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Background: Recent work has demonstrated the potentially protective effects of the apolipoprotein E (APOE) ε2 allele on cognitive functioning in individuals at risk for developing Alzheimer disease. However, little is known regarding the effect of ε2 genotype on rate of change in daily functioning over time. The aim of the current study was to examine the relationship between APOE genotype and change over time in ability to perform daily activities.Methods: We examined the relationship between APOE genotype and change in the ability to perform activities of daily living at 12- and 24-month intervals in 225 healthy comparison subjects, 381 individuals with amnestic mild cognitive impairment, and 189 individuals with Alzheimer disease who were enrolled in the Alzheimer's Disease Neuroimaging Initiative study. Neuropsychological measures were also collected at each follow-up.Results: Overall, individuals with at least one APOE-ε2 allele showed less functional decline over time and better performance on neuropsychological measures than those without an ε2 allele, even after controlling for potential confounders. When diagnostic groups were examined individually, presence of the ε2 allele continued to be associated with slower functional decline, although the relationship was no longer statistically significant in most cases, likely due to reduced statistical power.Conclusions: Our findings suggest that the APOE-ε2 allele provides a buffer against significant changes in daily functioning over time and is associated with better neuropsychological performance across a number of measures. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Mild cognitive impairment (MCI) may involve subtle functional losses that are not detected with typical self- or informant-report assessments of daily function. Information about the nature of functional difficulties in MCI can be used to augment common clinical assessment procedures, and aspects of function that are affected in MCI can serve as meaningful endpoints for intervention trials. DESIGN: Cross-sectional case and comparison group study. SETTING: University medical center. PARTICIPANTS: Fifty participants with MCI and 59 cognitively normal participants. MEASUREMENTS: The authors compared the groups on dimensions of both speed and accuracy in performing instrumental activities of daily living (IADLs), using a standardized Timed IADL measure that evaluates five functional domains commonly encountered in everyday life (telephone use, locating nutrition information on food labels, financial abilities, grocery shopping, medication management). RESULTS: Across Timed IADL domains, MCI participants demonstrated accuracy comparable with cognitively normal participants but took significantly longer to complete the functional activities, controlling for depressive symptoms (p< 0.001). Slower performance was demonstrated in each discrete domain except financial abilities. CONCLUSION: These results suggest that slower speed of task performance is an important component and perhaps an early marker of functional change in MCI that would not be detected using traditional measurements of daily function. Future research should address the question of whether performance-based functional measures, as well as simple queries regarding whether functional activities take longer than usual to complete, may improve the prediction of future cognitive decline and disease progression among those individuals in whom MCI represents impending dementia. [ABSTRACT FROM AUTHOR]