Decreased cognitive function in extended family members from the single late-onset-Alzheimer's-disease pedigree

A family history of dementia is associated with an increased risk of developing Alzheimer's disease (AD) late in life (LOAD). This study marked the first attempt to assess the familial contribution to differences in cognitive performance in a large family-based group in the Chinese community. We enrolled 168 participants without dementia from a single pedigree with 9 probable AD patients diagnosed after age 65. These participants were evaluated with a comprehensive neuropsychological battery, the Chinese version of the Mini Mental State Examination, and the Alzheimer Disease Assessment Scale-Cognitive Subscale. Analyses found that extended family members of the LOAD pedigree showed similar performance on measures of global cognitive function and semantic memory compared to controls, but lower scores on episodic memory, attention, and executive function measures. These results indicate that the genetic influences on certain sub-cognitive domains are more detectable despite normal global cognitive function, and that family members with the LOAD pedigree are at risk for developing LOAD by virtue of their family history with an additive risk due to increased age. The findings in this study support the importance of documenting if there is a positive family history of AD in clinical evaluations.