Browsing by Subject "Cognitive decline"
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Item Open Access Alzheimer's Disease Risk Genes and Cognitive Decline in a Healthy Population(2017-05-21) Cranston, JessicaIntroduction: Alzheimer’s disease (AD) is a devastating, progressive, irreversible brain disorder. Previous research has identified genes associated with the risk of developing AD. Variations in the Apolipoprotein E (APOE) gene show the largest effect size, with the ε4 isoform associated with highest risk. Genome Wide Association Studies (GWAS) have found other genes associated with AD, yet none with effects as large as APOE. Because AD diagnosis is often preceded by a long period of cognitive decline, we investigated the relationship between previously determined AD risk genes and cognitive decline to determine whether we could detect individuals at risk of imminent decline and at a high priority for clinical intervention. Methods: Cognitively healthy participants from the Duke “MURDOCK” study based in Kannapolis, NC participated in the study. They were aged 55+, had contributed DNA, and undergone two waves of cognitive assessments 4 years apart (n=713). An AD genetic risk score (AD-GRS) was derived for each individual based on the known 9 AD genes from recent meta-analyses. APOE was modeled separately. Scores were based on number of risk alleles and the associated odds ratio for each gene. To determine optimal measure of cognitive decline, the available cognitive tests were evaluated individually and in three different composite measures (1.Global; 2.Learning/Memory; 3.Memory-Weighted). Post-hoc analyses evaluated interactions between AD-GRS, APOE risk-score, combined risk-score, cognition, and cognitive decline as measured by composites and individual assessments. Results: APOE risk-score was associated with cognitive decline as measured by all of the composite measures. APOE risk-score was most highly associated to the newly constructed Predict Composite (composed of assessments most associated to risk genes), followed by the Memory-Weighted, the Learning/Memory, and lastly the Global Composite. APOE risk-score was associated with individual assessments except delayed recall. The AD-GRS was not associated with cognitive decline but associated with baseline cognition as measured by composites weighting memory. The combined risk-score was less associated with cognitive decline than APOE alone. Conclusions: APOE was associated with cognitive decline as best captured by the composites that weighted memory. Although associated with AD, the other risk genes were not associated with cognitive decline, yet are related to baseline cognition best captured by composites weighting memory. This suggests that for identifying individuals at risk of cognitive decline, focusing on APOE will be more useful than other AD risk alleles, and that the optimal composite for capturing change associated with AD appears to be one that is weighted with memory.Item Open Access Cognitive Function and Decline Among Older Adults: The Roles of Sensory Loss and Psychosocial Factors(2019) Ge, ShaoqingIn the context of rapid global aging, cognitive decline among older adults has become a major public health and social issue. A better understanding of the risk factors for cognitive decline is important for developing interventions to preserve cognitive function among older adults. Knowledge gaps still exist in understanding the impact of sensory loss (i.e., hearing loss and vision loss) and psychosocial factors (i.e., social support and loneliness) on cognitive function and cognitive decline. This dissertation aims to fill these knowledge gaps by (1) examining the relationship between psychosocial factors and cognitive function in a unique population: community-dwelling Chinese older adults in the United States (U.S.); (2) understanding the longitudinal relationship between sensory loss and cognitive decline among community-dwelling older adults in the United States; and (3) exploring the mechanisms that accelerate or decelerate cognitive decline by examining the inter-relationships between sensory loss, psychosocial factors, and cognitive decline. The primary study conducted for this dissertation used structural equational modeling (SEM) to model the potential moderation or mediation effect of psychosocial factors on the relationship between sensory loss and cognitive decline over time. Findings from this dissertation deepen our understanding of the important roles that social support, loneliness, and sensory loss can play in cognitive function and decline among community-dwelling older adults. Findings from this dissertation also highlight the importance of adequately addressing the physical and psychological challenges encountered by older adults. Subsequent recommendations are provided to health providers and policy makers to help better preserve and promote cognitive health among older adults using a more holistic approach.
Item Open Access Self-reported hearing loss, hearing aid use, and cognitive function among U.S. older adults.(International journal of population studies, 2022-01) West, Jessica S; Smith, Sherri L; Dupre, Matthew EThere has been increasing attention to the role of hearing loss as a potentially modifiable risk factor for Alzheimer's disease and related dementias. However, more nationally-representative studies are needed to understand the co-occurring changes in hearing loss and cognitive function in older adults over time, and how hearing aid use might influence this association. The purpose of this report is to examine how age-related changes in hearing loss and hearing aid use are associated with trajectories of cognitive function in a nationally-representative sample of U.S. older adults. We used 11 waves of longitudinal data from the Health and Retirement Study (HRS) from 1998 to 2018 to examine changes in self-reported hearing loss, hearing aid use, and cognitive function in adults 65 and older by race and ethnicity. Results from mixed models showed that greater levels of hearing loss were associated with lower levels of cognitive function at age 65 in non-Hispanic White, non-Hispanic Black, and Hispanic older adults. We also found that the associations diminished across age in White and Black individuals; but remained persistent in Hispanic individuals. The use of hearing aids was not associated with cognitive function in Black older adults but appeared protective for White and Hispanic older adults. Overall, the findings from this report suggest that the timely identification of hearing loss and subsequent acquisition of hearing aids may be important considerations for reducing declines in cognitive function that manifests differently in U.S. population subgroups.Item Open Access The Early Life Environment and Adult Cognitive and Mental Health(2023) Reuben, Aaron SMany diverse adult diseases, from diabetes to dementia, are increasingly viewed as arising, in part, from early life environmental influences. The so-called Developmental Origins of Health and Disease (DOHaD) research paradigm offers the potential to improve our understanding of the etiology of many hard-to-treat adult diseases by focusing researcher’s attention on the pre and post-natal and early childhood years, where small interventions could pay large dividends later on. Along with great potential, the DOHaD framework offers great challenges, as it is logistically and conceptually difficult to investigate the environmental origins of chronic diseases that may manifest only decades after harmful exposures. This dissertation presents a series of five original studies that sought to answer open empirical questions about the developmental origins of health and disease focusing on early-life factors that influence the health and aging of the brain. Three increasingly broad "levels" of the early life environment are considered across three sequential dissertation chapters: (1) the individual micro-physical level, (2) the family level, and (3) the neighborhood level. At each level this dissertation considers at least one exposure that has relevance to researchers and policy makers, either because, like exposure to neighborhood vegetation / greenery, it may offer a good route for intervention (e.g., the exposure is potentially modifiable) or because, like exposure to the heavy metal lead, it is understood to be more widespread than previously assumed. Studies were conducted using data from two population-representative longitudinal birth cohorts, the New Zealand-based Dunedin Multidisciplinary Health and Development Study (born in 1972-1973) and the United Kingdom-based Environmental Risk Longitudinal Twin Study (born in 1994-1995). Across the five studies, results supported the DOHaD framework and provided new evidence about the long-term consequences of childhood exposure to lead, adversity (e.g., physical and emotional abuse, household dysfunction, etc.), and neighborhood disadvantage. These negative early life events / exposures at the micro-physical, family, and neighborhood-levels associated, across multiple decades, with subtle and diverse poor brain-related outcomes later in life, including diminished cognitive capacity, increased symptoms of psychopathology, altered epigenetic controls, disadvantageous personality styles, and worse physical health. Results collectively reinforce the view that the early life represents a profound window of vulnerability and opportunity, with a lifespan perspective offering great potential for more efficacious public health research, clinical practice, and policy, as the diseases of the adult likely have roots in the life of the child.
Item Open Access The impact of residential status on cognitive decline among older adults in China: Results from a longitudinal study.(BMC Geriatr, 2017-05-15) Xu, Hanzhang; Dupre, Matthew E; Gu, Danan; Wu, BeiBACKGROUND: Residential status has been linked to numerous determinants of health and well-being. However, the influence of residential status on cognitive decline remains unclear. The purpose of this research was to assess the changes of cognitive function among older adults with different residential status (urban residents, rural-to-urban residents, rural residents, and urban-to-rural residents), over a 12-year period. METHODS: We used five waves of data (2002, 2005, 2008/2009, 2011/2012, and 2014) from the Chinese Longitudinal Healthy Longevity Survey with 17,333 older adults age 65 and over who were interviewed up to five times. Cognitive function was measured by the Mini Mental State Examination (MMSE). Multilevel models were used regarding the effects of residential status after adjusting for demographic characteristics, socioeconomic factors, family support, health behaviors, and health status. RESULTS: After controlling for covariates, significant differences in cognitive function were found across the four groups: rural-to-urban and rural residents had a higher level of cognition than urban residents at baseline. On average, cognitive function decreased over the course of the study period. Rural-to-urban and rural residents demonstrated a faster decline in cognitive function than urban residents. CONCLUSIONS: This study suggests that residential status has an impact on the rate of changes in cognition among older adults in China. Results from this study provide directions for future research that addresses health disparities, particularly in countries that are undergoing significant socioeconomic transitions.Item Open Access The Relationship Between Fitness and Structural Brain Integrity in Midlife: Implications for Biomarker Development and Aging Interventions(2021) d'Arbeloff, Tracy CAn aging global population and accompanying increases in the prevalence of age-related disorders are leading to greater financial, social, and health burdens. Alzheimer’s disease and related dementias are one such category of age-related disorders that are associated with progressive loss of physical and cognitive ability. One proposed preventative measure against risk for such dementias is improving cardiovascular fitness, which may help reverse or buffer age-related brain atrophy associated with worse aging-related outcomes and cognitive decline. However, research into this potential of cardiovascular fitness has suffered from extreme heterogeneity in study design methodology leading to a lack of cohesion in the field and undermining any potential causal evidence that may exist. In addition, while direct measures of cardiovascular fitness (e.g., VO2Max) and healthy lifestyle behaviors typically associated with better cardiovascular fitness (e.g., exercise, diet, smoking status) are not necessarily highly correlated, they are often conflated in existing research. This has contributed to a lack of clarity in generalizing and comparing results.
This dissertation presents results from four original research projects addressing open empirical questions about possible links between cardiovascular fitness, healthy lifestyle behaviors, and structural brain integrity in midlife, which has become a target of intervention research seeking to stave off cognitive decline and risk for dementia before irreversible damage has accrued. Each section of the dissertation builds on increasingly complex aspects of these links with the goal of providing supporting evidence that may aid future biomarker research and clinical trials design. All studies involved were conducted using behavioral data, physiological data, and structural MRI data from the Dunedin Study, which has followed a population-representative birth cohort to midlife.
Across four empirical sections, results collectively suggest that there is a modest association between cardiovascular fitness and both grey and white matter structural integrity as well as between healthy lifestyle behaviors and grey matter structural integrity. Further, results indicate that these associations may extend beyond cross-sectional data and have relevance for measures capturing the extent of age-related atrophy in the brain. In addition, the results reinforce prior findings that cardiovascular fitness and healthy lifestyle behaviors are independent constructs and suggest that the differentially mapping of these constructs onto specific features of brain integrity in midlife may be useful in directing the search for risk biomarkers and designing clinical trials.