Population demographic trends suggest an expected dramatic increase in age-associated dementias and a looming public health crisis. Current emphasis is on disease prevention, with a focus on older adults who express early cognitive impairment. The SMART (Statistical Modeling of Aging and Risk of Transitions) has successfully harmonized data from nine different longitudinal studies on aging involving records on 5,032 subjects, with 1,657 having autopsy information. We propose to identify authoritatively the roles of diabetes and hypertension on the occurrence and duration of pre-dementia states, as well as mixed pathology. The project has shown that self-reported diabetes is not a risk for Alzheimer pathology but is a risk for cerebrovascular pathology, that subjective memory complaints are a risk for a future cognitive impairment, and that transitioning to a subjective complaint or even to mild cognitive impairment is no guarantee of future dementia. The SMART renewal proposes to obtain Medicare claims data on its participants to determine the severity of diabetes, hypertension and other comorbidities that have not been investigated, such as renal disease, with a focus on improving the prediction of who is at risk for a transition to an impaired cognitive state and mixed dementia pathology. This will be accomplished through the following specific aims:
Aim 1. Update and extensively revise the existing SMART project database with additional participant data; obtain and integrate linked Medicare claims data; assess agreement between self-reported medical history and claims data.
Aim 2. Investigate the relationship of HTN, T2DM, and multimorbidity in advanced old age with AD and non-AD neuropathologies.
Aim 3. Investigate the relationship of HTN, T2DM, and multimorbidity in advanced old age with cognitive states including subjective memory complaints, mild cognitive impairment, and dementia.

Public Health Relevance

With the graying of America, the cost of caring for older adults with dementia will rise substantially over the next few decades. Current emphasis in the field is on primary and secondary prevention. This project will study diabetes and hypertension as risk factors for various forms of dementia inducing pathology, as well as the impaired clinical states that precede diagnosed dementia.

National Institute of Health (NIH)
National Institute on Aging (NIA)
Research Project (R01)
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Neurological, Aging and Musculoskeletal Epidemiology (NAME)
Program Officer
Anderson, Dallas
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University of Kentucky
Biostatistics & Other Math Sci
Schools of Arts and Sciences
United States
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Xiong, Chengjie; Luo, Jingqin; Chen, Ling et al. (2018) Estimating diagnostic accuracy for clustered ordinal diagnostic groups in the three-class case-Application to the early diagnosis of Alzheimer disease. Stat Methods Med Res 27:701-714
Jansen, Willemijn J; Wilson, Robert S; Visser, Pieter Jelle et al. (2018) Age and the association of dementia-related pathology with trajectories of cognitive decline. Neurobiol Aging 61:138-145
Roe, Catherine M; Barco, Peggy P; Head, Denise M et al. (2017) Amyloid Imaging, Cerebrospinal Fluid Biomarkers Predict Driving Performance Among Cognitively Normal Individuals. Alzheimer Dis Assoc Disord 31:69-72
Lou, Wenjie; Wan, Lijie; Abner, Erin L et al. (2017) Multi-state models and missing covariate data: Expectation-Maximization algorithm for likelihood estimation. Biostat Epidemiol 1:20-35
Abner, Erin L; Kryscio, Richard J; Schmitt, Frederick A et al. (2017) Outcomes after diagnosis of mild cognitive impairment in a large autopsy series. Ann Neurol 81:549-559
Galioto, Rachel; O'Leary, Kevin C; Thomas, J Graham et al. (2017) Lower inhibitory control interacts with greater pain catastrophizing to predict greater pain intensity in women with migraine and overweight/obesity. J Headache Pain 18:41
Ighodaro, Eseosa T; Nelson, Peter T; Kukull, Walter A et al. (2017) Challenges and Considerations Related to Studying Dementia in Blacks/African Americans. J Alzheimers Dis 60:1-10
Kryscio, Richard J; Abner, Erin L; Caban-Holt, Allison et al. (2017) Association of Antioxidant Supplement Use and Dementia in the Prevention of Alzheimer's Disease by Vitamin E and Selenium Trial (PREADViSE). JAMA Neurol 74:567-573
Bond, Dale S; Pavlovi?, Jelena M; Lipton, Richard B et al. (2017) Sexual Dysfunction in Women With Migraine and Overweight/Obesity: Relative Frequency and Association With Migraine Severity. Headache 57:417-427
Dodge, Hiroko H; Zhu, Jian; Woltjer, Randy et al. (2017) Risk of incident clinical diagnosis of Alzheimer's disease-type dementia attributable to pathology-confirmed vascular disease. Alzheimers Dement 13:613-623

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