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Towards Generating a Multimodal and Multivariate Classification Model from Imaging and Non-Imaging Measures for Accurate Diagnosis and Monitoring of Dementia in Parkinsons disease

Award Number: R01NS117547
ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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PROJECT SUMMARY The goal of the proposed research is to identify the best predictive biomarkers of dementia in Parkinson’s disease (PDD) through a multimodal and multivariate statistical model utilizing both neuroimaging derived measures (diffusion-weighted MRI (dMRI), resting-state functional MRI (rsfMRI), and T1-weighted MRI measures) and non- imaging measures such as demographics (age, sex, years of education), clinical (disease duration and severity), genetics (LRRK2), and CSF-measures (Total Tau, β-Amyloid, α-synuclein). It is critical to identify biomarkers that can predict dementia in Parkinson’s disease (PD) as approximately 50-80% of PD patients develop PDD within twelve years of diagnosis. Identifying pathophysiology-based biomarkers that could identify PD patients at high risk for PDD reliably is critical for better prognostication, correct identification of PDD in its prodromal stage to recruit in new disease-modifying clinical trials, and better understanding the pathophysiological processes underlining PDD. The proposed project has two important components. The first component of the project is to understand the pathophysiological mechanism underlying PDD through sophisticated voxelwise dMRI-derived measures estimated using a multi-shell high angular and spatial resolution dMRI data acquisition, and understanding network-level white matter (WM)-derived structural connectivity and rsfMRI-derived functional connectivity in PDD. The second component of the project is to identify the biomarkers that predict PDD through multivariate statistical modelling by combining these sophisticated pathologically relevant neuroimaging measures with non-imaging measures (such as clinical, demographics, genetics, and CSF-measures). We will recruit demographically matched healthy controls (HC) along with demographically, disease duration, and disease severity matched PD patients with mild cognitive impairment (PD-MCI), PD-non-MCI (PD-nMCI), and PDD for this project. We will acquire multi-shell dMRI data at three b-values, namely 500s/mm2, 1000s/mm2, and 2500s/mm2 with a high angular and spatial resolution and estimate various unbiased free-water (fiso) corrected Gaussian dMRI-derived measures along with non-Gaussian dMRI-derived measures such as diffusion kurtosis measures, and neurite orientation dispersion and density imaging measures. We will further compare these measures between the groups to identify significant dMRI-derived measures separating the groups, and understanding the neuroanatomical correlates of these measures with various neuropsychological scores. Furthermore, we will estimate dMRI-derived structural connectivity and rsfMRI-derived functional connectivity to understand network-level discrepancies predicting PDD. These pathologically relevant neuroimaging measures will be further combined with various non-imaging measures through a novel machine learning algorithm to identify the comprehensive and best predictors of PDD. The tools developed in our proposal also has great potential for significantly advancing the understanding of other neurodegenerative disorders such as Alzheimer’s disease (AD) thereby helping to understand AD- and PD-specific neuroanatomical changes predicting dementia.


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 = $681,430 )
2024	2024	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH STREET	BIRMINGHAM	AL	35294	JEFFERSON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	6	6/26/2024	NON-COMPETING CONTINUATION	$681,430
														Subtotal = $681,430

Issue Date FY: 2023 ( Subtotal = $649,253 )
2023	2023	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	005	5	7/17/2023	NON-COMPETING CONTINUATION	$680,270
2023	2022	CLEVELAND CLINIC LERNER COLLEGE OF MEDICINE OF CASE WESTERN RESERVE UNIVERSITY	9500 EUCLID AVE.	CLEVELAND	OH	44195	CUYAHOGA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	003	3	7/10/2023	NON-COMPETING CONTINUATION	-$200,541
2023	2022	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	4	6/26/2023	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$519,977
2023	2022	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH STREET	BIRMINGHAM	AL	35294	JEFFERSON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	004	4	7/10/2023	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$774,253
2023	2022	CLEVELAND CLINIC LERNER COLLEGE OF MEDICINE OF CASE WESTERN RESERVE UNIVERSITY	9500 EUCLID AVE.	CLEVELAND	OH	44195	CUYAHOGA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	6/23/2023	NON-COMPETING CONTINUATION	-$550,994
2023	2021	CLEVELAND CLINIC LERNER COLLEGE OF MEDICINE OF CASE WESTERN RESERVE UNIVERSITY	9500 EUCLID AVE.	CLEVELAND	OH	44195	CUYAHOGA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	2	7/10/2023	NON-COMPETING CONTINUATION	-$573,712
														Subtotal = $649,253

Issue Date FY: 2022 ( Subtotal = $751,535 )
2022	2022	CLEVELAND CLINIC LERNER COLLEGE OF MEDICINE/CWRU	9500 EUCLID AVE	CLEVELAND	OH	44195	CUYAHOGA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	8/29/2022	NON-COMPETING CONTINUATION	$751,535
														Subtotal = $751,535

Issue Date FY: 2021 ( Subtotal = $755,842 )
2021	2021	CLEVELAND CLINIC LERNER COLLEGE OF MEDICINE/CWRU	9500 EUCLID AVE	CLEVELAND	OH	44195	CUYAHOGA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	2	6/7/2021	NON-COMPETING CONTINUATION	$755,842
2021	2020	CLEVELAND CLINIC LERNER COLLEGE OF MEDICINE/CWRU	9500 EUCLID AVE	CLEVELAND	OH	44195	CUYAHOGA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	11/6/2020	NEW	$0
														Subtotal = $755,842

Issue Date FY: 2020 ( Subtotal = $762,479 )
2020	2020	CLEVELAND CLINIC LERNER COLLEGE OF MEDICINE/CWRU	9500 EUCLID AVE	CLEVELAND	OH	44195	CUYAHOGA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	8/18/2020	NEW	$762,479
														Subtotal = $762,479

Grand Total All Awards = $3,600,539

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Towards Generating a Multimodal and Multivariate Classification Model from Imaging and Non-Imaging Measures for Accurate Diagnosis and Monitoring of Dementia in Parkinsons disease

Award Number: R01NS117547

ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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