Dataset Information

Effect of APOE and CD33 on Cognitive Decline.

ABSTRACT:

Objective

An 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.

Methods

Participants 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.

Results

Individuals 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.

Conclusions

Individuals 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.

SUBMITTER: Hayden KM

PROVIDER: S-EPMC4478019 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Publications

Effect of APOE and CD33 on Cognitive Decline.

Hayden Kathleen M KM Lutz Michael W MW Kuchibhatla Maragatha M Germain Cassandra C Plassman Brenda L BL

PloS one 20150623 6

<h4>Objective</h4>An 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 ε4 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.<h4>Methods</h4>Participants in the Health and Retirement Study (HRS) over the ag ...[more]

PMID: 26102276

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Project description:IntroductionSubjects exhibiting subjective cognitive decline (SCD) are at an increased risk for mild cognitive impairment and dementia. Given the delay between risk exposure and disease onset, SCD individuals are increasingly considered a good target population for cost-effective lifestyle-based Alzheimer's disease prevention trials.MethodsThe PENSA study is a randomized, double-blind, controlled clinical trial that aims to evaluate the efficacy of a personalized multimodal intervention in lifestyle (diet counseling, physical activity, cognitive training, and social engagement) combined with the use of epigallocatechin gallate (EGCG) over 12 months, in slowing down cognitive decline and improving brain connectivity. The study population includes 200 individuals meeting SCD criteria and carrying the apolipoprotein E ε4 allele, who will be randomized into four treatment arms (multimodal intervention + EGCG/placebo, or lifestyle recommendations + EGCG/placebo). The primary efficacy outcome is change in the composite score for cognitive performance measured with the Alzheimer's Disease Cooperative Study Preclinical Alzheimer Cognitive Composite (ADCS-PACC-like) adding to the original version the Interference score from the Stroop Color and Word Test and the Five Digit Test. Secondary efficacy outcomes are (1) change in functional magnetic resonance imaging (fMRI) and structural neuronal connectivity (structural MRI) and (2) the safety assessment of the EGCG compound. This study is framed within the WW-FINGERS consortium.DiscussionThe use of new technologies (i.e., mobile ecological momentary assessments [EMAs], activity tracker) in the PENSA study allows the collection of continuous data on lifestyle behaviors (diet and physical activity) and mood, enabling a personalized design as well as an intensive follow-up of participants. These data will be used to give feedback to participants about their own performance along the intervention, promoting their involvement and adherence. The results of the study may aid researchers on the design of future clinical trials involving preventive lifestyle multicomponent interventions.

Dataset Information

Effect of APOE and CD33 on Cognitive Decline.

Objective

Methods

Results

Conclusions

Publications

Effect of APOE and CD33 on Cognitive Decline.

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