With the aging of the U.S. population, the importance of developing preventions and treatments for dementia is increasingly apparent. Evidence suggests that certain vascular risk factors like hypertension, smoking and diabetes, especially when they occur in midlife, may contribute to risk for dementia in late life, and possibly even to Alzheimer's dementia (AD), the most common cause of dementia. Thus, addressing the contributing factors related to vascular disease may be an important element in dementia prevention. What is not well understood is whether vascular risk factors actually cause the changes in the brain that cause AD (specifically, ?-amyloid plaques) or if having both Alzheimer's and vascular changes in the brain together makes the dementia worse. This study will explore these two hypotheses. The ARIC-PET Amyloid Imaging Study is an ancillary study of the Atherosclerosis Risk in Communities (ARIC) study, a large study involving, at its start 25 years ago, 16,000 individuals representative of 4 diverse U.S. communities. In 2011-2013, as part of the currently funded ARIC Neurocognitive (ARIC-NCS) study, the survivors will undergo neurologic evaluation, cognitive assessment, and, in a subset, brain MRI. We will recruit a further subset, 210 individuals aged 70-90 years from Jackson, MS or Hagerstown, MD with either normal cognition or mild cognitive impairment (MCI), to undergo a PET scan with 18F-AV-45, which is a marker used to identify ?-amyloid in the brain. In the last 2 years of the study, participants will undergo follow-up cognitive evaluation. The study will determine: 1) whether vascular risk factors and markers, especially from midlife, are associated with increased ?-amyloid binding, which would indicate that vascular disease directly contributes to AD changes in the brain, or 2) whether ?-amyloid deposits in the brain in combination with vascular risk factors and markers contribute to cognitive impairments and development of dementia. Study results may help optimize future treatment and prevention trials in individuals with mild cognitive impairment who are at risk for dementia. If strong associations are found between vascular disease and ?-amyloid plaque deposition, this will provide support for aggressive risk factor treatment as a means to decrease cognitive decline and incidence of dementia.
Millions of Americans have dementia, and Alzheimer's Disease is the most common type of dementia. Understanding the relationship between vascular risk factors and Alzheimer's disease will allow for better preventive strategies of Alzheimer's and other types of dementia, ultimately decreasing the burden of dementia and mild cognitive impairment in this country. !
| Walker, Keenan A; Windham, B Gwen; Brown, Charles H et al. (2018) The Association of Mid- and Late-Life Systemic Inflammation with Brain Amyloid Deposition: The ARIC-PET Study. J Alzheimers Dis 66:1041-1052 |
| Iadecola, Costantino; Gottesman, Rebecca F (2018) Cerebrovascular Alterations in Alzheimer Disease. Circ Res 123:406-408 |
| Gottesman, Rebecca F; Schneider, Andrea L C; Zhou, Yun et al. (2017) Association Between Midlife Vascular Risk Factors and Estimated Brain Amyloid Deposition. JAMA 317:1443-1450 |
| Gottesman, Rebecca F; Schneider, Andrea L C; Zhou, Yun et al. (2016) The ARIC-PET amyloid imaging study: Brain amyloid differences by age, race, sex, and APOE. Neurology 87:473-80 |
| Gross, Alden L; Power, Melinda C; Albert, Marilyn S et al. (2015) Application of Latent Variable Methods to the Study of Cognitive Decline When Tests Change over Time. Epidemiology 26:878-87 |
| Rawlings, Andreea M; Sharrett, A Richey; Schneider, Andrea L C et al. (2014) Diabetes in midlife and cognitive change over 20 years: a cohort study. Ann Intern Med 161:785-93 |
| Koton, Silvia; Schneider, Andrea L C; Rosamond, Wayne D et al. (2014) Stroke incidence and mortality trends in US communities, 1987 to 2011. JAMA 312:259-68 |
| Gottesman, Rebecca F; Sojkova, Jitka; Beason-Held, Lori L et al. (2012) Patterns of regional cerebral blood flow associated with low hemoglobin in the Baltimore Longitudinal Study of Aging. J Gerontol A Biol Sci Med Sci 67:963-9 |
| Chik, Yolanda; Gottesman, Rebecca F; Zeiler, Steven R et al. (2012) Differentiation of transverse sinus thrombosis from congenitally atretic cerebral transverse sinus with CT. Stroke 43:1968-70 |
| Christman, A L; Matsushita, K; Gottesman, R F et al. (2011) Glycated haemoglobin and cognitive decline: the Atherosclerosis Risk in Communities (ARIC) study. Diabetologia 54:1645-52 |
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