Maternal History and Impaired Memory Predict Decline to Dementia in Cognitively Normal Individuals

Cognitively normal individuals with a maternal history (MHnl) of late-onset Alzheimer's disease (AD) show reduced hippocampal glucose metabolism, increased fibrillar amyloid beta burden, and reduced gray matter volume as compared to normal individuals with a paternal history of AD (PHnl) or no history (noHnl). However, it remains unknown whether MHnl decline to AD at higher rates compared to those with no maternal history. This study examines whether there is a correlation between family history and the probability of decline to mild cognitive impairment (MCI) or AD. This 5-year longitudinal study, used three independently collected data sets to investigate subjects that were cognitively normal at baseline and either remained normal at follow-up (stable- NL) or progressed MCI or AD at follow-up (decliners). All data sets used the same neuropsychological measure of delayed memory (WMS-R Logical Memory II). The New York University and Washington University data sets were combined to comprise 210 stable NL and 44 decliners. The National Alzheimer's Coordinating Center (NACC) data set included 1347 stable NL and 98 decliners. Logistic regression was used to predict future clinical decline based on family history and baseline delayed memory performance as well as the interaction between them. The last evaluation before clinical decline was used as a baseline for decliners resulting in an interval of approximately 2 years. In both samples, family history alone was not a significant predictor of future clinical decline. However, in both samples there was a significant interaction between MHnl and delayed memory performance such that subjects with reduced memory and a positive MH showed a greater probability of future clinical decline (Χ 2 =5.2, p<.05, Odds Ratio=8.7, 95%CI: 1.3-58.4). There was no relationship between PHn1 or noHnl in their interaction with delayed memory on clinical decline.