An estimated 5.3 million Americans currently have Alzheimer's disease (AD), and the number is expected to increase rapidly with the aging of the baby boom generation. There is a growing consensus that AD represents an advanced state of brain failure that is preceded by many years of pathological changes. The limited effectiveness of current therapies and the failure of recent clinical trials to identify effective therapies for D suggest that current treatments are intervening at a late stage of the disease when significant improvement is less likely. A major barrier to early intervention is our lack of knowledge about which biologic or environmental factors are associated with cognitive decline and eventually result in the clinical syndromes of mild cognitive impairment (MCI) or AD. The Wisconsin Registry for Alzheimer's Prevention (WRAP) is a longitudinal cohort study of 1,527 middle-aged persons with and without a family history of AD that is designed to identify genetic and environmental factors that are associated with the earliest signs of AD. The purpose of this research is to conduct cognitive, laboratory and neuroimaging assessments at 2-year intervals to identify the health, lifestyle and genetic risk factors that influence biomarker expression of A in persons who are currently asymptomatic, but are at an increased risk of developing the disease. This study will combine biomarker measurements collected over the past 10 years with biomarker, genetic and environmental data collected with this renewal to describe the neurobiology of preclinical AD. At the present time, the temporal course of biomarker changes in preclinical AD, and the factors that influence change during the decade before the development of clinical symptoms are unknown. This information is essential for the development of clinical trials evaluating disease-modifying therapies designed to delay the onset or slow the progression of AD.

Public Health Relevance

of this study is that Alzheimer's disease (AD) represents a major social and public health problem which will worsen as our population ages. The findings of this study have the potential to define the neurobiology of preclinical AD which is a prerequisite for developing and implementing interventions that will either delay the onset or slow the progression of the disease.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
5R01AG027161-07
Application #
8724313
Study Section
Special Emphasis Panel (ZAG1-ZIJ-8 (04))
Program Officer
Hsiao, John
Project Start
2006-01-01
Project End
2018-03-31
Budget Start
2014-04-01
Budget End
2015-03-31
Support Year
7
Fiscal Year
2014
Total Cost
$860,098
Indirect Cost
$288,604
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
Willette, Auriel A; Johnson, Sterling C; Birdsill, Alex C et al. (2015) Insulin resistance predicts brain amyloid deposition in late middle-aged adults. Alzheimers Dement 11:504-510.e1
Okonkwo, Ozioma C; Schultz, Stephanie A; Oh, Jennifer M et al. (2014) Physical activity attenuates age-related biomarker alterations in preclinical AD. Neurology 83:1753-60
Koscik, Rebecca L; La Rue, Asenath; Jonaitis, Erin M et al. (2014) Emergence of mild cognitive impairment in late middle-aged adults in the wisconsin registry for Alzheimer's prevention. Dement Geriatr Cogn Disord 38:16-30
Ly, Martina; Canu, Elisa; Xu, Guofan et al. (2014) Midlife measurements of white matter microstructure predict subsequent regional white matter atrophy in healthy adults. Hum Brain Mapp 35:2044-54
Birdsill, Alex C; Koscik, Rebecca L; Jonaitis, Erin M et al. (2014) Regional white matter hyperintensities: aging, Alzheimer's disease risk, and cognitive function. Neurobiol Aging 35:769-76
Engelman, Corinne D; Koscik, Rebecca L; Jonaitis, Erin M et al. (2014) Investigation of triggering receptor expressed on myeloid cells 2 variant in the Wisconsin Registry for Alzheimer's Prevention. Neurobiol Aging 35:1252-4
Jackson, Daren C; Lin, Jack J; Chambers, Karlee L et al. (2014) Birth weight and cognition in children with epilepsy. Epilepsia 55:901-8
Okonkwo, Ozioma C; Oh, Jennifer M; Koscik, Rebecca et al. (2014) Amyloid burden, neuronal function, and cognitive decline in middle-aged adults at risk for Alzheimer's disease. J Int Neuropsychol Soc 20:422-33
Mielke, Michelle M; Haughey, Norman J; Bandaru, Veera V R et al. (2014) Cerebrospinal fluid sphingolipids, ?-amyloid, and tau in adults at risk for Alzheimer's disease. Neurobiol Aging 35:2486-94
Johnson, Sterling C; Christian, Bradley T; Okonkwo, Ozioma C et al. (2014) Amyloid burden and neural function in people at risk for Alzheimer's Disease. Neurobiol Aging 35:576-84

Showing the most recent 10 out of 30 publications