Strittmatter, Warren J

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GENETIC EPIDEMIOLOGY OF AGING IN A MULTIETHNIC COMMUNITY

Mayeux, Richard

30 September 2000 - 31 July 2003
NATIONAL INSTITUTE ON AGING
Total Funding: $ 2,268,838

(Abstract from application) For this exploratory proposal, we will develop the hypothesis that active survival into old age is highly dependent on the preservation of cognitive and physical function, and that the preservation of these functions is, in part, inherited. We will use longitudinal data from two cohorts of elderly African-Americans, Caribbean Hispanics and whites in northern Manhattan and their families to identify potential candidate phenotype definitions for genetic analysis. The phenotypes of interest will be related to the rate-of-change with age in cognitive and physical function, and to the age at which individuals reach critical stages in these functional domains. First, previously collected longitudinal data will be used to determine the rate-of-change with age in specific measures of cognitive performance and physical function, develop specific indicators of clinically meaningful changes corresponding to the loss of ability and determine the age-at-onset of these changes within strata defined by ethnic group, major disease categories, lifestyle factors and specific allelic polymorphisms. Interactions between genotypes and disease and lifestyle factors will be explored for their combined effects on the rate-of-change and the age-at-onset of specified changes in cognitive or physical function. Shared genetic effects on the phenotypic measures and years of total and active survival will be investigated in these individuals and their first-degree family members. In a recently established cohort we will recruit their same-sex siblings to analyze concordance in cognitive and physical function, concordance in rate-of-change in these functions based on retrospective interviews and familial aggregation of time-to-event measures in probands and first-degree relatives. We will collect and store DNA from examined siblings for future linkage or association studies, and we will assess the feasibility of repeated examinations in the siblings, in terms of participation and attrition rates, loss to follow-up, location of examinations, clinical procedures to be included, etc. We will use the experience in this multi-ethnic community to obtain information about phenotype definitions, study designs, sample size requirements, and analytic tools to detecting genes influencing the rate-of-change in cognitive and physical function.

10 Resulting Publications

• 1.

  2013

  Joshua Z Willey; Nikolaos Scarmeas; Frank A Provenzano; José A Luchsinger; Richard Mayeux; Adam M Brickman

  White matter hyperintensity volume and impaired mobility among older adults.

  Journal of neurology 2013;260(3):884-90.

• 2.

  2012

  Christiane Reitz; Christopher Conrad; Katherine Roszkowski; Robert S Rogers; Richard Mayeux

  Effect of genetic variation in LRRTM3 on risk of Alzheimer disease.

  Archives of neurology 2012;69(7):894-900.

• 3.

  2012

  Christiane Reitz; Rong Cheng; Nicole Schupf; Joseph H Lee; Pankaj D Mehta; Ekaterina Rogaeva; Peter St George-Hyslop; Richard Mayeux

  Association between variants in IDE-KIF11-HHEX and plasma amyloid β levels.

  Neurobiology of aging 2012;33(1):199.e13-7.

• 4.

  2011

  Christiane Reitz; Rong Cheng; Ekaterina Rogaeva; Joseph H Lee; Shinya Tokuhiro; Fanggeng Zou; Karolien Bettens; Kristel Sleegers; Eng King Tan; Ryo Kimura; et al.

  Meta-analysis of the association between variants in SORL1 and Alzheimer disease.

  Archives of neurology 2011;68(1):99-106.

• 5.

  2008

  Jennifer L Akerblom; Rosann Costa; Jose A Luchsinger; Jennifer J Manly; Ming-Xin Tang; Joseph H Lee; Richard Mayeux; Nicole Schupf

  Relation of plasma lipids to all-cause mortality in Caucasian, African-American and Hispanic elders.

  Age and ageing 2008;37(2):207-13.

• 6.

  2005

  N Schupf; M-X Tang; S M Albert; R Costa; H Andrews; J H Lee; R Mayeux

  Decline in cognitive and functional skills increases mortality risk in nondemented elderly.

  Neurology 2005;65(8):1218-26.

• 7.

  2005

  Nicole Schupf; Rosann Costa; Jose Luchsinger; Ming-Xin Tang; Joseph H Lee; Richard Mayeux

  Relationship between plasma lipids and all-cause mortality in nondemented elderly.

  Journal of the American Geriatrics Society 2005;53(2):219-26.

• 8.

  2004

  Nicole Schupf; Rosann Costa; Ming-Xin Tang; Howard Andrews; Benjamin Tycko; Joseph H Lee; Richard Mayeux

  Preservation of cognitive and functional ability as markers of longevity.

  Neurobiology of aging 2004;25(9):1231-40.

• 9.

  2004

  Joseph H Lee; Antonia Flaquer; Rosann Costa; Howard Andrews; Peter Cross; Rafael Lantigua; Nicole Schupf; Ming-Xin Tang; Richard Mayeux

  Genetic influences on life span and survival among elderly African-Americans, Caribbean Hispanics, and Caucasians.

  American journal of medical genetics. Part A 2004;128A(2):159-64.

• 10.

  2001

  J H Lee; M X Tang; N Schupf; Y Stern; D M Jacobs; B Tycko; R Mayeux

  Mortality and apolipoprotein E in Hispanic, African-American, and Caucasian elders.

  American journal of medical genetics 2001;103(2):121-7.

Scientific Context

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