Unraveling the earliest phases of vascular cognitive impairment and dementia using cadasil – a monogenic form of small vessel cerebrovascular disease

Ended Project Grant Awarded Last action

Award ID
RF1AG074608
Recipient
Awarding agency
Obligated
$62,304,220

Award facts

Assistance listing
93.866 Aging Research
Completion date
Originally
Funding
  • $49,737,510.00 Federal
  • $12,566,710.00 Non-federal
Place of performance
Madison, WI 53715, USA

Award details come from USAspending.gov.

Description

As the agency reported it.

Abstract
The project addresses vascular contributions to cognitive impairment and dementia (vcid) using a design that exploits the enrollment of persons with the autosomal dominant gene for cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (cadasil). Exploration of vcid by focusing on the rare heritable monogenic disorder, cadasil, will advance knowledge of the full spectrum of vascular dementia from presymptomatic gene carriers through dementia and will facilitate an examination of mixed dementia in cadasil participants also having ad. This research is novel from any other in its efforts to study a single-gene vascular dementia group throughout the life span in an effort to reduce vascular dementia heterogeneities selecting persons enriched for certain future vascular disease secondary to NOTCH3 gene mutation. Cadasil is caused by a mutation in the gene NOTCH3, which encodes a receptor protein. Although rare, cadasil is the most common heritable cause (due to a single gene mutation) of vascular dementia. Many consider cadasil to be a good single gene model of small vessel disease and vascular dementia. By improving our understanding of cadasil and its progression, we will be better able to understand vcid as well as mixed dementias having both cadasil and the most common sporadic dementia, alzheimer's disease. This is particularly important because of the fact that many cases of alzheimer's disease have CO- occurring vascular dementia. More than 200 genetic variations in NOTCH3 have been identified, but IT is not known which cause milder, or more severe, forms of vcid. Furthermore, among the NOTCH3 mutations known to cause cadasil, and even within cadasil families, there is wide variability in age at onset, disease progression, brain imaging abnormalities and presentation of symptoms. Some recent data reported by the cadasil european consortium suggests that patients with mutations in certain parts of NOTCH3 cause a more severe form of cadasil than do mutations in other parts of the gene. IT's also likely that variations in other genes influence the effect of NOTCH3 mutations on vcid. Unfortunately, no large cohort of cadasil patients for clinical research has been organized in north america. Better understanding of the associations between clinical presentation, potential disease modifiers (i.e., risk factors) and NOTCH3, as well as other gene variations in a new cohort in the united states could improve understanding of the causes and severity contributions to various forms of small-vessel disease and vascular dementia. To accomplish this, we will recruit, characterize and follow longitudinally a cohort of 400 NOTCH3 variant/mutation carriers, plus 100 non- carriers as controls, from U.S. Cadasil families. Participants will be evaluated every 18 months with detailed neurological, cognitive, behavioral, functional, blood, genetic and brain MRI assessments. This study will provide critical information regarding cadasil that will also advance understanding for the most common type of mixed dementias (VIZ., vcid and ad).

Transactions

Action Federal Non-federal Date
Amendment $0 $0
Amendment $0 $0
Amendment $0 $0
Amendment $7,360,030 $0
Amendment $7,360,030 $0
Amendment $7,360,030 $0
Amendment $0 $0
Amendment $0 $0
Amendment $0 $0
Amendment $1,262,000 $0
Amendment $1,262,000 $0
Amendment $0 $0
Amendment $0 $0
Amendment $0 $0
Amendment $0 $0
Amendment $0 $0
Amendment $0 $0
Amendment $12,566,710 $0
Original award $12,566,710 $12,566,710
Show all 19

Subawards

Subrecipient Amount Awarded
Loyola University Of Chicago Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) is the most common form of hereditary vascular dementia.… $127,218
University Of Washington Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) is the most common form of hereditary vascular dementia.… $91,831
The Regents Of The University Of California. San Francisco Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) is the most common form of hereditary vascular dementia.… $78,168
Trustees Of Indiana University $163,707
University Of Texas Health Science Center At Houston $323,581
Georgia State University Research Foundation Inc. $544,307
Butler Hospital Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) is the most common form of hereditary vascular dementia.… $156,220
Butler Hospital Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) is the most common form of hereditary vascular dementia.… $60,661
University Of Utah Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) is the most common form of hereditary vascular dementia.… $74,790
Oregon Health & Science University $50,521
The Regents Of The University Of California. San Francisco $30,766
The Trustees Of Columbia University In The City Of New York $59,541
Emory University $44,720
Georgia State University Research Foundation Inc. Aim 1: To characterize the initial presentation and course of clinical, neuroimaging, and fluid markers of CADASIL participants and compare them with… $526,910
The Regents Of The University Of California. San Francisco Aim 1: To characterize the initial presentation and course of clinical, neuroimaging, and fluid markers of CADASIL participants and compare them with… $295,376
Butler Hospital Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) is the most common form of hereditary vascular dementia.… $53,992
Georgia State University Research Foundation Inc. Aim 1: To characterize the initial presentation and course of clinical, neuroimaging, and fluid markers of CADASIL participants and compare them with… $796,550
University Of California, LOS Angeles $57,824
University Of Utah Under oversight of a centralized IRB, sites will be enrolling participants with CADASIL, a form of vascular dementia. Patients will have 3 visits over the… $65,153
University Of Texas Health Science Center At Houston Funds are provided for year 1 of a 5-year research project. The PI Fornage and her team agree to work with the CADASIL Consortium to complete the Aims and… $18,160
The Regents Of The University Of Colorado Under oversight of a centralized IRB, sites will be enrolling participants with CADASIL, a form of vascular dementia. Patients will have 3 visits over the… $66,873
Trustees Of Indiana University The NINDS biorepository / BioSEND (estimated at $804,000 total years 1-5) with annually-collected participant samples stored over 5 years) will conduct… $536,354
Loyola University Of Chicago Aim 1: To characterize the initial presentation and course of clinical, neuroimaging, and fluid markers of CADASIL participants and compare them with… $304,696
Butler Hospital Dr. Salloway will collaborate with Dr. Jane Paulsen at the University of Wisconsin Madison and Dr. Michael Geschwind at the University of California, San… $555,220
Show all 24

Quick answers

Who received award RF1AG074608?

RF1AG074608 was awarded to University Of Wisconsin System by National Institute on Aging (National Institutes of Health) on September 30, 2021.

How much is award RF1AG074608 worth?

$62,304,220 has been obligated on RF1AG074608: $49,737,510 in federal funding and $12,566,710 in non-federal funding.

On GovTribe

See this award's full record

  • Every transaction and subaward
  • The recipient's other awards and teaming partners
  • Similar grant awards
  • Ask GovTribe AI about this award
Try for free Login