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Cognitive heterogeneity in those with high Alzheimer's Disease Risk

Award Number: R01AG062109
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/30/2018
PERIOD OF PERFORMANCE END DATE: 11/30/2028

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Cognitive heterogeneity in those with high Alzheimer's Disease Risk - PROJECT SUMMARY The insidious nature of Alzheimer’s disease (AD) spans decades and adds complexity to detect the disease earlier in its course. A significant consideration is that those identified as at risk for AD may not necessarily develop clinically expressed disease. Traditional methods for detecting behavioral indices associated with those with AD risk have relied mainly on cognitive changes characterized by neuropsychological (NP) test performances. But heterogeneity exists both within and across cognitive performance measures, suggesting that NP tests themselves are not sufficiently reliable in differentiating those at risk of progressing from preclinical to clinical AD versus those who do not. Thus, the primary objective of this renewal application is to develop a data-driven framework to better elucidate the cognitive heterogeneity associated with the earliest stages of AD, particularly at the preclinical (pre-symptomatic) and prodromal (mild cognitive impairment; MCI) stages. To meet this objective, we will profile the cognitive characteristics of persons with high risk AD (e.g., A+ and/or T+; amyloid / tau) from 1) plasma, 2) post-mortem tissue and 3) positron emission tomography (PET) scans to determine what cognitive profiles differentiate those who will and will not progress (e.g., asymptomatic [does not progress] versus pre-symptomatic [does progress]; MCI stable versus MCI progressors). Cognitive characterization will utilize standardized scores from NP tests and novel digital cognitive metrics. We will also evaluate whether the addition of neuroimaging measures as a biomarker of “N” (neurodegeneration) combined with cognitive metrics will increase high AD risk group differentiation. We will further leverage the richness of the Framingham Heart Study’s 7+ decades of demographic, clinical and other biomarker data to link cognitive signatures of those with high-risk AD at their symptomatic origins. As an attempt to tie our findings with the frameworks conducting population-level risk assessments, in an exploratory analysis, we will fuse information collected at the pre-symptomatic/MCI stages and develop multimodal data analytic approaches to predict those who are at high risk of developing the disease and compare our findings with traditional statistical methods. The scientific importance of outcomes from our approach is the potential contribution to the growing body of literature focused on precision identification of individuals who are at high disease risk and most likely to progress to clinically expressed disease, and thus on whom intervention is most likely to be warranted and effective.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $735,340 )
2026	2026	TRUSTEES OF BOSTON UNIVERSITY	85 EAST NEWTON ST # M-921	BOSTON	MA	02118	SUFFOLK	USA	Aging Research	000	3	11/25/2025	NON-COMPETING CONTINUATION	$735,340
														Subtotal = $735,340

Issue Date FY: 2025 ( Subtotal = $817,404 )
2025	2025	TRUSTEES OF BOSTON UNIVERSITY	85 EAST NEWTON ST # M-921	BOSTON	MA	02118	SUFFOLK	USA	Aging Research	000	2	11/26/2024	COMPETING CONTINUATION	$817,404
														Subtotal = $817,404

Grand Total All Awards = $1,552,744

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Cognitive heterogeneity in those with high Alzheimer's Disease Risk

Award Number: R01AG062109

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 09/30/2018

PERIOD OF PERFORMANCE END DATE: 11/30/2028

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