Neuroprotection and Neurodegeneration in Alzheimer’s Disease: Role of Cardiovascular Disease Risk Factors, Implications for Dementia Rates, and Prevention with Aerobic Exercise in African Americans (original) (raw)
Related papers
2005
Physical activity may help preserve cognitive function and decrease dementia risk, but epidemiologic findings are inconsistent. The authors conducted a prospective study to determine the association between physical activity and risk of dementia, Alzheimer's disease, and vascular dementia. The US study population comprised 3,375 men and women aged 65 years or older, free of dementia at baseline, who participated in the Cardiovascular Health Cognition Study in 1992-2000. Leisure-time energy expenditure and an activity index reflecting number of different physical activities were calculated. Analyses were based on Cox proportional hazards models. There were 480 incident cases of dementia over an average of 5.4 years of follow-up. After multivariate adjustment, participants in the highest quartile of physical energy expenditure had a relative risk of dementia of 0.85 (95% confidence interval: 0.61, 1.19) compared with those in the lowest quartile, and participants engaging in 4 activities had a relative risk of dementia of 0.51 (95% confidence interval: 0.33, 0.79) compared with those engaging in 0-1 activity. These associations were more marked in apolipoprotein E genotype (APOE) e4 allele noncarriers but were absent in carriers. A similar pattern was observed for Alzheimer's disease and vascular dementia. Mechanisms to explain the observed relations deserve further study.
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.
Experimental gerontology, 2017
Possession of the Apolipoprotein E (APOE) gene ε4 allele is the most prevalent genetic risk factor for late onset Alzheimer's disease (AD). Recent evidence suggests that APOE genotype differentially affects the expression of brain-derived neurotrophic factor (BDNF). Notably, aerobic exercise-induced upregulation of BDNF is well documented; and exercise has been shown to improve cognitive function. As BDNF is known for its role in neuroplasticity and survival, its upregulation is a proposed mechanism for the neuroprotective effects of physical exercise. In this pilot study designed to analyze exercise-induced BDNF upregulation in an understudied population, we examined the effects of APOEε4 (ε4) carrier status on changes in BDNF expression after a standardized exercise program. African Americans, age 55years and older, diagnosed with mild cognitive impairment participated in a six-month, supervised program of either stretch (control treatment) or aerobic (experimental treatment) ...
Molecular Psychiatry, 2006
High fat diets and sedentary lifestyles are becoming major concerns for Western countries. They have led to a growing incidence of obesity, dyslipidemia, high blood pressure, and a condition known as the insulin-resistance syndrome or metabolic syndrome. These health conditions are well known to develop along with, or be precursors to atherosclerosis, cardiovascular disease, and diabetes. Recent studies have found that most of these disorders can also be linked to an increased risk of Alzheimer's disease (AD). To complicate matters, possession of one or more apolipoprotein E e4 (APOE e4) alleles further increases the risk or severity of many of these conditions, including AD. ApoE has roles in cholesterol metabolism and Ab clearance, both of which are thought to be significant in AD pathogenesis. The apparent inadequacies of ApoE e4 in these roles may explain the increased risk of AD in subjects carrying one or more APOE e4 alleles. This review describes some of the physiological and biochemical changes that the above conditions cause, and how they are related to the risk of AD. A diversity of topics is covered, including cholesterol metabolism, glucose regulation, diabetes, insulin, ApoE function, amyloid precursor protein metabolism, and in particular their relevance to AD. It can be seen that abnormal lipid, cholesterol and glucose metabolism are consistently indicated as central in the pathophysiology, and possibly the pathogenesis of AD. As diagnosis of mild cognitive impairment and early AD are becoming more reliable, and as evidence is accumulating that health conditions such as diabetes, obesity, and coronary artery disease are risk factors for AD, appropriate changes to diets and lifestyles will likely reduce AD risk, and also improve the prognosis for people already suffering from such conditions.
Annals of Neurology, 1997
As a part of our ongoing study on Alzheimer's disease (AD) in elderly African Americans, we obtained clinical assessment and apolipoprotein E (ApoE) genotype data on 288 individuals (including 60 with AD). The ApoE ~4 allele frequency was significantly increased in AD patients compared with controls. The age-adjusted odds ratio (OR) for AD in ~4 homozygotes was 4.83 (95% confidence interval [CI], 1.71-13.64) compared with the ~3 /~3 genotype, but the OR for AD with the ~3 /~4 genotype did not reach significance (1.20; 95% CI, 0.58-2.45). These findings suggest that the association between ApoE ~4 and AD is weaker in African Americans than in whites. Sahota A, Yang M, Gao S, Hui SL, Baiyewu 0, Gureje 0, Oluwole S, Ogunniyi A, Hall KS, Hendrie HC. Apolipoprotein E-associated risk for Alzheimer's disease in the African-American population is genotype dependent. Ann Neurol 1997;42:659-661 T h e ~4 allele of apolipoprotein E (ApoE) has been identified as a major risk factor in the development of late-onset Alzheimer's disease (AD) in the white population [I], and this has been confirmed in numerous follow-up studies [2, 31. In contrast, there are very few studies on ApoE and A D in populations of African origin, and the results have been conflicting. O u r pilot study in elderly African Americans at Indianapolis, Indiana, suggested that the ~4 allele of ApoE was a risk factor for the development of AD, but the risk was greater for homozygotes compared with heterozygotes From the
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.
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.
Association of Apolipoprotein E Genotype and Alzheimer Disease in African Americans
Archives of Neurology, 2006
Background-Alzheimer disease (AD) is the most frequent cause of dementia. Even though the incidence of AD in the African American population is similar to or higher than that in persons of European descent, AD in African Americans is understudied. Identification of genetic risk factors in African Americans is essential for understanding the etiology of AD.