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.

Public Health Relevance

Alcohol use is common among older adults but it is not known whether alcohol protects against cognitive decline with age, or exacerbates it. We also do not know how nutrition, which can interact with alcohol, relates to cognitive function and brain changes in aging. This project will examine the association of past and current alcohol use and nutrition on change in cognitive function over time, and on neuroimaging measures of late-life brain structural integrity to obtain vital new information on whether and how these modifiable lifestyle variables affect cognitive function and brain health in the elderly.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Research Project (R01)
Project #
1R01AA021187-01A1
Application #
8399360
Study Section
Aging Systems and Geriatrics Study Section (ASG)
Program Officer
Matochik, John A
Project Start
2013-09-15
Project End
2018-06-30
Budget Start
2013-09-15
Budget End
2014-06-30
Support Year
1
Fiscal Year
2013
Total Cost
$594,918
Indirect Cost
$211,100
Name
University of California San Diego
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093
McEvoy, Linda K; Fennema-Notestine, Christine; Elman, Jeremy A et al. (2018) Alcohol intake and brain white matter in middle aged men: Microscopic and macroscopic differences. Neuroimage Clin 18:390-398
Richard, Erin L; Kritz-Silverstein, Donna; Laughlin, Gail A et al. (2017) Alcohol Intake and Cognitively Healthy Longevity in Community-Dwelling Adults: The Rancho Bernardo Study. J Alzheimers Dis 59:803-814
Mills, Paul J; Kania-Korwel, Izabela; Fagan, John et al. (2017) Excretion of the Herbicide Glyphosate in Older Adults Between 1993 and 2016. JAMA 318:1610-1611
Reas, Emilie T; Laughlin, Gail A; Bergstrom, Jaclyn et al. (2017) Effects of Sex and Education on Cognitive Change Over a 27-Year Period in Older Adults: The Rancho Bernardo Study. Am J Geriatr Psychiatry 25:889-899
Karunamuni, Roshan A; Seibert, Tyler M; White, Nathan S et al. (2017) Abnormalities in hippocampal volume of glioma patients prior to radiotherapy. Acta Oncol 56:427-430
Rush, T M; Kritz-Silverstein, D; Laughlin, G A et al. (2017) Association between Dietary Sodium Intake and Cognitive Function in Older Adults. J Nutr Health Aging 21:276-283
Laughlin, Gail A; Kritz-Silverstein, Donna; Bergstrom, Jaclyn et al. (2017) Vitamin D Insufficiency and Cognitive Function Trajectories in Older Adults: The Rancho Bernardo Study. J Alzheimers Dis 58:871-883
Fennema-Notestine, Christine; McEvoy, Linda K; Notestine, Randy et al. (2016) White matter disease in midlife is heritable, related to hypertension, and shares some genetic influence with systolic blood pressure. Neuroimage Clin 12:737-745
Reas, E T; Laughlin, G A; Kritz-Silverstein, D et al. (2016) Moderate, Regular Alcohol Consumption is Associated with Higher Cognitive Function in Older Community-Dwelling Adults. J Prev Alzheimers Dis 3:105-113
Oania, Rafael; McEvoy, Linda K (2015) Plasma leptin levels are not predictive of dementia in patients with mild cognitive impairment. Age Ageing 44:53-8

Showing the most recent 10 out of 11 publications