in dementia: a failed attempt to take into account variable time-zero severity

Kiddle

Parodi

Johnston

et al. 2016

Preprint

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“…However, this relationship may not apply to ε4 carriers. Up to three servings of wine per day has been associated with a lower risk of AD for ε4 non-carriers (30), while consumption of any amount of alcohol may increase the risk of AD for ε4 carriers (20, 31, 32). In one study, both light (1-6 drinks per week) and moderate (7-14 drinks per week) alcohol consumption was associated with improvement in learning and memory for ε4 non-carriers, but with a decline in learning and memory for ε4 carriers (31).…”

Section: Multi-modal Lifestyle Considerationsmentioning

confidence: 99%

“…Up to three servings of wine per day has been associated with a lower risk of AD for ε4 non-carriers (30), while consumption of any amount of alcohol may increase the risk of AD for ε4 carriers (20, 31, 32). In one study, both light (1-6 drinks per week) and moderate (7-14 drinks per week) alcohol consumption was associated with improvement in learning and memory for ε4 non-carriers, but with a decline in learning and memory for ε4 carriers (31). Similarly, in other studies ε4 carriers who consumed alcohol one or more times per month had a higher risk of AD than those who never consumed alcohol (20) and the risk of AD for ε4 carriers increased with increasing amounts of alcohol consumption (32).…”

Section: Multi-modal Lifestyle Considerationsmentioning

confidence: 99%

Clinical Application of Apoe in Alzheimer’s Prevention: A Precision Medicine Approach

et al. 2018

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Population-attributable risk models estimate that up to one-third of Alzheimer’s disease (AD) cases may be preventable through risk factor modification. The field of AD prevention has largely focused on addressing these factors through universal risk reduction strategies for the general population. However, targeting these strategies in a clinical precision medicine fashion, including the use of genetic risk factors, allows for potentially greater impact on AD risk reduction. Apolipoprotein E (APOE), and specifically the APOE ε4 variant, is one of the most well-established genetic influencers on late-onset AD risk. In this review, we evaluate the impact of APOE ε4 carrier status on AD prevention interventions, including lifestyle, nutrigenomic, pharmacogenomic, AD comorbidities, and other biological and behavioral considerations. Using a clinical precision medicine strategy that incorporates APOE ε4 carrier status may provide a highly targeted and distinct approach to AD prevention with greater potential for success.

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“…Moderate alcohol has a protective effect against cardiovascular disease risk factors, while red wine has an additional benefit that may be ascribed to the presence of polyphenol antioxidants in the wine. Although the antioxidant effects of red wine are well documented, it seems clear that alcohol intake may be contra-indicated in individuals with certain genetic alterations that occur relatively frequently in the general population [20]. Long-term intervention strategies for health promotion including lifestyle modification and safer daily drinking habits may therefore be more effective when guided from the genetic background.…”

Section: Resultsmentioning

confidence: 99%

Assessment of the impact of hereditary factors on biochemical parameters of cardiovascular risk in relation to moderate alcohol consumption

Kotze

Marnewick

Kidd

et al. 2014

Nutrition and Aging

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Alcohol intake is associated with variation in many biochemical markers and metabolic processes implicated in cardiovascular disease (CVD) and other non-communicable diseases associated with advanced aging. Some changes are beneficial, while others may be harmful in relation to individual differences in genetic background. The objective of this study was to compare the effects of alternative moderate consumption of red wine and brandy on the lipid profile in the same experimental population of healthy adults and to identify genetic risk factors that may contribute to differences in response. An 8-week randomised crossover intervention study of red wine versus brandy consumption was performed in 37 healthy volunteers (19 males and 18 females) between the ages of 26 and 71 years. The assessments included anthropometric measurements, biochemical determinations and genetic analysis using a multi-gene CVD test. The level of total glutathione as an indicator of antioxidant capacity was significantly decreased only after the brandy intervention when compared to the baseline (p = 0.002). Both the brandy and wine intervention resulted in a significant increase in HDL-cholesterol (p < 0.001). Significant differential effects were shown in relation to genetic variation in the APOE (p = 0.027) and MTHFR (p = 0.048) genes, known to be associated with hyper-responsiveness to alcohol intake. Novel findings included a statistically significant increase of both total cholesterol (p = 0.016) and triglyceride (p = 0.022) levels with alcohol intake only in individuals who tested positive for the low-penetrance H63D and/or C282Y mutations in the HFE gene. This study confirmed the well-established protective effect of moderate alcohol consumption on the lipid profile, especially red wine. Since the genetic background influences the effect of alcohol on biochemical parameters of CVD risk, safe limits of wine and brandy consumption may in future be based partly on the genetic profile.

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The Relationship Between Midlife and Late Life Alcohol Consumption, APOE e4 and the Decline in Learning and Memory Among Older Adults

Abstract: Light to moderate alcohol consumption during late life may protect against a decline in learning and memory for non-APOE e4 allele carriers, but not for older adults who carry one or more APOE e4 alleles.

Cited by 31 publications

References 44 publications

Heterogeneity of cognitive decline in dementia: a failed attempt to take into account variable time-zero severity

Heterogeneity of cognitive decline in dementia: a failed attempt to take into account variable time-zero severity

Clinical Application of Apoe in Alzheimer’s Prevention: A Precision Medicine Approach

Assessment of the impact of hereditary factors on biochemical parameters of cardiovascular risk in relation to moderate alcohol consumption

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