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CNS Deficits: Interaction of Age and Alcoholism

Award Number: R01AA005965
ORGANIZATION: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/01/1983
PERIOD OF PERFORMANCE END DATE: 04/30/2026

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CNS Deficits: Interaction of Age and Alcoholism - PROJECT SUMMARY / ABSTRACT Hazardous alcohol use has grown substantially in the aging population. It remains unknown whether Alcohol Use Disorder (AUD) and its alcohol-related cognitive and brain decline increases risk for diagnostic mild cognitive impairment (MCI) or even can result in classic irreversible dementia. Motivating the proposal are 1) our longitudinal findings of accelerated aging of selective brain structures in AUD; 2) results of an animal model of high alcohol exposure in old compared with young, well-nourished male and female rats; and 3) preliminary results from non-alcoholic individuals meeting MCI criteria compared with AUD with similar extent of cognitive deficits revealing different age-related patterns of brain degradation. The findings led us to consider factors of nutritional deficiency and cytokine dysregulation that occur in both AUD and MCI and have the potential to contribute to common and unique disruption, accelerated by aging, of selective brain circuitry and cognitive sequelae in each diagnosis. We will test 180 actively drinking men and women (60 AUD, 60 non-alcoholic MCI, and 60 age-matched controls) before and after 18-24 months with structural MRI and diffusion tensor imaging (DTI). Recognizing mnemonic compromise associated with AUD and MCI, primary hypotheses will target the integrity of nodes and connections of Papez (limbic) circuit; white matter integrity will be assessed with deterministic fiber tracking and node-to-node integrity with probabilistic fiber tracking. Causal modeling will test the influence of specific independent variables of alcohol, nutrition, age, and sex hypothesized to have direct effects on inflammation and thalamic-hippocampal or cingulate-entorhinal connectivity, which, in turn, exert mediating influences on episodic memory. In addition to quantification of alcohol use and nutritional and inflammatory markers, modifiable risk factors to be examined include smoking, licit and illicit drugs, obesity-BMI, blood pressure, and physical activity. The parallel animal study will focus on the interaction of alcohol binge exposure and nutritional challenge with graded levels of thiamine deficiency and resulting cytokine, brain structure and connectivity, and behavioral sequelae in rats. AIM 1: In cross-sectional study, model for each diagnosis the influence of independent variables (i.e., alcohol, nutrition, age, and sex) and hypothesized mediating factors (i.e., inflammation) affecting neurocircuitry substrates of episodic memory. AIM 2: In longitudinal study, use trajectory analysis to quantify interim change in targeted neurocircuitry as a function of age. Causal modeling will use longitudinal change data of the independent variables. AIM 3: In longitudinal study, determine whether nutritional (thiamine) deficits are sufficient to produce enduring MR-detectable responses to high blood alcohol levels in wild-type Wistar rats.


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 = $825,680 )
2025	2025	SRI INTERNATIONAL	333 RAVENSWOOD AVE	MENLO PARK	CA	94025	SAN MATEO	USA	Alcohol Research Programs	000	39	5/29/2025	NON-COMPETING CONTINUATION	$825,680
														Subtotal = $825,680

Issue Date FY: 2024 ( Subtotal = $833,707 )
2024	2024	SRI INTERNATIONAL	333 RAVENSWOOD AVE	MENLO PARK	CA	94025	SAN MATEO	USA	Alcohol Research Programs	000	38	5/10/2024	NON-COMPETING CONTINUATION	$833,707
														Subtotal = $833,707

Issue Date FY: 2023 ( Subtotal = $825,423 )
2023	2023	SRI INTERNATIONAL	333 RAVENSWOOD AVE	MENLO PARK	CA	94025	SAN MATEO	USA	Alcohol Research Programs	000	37	4/24/2023	NON-COMPETING CONTINUATION	$825,423
														Subtotal = $825,423

Issue Date FY: 2022 ( Subtotal = $812,395 )
2022	2022	SRI INTERNATIONAL	333 RAVENSWOOD AVE	MENLO PARK	CA	94025	SAN MATEO	USA	Alcohol Research Programs	001	36	5/10/2022	NON-COMPETING CONTINUATION	$812,395
2022	2019	SRI INTERNATIONAL	333 RAVENSWOOD AVE	MENLO PARK	CA	94025	SAN MATEO	USA	Alcohol Research Programs	000	34	3/8/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $812,395

Issue Date FY: 2021 ( Subtotal = $823,091 )
2021	2021	SRI INTERNATIONAL	333 RAVENSWOOD AVE	MENLO PARK	CA	94025	SAN MATEO	USA	Alcohol Research Programs	002	35	8/6/2021	COMPETING CONTINUATION	$823,091
2021	2019	SRI INTERNATIONAL	333 RAVENSWOOD AVE	MENLO PARK	CA	94025	SAN MATEO	USA	Alcohol Research Programs	000	34	3/11/2021	NON-COMPETING CONTINUATION	$0
2021	2019	SRI INTERNATIONAL	333 RAVENSWOOD AVE	MENLO PARK	CA	94025	SAN MATEO	USA	Alcohol Research Programs	001	34	8/6/2021	NON-COMPETING CONTINUATION	$0
														Subtotal = $823,091

Issue Date FY: 2019 ( Subtotal = $777,627 )
2019	2019	SRI INTERNATIONAL	333 RAVENSWOOD AVE	MENLO PARK	CA	94025	SAN MATEO	USA	Alcohol Research Programs	000	34	3/14/2019	NON-COMPETING CONTINUATION	$777,627
														Subtotal = $777,627

Issue Date FY: 2018 ( Subtotal = $1,209,464 )
2018	2018	SRI INTERNATIONAL	333 RAVENSWOOD AVE	MENLO PARK	CA	94025	SAN MATEO	USA	Alcohol Research Programs	001	33	5/30/2018	NON-COMPETING CONTINUATION	$77,618
2018	2018	SRI INTERNATIONAL	333 RAVENSWOOD AVE	MENLO PARK	CA	94025	SAN MATEO	USA	Alcohol Research Programs	000	33	3/26/2018	NON-COMPETING CONTINUATION	$698,563
2018	2018	SRI INTERNATIONAL	333 RAVENSWOOD AVE	MENLO PARK	CA	94025	SAN MATEO	USA	Alcohol Research Programs	002	33	9/17/2018	SUPPLEMENT FOR EXPANSION	$433,283
														Subtotal = $1,209,464

Issue Date FY: 2017 ( Subtotal = $775,862 )
2017	2017	SRI INTERNATIONAL	333 RAVENSWOOD AVE	MENLO PARK	CA	94025	SAN MATEO	USA	Alcohol Research Programs	000	32	3/23/2017	NON-COMPETING CONTINUATION	$698,277
2017	2017	SRI INTERNATIONAL	333 RAVENSWOOD AVE	MENLO PARK	CA	94025	SAN MATEO	USA	Alcohol Research Programs	001	32	7/19/2017	NON-COMPETING CONTINUATION	$77,585
														Subtotal = $775,862

Issue Date FY: 2016 ( Subtotal = $798,663 )
2016	2016	STANFORD RESEARCH INSTITUTE INTERNATIONAL	333 RAVENSWOOD AVENUE, AG139	MENLO PARK	CA	94025	SAN MATEO	USA	Alcohol Research Programs	000	31	3/25/2016	NON-COMPETING CONTINUATION	$779,052
2016	2016	STANFORD RESEARCH INSTITUTE INTERNATIONAL	333 RAVENSWOOD AVENUE, AG139	MENLO PARK	CA	94025	SAN MATEO	USA	Alcohol Research Programs	001	31	9/1/2016	SUPPLEMENT FOR EXPANSION	$19,611
														Subtotal = $798,663

Issue Date FY: 2015 ( Subtotal = $785,992 )
2015	2015	STANFORD RESEARCH INSTITUTE INTERNATIONAL	333 RAVENSWOOD AVENUE, AG139	MENLO PARK	CA	94025	SAN MATEO	USA	Alcohol Research Programs	000	30	3/30/2015	COMPETING CONTINUATION	$785,992
														Subtotal = $785,992

Issue Date FY: 2013 ( Subtotal = $0 )
2013	2011	STANFORD RESEARCH INSTITUTE INTERNATIONAL	333 RAVENSWOOD AVENUE, AG139	MENLO PARK	CA	94025	SAN MATEO	USA	Alcohol Research Programs	000	29	6/13/2013	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2011 ( Subtotal = $723,428 )
2011	2011	STANFORD RESEARCH INSTITUTE INTERNATIONAL	333 RAVENSWOOD AVENUE, AG139	MENLO PARK	CA	94025	SAN MATEO	USA	Alcohol Research Programs	000	29	7/8/2011	NON-COMPETING CONTINUATION	$723,428
														Subtotal = $723,428

Issue Date FY: 2010 ( Subtotal = $926,751 )
2010	2010	STANFORD RESEARCH INSTITUTE INTERNATIONAL	333 RAVENSWOOD AVENUE, AG139	MENLO PARK	CA	94025	SAN MATEO	USA	Alcohol Research Programs	001	28	6/23/2010	NON-COMPETING CONTINUATION	$878,720
2010	2010	STANFORD RESEARCH INSTITUTE INTERNATIONAL	333 RAVENSWOOD AVENUE, AG139	MENLO PARK	CA	94025	SAN MATEO	USA	Alcohol Research Programs	000	27	4/7/2010	SUPPLEMENT FOR EXPANSION	$48,031
														Subtotal = $926,751

Issue Date FY: 2009 ( Subtotal = $1,257,915 )
2009	2009	STANFORD RESEARCH INSTITUTE INTERNATIONAL	333 RAVENSWOOD AVENUE, AG139	MENLO PARK	CA	94025	SAN MATEO	USA	Alcohol Research Programs	000	27	6/30/2009	NON-COMPETING CONTINUATION	$859,553
2009	2009	STANFORD RESEARCH INSTITUTE INTERNATIONAL	333 RAVENSWOOD AVENUE, AG139	MENLO PARK	CA	94025	SAN MATEO	USA	Trans-NIH Recovery Act Research Support	001	27	7/16/2009	SUPPLEMENT FOR EXPANSION	$459,835
2009	2009	STANFORD RESEARCH INSTITUTE INTERNATIONAL	333 RAVENSWOOD AVENUE, AG139	MENLO PARK	CA	94025	SAN MATEO	USA	Trans-NIH Recovery Act Research Support	002	27	9/29/2009	SUPPLEMENT FOR EXPANSION	-$61,473
														Subtotal = $1,257,915

Issue Date FY: 2008 ( Subtotal = $933,291 )
2008	2008	STANFORD RESEARCH INSTITUTE INTERNATIONAL	333 RAVENSWOOD AVENUE, AG139	MENLO PARK	CA	94025	SAN MATEO	USA	Alcohol Research Programs	000	26	6/18/2008	NON-COMPETING CONTINUATION	$886,364
2008	2008	STANFORD RESEARCH INSTITUTE INTERNATIONAL	333 RAVENSWOOD AVENUE, AG139	MENLO PARK	CA	94025	SAN MATEO	USA	Alcohol Research Programs	001	25	4/11/2008	SUPPLEMENT FOR EXPANSION	$46,927
														Subtotal = $933,291

Issue Date FY: 2007 ( Subtotal = $701,557 )
2007	2007	STANFORD RESEARCH INSTITUTE INTERNATIONAL	333 RAVENSWOOD AVENUE, AG139	MENLO PARK	CA	94025	SAN MATEO	USA	Alcohol Research Programs	000	25	8/21/2007	COMPETING CONTINUATION	$701,557
														Subtotal = $701,557

Grand Total All Awards = $13,010,846

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CNS Deficits: Interaction of Age and Alcoholism

Award Number: R01AA005965

ORGANIZATION: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 07/01/1983

PERIOD OF PERFORMANCE END DATE: 04/30/2026

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