Functional Competence in Alzheimer's Disease: A Novel Assessment Approach to Enhance Prediction of Risk in the Elderly - Project Summary/Abstract By the year 2050, as many as 16 million individuals in the US will express symptoms of Alzheimer’s disease (AD), a progressive neurodegenerative disorder marked by difficulties in memory, cognition and instrumental activities of daily living (IADL). The 2015 White House Conference on Aging emphasized a critical need for sensitive instruments to capture reduced functional capacity as a means to maximize independent living and protect older adults from exploitation and abuse. Furthermore, the Food and Drug Administration (FDA) recently recommended the measurement of subtle functional and cognitive changes during the preclinical stages as a potential global outcome to evaluate the efficacy of treatment strategies and disease modifying therapies in dementia research. However, despite the well-established importance of IADL detection, there is a lack of research on when and how functional declines first become compromised and associated brain changes along the disease spectrum. Prior research has failed to examine the emergence of subtle functional deficits during early dementia stages such as among those with subjective cognitive decline (SCD) and how such deficits advance in later stages, i.e., mild cognitive impairment (MCI), mild Alzheimer’s disease (AD). Additionally, no formal studies have assessed sex differences in terms of the neural and cognitive basis for functional abilities, considering the higher prevalence of IADL impairments in women. Given these critical gaps in the literature, our project aims to track functional decline along the AD continuum utilizing sensitive performance-based assessments, investigate sex differences and explore its association with neuroimaging data. There is growing interest in utilizing performance-based assessments in clinical trials as subtle errors in these tasks can potentially differentiate among preclinical, prodromal and more advanced disease stages. In order for clinical trials to be successful, there is a strong need to incorporate these sensitive instruments given their potential accuracy in capturing functional impairments during the preclinical or prodromal disease stages. Thus, in the proposed study, among older adults who are cognitively unimpaired and those with SCD, MCI, mild AD, we will: (1) elucidate new insights into IADL impairments during early and advanced disease stages, (2) investigate cognitive and brain changes contributing to sex differences in patterns of IADL impairments and (3) characterize the relationship between changes in functional brain networks and IADL deficits. The achievement of our stated aims will result in an improved ability to detect and identify emerging functional impairments in individuals along the AD continuum. Study findings also will contribute to our long-term goals of developing safeguards to prevent functional deficits and potential hazardous behaviors consequent to these impairments.
