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COGNITIVE TRAINING AND NEUROPLASTICITY IN MILD COGNITIVE IMPAIRMENT

Award Number: R01AG052440
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/15/2017
PERIOD OF PERFORMANCE END DATE: 02/28/2029

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COGNITIVE TRAINING AND NEUROPLASTICITY IN MILD COGNITIVE IMPAIRMENT - Effective, clinically meaningful treatments are lacking for patients with mild cognitive impairment (MCI), which is associated with increased risk of transition to dementia. Cognitive training represents an important therapeutic strategy. In our recently completed two-site, blinded, COG-IT trial (R01AG052440, PI Devanand), 107 participants with MCI were randomized to web-based cognitive videogames (computerized cognitive training, n=51) or computerized crossword puzzles (n=56) for 12 weeks of intensive training followed by booster sessions for a total of 78 weeks. Crossword puzzles were superior to computerized cognitive training on the primary cognitive outcome (ADAS-Cog11; effect size 0.43 at 12 weeks and 0.34 at 78 weeks) and function (Functional Activities Questionnaire) with decreased brain atrophy on MRI over 78 weeks. Building on these findings, for this competitive renewal we propose a 78-week clinical trial, WORDFIT, involving 4 U.S. academic sites that compares high dose crosswords (4 puzzles per week) to low dose crosswords (1 puzzle per week) and a health education control group in the initial acute phase of 12 weeks. Subsequent booster sessions will occur up to 78 weeks. Blinded assessments will occur at baseline and weeks 12, 32, 52, and 78. Sample size will be 240 with 80 participants per group. Sites led by Dr. Devanand (PI) at Columbia and Dr. Doraiswamy at Duke, who were the investigators in the COG-IT trial, will be joined by sites at University of Miami (PI Dr. Philip Harvey) and University of Washington (PI Dr. Angela Hanson). On measures of cognition (primary outcome ADAS-Cog14) and informant report of function (secondary outcome Functional Activities Questionnaire), we hypothesize that the high dose crosswords will show superior efficacy to the control group and that there will be an increasing trend in treatment effects across the three ordered groups (control < low dose crosswords < high dose crosswords). We will evaluate changes in MRI hippocampal volume and cortical thickness in relation to changes in cognition and function and explore whether reduction in plasma neurofilament light (marker of neurodegeneration) and plasma ptau181 (marker of Alzheimer's Disease) will be associated with efficacy for high dose crosswords compared to control. In summary, in our completed COG-IT trial in MCI, home-based computerized crossword puzzles training showed superior efficacy to computerized cognitive training on cognition and function with decreased brain atrophy over 78 weeks, but there was no control group. If these findings are confirmed and expanded with two crossword conditions and a control group in WORDFIT, crosswords training could become a low-cost, home-based, scalable, cognitive enhancement tool for people with MCI, which is a common condition and major public health problem worldwide.


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 = $1,670,656 )
2025	2025	THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Aging Research	003	7	6/20/2025	NON-COMPETING CONTINUATION	$136,378
2025	2025	THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Aging Research	002	7	3/19/2025	NON-COMPETING CONTINUATION	$1,534,278
2025	2024	THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Aging Research	001	6	3/11/2025	COMPETING CONTINUATION	$6,452
2025	2021	THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Aging Research	000	5	3/11/2025	NON-COMPETING CONTINUATION	-$6,452
														Subtotal = $1,670,656

Issue Date FY: 2024 ( Subtotal = $1,813,346 )
2024	2024	THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Aging Research	001	6	2/29/2024	COMPETING CONTINUATION	$1,813,346
2024	2024	THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Aging Research	002	6	7/5/2024	COMPETING CONTINUATION	$0
2024	2021	THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Aging Research	000	5	2/21/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $1,813,346

Issue Date FY: 2023 ( Subtotal = $0 )
2023	2021	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK, THE	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Aging Research	000	5	3/2/2023	NON-COMPETING CONTINUATION	$0
2023	2021	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK, THE	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Aging Research	001	5	9/1/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2021 ( Subtotal = $880,337 )
2021	2021	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK, THE	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Aging Research	000	5	4/19/2021	NON-COMPETING CONTINUATION	$880,337
														Subtotal = $880,337

Issue Date FY: 2020 ( Subtotal = $922,625 )
2020	2020	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Aging Research	001	4	4/17/2020	NON-COMPETING CONTINUATION	$891,038
2020	2020	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Aging Research	000	3	4/13/2020	SUPPLEMENT FOR EXPANSION	$31,587
2020	2020	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Aging Research	002	3	4/27/2020	SUPPLEMENT FOR EXPANSION	$0
														Subtotal = $922,625

Issue Date FY: 2019 ( Subtotal = $739,075 )
2019	2019	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Aging Research	000	3	5/23/2019	NON-COMPETING CONTINUATION	$739,075
														Subtotal = $739,075

Issue Date FY: 2018 ( Subtotal = $749,559 )
2018	2018	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Aging Research	000	2	4/30/2018	NON-COMPETING CONTINUATION	$749,559
														Subtotal = $749,559

Issue Date FY: 2017 ( Subtotal = $781,608 )
2017	2017	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Aging Research	001	1	7/28/2017	NEW	-$59,556
2017	2017	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Aging Research	000	1	7/13/2017	NEW	$841,164
														Subtotal = $781,608

Grand Total All Awards = $7,557,206

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COGNITIVE TRAINING AND NEUROPLASTICITY IN MILD COGNITIVE IMPAIRMENT

Award Number: R01AG052440

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 07/15/2017

PERIOD OF PERFORMANCE END DATE: 02/28/2029

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