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Early detection & monitoring of memory decline in a representative sample of older adults at risk for Alzheimer's disease and related dementias

Award Number: R03AG089320
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/01/2024
PERIOD OF PERFORMANCE END DATE: 06/30/2026

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Early detection & monitoring of memory decline in a representative sample of older adults at risk for Alzheimer's disease and related dementias - Project Summary/Abstract Early detection and sensitive tracking of cognitive changes related to Alzheimer’s disease (AD) pathology (amyloid-Aβ and tau), particularly those that are scaleable to the large at-risk population of older adults, are urgently needed. Promising digital tools to measure cognitive changes must be validated in demographically diverse groups to ensure that research advancements are generalizable to those most at-risk for cognitive decline. Our recent work suggests that diminished learning over repeated evaluations (i.e., testing memory for the same content for 12min/day for 7 days) reveals subtle Aβ-related memory failures that are otherwise undetectable using single timepoint measures. More specifically, 29 Aβ+ clinically unimpaired (CU) older adults failed to improve at the same rate as their 97 Aβ- CU peers when asked to learn and recall identical content daily with this group difference emerging after ~3 days. We now seek to determine whether this Personal Learning Curve (PLC) paradigm can be used to detect early memory failures related to AD biomarkers in a larger and more diverse and representative sample and whether PLCs can sensitively track longitudinal cognitive decline when repeated bi-annually. We have the unique opportunity to recruit an extremely well-characterized and representative at-risk sample (i.e., 32% from URG, family history of cognitive decline, hypertension, geographic diversity, English and Spanish speaking) with AD biomarkers (global Aβ, temporal tau quantified via Positron Emission Tomography-PET) and annual cognitive testing. Recruited participants (n=300) will have completed the active phase of U.S. POINTER, a two-year clinical trial of two different multi-domain lifestyle interventions to protect brain health. We will explore whether a PLC, collected 12min/day for 7 days on personal devices, is a valid and sensitive marker of memory decline in this representative population and whether repeating a PLC every 6 months for 12 months will reveal AD-relevant longitudinal cognitive decline. In exploratory analyses, we will examine PLCs in relation to cardiovascular risk factors (e.g., systolic blood pressure, white matter hyperintensities via Magnetic Resonance (MR) Imaging) and non-specific markers of neurodegeneration (e.g., entorhinal tau, hippocampal atrophy). If successful, this proposal will provide a rapidly obtainable, repeatable, high-resolution snapshot of clinically relevant memory failures to facilitate early detection of cognitive decline as well as provide a novel method to assess treatment response more rapidly. Doing so in a representative population will ensure that the most promising novel and accessible digital cognitive tools are generalizable to the broader at-risk population.


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: 2024 ( Subtotal = $353,391 )
2024	2024	BRIGHAM & WOMENS HOSPITAL INC	75 FRANCIS ST	BOSTON	MA	02115	SUFFOLK	USA	Aging Research	000	1	8/26/2024	NEW	$353,391
														Subtotal = $353,391

Grand Total All Awards = $353,391

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Early detection & monitoring of memory decline in a representative sample of older adults at risk for Alzheimer's disease and related dementias

Award Number: R03AG089320

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/01/2024

PERIOD OF PERFORMANCE END DATE: 06/30/2026

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