Background and Objectives There is increasing evidence that changes in everyday functional abilities are among the first signs of incipient neurodegenerative disease. The present study sought to examine whether specific types of early functional limitations in cognitively normal older adults are associated with the subsequent development of mild cognitive impairment (MCI), as well as the relative predictive value of self- versus informant-report in predicting diagnostic conversion to MCI. Design Participants received baseline and annual multidisciplinary clinical evaluations including a physical and neurological exam, imaging, lab work, and neuropsychological testing. Setting Data used in this study was collected as part of a longitudinal research cohort at the University of California, Davis Alzheimer’s Disease Center (ADC). Participants Participants (n = 324) were diagnosed as having normal cognition at study baseline, had an informant who could complete informant-based ratings, and had at least one follow-up visit. Measurements Participants and informants each completed The Everyday Cognition (ECog) scale, an instrument designed to measure everyday function across six cognitive domains. Results Both self- and informant-reported functional limitations on the ECog were associated with a significant increase in risk of diagnostic conversion to MCI (informant: HR = 2.0, 95% CI = 1.3–3.2, p = .002), with self-report having a slightly higher hazard ratio (HR = 2.3, 95% CI = 1.4–3.6, p < .001). When controlling for baseline cognitive abilities, the effect remained significant for both self- and informant-reported functional limitations. Conclusion Deficits in everyday memory and executive function domains were the strongest predictors of diagnostic conversion to MCI. These results indicate detection of early functional limitations may be clinically useful in assessing the future risk of developing cognitive impairment in cognitively normal older adults.

Use of compensation strategies is associated with higher levels of functioning in daily life among older adults. Findings provide strong rational for development of interventions that directly target such strategies.

Background Cognitive processing speed is important for performing everyday activities in persons with mild cognitive impairment (MCI). However, its role in daily function has not been examined while simultaneously accounting for contributions of Alzheimer’s disease (AD) risk biomarkers. We examine the relationships of processing speed and genetic and neuroimaging biomarkers to composites of daily function, mobility, and driving. Method We used baseline data from 103 participants on the MCI/mild dementia spectrum from the Applying Programs to Preserve Skills trial. Linear regression models examined relationships of processing speed, structural magnetic resonance imaging (MRI), and genetic risk alleles for AD to composites of performance-based instrumental activities of daily living (IADLs), community mobility, and on-road driving evaluations. Results In multivariable models, processing speed and the brain MRI neurodegeneration biomarker Spatial Pattern of Abnormality for Recognition of Early Alzheimer’s disease (SPARE-AD) were significantly associated with functional and mobility composite performance. Better processing speed and younger age were associated with on-road driving ratings. Genetic risk markers, left hippocampal atrophy, and white matter lesion volumes were not significant correlates of these abilities. Processing speed had a strong positive association with IADL function (p &lt; .001), mobility (p &lt; .001), and driving (p = .002). Conclusions Cognitive processing speed is strongly and consistently associated with critical daily functions in persons with MCI in models including genetic and neuroimaging biomarkers of AD risk. SPARE-AD scores also significantly correlate with IADL performance and mobility. Results highlight the central role of processing speed in everyday task performance among persons with MCI/mild dementia.

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