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The spectrum of cognitive impairment including Alzheimer’s Disease and Related Dementias after liver transplantation

Award Number: R01AG059183
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 06/15/2018
PERIOD OF PERFORMANCE END DATE: 05/31/2028

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The spectrum of cognitive impairment including Alzheimer’s Disease and Related Dementias after liver transplantation - PROJECT SUMMARY Our highly successful multi-center Functional Assessment in Liver Transplantation (FrAILT) Study, funded by the NIH since 2013, has definitively characterized physical frailty in patients with cirrhosis undergoing liver transplantation (LT) and provided the foundation to codify physical frailty assessment through national guidelines for cirrhosis/LT patient management. As we closed the knowledge gap around physical frailty, we identified a new gap in LT patients—cognitive “frailty”, or more precisely, the manifestation of cognitive impairment. In 2 pilot studies, we found that 30-60% of LT recipients met criteria for cognitive impairment. Yet, currently, the spectrum of post-LT cognitive impairment—from subtle attentional changes to Alzheimer’s Disease and Related Dementias (ADRD)—is not well characterized. As a result, clinicians do not screen for cognitive impairment in the post-LT setting, and LT patients are not referred to specialists for timely diagnosis/management. In this competing renewal, we will leverage our multi-center FrAILT Study to address this unmet need. We hypothesize that LT patients experience premature cognitive syndromes, including ADRD, after LT (relative to the general population), that cognitive impairment impacts post-LT global functional health, and that physical frailty is a major predictor of post-LT cognitive impairment. There is strong scientific premise for these hypotheses, as many risk factors for cirrhosis are linked with cognitive impairment. These include common ADRD comorbidities (e.g., diabetes, hypertension), heavy alcohol use, hepatic encephalopathy, post-LT delirium, and immunosuppression. Physical frailty itself, prevalent in LT patients, shares common pathways with ADRD. The scientific goal of this competing renewal is to deeply characterize the spectrum of cognitive impairment including ADRD in post-LT patients. To accomplish this, we will extend the FrAILT Study at 6 U.S. sites and expand our assessment protocol with neurocognitive screening in ~2,000 post-LT FrAILT patients. Additionally, we will establish new “neuro- hepatology” collaborations with 5 of our sites’ AD Research Centers (ADRC) to conduct deep cognitive profiling—through comprehensive neurocognitive assessments and brain imaging—in 150 post-LT patients who display cognitive impairment. Specifically, we aim to: 1) Characterize the prevalence/incidence of and identify factors associated with post-LT cognitive impairment and evaluate its association with post-LT global functional health; 2) Characterize trajectories of cognitive function in the first year post-LT; 3) conduct deep cognitive profiling to differentiate among the etiologies of dementia. Our established multi-center FrAILT Study is uniquely poised to address this enormous unmet need for deep characterization of cognitive impairment in LT patients who have a high burden of conventional ADRD risks but have traditionally been excluded from ADRD studies. Further, we will develop a novel cohort with rich cognitive data that may yield novel insights into liver- and transplant-related contributors to ADRD in other (general, solid organ transplant) populations.


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: 2025 ( Subtotal = $1,449,283 )
2025	2025	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94103	SAN FRANCISCO	USA	Aging Research	002	8	6/12/2025	NON-COMPETING CONTINUATION	$118,308
2025	2025	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94103	SAN FRANCISCO	USA	Aging Research	001	8	4/18/2025	NON-COMPETING CONTINUATION	$1,330,975
2025	2022	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94103	SAN FRANCISCO	USA	Aging Research	000	5	3/20/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $1,449,283

Issue Date FY: 2024 ( Subtotal = $1,471,072 )
2024	2024	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94103	SAN FRANCISCO	USA	Aging Research	000	7	7/22/2024	NON-COMPETING CONTINUATION	$1,471,072
														Subtotal = $1,471,072

Issue Date FY: 2023 ( Subtotal = $1,377,684 )
2023	2023	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Aging Research	001	6	8/30/2023	COMPETING CONTINUATION	$1,377,684
2023	2022	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Aging Research	000	5	8/19/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $1,377,684

Issue Date FY: 2022 ( Subtotal = $662,776 )
2022	2022	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Aging Research	000	5	8/26/2022	NON-COMPETING CONTINUATION	$662,776
														Subtotal = $662,776

Issue Date FY: 2021 ( Subtotal = $1,369,990 )
2021	2021	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Aging Research	001	4	7/2/2021	NON-COMPETING CONTINUATION	$667,233
2021	2021	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Aging Research	002	4	8/19/2021	SUPPLEMENT FOR EXPANSION	$301,110
2021	2021	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Aging Research	000	3	4/5/2021	SUPPLEMENT FOR EXPANSION	$401,647
														Subtotal = $1,369,990

Issue Date FY: 2020 ( Subtotal = $676,976 )
2020	2020	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Aging Research	000	3	7/22/2020	NON-COMPETING CONTINUATION	$676,976
														Subtotal = $676,976

Issue Date FY: 2019 ( Subtotal = $682,697 )
2019	2019	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Aging Research	000	2	7/18/2019	NON-COMPETING CONTINUATION	$682,697
														Subtotal = $682,697

Issue Date FY: 2018 ( Subtotal = $744,993 )
2018	2018	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Aging Research	001	1	8/30/2018	NEW	$31,437
2018	2018	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 420	SAN FRANCISCO	CA	94103	SAN FRANCISCO	USA	Aging Research	000	1	6/13/2018	NEW	$713,556
														Subtotal = $744,993

Grand Total All Awards = $8,435,471

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The spectrum of cognitive impairment including Alzheimer’s Disease and Related Dementias after liver transplantation

Award Number: R01AG059183

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 06/15/2018

PERIOD OF PERFORMANCE END DATE: 05/31/2028

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