Multisensory, Motor, and Biomarker Changes in Aging and Preclinical Alzheimer's Disease

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PARENT GRANT ABSTRACT (RF1 AG066837) Alzheimer’s disease (AD) and other causes of cognitive impairment are growing public health problems with the aging of the large baby boom generation and there is a shortage of workers and facilities to meet the future care needs of those with AD and other dementias. AD-related brain changes may occur years or decades before the onset of symptoms and, therefore, it is important to identify, in midlife, people at high risk for AD to provide ample opportunity to intervene when it may be possible to delay the onset of clinically significant symptoms and loss of independence. Longitudinal studies have shown that sensory (hearing, vision, olfaction) and motor impairments are associated with increased risk of cognitive impairment, dementia, or AD. This project is to study the impact of aging changes in sensory function (hearing, olfaction, vision, and taste) and motor function on the 10-yr risk of pre-clinical AD in middle-aged adults. The Beaver Dam Offspring Study is a longitudinal cohort study of sensory and cognitive aging in the adult offspring of the population-based Epidemiology of Hearing Loss Study cohort. Data from participants (N=1536, mean age 49 years) who have stored serum samples from the baseline (2005-2008), 5-yr follow-up (2010-2013) and 10-yr follow-up (2015- 2017) examinations will be included. Stored samples from the three time points will be assayed for serum amyloid β40 and β42 (Aβ40, Aβ42), serum total tau (TT) and neurofilament light chain (NfL); biomarkers of Alzheimer’s pathology, neuronal injury and neurodegeneration. Least squares multiple linear regression models and longitudinal linear mixed effects models will be used to determine if sensory and motor function and other traditional risk factors for AD and dementia are associated with levels of Aβ, TT and NfL at baseline and 10-year change, respectively, in these serum biomarkers. The biomarkers, Aβ, TT and NfL, and thickness of the macular ganglion cell inner plexiform layer (mGCIPL) will be applied to a modification of the NIA-Alzheimer’s Association AT(N) framework to identify preclinical Alzheimer’s and non-Alzheimer’s neuropathology in midlife. Using this modified framework and traditional cognitive outcomes we will determine if sensory and motor changes in aging contribute to 10-year risk prediction models for biologically and functionally defined preclinical AD. The best prediction model results will be extended to create clinically useful risk scores. Risk scores for asymptomatic middle-aged people which are based on practical test batteries will be useful in clinical and research settings.