P4‐005: Family history of dementia predicts cognitive decline in cognitively normal subjects

There are a variety of risk factors associated with cognitive decline in Alzheimer's disease, however the genetic component remains uncertain. The goal of this project was to characterize cognitive decline in a large cohort of well-characterized nondemented individuals in our KU Alzheimer's Disease Center Registry who had at least 2 visits (one year apart), and had data on a family history of dementia and APOE genotype. We tested for an association between decline (change in clinical dementia rating (CDR) from 0 to 0.5 over the course of 1 to 4 years) and a family history of AD, or ApoE4 genotype, using Kendall's tau coefficient. There were 119 individuals that began as nondemented subjects, with a CDR=0 at baseline, and 8 of these had cognitive decline at a later visit (all with a CDR=0.5). There were no differences in the individuals that declined or maintained their CDR in age, sex, or baseline MMSE, although those that declined had a significantly higher level of education at baseline (p=.017). There was a trend for an association of family history and decline, such that 7 out of 8 individuals that declined had a family history, with 6 out of 8 of these subjects having a maternal family history of dementia (p=.052). There was no significant association between the presence of an ApoE4 allele and decline, in fact no individuals that declined had an ApoE4 allele. While this is a small sample, there is some evidence for the role of a family history, or related genetic associations, in predicting decline in cognition related to Alzheimer's disease. There is growing evidence in the literature that there is something other than APOE that is possibly determining risk and progression in subjects with a family history of AD.