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Clinical Pathological Study of Cognitive Impairment in Essential Tremor

Award Number: R01NS086736
ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 06/01/2014
PERIOD OF PERFORMANCE END DATE: 05/31/2025

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Clinical Pathological Study of Cognitive Impairment in Essential Tremor - Essential tremor (ET) is among the most prevalent neurological diseases. Although it was long considered a purely motor disorder, ET is increasingly being regarded as more complex, with an emerging recognition of cognitive dysfunction. While cognitive deficits can be mild, other patients dement. Several epidemiological studies reveal a higher prevalence of mild cognitive impairment (MCI) and 1.5 to 2-fold increased risk of Alzheimer's disease (AD) in ET. Yet the study of cognition/dementia in ET is nascent. Our data are limited and patchy - the most basic “whats” (i.e., clinical features, clinical course) and “whys” (i.e., postmortem basis) are uncharted. In sum, there is a cognitive side to ET, and we know little about it. For the past 4 years, we have established and begun to follow an ET cohort to address several of these unknowns (Clinical-Pathological Study of Cognitive Impairment in ET, COGNET). COGNET is the largest (230 enrolled; 195 living), most comprehensive, and only active prospective cohort of ET patients. Key elements are detailed, motor-free, longitudinal cognitive testing, consensus cognitive diagnoses (normal cognition [NC], MCI, dementia), and autopsy data. The study called for a baseline and two follow-up assessments. Currently, mean follow-up from baseline is only 1.50 ± 0.21 years (range = 0.31 - 2.29). Thirty-five died. The data have allowed us to begin to characterize the cognitive deficits in ET and study their pathological bases. Yet, there remain large, obvious gaps in knowledge. First, clinically, are the cognitive impairments in ET progressive? Do they progress at a faster rate than in the general population? What are the conversion rates to MCI and dementia? What are the clinical predictors of cognitive decline? Are cognitive deficits characteristic of AD predictive of worse clinical outcomes? It turns out that we know virtually nothing about the predictors, course and outcomes of cognitive impairments in ET, and such information cannot simply be taken from the general population. With a cohort now successfully assembled and longitudinal cognitive phenotyping ongoing, COGNET is poised to tackle important prognostic issues regarding the predictors and dynamics of cognitive deficits in ET (Aim 1). Second, pathologically, what is the basis for cognitive deficits in ET? Our studies point to heterogeneous deficits with heterogeneous bases, including AD pathologies. We only have 35 postmortems, and our nascent study of the pathological basis for cognitive deficits must grow and come to maturity (Aim 2). We now propose to continue this cohort, adding new measures to characterize the predictors and outcomes of cognitive impairments in ET. We propose enrolling 100 additional ET cases (proposed total n = 295). AIM 1. To provide the first long-term prospective, longitudinal characterization of cognition in ET to address unanswered prognostic questions about cognitive impairment in ET (e.g., conversion rates to MCI and dementia). AIM 2. To finalize our clinicopatho- logical study of ET by comparing the neuropathological features of 100 ET to 300 matched non-ET cases, and identifying the cognitive predictors of specific neuropathologies, particularly AD and other tauopathies.


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 = $0 )
2024	2023	THE UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER	5323 HARRY HINES BLVD	DALLAS	TX	75390	DALLAS	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	11	7/11/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $1,026,412 )
2023	2023	UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER, THE	5323 HARRY HINES BLVD	DALLAS	TX	75390	DALLAS	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	11	6/15/2023	NON-COMPETING CONTINUATION	$1,026,412
2023	2022	UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER, THE	5323 HARRY HINES BLVD	DALLAS	TX	75390	DALLAS	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	10	10/26/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $1,026,412

Issue Date FY: 2022 ( Subtotal = $1,026,424 )
2022	2022	UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER, THE	5323 HARRY HINES BLVD	DALLAS	TX	75390	DALLAS	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	10	7/25/2022	NON-COMPETING CONTINUATION	$1,026,424
														Subtotal = $1,026,424

Issue Date FY: 2021 ( Subtotal = $1,026,260 )
2021	2021	UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER, THE	5323 HARRY HINES BLVD	DALLAS	TX	75390	DALLAS	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	004	9	5/20/2021	NON-COMPETING CONTINUATION	$1,026,260
2021	2020	UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER, THE	5323 HARRY HINES BLVD	DALLAS	TX	75390	DALLAS	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	003	8	3/3/2021	NON-COMPETING CONTINUATION	$0
2021	2019	UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER, THE	5323 HARRY HINES BLVD	DALLAS	TX	75390	DALLAS	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	7	2/26/2021	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$65,339
2021	2019	YALE UNIVERSITY	105 WALL ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	6	2/26/2021	COMPETING CONTINUATION	-$65,339
2021	2019	UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER, THE	5323 HARRY HINES BLVD	DALLAS	TX	75390	DALLAS	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	7	3/3/2021	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
														Subtotal = $1,026,260

Issue Date FY: 2020 ( Subtotal = $1,045,915 )
2020	2020	UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER, THE	5323 HARRY HINES BLVD	DALLAS	TX	75390	DALLAS	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	004	8	8/27/2020	NON-COMPETING CONTINUATION	$1,045,915
2020	2019	YALE UNIVERSITY	105 WALL ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	6	2/16/2020	COMPETING CONTINUATION	$120,932
2020	2019	YALE UNIVERSITY	105 WALL ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	003	6	8/18/2020	COMPETING CONTINUATION	-$765,459
2020	2019	UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER, THE	5323 HARRY HINES BLVD	DALLAS	TX	75390	DALLAS	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	7	8/17/2020	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$765,459
2020	2018	YALE UNIVERSITY	105 WALL ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	5	2/16/2020	NON-COMPETING CONTINUATION	-$120,932
														Subtotal = $1,045,915

Issue Date FY: 2019 ( Subtotal = $1,114,066 )
2019	2019	YALE UNIVERSITY	105 WALL ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	6	8/23/2019	COMPETING CONTINUATION	$1,114,066
2019	2018	YALE UNIVERSITY	105 WALL ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	5	8/28/2019	NON-COMPETING CONTINUATION	$0
														Subtotal = $1,114,066

Issue Date FY: 2018 ( Subtotal = $553,575 )
2018	2018	YALE UNIVERSITY	105 WALL ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	5	5/4/2018	NON-COMPETING CONTINUATION	$553,575
														Subtotal = $553,575

Issue Date FY: 2017 ( Subtotal = $556,843 )
2017	2017	YALE UNIVERSITY	105 WALL ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	4	5/25/2017	NON-COMPETING CONTINUATION	$55,685
2017	2017	YALE UNIVERSITY	105 WALL ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	4	5/12/2017	NON-COMPETING CONTINUATION	$501,158
														Subtotal = $556,843

Issue Date FY: 2016 ( Subtotal = $458,090 )
2016	2016	YALE UNIVERSITY	47 College Street	NEW HAVEN	CT	06520	SOUTH CENTRAL CT	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	3	5/19/2016	NON-COMPETING CONTINUATION	$560,824
2016	2015	YALE UNIVERSITY	47 College Street	NEW HAVEN	CT	06520	SOUTH CENTRAL CT	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	1/27/2016	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	-$102,734
														Subtotal = $458,090

Issue Date FY: 2015 ( Subtotal = $664,519 )
2015	2015	YALE UNIVERSITY	47 College Street	NEW HAVEN	CT	06520	SOUTH CENTRAL CT	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	9/24/2015	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$664,519
														Subtotal = $664,519

Issue Date FY: 2014 ( Subtotal = $664,896 )
2014	2014	COLUMBIA UNIVERSITY	615 WEST 131ST ST, 4TH FLOOR	NEW YORK	NY	10027	NEW YORK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	5/15/2014	NEW	$664,896
														Subtotal = $664,896

Grand Total All Awards = $8,137,000

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Clinical Pathological Study of Cognitive Impairment in Essential Tremor

Award Number: R01NS086736

ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 06/01/2014

PERIOD OF PERFORMANCE END DATE: 05/31/2025

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