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Do menopausal status and APOE4 genotype alter the long-term effects of intensive lifestyle intervention on cognitive function in women with type 2 diabetes mellitus?

ABSTRACT: In the Look AHEAD trial, randomization to Intensive Lifestyle Intervention (ILI) or Diabetes Support and Education (DSE) did not result in differences in cognitive outcomes. However, menopause and APOE genotype are factors that affect the response to this intervention. The effect of this intervention on a single cognitive assessment was examined in 3 groups of women: premenopausal or <5 years postmenopausal (N = 594), within 5-10 years (n = 388), and ≥10 years postmenopausal (n = 963), and as a function of continuous years since menopause. The late postmenopausal group in the ILI had worse composite z-scores compared to those in the DSE, whereas the younger premenopausal or early postmenopausal women in the ILI had better composite z-scores than the DSE. A significant interaction between years since menopause and intervention arm, but not baseline age, was observed on executive function domains. ILI appeared only to benefit cognitive function among non-APOE4 carriers during premenopause or early postmenopause. These findings emphasize the importance of assessing menopause and APOE status to understand how weight loss impacts cognition.

SUBMITTER: Yassine HN

PROVIDER: S-EPMC7269875 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Do menopausal status and APOE4 genotype alter the long-term effects of intensive lifestyle intervention on cognitive function in women with type 2 diabetes mellitus?

Yassine Hussein N HN Anderson Andrea A Brinton Roberta R Carmichael Owen O Espeland Mark A MA Hoscheidt Siobhan S Hugenschmidt Christina E CE Keller Jeffrey N JN Peters Anne A Pi-Sunyer Xavier X

Neurobiology of aging 20200408

In the Look AHEAD trial, randomization to Intensive Lifestyle Intervention (ILI) or Diabetes Support and Education (DSE) did not result in differences in cognitive outcomes. However, menopause and APOE genotype are factors that affect the response to this intervention. The effect of this intervention on a single cognitive assessment was examined in 3 groups of women: premenopausal or <5 years postmenopausal (N = 594), within 5-10 years (n = 388), and ≥10 years postmenopausal (n = 963), and as a ...[more]

PMID: 32388179

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Project description:ObjectiveTo assess whether an average of 10 years of lifestyle intervention designed to reduce weight and increase physical activity lowers the prevalence of cognitive impairment among adults at increased risk due to type 2 diabetes and obesity or overweight.MethodsCentral adjudication of mild cognitive impairment and probable dementia was based on standardized cognitive test battery scores administered to 3,802 individuals who had been randomly assigned, with equal probability, to either the lifestyle intervention or the diabetes support and education control. When scores fell below a prespecified threshold, functional information was obtained through proxy interview.ResultsCompared with control, the intensive lifestyle intervention induced and maintained marked differences in weight loss and self-reported physical activity throughout follow-up. At an average (range) of 11.4 (9.5-13.5) years after enrollment, when participants' mean age was 69.6 (54.9-87.2) years, the prevalence of mild cognitive impairment and probable dementia was 6.4% and 1.8%, respectively, in the intervention group, compared with 6.6% and 1.8%, respectively, in the control group (p = 0.93). The lack of an intervention effect on the prevalence of cognitive impairment was consistent among individuals grouped by cardiovascular disease history, diabetes duration, sex, and APOE ε4 allele status (all p ≥ 0.50). However, there was evidence (p = 0.03) that the intervention effect ranged from benefit to harm across participants ordered from lowest to highest baseline BMI.ConclusionsTen years of behavioral weight loss intervention did not result in an overall difference in the prevalence of cognitive impairment among overweight or obese adults with type 2 diabetes.Clinicaltrialsgov identifierNCT00017953 (Action for Health in Diabetes).Level of evidenceThis study provides Class II evidence that for overweight adults with type 2 diabetes, a lifestyle intervention designed to reduce weight and increase physical activity does not lower the risk of cognitive impairment.

Project description:BackgroundIn light of advancements in machine learning techniques, many studies have implemented machine learning approaches combined with data measures to predict and classify Alzheimer's disease. Studies that predicted cognitive status with longitudinal follow-up of amyloid-positive individuals remain scarce, however.ObjectiveWe developed models based on voxel-wise functional connectivity (FC) density mapping and the presence of the ApoE4 genotype to predict whether amyloid-positive individuals would experience cognitive decline after 1 year.MethodsWe divided 122 participants into cognitive decline and stable cognition groups based on the participants' change rates in Mini-Mental State Examination scores. In addition, we included 68 participants from Alzheimer's Disease Neuroimaging Initiative (ADNI) database as an external validation data set. Subsequently, we developed two classification models: the first model included 99 voxels, and the second model included 99 voxels and the ApoE4 genotype as features to train the models by Wide Neural Network algorithm with fivefold cross-validation and to predict the classes in the hold-out test and ADNI data sets.ResultsThe results revealed that both models demonstrated high accuracy in classifying the two groups in the hold-out test data set. The model for FC demonstrated good performance, with a mean F 1-score of 0.86. The model for FC combined with the ApoE4 genotype achieved superior performance, with a mean F 1-score of 0.90. In the ADNI data set, the two models demonstrated stable performances, with mean F 1-scores of 0.77 in the first and second models.ConclusionOur findings suggest that the proposed models exhibited promising accuracy for predicting cognitive status after 1 year in amyloid-positive individuals. Notably, the combination of FC and the ApoE4 genotype increased prediction accuracy. These findings can assist clinicians in predicting changes in cognitive status in individuals with a high risk of Alzheimer's disease and can assist future studies in developing precise treatment and prevention strategies.

Project description:BackgroundAlzheimer's disease is caused by modifiable and non-modifiable risk factors. Randomised controlled trials have investigated whether the strongest genetic risk factor for Alzheimer's disease, APOE4, impacts the effectiveness of exercise on health. Systematic reviews are yet to evaluate the effect of exercise on physical and cognitive outcomes in APOE genotyped participants. A quality assessment of these randomised controlled trials is needed to understand the impact genotype has on the potential success of intervention. This systematic review aimed to determine if the APOE4 genotype influences the effectiveness of exercise-based randomised controlled trials.MethodSearches on MEDLINE, EMBASE, and PsycINFO identified eligible exercise based randomised controlled trials incorporating participants with varied cognitive abilities. Quality assessments were conducted.ResultsNineteen studies met the inclusion criteria for systematic review, and 3 for the meta-analysis. Very low to moderate quality evidence showed that APOE4 carriers benefitted more than APOE4 non-carriers on cognitive (e.g. executive function, learning) and physical (e.g. relative telomere length) outcomes after exercise; and that APOE4 non-carriers benefited over carriers for physical (serum BDNF, gait speed) and cognitive (global cognition, verbal memory) markers. Very low quality evidence indicated that there was no evidence of difference between APOE4 carriers and non-carriers on physical function outcomes in meta-analysis. Several areas of study design and reporting, including maintenance of relative exercise intensity and complete statistical reporting, were identified as needing improvement.DiscussionThis systematic review found very limited evidence to suggest that exercise interventions can benefit APOE4 carriers and non-carriers equally, though conclusions were limited by evidence quality. Further randomised controlled trials, stratifying participants by APOE status are required to better understand the relationship between APOE genotype and the effect of exercise on health-related outcomes.Trial registrationThis review was registered with PROSPERO (CRD42023436842). Registered on June 16, 2023.

Dataset Information

Do menopausal status and APOE4 genotype alter the long-term effects of intensive lifestyle intervention on cognitive function in women with type 2 diabetes mellitus?

Publications

Do menopausal status and APOE4 genotype alter the long-term effects of intensive lifestyle intervention on cognitive function in women with type 2 diabetes mellitus?

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