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.
| Ghani, Mahdi; Reitz, Christiane; Cheng, Rong et al. (2015) Association of Long Runs of Homozygosity With Alzheimer Disease Among African American Individuals. JAMA Neurol 72:1313-23 |
| Willey, Joshua Z; Scarmeas, Nikolaos; Provenzano, Frank A et al. (2013) White matter hyperintensity volume and impaired mobility among older adults. J Neurol 260:884-90 |
| Honig, Lawrence S; Boyd, Clara D (2013) Treatment of Alzheimer's Disease: Current Management and Experimental Therapeutics. Curr Transl Geriatr Exp Gerontol Rep 2:174-181 |
| Reitz, Christiane; Conrad, Christopher; Roszkowski, Katherine et al. (2012) Effect of genetic variation in LRRTM3 on risk of Alzheimer disease. Arch Neurol 69:894-900 |
| Reitz, Christiane; Cheng, Rong; Schupf, Nicole et al. (2012) Association between variants in IDE-KIF11-HHEX and plasma amyloid ? levels. Neurobiol Aging 33:199.e13-7 |
| Reitz, Christiane; Cheng, Rong; Rogaeva, Ekaterina et al. (2011) Meta-analysis of the association between variants in SORL1 and Alzheimer disease. Arch Neurol 68:99-106 |
| Akerblom, Jennifer L; Costa, Rosann; Luchsinger, Jose A et al. (2008) Relation of plasma lipids to all-cause mortality in Caucasian, African-American and Hispanic elders. Age Ageing 37:207-13 |
| Schupf, Nicole; Costa, Rosann; Luchsinger, Jose et al. (2005) Relationship between plasma lipids and all-cause mortality in nondemented elderly. J Am Geriatr Soc 53:219-26 |
| Schupf, N; Tang, M-X; Albert, S M et al. (2005) Decline in cognitive and functional skills increases mortality risk in nondemented elderly. Neurology 65:1218-26 |
| Schupf, Nicole; Costa, Rosann; Tang, Ming-Xin et al. (2004) Preservation of cognitive and functional ability as markers of longevity. Neurobiol Aging 25:1231-40 |
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