To reduce the increasing societal and financial burden of Alzheimer's disease and related dementias (ADRD), prevention is critical. Even small improvements of the modifiable dementia risk factors on the individual level have the potential to lead to a substantial reduction of dementia cases at the population level. The disease processes occur for years though symptoms typically appear after age 60. Thus, identifying those at risk early for intervention is crucial. Studies among adults aged 60 years and older have identified performance-based measures of impairment in physical function as early indicators of ADRD, three or more years prior to onset. To improve earlier prediction of ADRD, we need research on adults aged 51-59 years to assess the relationship between physical functional impairment and likelihood of ADRD onset years later. Further, given the burden of administering performance-based measures of physical function, it would be advantageous to use patient- reported metrics of limitation in physical function for ADRD prediction. We propose using the 1998-2018 nationally representative Health and Retirement Study (HRS) of adults aged 51-59 years to determine the extent to which patient-reported measures of function would facilitate efficient ADRD risk identification. Primary study aims are to: 1) To identify the extent to which self-reported measures of physical function in midlife predict future late-onset ADRD. We will use standardized (RAND HRS) self-reported measures of function and the Langa-Weir ADRD algorithm available in the HRS. Working hypothesis: Limitations in physical function, defined using summary measures of self-reported physical function predict onset of ADRD 4 to 20 years later. 2) Verify that sub-groups of adults, defined by limitations in physical function, aged 51-59 are at higher risk of developing ADRD. We will verify existence of sub-groups (identified in our preliminary analyses) using a computational systems approach (cluster analysis) are predictive of onset of ADRD through 2018, in adjusted analyses. Working hypothesis: Sub-groups of middle-aged adults with unique patterns of limitations in physical function are at higher risk of developing ADRD than those without physical functional deficit 4 to 20 years later, independent of related factors. This proposal addresses the objectives of PAS-19-391 in several ways. First, the Principal investigator (PI), an early stage investigator, is committed to a career in ADRD research. Second, the investigative team has training in non-neurological medical fields and will shift their research focus to ADRD prevention within their fields. Third, the PI has experience with an existing dataset (HRS); and will use it to assess age-related changes in non-cognitive processes that may be early signs of ADRD. Finally, the PI published an HRS study reporting that physical functional decline precedes the onset of diabetes, a risk factor for ADRD. Our proposal builds on this work. The successful completion of the proposed study will ascertain the extent to which self-reported impairment in physical function during midlife, predicts future ADRD, thereby offering a new, efficient mechanism for early identification of ADRD.
The proposed research is relevant to public health because the number of people living with dementia is expected to triple worldwide by 2050 unless effective measures to treat or delay the onset of the disease are implemented.1 The same study found that about 35% of ADRD could be delayed or prevented through modifiable health and lifestyle factors from different phases of life. To identify adults at risk of ADRD early, our study among adults aged 51-59 seeks to determine the extent to which self-reported measures of physical function are early indicators of ADRD and to identify sub-groups of people with unique patterns of limitation in physical function that are early indicators of ADRD.