2007 — 2011 |
Mcevoy, Linda Kathleen |
K01Activity Code Description: For support of a scientist, committed to research, in need of both advanced research training and additional experience. |
Structure and Functional Imaging of Age-Related Changes in Working Memory @ University of California San Diego
[unreadable] DESCRIPTION (provided by applicant): This project proposes to use structural and functional neuroimaging methods to better understand how the brain changes in healthy aging, and the consequences of those changes on cognitive function. It examines age-related changes in working memory ability - a fundamental capacity that underlies many complex cognitive behaviors, and that declines with age. The central hypothesis of this study is that working memory ability arises from coherent neural oscillatory activity in a network of brain regions, and that age-related declines in working memory ability reflect the breakdown of coherent neural activity in this network due to age-related changes in white matter structure. To test this hypothesis, high temporal resolution methods of electro- and magnetoencephalography (EEC and MEG) will be integrated with the high spatial resolution method of functional magnetic resonance imaging (MRI) to characterize the dynamic spatiotemporal patterns of brain activity that underlie working memory ability in young adults, and to determine how healthy aging affects these patterns. Diffusion tensor imaging (DTI) will be used to assess white matter microstructural integrity, and age-related reductions in coherent activity between distributed neural regions will be related to age-related reductions in white matter integrity. It is hypothesized that age-related changes in frontal white matter disrupts the coherent activity in frontal-parietal networks necessary for working memory task performance, and that the reduction in frontal white matter integrity contributes to age-related reductions in regional frontal cortical thickness. To achieve these research goals, the candidate, who has a strong background in MEG and EEC research, seeks training through formal coursework and interaction with her sponsors in structural and functional MRI acquisition and analyses, multimodal integration of MEG/EEG and MRI data, cortical reconstruction, parcellation, and quantification, and DTI acquisition and analyses. Her sponsors, leaders in the field of neuroimaging and multimodal analyses, and the supportive and resource- rich environment of UCSD, will ensure the candidate's mastery of these new techniques. Relevance: This project will further understanding of the structural and functional changes in the brain that occur as part of normal aging, and that underlie age-related changes in cognitive ability. This knowledge will provide a basis for better understanding of pathological brain changes that occur in age-related disorders. [unreadable] [unreadable] [unreadable]
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2013 — 2017 |
Mcevoy, Linda Kathleen |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Association of Alcohol and Nutrition With Cognition and Brain Structure in Aging @ University of California San Diego
DESCRIPTION (provided by applicant): With the rapidly growing elderly U.S. population, a better understanding of how alcohol and nutrition interact to protect against or accelerate cognitive decline and age-related brain changes could have profound implications for public health. A large proportion of the adult population regularly consumes alcohol but little is known about how mid and later life alcohol use impacts cognitive function and brain integrity in old age. Even less is known about whether nutrition, which may interact with alcohol at behavioral and physiological levels, influences cognitive function and brain structure. This interdisciplinary proposal, involving experts in epidemiology, cognitive neuroscience, neuroimaging and biostatistics will analyze existing as well as newly collected data from a large, population-based NIH-funded cohort study of older adults, now in its 39th year, the RBS (The Rancho Bernardo Study, RBS; Dr. Barrett-Connor, P.I.). The RBS has an exceptionally rich database for exploring the association of mid and late life alcohol consumption with cognitive function. It contains measures of alcohol intake, including data on frequency, amount and type of alcohol consumed obtained up to 7 times on a given participant over ~25 year period, cognitive function tests assessing different cognitive domains obtained up to 6 times on a given participant over ~20 year follow-up period, and detailed dietary information from up to three administrations of the Harvard Willett Food Frequency questionnaire over ~10 years. It also contains a large number of medical health-related variables, validated medication use, mood and lifestyle measures, which will allow control for numerous potentially confounding covariates and effect modifiers. Analysis of this existing data will allow us to determine how current and prior alcohol use relates to change in cognitive function over time in older adults and how nutrition influences these associations, while controlling for relevant covariates such as education level, smoking, physical activity, medical status (e.g. diabetes, cardiovascular disease), cardiovascular disease risk factors, and medications. We will also collect a comprehensive set of sensitive structural MRI and diffusion tensor imaging (DTI) data, using state-of-the-art image acquisition and analysis procedures, from a subset (n=300) of RBS participants who showed a range of alcohol use at baseline. This will allow us to examine how past and current alcohol use relates to measures of late-life brain structural integrity, and assess whether nutrition modifies these associations, whie controlling for numerous covariates. This study will increase basic knowledge of the association of alcohol and diet on cognitive function and brain health in the elderly, and could result in lifestyle recommendations to promote successful cognitive and brain aging. Because age-related cognitive impairment is a major contributor to loss of independence and lower quality of life in older adults, and because care for cognitively impaired individuals places an enormous financial burden on society, improved understanding of whether and how modifiable behaviors affect cognitive function in aging could have enormous public health impact.
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2016 |
Laughlin, Gail A (co-PI) [⬀] Mcevoy, Linda Kathleen |
RF1Activity Code Description: To support a discrete, specific, circumscribed project to be performed by the named investigator(s) in an area representing specific interest and competencies based on the mission of the agency, using standard peer review criteria. This is the multi-year funded equivalent of the R01 but can be used also for multi-year funding of other research project grants such as R03, R21 as appropriate. |
Archiving the Rancho Bernardo Study of Healthy Aging @ University of California San Diego
Project Summary/Abstract The goal of this project is to curate and archive more than 40 years of data from the Rancho Bernardo Study (RBS) of Healthy Aging to ensure that this unique and irreplaceable resource remains available to current and future researchers. RBS is one of the longest, continuously NIH-funded, population-based observational cohorts in existence. Initiated in 1972 as part of the NIH Lipid Research Clinic Prevalence Study, participants have been followed ever since via 12 research clinic visits at approximate 4 year intervals and 30 annual mailers. RBS has focused on cardiovascular disease since its inception, and was expanded to include assessment of cognitive function at the 1988 clinic visit and at each of 7 subsequent visits. Numerous health, lifestyle, biomarker and psychosocial measures were also collected in these visits, as well as in prior visits and yearly mailers. Participants in the RBS Cognitive Function cohort (n=2590; mean age 72 at time of first cognitive assessment) have a maximum of 8 cognitive assessments over a 28-year period, with a wealth of health-related information available stretching back ~15 years prior to the first cognitive assessment, at a time when most participants were middle-aged (mean age 54). This enables investigation of whether and how mid- life health, lifestyle, and psychosocial factors predict trajectories of cognitive function and cognitive outcomes in older age, and enables investigation of whether associations between risk factors and cognitive function change with age, or differ by sex or other effect modifiers. This valuable public health resource is vulnerable to loss because data exist on a local server, or as hard copies in various locations. Access to, and knowledge of the data relies on a small number of long-serving faculty and staff, several of whom are nearing retirement age. Thus in response to one of the particular areas of emphasis, ?Electronic archiving of cohort data? in PAR-15- 356: ?Major Opportunities for Research in Epidemiology of Alzheimer's Disease and Cognitive Resilience? this project will use modern electronic archiving techniques to organize and archive the vast RBS data onto an easily-searchable, cloud-based relational database. We will immortalize and maximize the usefulness of the RBS database through accomplishment of the following aims. Aim 1. Continued follow-up for morbidity and mortality: We currently have over 94% vital status follow up of the original 6,339 participants with death certificates obtained for 85% of decedents. We will continue to follow surviving participants with yearly mailers to assess health status, clinical events and vitality. Death certificates will be obtained on decedents. Aim 2. Documentation and electronic archiving of all study data: Data will be inventoried, categorized, documented, and a complete data dictionary will be generated. All data and study-related documents will be uploaded to REDCap (Research Electronic Data Capture), a widely used secure, HIPAA-compliant, web-based application for managing databases. Aim 3. Resource sharing and data dissemination: A public website will be developed that describes the RBS and provides access to all study documents and HIPAA-compliant datasets.
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2019 — 2020 |
Mcevoy, Linda Kathleen |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Moderate Alcohol Use: Risk or Protective Factor For Age-Related Cognitive Decline, Mild Cognitive Impairment, and Brain Health in Aging @ University of California, San Diego
ABSTRACT With the increasing prevalence of alcohol use among older adults, it is imperative to better understand the association of alcohol use with risk of mild cognitive impairment (MCI) and brain health in aging. Although many studies suggest that moderate drinking may protect against age-related cognitive impairment and dementia, few studies have demonstrated a protective association of moderate drinking with rates of cognitive decline, or with neuroimaging measures of preserved brain health. Most neuroimaging studies have shown detrimental associations of alcohol with global or regional brain volumes. It is possible that findings of protective associations of moderate drinking on risk of cognitive impairment and dementia stem from inadequate control for confounders since individuals who drink moderately also tend to be of higher socioeconomic status and to engage in other healthy behaviors (such as regular exercise), that are themselves associated with reduced risk of dementia. Conversely, it is also possible that existing studies relating alcohol use to rates of cognitive decline or neuroimaging measures have not used sufficiently sensitive methods to detect subtle, positive associations. Individual differences in genetic predisposition to Alzheimer's disease, or in alcohol metabolizing enzymes, may also obscure effects. The goal of this project, which is responsive to PAR-17-054 ?Leveraging Existing Cohort Studies to Clarify Risk and Protective Factors for Alzheimer's Disease and Related Dementias (R01)? is to clarify the association of alcohol use with cognitive decline, risk of MCI and neuroimaging metrics of brain health in aging by leveraging a unique existing cohort study, the Vietnam Era Twin Study of Aging (VETSA). VETSA is a longitudinal study of ~1500 monozygotic and dizygotic male twin pairs that examines genetic and environmental influences on aging. It contains detailed repeated measures of alcohol use, cognitive function, and brain imaging measures (on a subset of participants), along with a wealth of information on potential confounders. We will determine how alcohol use is associated with rates of cognitive decline and risk of MCI (Aim 1); and with regional brain grey and white matter microstructure and white matter lesion burden (Aim 2). We will determine if observed associations are due to differences in confounding variables, such as socioeconomic status, health status, health behaviors, cognitive reserve or genetic status. Examination of shared heritability between drinking and cognitive/brain outcomes will further inform on potential causal effects of alcohol, as will analyses of discordant twin-pairs. We will also examine whether associations of alcohol with cognitive and brain aging differ by health or genetic status (including polygenic risk for Alzheimer's disease, or for reduced alcohol metabolism; Aim 3). Improved knowledge of whether alcohol is associated with increased or decreased risk of MCI has potential for direct public health impact. This study will inform guidelines for alcohol limits to preserve brain health in aging and will provide for individualized recommendations on alcohol use based upon health and genetic status.
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