A major challenge in the field of aging and dementia is the inability to predict asymptomatic individuals who will develop dementia and, in particular, Alzheimer's disease. Abnormal brain changes precede clinical cognitive changes by 10 to 20 years providing a window of opportunity to prevent dementia. The National Institute on Aging and the Alzheimer's Association published guidelines to characterize the pre-clinical and mild cognitive impairment (MCI) stages of Alzheimer's disease, placing a major emphasis on biomarkers. However, we have limited information on the prevalence of biomarkers at the population-level in mid-life and late- life, and on their ability to predict cognitive outcomes. In addition, the assessment of abnormal brain changes in asymptomatic individuals using imaging biomarkers may not be a cost-effective screening approach for secondary prevention and may not be applicable to all persons. The few risk scores that have been proposed thus far to predict dementia do not assess the risk of MCI and do not consider biomarker abnormalities. The broad, long-term goal of this renewal application is to develop tools to predict and prevent cognitive decline and dementia. To accomplish this goal we propose 4 specific aims: 1) To estimate the prevalence of neuroimaging biomarkers such as brain amyloid accumulation, neurodegenerative pathology, and vascular pathology in a defined population;2) To prospectively examine the association of these imaging biomarkers with cognitive outcomes;3) To develop risk scores to predict biomarkers and cognitive outcomes;and 4) To provide data and materials for related projects. To successfully address these gaps in knowledge and to accomplish our study goal, this project will capitalize on 2 unique and established resources available in the Olmsted County, MN population. The population-based and prospective Mayo Clinic Study of Aging has enrolled nearly 4,000 participants to date;of whom over 1,000 have extensive neuroimaging biomarkers of amyloid deposition and neurodegeneration. The Rochester Epidemiology Project medical records-linkage system is used to recruit population-based samples, to identify demographics and clinical risk factors, to study cognitive outcomes for subjects who could not be studied face-to-face, and to compute weights to adjust for non-participation. At the completion of this project, we will have estimated the population-based prevalence of neuroimaging biomarkers, determined their predictive value for cognitive outcomes, developed a risk score to predict imaging biomarkers, and determined the added predictive value of a risk score that includes neuroimaging biomarkers. These findings will provide critical information for public health planning, endpoints for therapeutic trials, and cost effective tools for the early detection of brain abnormalities and cognitive outcomes.
Currently, it is impossible to identify persons who will develop problems with memory and thinking when they get older, and in those who develop Alzheimer's disease, there is no cure. The Mayo Clinic Study of Aging will develop ways to predict problems with memory and thinking many years before they manifest, so that people at higher risk can receive appropriate intervention. Our findings are essential for health care planning, and may help reduce the cost of dementia in the US.
|Roberts, Rosebud O; Knopman, David S; Przybelski, Scott A et al. (2014) Association of type 2 diabetes with brain atrophy and cognitive impairment. Neurology 82:1132-41|
|Rocca, Walter A; Mielke, Michelle M; Vemuri, Prashanthi et al. (2014) Sex and gender differences in the causes of dementia: a narrative review. Maturitas 79:196-201|
|van Blitterswijk, Marka; Mullen, Bianca; Wojtas, Aleksandra et al. (2014) Genetic modifiers in carriers of repeat expansions in the C9ORF72 gene. Mol Neurodegener 9:38|
|Mielke, Michelle M; Weigand, Stephen D; Wiste, Heather J et al. (2014) Independent comparison of CogState computerized testing and a standard cognitive battery with neuroimaging. Alzheimers Dement 10:779-89|
|Gusareva, Elena S; Carrasquillo, Minerva M; Bellenguez, Céline et al. (2014) Genome-wide association interaction analysis for Alzheimer's disease. Neurobiol Aging 35:2436-43|
|Vemuri, Prashanthi; Lesnick, Timothy G; Przybelski, Scott A et al. (2014) Association of lifetime intellectual enrichment with cognitive decline in the older population. JAMA Neurol 71:1017-24|
|Jack Jr, Clifford R; Wiste, Heather J; Weigand, Stephen D et al. (2014) Age-specific population frequencies of cerebral ?-amyloidosis and neurodegeneration among people with normal cognitive function aged 50-89 years: a cross-sectional study. Lancet Neurol 13:997-1005|
|Roberts, Rosebud O; Boardman, Lisa A; Cha, Ruth H et al. (2014) Short and long telomeres increase risk of amnestic mild cognitive impairment. Mech Ageing Dev 141-142:64-9|
|Knopman, David S; Jack Jr, Clifford R; Wiste, Heather J et al. (2014) 18F-fluorodeoxyglucose positron emission tomography, aging, and apolipoprotein E genotype in cognitively normal persons. Neurobiol Aging 35:2096-106|
|Broski, Stephen M; Hunt, Christopher H; Johnson, Geoffrey B et al. (2014) Structural and functional imaging in parkinsonian syndromes. Radiographics 34:1273-92|
Showing the most recent 10 out of 378 publications