Obesity is associated with Alzheimer's disease (AD), particularly in women. However, changes in body weight and body mass index (BMI) throughout the progressive course of AD have also been reported, resulting in a low body weight or low BMI predicting mortality among those who have the disease. Thus, temporal changes in body weight and BMI may not only influence AD risk, but also progression, and ultimately death. The role of BMI in AD also underscores the importance of timing of risk factors, both in relationship to disease onset and whether they occur in early-, mid-, or late-life; and illustrates the change in direction of risk factor-disease relationships that may occur at certain points in late life. The goals of this project are to evaluate the role of BMI and related vascular and genetic factors in relationship to AD in three population-based, longitudinal studies containing epidemiologic, clinical, and biologic data related to psychiatric disorders of aging that are unsurpassed in the world. We propose to: 1) Characterize the role of overweight and obesity in AD and other dementias in women and men across three population-based studies in Goteborg, Sweden. Participants in these studies, born between 1901 and 1930, have been followed prospectively from baseline ages of 38 to 70, and 95 years. 2) Evaluate the role of overweight and obesity in AD and other dementias with consideration for 'critical periods' of adiposity exposure, the length of time between an adiposity measurement and onset of dementia, the role of current overweight and obesity outpoints in relationship to dementia risk, and examination of risk factors by age group with consideration for birth cohort. 3) Assess the role of genetic polymorphisms related to the vascular etiology of AD and other dementias, and their potential interaction with obesity. 4) Consider physical activity and other vascular risk factors, such as blood pressure and blood lipids, and their potential interaction with obesity and genetic factors to modulate risk for AD and other dementias. Understanding the life course of overweight and obesity in relationship to dementia will assist the future design of tailor-made intervention programs based on age and previous weight patterns, and assist in the evaluation of better outpoints for overweight and obesity that optimize health in the oldest age groups. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Small Research Grants (R03)
Project #
5R03AG026098-02
Application #
7241454
Study Section
Special Emphasis Panel (ZRG1-HOP-C (90))
Program Officer
Anderson, Dallas
Project Start
2006-07-01
Project End
2009-06-30
Budget Start
2007-07-01
Budget End
2009-06-30
Support Year
2
Fiscal Year
2007
Total Cost
$62,521
Indirect Cost
Name
Medical College of Wisconsin
Department
Family Medicine
Type
Schools of Medicine
DUNS #
937639060
City
Milwaukee
State
WI
Country
United States
Zip Code
53226
Gudmundsson, P; Lindwall, M; Gustafson, D R et al. (2015) Longitudinal associations between physical activity and depression scores in Swedish women followed 32 years. Acta Psychiatr Scand 132:451-8
Arnoldussen, Ilse A C; Kiliaan, Amanda J; Gustafson, Deborah R (2014) Obesity and dementia: adipokines interact with the brain. Eur Neuropsychopharmacol 24:1982-99
Gustafson, Deborah R (2012) Adiposity and cognitive decline: underlying mechanisms. J Alzheimers Dis 30 Suppl 2:S97-112
Johansson, Lena; Skoog, Ingmar; Gustafson, Deborah R et al. (2012) Midlife psychological distress associated with late-life brain atrophy and white matter lesions: a 32-year population study of women. Psychosom Med 74:120-5
Sigstrom, Robert; Ostling, Svante; Karlsson, Bjorn et al. (2011) A population-based study on phobic fears and DSM-IV specific phobia in 70-year olds. J Anxiety Disord 25:148-53
Sacuiu, S; Gustafson, D; Sjogren, M et al. (2010) Secular changes in cognitive predictors of dementia and mortality in 70-year-olds. Neurology 75:779-85
Gudmundsson, Pia; Skoog, Ingmar; Waern, Margda et al. (2010) Is there a CSF biomarker profile related to depression in elderly women? Psychiatry Res 176:174-8
Olesen, Pernille J; Gustafson, Deborah R; Simoni, Michela et al. (2010) Temporal lobe atrophy and white matter lesions are related to major depression over 5 years in the elderly. Neuropsychopharmacology 35:2638-45
Gustafson, Deborah R (2010) Adiposity hormones and dementia. J Neurol Sci 299:30-4
Mielke, M M; Zandi, P P; Shao, H et al. (2010) The 32-year relationship between cholesterol and dementia from midlife to late life. Neurology 75:1888-95

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