The proposed renewal application, entitled MRI, Cognitive, Genetic and Biomarker Precursors of AD & Dementia in Young Adults seeks to extend the study of preclinical dementia to a community-based sample of younger aged adults decades before possible onset of clinical symptoms. In the previous grant cycle, the Framingham Heart Study Generation 3 and its smaller multi-ethnic Omni Generation 2 cohorts were administered a neuropsychological test battery (NP; n=2498) and a brain MRI scan (n=2279). These cohorts had been previously characterized in detail through their participation in two health examinations, administered between 2002-2009, in which numerous lifestyle, genetic and circulating biomarkers have been measured. By proposing a repeat administration of the NP and MRI protocols we will establish the first population cohort able to estimate the heterogeneity of change in detectable differences in cognitive performance and brain structure. To meet this primary aim of earlier detection, we have incorporated novel cognitive indices that include error responses and latency metrics acquired through participant use of a digital pen and predict that for persons in whom change is evident, we will observe at least three distinct cognitive phenotypes - amnestic, executive function, and mixed, based on traditional and novel neuropsychological test performance measures. For detecting MRI changes, we will not only evaluate longitudinal measures but also construct a measure of brain structural health based on combined measures of white matter hyperintensities, gray matter regional volumes, cortical thickness and fractional anisotropy measures in specified regions. Another central aim of this proposal is to determine whether early vascular risk and other health measures, genetic factors and newer biomarkers are predictive of incident decline in cognition and brain morphology previously linked to increased risk of AD. Finally, we will test novel computational analytic methods to construct multi-marker preclinical risk scores predictive of cognitive and neuroimaging changes. Dementia is not an inevitable consequence of brain aging and determining the earliest age in which brain aging is detectable and the risk factors related to these early signs of change may lead to new pathways for intervention and prevention.
The proposed application seeks to document the detectable longitudinal changes in cognitive function and brain structure in a younger adult community based sample. This study will capitalize on already available health, genetic and biomarker measures to identify those that are predictive of cognitive decline and brain atrophy, which may be indicators of future risk for dementia. Results may inform strategies for risk reduction and disease prevention.
|Seiler, Stephan; Fletcher, Evan; Hassan-Ali, Kinsy et al. (2018) Cerebral tract integrity relates to white matter hyperintensities, cortex volume, and cognition. Neurobiol Aging 72:14-22|
|Nishtala, Arvind; Piers, Ryan J; Himali, Jayandra J et al. (2018) Atrial fibrillation and cognitive decline in the Framingham Heart Study. Heart Rhythm 15:166-172|
|Bangen, Katherine J; Preis, Sarah R; Delano-Wood, Lisa et al. (2018) Baseline White Matter Hyperintensities and Hippocampal Volume are Associated With Conversion From Normal Cognition to Mild Cognitive Impairment in the Framingham Offspring Study. Alzheimer Dis Assoc Disord 32:50-56|
|Tynkkynen, Juho; Chouraki, Vincent; van der Lee, Sven J et al. (2018) Association of branched-chain amino acids and other circulating metabolites with risk of incident dementia and Alzheimer's disease: A prospective study in eight cohorts. Alzheimers Dement 14:723-733|
|Li, Jinlei; Ogrodnik, Matthew; Devine, Sherral et al. (2018) Practical risk score for 5-, 10-, and 20-year prediction of dementia in elderly persons: Framingham Heart Study. Alzheimers Dement 14:35-42|
|Adams, Shayna; Conner, Sarah; Himali, Jayandra J et al. (2018) Vascular risk factor burden and new-onset depression in the community. Prev Med 111:348-350|
|Weinstein, Galit; Preis, Sarah R; Beiser, Alexa S et al. (2017) Clinical and Environmental Correlates of Serum BDNF: A Descriptive Study with Plausible Implications for AD Research. Curr Alzheimer Res 14:722-730|
|Pase, Matthew P; Seshadri, Sudha; Jacques, Paul F (2017) Response by Pase et al to Letter Regarding Article, ""Sugar- and Artificially Sweetened Beverages and the Risks of Incident Stroke and Dementia: A Prospective Cohort Study"". Stroke 48:e181|
|Neu, Scott C; Pa, Judy; Kukull, Walter et al. (2017) Apolipoprotein E Genotype and Sex Risk Factors for Alzheimer Disease: A Meta-analysis. JAMA Neurol 74:1178-1189|
|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|
Showing the most recent 10 out of 48 publications