Wednesday, January 15, 2025
1/15/2025
PROJECT SUMMARY Identification of dietary factors that delay decline in cognitive function has important implications for reducing the burden of Alzheimer’s dementia (AD) and reducing health care costs as the population ages. Inadequate intakes of vitamin K and vitamin D are common among the elderly, and there is growing evidence that both nutrients have biological roles in the pathogenesis of Alzheimer’s disease (AD) and related pathologies, and the risk of Alzheimer’s dementia. We demonstrated in the Rush Memory and Aging Project (MAP) study that higher postmortem brain levels of vitamin K and vitamin D were associated with better cognitive function prior to death. Further investigation of neuropathologically-defined outcomes revealed that higher brain vitamin K concentrations were associated with lower global AD pathology, specifically fewer neurofibrillary tangles, and with lesser Lewy bodies (sine qua non of Parkinson’s disease and Lewy Body Dementia). There is now an urgent need for additional research to clarify the biologic mechanism(s) underlying these cognitive protective effects. Based on our collective prior research and exciting new research findings generated during the current project period, we propose an overall goal to elucidate associations between Vitamin K and Vitamin D with brain structure (neuropathology and neuroimaging outcomes) and brain function (cognitive and motor) in older persons from two well-characterized community-based studies, MAP and the Rush Minority Aging Research Study (MARS). Guided by strong preliminary data, this objective will be accomplished by pursuing two aims: Specific Aim 1: Determine associations of Vitamin K and Vitamin D with MRI-derived indices of white and gray matter tissue integrity and measures of brain neuropathology in: (a) postmortem brain samples; and (b) antemortem blood samples; and Specific Aim 2: Determine the associations of brain vitamin K and vitamin D with motor function and parkinsonian signs. The proposed approach is innovative because this highly productive and multidisciplinary team will: (1) expand our brain structure outcomes to include neuroimaging that leverage novel deep-learning approaches, in addition to neuropathologic outcomes, to determine if these two vitamins are involved in changes in brain tissue integrity that occur in AD and related pathologies; (2) expand brain function outcomes to include existing outcomes of motor function and parkinsonian signs, in addition to cognitive outcomes, for novel insight into common mechanisms underlying age-related cognitive and physical function declines; and (3) add African-American decedents with autopsies from MARS to enhance generalizability of the findings. The proposed research is significant because intakes of these two nutrients, which are generally below the recommended amounts in older persons, are modifiable, low-cost, and safe when consumed in higher amounts. Successful completion of the proposed study will provide the foundation for future studies on the impact of modifying vitamin K and/or vitamin D on AD risk.
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