Evidence from our group and others indicate the presence of relatively rare genes associated with protection from cognitive deterioration, but efforts to identify such genes are hampered by the overall absence of useful phenotypes reliably associated with specific genes conferring increased protection from cognitive decline as well as likely genetic heterogeneity. One phenotype, however, good cognitive functioning in 90+ year olds, has been associated with familial/genetic protection. Nevertheless, nondemented nonagenarians and centenarians are rare, have no truly appropriate comparison group, and genes associated with good cognitive functioning may well be different than genetic and other factors associated with longevity. The major goal of this pilot project is to create the groundwork for a larger (R01) project focused on identifying neuropsychological phenotypes associated with genes with infrequent protective alleles in moderately elderly individuals at risk for dementia in the genetic founder population of the Central Valley of Costa Rica (CVCR). With the collaboration of the University of Costa Rica and the strong support of the Costa Rican Society of Geriatric Physicians, we will identify and recruit nondemented nonagenarians and centenarian probands and their offspring who are 60+ years of age. These probands and their offspring will be assessed on a battery of neuropsychological tests. The test performance in the offspring of these probands will be compared with two groups: a) the 60+ year old offspring of demented nonagenarians (thus contrasting on the difference in the proband's cognitive status while controlling for longevity); and, b) the 60+ year old siblings of nondemented individuals comparably aged to the primary offspring group but with shorter lived nondemented parents (thus contrasting the difference in the proband's age while controlling for cognitive status). We hypothesize that offspring of non-demented very elderly probands will have better neuropsychological functioning than the two comparison groups. Ultimately, a greatly enlarged longitudinal/genetic study using this population will identify new phenotypes for molecular genetic studies aimed at identifying genes with genetic protective variants.
| Valerio, Daniel; Raventos, Henriette; Schmeidler, James et al. (2014) Association of apolipoprotein E-e4 and dementia declines with age. Am J Geriatr Psychiatry 22:957-60 |
| Greenwood, Tiffany A; Beeri, Michal S; Schmeidler, James et al. (2011) Heritability of cognitive functions in families of successful cognitive aging probands from the Central Valley of Costa Rica. J Alzheimers Dis 27:897-907 |
| Silverman, Jeremy M; Schnaider-Beeri, Michal; Grossman, Hillel T et al. (2008) A phenotype for genetic studies of successful cognitive aging. Am J Med Genet B Neuropsychiatr Genet 147B:167-73 |
