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 #
5R01AG027161-04
Application #
7795781
Study Section
National Institute on Aging Initial Review Group (NIA)
Program Officer
Hsiao, John
Project Start
2007-04-15
Project End
2012-03-31
Budget Start
2010-04-01
Budget End
2011-03-31
Support Year
4
Fiscal Year
2010
Total Cost
$721,917
Indirect Cost
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
Nicholas, Christopher R; Hoscheidt, Siobhan M; Clark, Lindsay R et al. (2017) Positive affect predicts cerebral glucose metabolism in late middle-aged adults. Soc Cogn Affect Neurosci 12:993-1000
Hermann, Bruce P; Sager, Mark A; Koscik, Rebecca L et al. (2017) Vascular, inflammatory, and metabolic factors associated with cognition in aging persons with chronic epilepsy. Epilepsia 58:e152-e156
Dougherty, Ryan J; Schultz, Stephanie A; Boots, Elizabeth A et al. (2017) Relationships between cardiorespiratory fitness, hippocampal volume, and episodic memory in a population at risk for Alzheimer's disease. Brain Behav 7:e00625
Dean 3rd, Douglas C; Hurley, Samuel A; Kecskemeti, Steven R et al. (2017) Association of Amyloid Pathology With Myelin Alteration in Preclinical Alzheimer Disease. JAMA Neurol 74:41-49
Berman, Sara E; Koscik, Rebecca L; Clark, Lindsay R et al. (2017) Use of the Quick Dementia Rating System (QDRS) as an Initial Screening Measure in a Longitudinal Cohort at Risk for Alzheimer's Disease. J Alzheimers Dis Rep 1:9-13
Sprecher, Kate E; Koscik, Rebecca L; Carlsson, Cynthia M et al. (2017) Poor sleep is associated with CSF biomarkers of amyloid pathology in cognitively normal adults. Neurology 89:445-453
Casaletto, Kaitlin B; Elahi, Fanny M; Bettcher, Brianne M et al. (2017) Neurogranin, a synaptic protein, is associated with memory independent of Alzheimer biomarkers. Neurology 89:1782-1788
Mueller, Kimberly D; Koscik, Rebecca L; Clark, Lindsay R et al. (2017) The Latent Structure and Test-Retest Stability of Connected Language Measures in the Wisconsin Registry for Alzheimer's Prevention (WRAP). Arch Clin Neuropsychol :1-13
Racine, Annie M; Merluzzi, Andrew P; Adluru, Nagesh et al. (2017) Association of longitudinal white matter degeneration and cerebrospinal fluid biomarkers of neurodegeneration, inflammation and Alzheimer's disease in late-middle-aged adults. Brain Imaging Behav :
Dougherty, Ryan J; Schultz, Stephanie A; Kirby, Taylor K et al. (2017) Moderate Physical Activity is Associated with Cerebral Glucose Metabolism in Adults at Risk for Alzheimer's Disease. J Alzheimers Dis 58:1089-1097

Showing the most recent 10 out of 100 publications