The expected rapid increase in the prevalence of Alzheimer's disease (AD) will have a significant impact on the economic and social structure of this country and as a result, there is a critical need for research focusing on developing early intervention and prevention strategies. One approach to developing primary prevention strategies for AD is to study cognitive and neurobiological changes occurring in middle-aged individuals who do not have dementia but may be at increased risk for developing the disease. One such group is the adult children of persons with AD who are at increased risk of developing the disease due to heredity, environmental and health risk factors shared with affected parents. The University of Wisconsin is prepared to conduct such a study because of the existence of the Wisconsin Registry for Alzheimer's Prevention (WRAP). WRAP focuses specifically on adult children of persons with AD in an effort to facilitate early detection and develop strategies to reduce the risk of developing AD. To date, we have archived DMA, plasma and serum samples and conducted extensive assessments on over 825 adult children of persons with AD and control subjects without a family history. The purpose of this prospective cohort study is to conduct a second wave of laboratory and neuropsychological testing and structural and functional MRI in order to define patterns and predictors of cognitive change over a 4-year re-test interval. Our long term goal is to identify health and lifestyle variables associated with abnormal cognitive aging and the development of AD and to use this information to develop interventions that will prevent or delay the onset of the disease. Our overall hypothesis is that adult children of persons with AD will exhibit signs of abnormal cognitive aging with declines in learning, memory and executive function and volumetric and fMRI abnormalities that will be predicted by specific genetic, vascular and lifestyle risk factors for AD.
The Specific Aims are: 1) determine the differential effects of family history of AD and apolipoprotein (APOE) 4 allele on the cognitive aging of participants;2) determine the effects of vascular and lifestyle risk factors on the cognitive aging of participants;and 3) examine the differential effect of family history of AD and the APOE 4 allele on brain aging as determined by rates of longitudinal decline in brain volume and fMRI activation during episodic memory tests that are known to activate regions of the brain affected by AD.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
3R01AG027161-05S1
Application #
8461726
Study Section
National Institute on Aging Initial Review Group (NIA)
Program Officer
Hsiao, John
Project Start
2007-04-15
Project End
2013-03-31
Budget Start
2012-05-15
Budget End
2013-03-31
Support Year
5
Fiscal Year
2012
Total Cost
$340,000
Indirect Cost
$114,086
Name
University of Wisconsin Madison
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715
Betthauser, Tobey; Lao, Patrick J; Murali, Dhanabalan et al. (2016) In vivo comparison of tau radioligands 18F-THK-5351 and 18F-THK-5317. J Nucl Med :
Kim, Won Hwa; Hwang, Seong Jae; Adluru, Nagesh et al. (2016) Adaptive Signal Recovery on Graphs via Harmonic Analysis for Experimental Design in Neuroimaging. Comput Vis ECCV 9910:188-205
Ly, Martina; Adluru, Nagesh; Destiche, Daniel J et al. (2016) Fornix Microstructure and Memory Performance Is Associated with Altered Neural Connectivity during Episodic Recognition. J Int Neuropsychol Soc 22:191-204
Racine, Annie M; Koscik, Rebecca L; Nicholas, Christopher R et al. (2016) Cerebrospinal fluid ratios with Aβ42 predict preclinical brain β-amyloid accumulation. Alzheimers Dement (Amst) 2:27-38
Dougherty, Ryan J; Ellingson, Laura D; Schultz, Stephanie A et al. (2016) Meeting physical activity recommendations may be protective against temporal lobe atrophy in older adults at risk for Alzheimer's disease. Alzheimers Dement (Amst) 4:14-7
Racine, Annie M; Clark, Lindsay R; Berman, Sara E et al. (2016) Associations between Performance on an Abbreviated CogState Battery, Other Measures of Cognitive Function, and Biomarkers in People at Risk for Alzheimer's Disease. J Alzheimers Dis 54:1395-1408
Merluzzi, Andrew P; Dean 3rd, Douglas C; Adluru, Nagesh et al. (2016) Age-dependent differences in brain tissue microstructure assessed with neurite orientation dispersion and density imaging. Neurobiol Aging 43:79-88
Melah, Kelsey E; Lu, Sharon Yuan-Fu; Hoscheidt, Siobhan M et al. (2016) Cerebrospinal Fluid Markers of Alzheimer's Disease Pathology and Microglial Activation are Associated with Altered White Matter Microstructure in Asymptomatic Adults at Risk for Alzheimer's Disease. J Alzheimers Dis 50:873-86
Law, Lena L; Schultz, Stephanie A; Boots, Elizabeth A et al. (2016) Chronotropic Response and Cognitive Function in a Cohort at Risk for Alzheimer's Disease. J Alzheimers Dis :
Kim, Hyunwoo J; Smith, Brandon M; Adluru, Nagesh et al. (2016) Abundant Inverse Regression using Sufficient Reduction and its Applications. Comput Vis ECCV 9907:570-584

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