Physical Activity, APOE Genotype, and Dementia Risk: Findings from the Cardiovascular Health Cognition Study (original) (raw)
Related papers
Frontiers in Aging Neuroscience
Previous studies have indicated that physical activity may be beneficial in reducing the risk for Alzheimer's disease (AD), although the underlying mechanisms are not fully understood. The goal of this study was to evaluate the relationship between habitual physical activity levels and brain amyloid deposition and AD-related blood biomarkers (i.e., measured using a novel high-performance mass spectrometry-based assay), in apolipoprotein E (APOE) ε4 carriers and noncarriers. We evaluated 143 cognitively normal older adults, all of whom had brain amyloid deposition assessed using positron emission tomography and had their physical activity levels measured using the International Physical Activity Questionnaire (IPAQ). We observed an inverse correlation between brain amyloidosis and plasma beta-amyloid (Aβ)1−42 but found no association between brain amyloid and plasma Aβ1−40 and amyloid precursor protein (APP)669−711. Additionally, higher levels of physical activity were associated...
Journal of the American Geriatrics Society, 2016
Objectives-To investigate the timing (mid-vs. late life) of physical activity, APOE ε4 and the risk of incident mild cognitive impairment (MCI) in a population-based setting. Design-Prospective cohort study. Setting-The Mayo Clinic Study of Aging in Olmsted County, Minnesota. Participants-We followed 1830 cognitively normal elderly persons (median age: 78 years, 50.2% females) for a median of 3.2 years. Measurements-Light, moderate and vigorous physical activities in mid-and late life were assessed by a validated questionnaire. MCI was measured by an expert consensus panel based on published criteria. We used Cox proportional hazards models to calculate hazard ratios (HR) and 95% confidence intervals (95% CI) with age as a time scale, after adjusting for sex, education, medical comorbidity, and depression.
The Physical Activity and Alzheimer's Disease (PAAD) Study: Cognitive outcomes
Annals of behavioral medicine : a publication of the Society of Behavioral Medicine, 2018
Alzheimer's disease is a progressive disease that degrades cognitive functioning and ultimately results in death. Currently, there is no cure for Alzheimer's disease and, hence, the identification of preventative strategies is important. Physical activity (PA) is a behavioral intervention that holds promise with respect to delaying the onset of Alzheimer's disease. The purpose of this study was to explore the differential cognitive benefits achieved in response to PA as a function of a person's genetic risk for AD. Older cognitively normal adults (50-65 years) with a family history of AD (FHxAD) participated in an 8-month PA program. Cognitive performance was measured at baseline, pretest, midtest, and posttest and changes over time were assessed as a function of apolipoprotein E (APOE) status (carriers: 1-2 copies of the ɛ4 allele; noncarriers: 0 copies of the ɛ4 allele). Improvements in memory were associated with PA participation irrespective of APOE ɛ4 carrier st...
2019
Introduction: Alzheimer's disease (AD) is fast becoming a public health priority. In the absence of effective drug treatment, the focus has shifted towards lifestyle change for prevention. Physical activity (PA) engagement is consistently associated with preserved cognition and lower risk of cognitive decline among older adults. Whether PA mitigates enhanced risk for dementia via APOEε4 allele carriage, demographic and/or biomarker risk factors is less understood. This thesis aimed to evaluate the longitudinal relationship between PA and cognition among cognitively healthy older adults, alongside the role of other demographic, genetic and peripheral biomarkers. Methods: Data of 901 cognitively healthy older adults (60-85 years; mean age = 68.7 ± 3.9) collected as part of a prospective observational cohort study, CHARIOT: PRO, were utilised. The mean follow-up period was 18.5 months (SD 1.7), ranging from baseline to 30-months. Mixedmodels regression methods were used to analyse the associations between PA and cognition over time, including effect modification by APOEɛ4 carrier status, age, and sex. Moderation and mediation by peripheral amyloid-beta and brain-derived-neurotrophic-factor (BDNF) were explored. All analyses were controlled for a priori selected health and demographic factors. Results: Being physically active was positively associated with longitudinal cognitive performance, with the largest effect sizes among those reporting high PA in both mid-and late-life. The positive association between late-life PA and delayed memory trajectories were augmented among APOEε4 carriers, when compared to non-carriers. Conversely, APOEε4 stratified analysis found associations to be consistently augmented among APOEε4 non-carriers for remaining domains. Age and sex did not significantly modify the association between PA and cognition. BDNF was not associated with PA or cognition, nor modified by APOEε4 carrier status. There was an inverse association between amyloid-beta plasma levels and global cognition and attention index scores, which were modified by late-life PA, especially among APOEε4 non-carriers. Conclusion: This thesis highlights the benefits of PA in mitigating cognitive decline in older age, especially among certain risk groups. Elucidating the complex interrelations between modifiable and non-modifiable risk factors for AD will aid in promoting lifestyle intervention as a viable preventative strategy for public health recommendations.
International Journal of Alzheimer's Disease, 2012
Prevalence of Alzheimer's disease (AD) will reach epidemic proportions in the United States and worldwide in the coming decades, and with substantially higher rates in African Americans (AAs) than in Whites. Older age, family history, low levels of education, and ε4 allele of the apolipoprotein E (APOE) gene are recognized risk factors for the neurodegeneration in AD and related disorders. In AAs, the contributions of APOE gene to AD risk continue to engender a considerable debate. In addition to the established role of cardiovascular disease (CVD) risk in vascular dementia, it is now believed that CVD risk and its endophenotype may directly comediate AD phenotype. Given the pleiotropic effects of APOE on CVD and AD risks, the higher rates of CVD risks in AAs than in Whites, it is likely that CVD risks contribute to the disproportionately higher rates of AD in AAs. Though the advantageous effects of aerobic exercise on cognition is increasingly recognized, this evidence is hardly definitive, and data on AAs is lacking. In this paper, we will discuss the roles of CVD risk factors in the development of AD and related dementias, the susceptibility of these risk factors to physiologic adaptation, and fitness-related improvements in cognitive function. Its relevance to AD prevention in AAs is emphasized.
Apolipoprotein E ɛ4 magnifies lifestyle risks for dementia: a population-based study
Journal of Cellular and Molecular Medicine, 2008
The risk of dementia and Alzheimer's disease (AD) probably results from an interaction between genetic and environmental factors. The aim of this study was to investigate the effects and putative interactions between the apoE 4 allele and lifestyle related risk factors for dementia and AD. Participants of the Cardiovascular Risk Factors, Aging, and Dementia (CAIDE) study were derived from random, population-based samples previously studied in 1972, 1977, 1982 or 1987. After an average follow-up of 21 years, 1449 individuals (72.5%) aged 65-79 years were re-examined in 1998. The apoE 4 allele was an independent risk factor for dementia/AD even after adjustments for sociodemographic, lifestyle and vascular factors (odds ratio [OR] ϭ 2.83, 95% confidence interval [CI] ϭ 1. 61-4.97). Physical inactivity, alcohol drinking and smoking increased the risk of dementia/AD particularly among the apoE 4 carriers. Furthermore, lowmoderate intake of polyunsaturated, and moderate-high intake of saturated fats were associated with an increased risk of dementia/AD more pronouncedly among apoE 4 carriers. Composite effect of the lifestyle factors was particularly seen among the 4 carriers (OR ϭ 11.42, 95% CI ϭ 1. 94-67.07 in the 4 th quartile). Physical inactivity, dietary fat intake, alcohol drinking and smoking at midlife are associated with the risk of dementia and AD, especially among the apoE 4 carriers. The apoE 4 carriers may be more vulnerable to environmental factors, and thus, lifestyle interventions may greatly modify dementia risk particularly among the genetically susceptible individuals.
Patients with Alzheimer's disease who carry the APOE ε4 allele benefit more from physical exercise
Alzheimer's & Dementia: Translational Research & Clinical Interventions, 2019
Introduction: Our group has completed an exercise study of 200 patients with mild Alzheimer's disease. We found improvements in cognitive, neuropsychiatric, and physical measures in the participants who adhered to the protocol. Epidemiological studies in healthy elderly suggest that exercise preserves cognitive and physical abilities to a higher extent in APOE ε4 carriers. Methods: In this post hoc subgroup analysis study, we investigated whether the beneficial effect of an exercise intervention in patients with mild AD was dependent on the patients' APOE genotype. Results: We found that patients who were APOE ε4 carriers benefitted more from the exercise intervention by preservation of cognitive performance and improvement in physical measures. Discussion: This exploratory study establishes a possible connection between the beneficial effects of exercise in AD and the patients' APOE genotype. These findings, if validated, could greatly impact the clinical management of patients with AD and those at risk for developing AD.
Physical Activity, Diet, and Risk of Alzheimer Disease
JAMA, 2009
Context Both higher adherence to a Mediterranean-type diet and more physical activity have been independently associated with lower Alzheimer disease (AD) risk but their combined association has not been investigated. Objective To investigate the combined association of diet and physical activity with AD risk. Design, Setting, and Patients Prospective cohort study of 2 cohorts comprising 1880 community-dwelling elders without dementia living in New York, New York, with both diet and physical activity information available. Standardized neurological and neuropsychological measures were administered approximately every 1.5 years from 1992 through 2006. Adherence to a Mediterranean-type diet (scale of 0-9; trichotomized into low, middle, or high; and dichotomized into low or high) and physical activity (sum of weekly participation in various physical activities, weighted by the type of physical activity [light, moderate, vigorous]; trichotomized into no physical activity, some, or much; and dichotomized into low or high), separately and combined, were the main predictors in Cox models. Models were adjusted for cohort, age, sex, ethnicity, education, apolipoprotein E genotype, caloric intake, body mass index, smoking status, depression, leisure activities, a comorbidity index, and baseline Clinical Dementia Rating score. Main Outcome Measure Time to incident AD. Results A total of 282 incident AD cases occurred during a mean (SD) of 5.4 (3.3) years of follow-up. When considered simultaneously, both Mediterranean-type diet adherence (compared with low diet score, hazard ratio [HR] for middle diet score was 0.98 [95% confidence interval {CI}, 0.72-1.33]; the HR for high diet score was 0.60 [95% CI, 0.42-0.87]; P=.008 for trend) and physical activity (compared with no physical activity, the HR for some physical activity was 0.75 [95% CI, 0.54-1.04]; the HR for much physical activity was 0.67 [95% CI, 0.47-0.95]; P=.03 for trend) were associated with lower AD risk. Compared with individuals neither adhering to the diet nor participating in physical activity (low diet score and no physical activity; absolute AD risk of 19%), those both adhering to the diet and participating in physical activity (high diet score and high physical activity) had a lower risk of AD (absolute risk, 12%; HR, 0.65 [95% CI, 0.44-0.96]; P=.03 for trend). Conclusion In this study, both higher Mediterranean-type diet adherence and higher physical activity were independently associated with reduced risk for AD.