# Worldwide Tractometry Initiative to Investigate Brain Microstructure, Cognitive Impairment & Dementia in Parkinsons Disease

> **NIH NIH RF1** · UNIVERSITY OF SOUTHERN CALIFORNIA · 2024 · $2,243,095

## Abstract

ABSTRACT
Here we launch an international initiative to understand Parkinson’s disease dementia (PDD), using a novel
tractometry approach for fine-scale mapping of the brain’s microstructure. Up to 80% of the 8.5 million people
diagnosed with Parkinson’s disease (PD) worldwide will develop dementia within a decade of diagnosis, with
devastating consequences for everyday functioning, caregiver burden, and heightened morbidity and mortality.
In addition to the immense personal toll of dementia in PD, the economic burden of PD in North America will
exceed $37 billion by 2037. Symptomatic treatments are available, but no disease modifying therapeutics exist,
making PD a lifelong, incurable disorder. Recent innovations in imaging - by us and others - reveal early
microstructural changes in brain white matter (WM); their progression is strongly associated with dementia onset
and with mild cognitive impairment (MCI) in people living with PD. Even so, prior PDD studies are plagued by
small sample sizes, low statistical power, poor replication, and findings whose generalizability and reliability is
unknown. With so many studies assessing so few patients, there is a pressing need to integrate international
data to achieve samples with the statistical power to detect prognostic markers in PDD. To address this, we
launch a global initiative with unprecedented power to understand what leads to dementia in PD - what are the
primary risk factors, and what processes in the brain are progressing in those who develop dementia in PD
versus those who do not. Building on our pilot data that merged global data in an internationally coordinated
analysis of diffusion tensor images from 1,654 individuals with PD and 885 controls from 17 sites in 9
countries, our work will reveal how WM microstructure deteriorates as dementia develops in PD, which WM
pathways show changes associated with dementia, and which individuals diagnosed with PD are most likely to
progress to dementia. We deploy - on a global scale - our novel tractometry method, Bundle Analytics (BUAN),
to map fine-scale microstructural alterations in PD-related dementia, and its precursor, PD with MCI (N=3,539
participants scanned with MRI). Our Specific Aims are to: (1) Create an age-dependent statistical reference
model for WM microstructure in the brain's fiber bundles throughout adult life; (2) Identify along-tract
microstructural biomarkers of PDD; and (3) predict decline to dementia from PD with MCI, identifying
which subjects will progress to dementia is crucial for personalized treatment planning. To boost predictive
accuracy, we will merge global data on vascular disease assessed with FLAIR imaging, based on pilot work that
revealed in patients with PD-MCI that WMH volume was associated with PD dementia conversion. Overall, we
hypothesize that tractometry and FLAIR imaging will each add significant prognostic value relative to the baseline
clinical data alone; by identifying which neuroimaging data predi...

## Key facts

- **NIH application ID:** 10872052
- **Project number:** 1RF1NS136995-01
- **Recipient organization:** UNIVERSITY OF SOUTHERN CALIFORNIA
- **Principal Investigator:** Neda Jahanshad
- **Activity code:** RF1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $2,243,095
- **Award type:** 1
- **Project period:** 2024-06-01 → 2027-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10872052

## Citation

> US National Institutes of Health, RePORTER application 10872052, Worldwide Tractometry Initiative to Investigate Brain Microstructure, Cognitive Impairment & Dementia in Parkinsons Disease (1RF1NS136995-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10872052. Licensed CC0.

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