Deficits in Inhibition and Flexibility are Associated with the APOE-E4 Allele in Nondemented Older Adults

This prospective study of nondemented older adults at genetic risk for AD and other types of dementia (i.e., APOE e4 allele) utilized a new Stroop test that includes a dual executive-function condition requiring both response inhibition and cognitive switching. Results indicated that, relative to non-e4 subjects, the e4 group committed more errors, but only on the new Inhibition/Switching condition. In addition, error-rate variance on this task was more heterogeneous for the e4 compared to the non-e4 group, and errors rates correlated significantly with global cognitive status (i.e., DRS scores) for the e4 group but not for the non-e4 group. These findings suggest that vulnerability to errors in response inhibition and cognitive flexibility is present in persons at risk for AD and may signal early emergence of executive dysfunction in preclinical AD. The association between these subtle executive-function deficits and the overall cognitive functioning of at-risk individuals provides further evidence of their utility as a possible preclinical marker of AD. Preparation of this article was supported in part by a Veterans Administration Merit Review Grant (DD), a VA Career Development Award (MJ) and by National Institute on Aging Grants RO1 AG12674 (MB) and P50 AG05131 (UCSD ADRC; DS).

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