Funded by NIA since 1989, the Epidemiology of Dementia Study has focused on identifying incident cases of dementia and determining the risk factors associated with clinical dementia, particularly Alzheimer's disease (AD) in the large prospective community-based Framingham Study. Beginning with the establishment of a dementia-free cohort in 1976-78, this study has documented >600 subjects with incident dementia, largely from the Original cohort recruited in 1948. In recent years, with the aging of the children of the Original cohort (and their spouses), a number of these Generation 2 subjects have been documented to have cognitive decline, and MRI markers of brain injury as well as Mild Cognitive Impairment (MCI) and dementia. We have provided community-based estimates of incidence and lifetime risk of AD, the risk of dementia following stroke, and have identified a number of lifestyle, vascular, novel biomarker and more recently genetic risk factors for AD. Through an ongoing brain donation program established in 1995, we have performed detailed neuropathologic examination of approximately 140 brains. In this application we will focus on identifying persons with subclinical disease by intensifying surveillance to identify subjects with probable MCI and will follow them with annual assessments. We will relate a wealth of previously collected risk factors to the risk of incident AD and all-dementia, to AD endophenotypes, and to the risk of conversion from MCI to clinical AD. These risk factors include genetic (genome-wide, candidate gene and gene expression) and environmental (lifestyle, vascular, metabolic measures gathered repeatedly since midlife) data, circulating biomarker levels and baseline imaging data. To this array of putative risk markers we propose to add: (1) a key biomarker, circulating beta-amyloid (A240 and A242) levels;(2) a third round of quantitative brain MRI and NP testing to more precisely document change, and distinguish those with consistent signs of brain atrophy and cognitive decline at highest risk of transitioning to MCI and/or dementia;and, (3) detailed post-processing MR analyses of additional regions of interest from prior and newly acquired MRI images to enhance detection of subtle changes in brain morphology over time. The goal is to incorporate these new and existing data into a risk prediction score for AD and dementia and validate it in an independent epidemiological cohort.
The aim of this risk profile is to identify persons at highest risk for developing AD, thus permitting targeted preventive and therapeutic interventions, including enrollment of susceptible subjects for clinical trials of promising therapies.
Funded by NIA since 1989, the Epidemiology of Dementia Study has focused on determining the incidence and risk factors predisposing to dementia generally, and Alzheimer's disease (AD) specifically, in a large, multi-generational, community-based prospective epidemiologic study. Since detecting early disease is important for effective prevention, we have recently focused on identifying persons with Mild Cognitive Impairment (MCI). We have studied participants, with two sets of brain MRI and cognitive tests done 5 years apart. In this renewal we have added a key biomarker (beta-amyloid), better imaging and cognitive data. We propose to develop a dementia (and AD) risk score based on these new data, and on the genetic, lifestyle, vascular, metabolic, biomarker and imaging data already available (collected over 4-6 decades). The purpose of this risk score is to accurately identify high-risk persons for enrollment in preventive and treatment trials.
|Traylor, Matthew; Malik, Rainer; Nalls, Mike A et al. (2017) Genetic variation at 16q24.2 is associated with small vessel stroke. Ann Neurol 81:383-394|
|Snyder, Heather M; Ahles, Tim; Calderwood, Stuart et al. (2017) Exploring the nexus of Alzheimer's disease and related dementias with cancer and cancer therapies: A convening of the Alzheimer's Association & Alzheimer's Drug Discovery Foundation. Alzheimers Dement 13:267-273|
|Romero, José R; Beiser, Alexa; Himali, Jayandra J et al. (2017) Cerebral microbleeds and risk of incident dementia: the Framingham Heart Study. Neurobiol Aging 54:94-99|
|Thaker, A A; Weinberg, B D; Dillon, W P et al. (2017) Entorhinal Cortex: Antemortem Cortical Thickness and Postmortem Neurofibrillary Tangles and Amyloid Pathology. AJNR Am J Neuroradiol 38:961-965|
|Aparicio, Hugo J; Petrea, Rodica E; Massaro, Joseph M et al. (2017) Association of descending thoracic aortic plaque with brain atrophy and white matter hyperintensities: The Framingham Heart Study. Atherosclerosis 265:305-311|
|Lindemer, Emily R; Greve, Douglas N; Fischl, Bruce et al. (2017) Differential Regional Distribution of Juxtacortical White Matter Signal Abnormalities in Aging and Alzheimer's Disease. J Alzheimers Dis 57:293-303|
|Lubitz, Steven A; Yin, Xiaoyan; McManus, David D et al. (2017) Stroke as the Initial Manifestation of Atrial Fibrillation: The Framingham Heart Study. Stroke 48:490-492|
|Lin, Honghuang; Satizabal, Claudia; Xie, Zhijun et al. (2017) Whole blood gene expression and white matter Hyperintensities. Mol Neurodegener 12:67|
|Pase, Matthew P; Himali, Jayandra J; Beiser, Alexa S et al. (2017) Sugar- and Artificially Sweetened Beverages and the Risks of Incident Stroke and Dementia: A Prospective Cohort Study. Stroke 48:1139-1146|
|Desikan, Rahul S; Fan, Chun Chieh; Wang, Yunpeng et al. (2017) Genetic assessment of age-associated Alzheimer disease risk: Development and validation of a polygenic hazard score. PLoS Med 14:e1002258|
Showing the most recent 10 out of 323 publications