In this Program Project we plan to expand the evidence indicating that life span is strongly inherited in families with exceptional longevity. Avoiding age-related and dementia-related cognitive decline are essential to successful aging. Our studies of centenarians and their offspring (LonGenity) have lead to the identification of a number of longevity genes and corresponding phenotypes. At cross-section, we have shown that some of these genotypes (e.g., cholesterol ester transfer protein, ApOCS and adiponectin) and phenotypes (e.g., HDL level, lipoprotein particle size distribution, adiponectin level) are also associated with preservation of cognitive function. Herein, we propose to expand and follow a cohort of offspring of parents with exceptional longevity (OPEL, n=600) as well as a control sample of offspring of parents with usual survival (OPUS, n=600). Both groups will be followed with annual in-person clinical and neuropsychological assessments to identify incident amnestic Mild Cognitive Impairment and dementia. This project will allows us to assess the contribution of three levels of exposure variables (exceptional parental longevity, longevity genotypes and longevity phenotypes) on two levels of cognitive outcomevariables. The outcomes of interest here are cognitive decline in the domains of memory and executive function as well as amnestic Mild Cognitive Impairment (aMCI) and dementia. We hypothesize that offspring of probands with exceptional longevity have a reduced rate of cognitive decline and a reduced incidence of dementia and aMCI and that favorable cognitive outcomes are associated with specific longevity genotypes and phenotypes. The Clinical Core will collect the data and information will be made available through the Statistics and Data Management Core and its Bioinformatics Sharing facility. The correlation between CVD and its risks with cognitive decline will assess through interaction with project 3. Newly discovered genes in projects 1&2 will be made available for testing cognitive hypotheses in this longitudinal study.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Program Projects (P01)
Project #
3P01AG027734-05S3
Application #
8544709
Study Section
Special Emphasis Panel (ZAG1-ZIJ-2)
Project Start
Project End
Budget Start
2011-08-01
Budget End
2012-07-31
Support Year
5
Fiscal Year
2012
Total Cost
$19,046
Indirect Cost
$7,641
Name
Albert Einstein College of Medicine
Department
Type
DUNS #
110521739
City
Bronx
State
NY
Country
United States
Zip Code
10461
Ezzati, Ali; Wang, Cuiling; Lipton, Richard B et al. (2017) Association Between Vascular Pathology and Rate of Cognitive Decline Independent of Alzheimer's Disease Pathology. J Am Geriatr Soc 65:1836-1841
Manning, Alisa (see original citation for additional authors) (2017) A Low-Frequency Inactivating AKT2 Variant Enriched in the Finnish Population Is Associated With Fasting Insulin Levels and Type 2 Diabetes Risk. Diabetes 66:2019-2032
Sundermann, Erin E; Katz, Mindy J; Lipton, Richard B (2017) Sex Differences in the Relationship between Depressive Symptoms and Risk of Amnestic Mild Cognitive Impairment. Am J Geriatr Psychiatry 25:13-22
Seng, Elizabeth K; Buse, Dawn C; Klepper, Jaclyn E et al. (2017) Psychological Factors Associated With Chronic Migraine and Severe Migraine-Related Disability: An Observational Study in a Tertiary Headache Center. Headache 57:593-604
Kato, Kaori; Zweig, Richard; Schechter, Clyde B et al. (2016) Positive attitude toward life, emotional expression, self-rated health, and depressive symptoms among centenarians and near-centenarians. Aging Ment Health 20:930-9
Roshandel, Delnaz; Klein, Ronald; Klein, Barbara E K et al. (2016) New Locus for Skin Intrinsic Fluorescence in Type 1 Diabetes Also Associated With Blood and Skin Glycated Proteins. Diabetes 65:2060-71
Sundermann, Erin E; Biegon, Anat; Rubin, Leah H et al. (2016) Better verbal memory in women than men in MCI despite similar levels of hippocampal atrophy. Neurology 86:1368-76
Perice, Leland; Barzilai, Nir; Verghese, Joe et al. (2016) Lower circulating insulin-like growth factor-I is associated with better cognition in females with exceptional longevity without compromise to muscle mass and function. Aging (Albany NY) 8:2414-2424
Sundermann, Erin Elizabeth; Wang, Cuiling; Katz, Mindy et al. (2016) Cholesteryl ester transfer protein genotype modifies the effect of apolipoprotein ?4 on memory decline in older adults. Neurobiol Aging 41:200.e7-200.e12
Baskovich, Brett; Hiraki, Susan; Upadhyay, Kinnari et al. (2016) Expanded genetic screening panel for the Ashkenazi Jewish population. Genet Med 18:522-8

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