# Functional MRI Biomarkers Predicting Cognitive Progression in PD

> **NIH NIH R01** · UNIVERSITY OF MARYLAND BALTIMORE · 2021 · $473,603

## Abstract

Parkinson’s disease (PD) is a neurodegenerative disease with initial motor symptoms attributed to
nigrostriatal dopamine depletion, but with increasing awareness of a non-motor symptom complex. Dopamine
replacement therapy (DRT) is the most effective treatment for motor features, but fails to effectively treat non-
motor features such as cognitive deficits. In fact, DRT can have a deleterious effect on attention and memory,
suggesting that these early cognitive deficits may be unreliable markers for future cognitive progression. Mild
cognitive impairment (MCI) in PD is common, and can progress at variable rates to dementia, but eventually
results in disability and poor quality of life for most patients. Diffuse Lewy body disease is likely the primary
pathological substrate for cognitive decline in PD, although reliable biomarkers predicting pathologic burden
and risk of conversion to dementia have not been identified. The subgroup of PD patients experiencing visual
hallucinations can develop dementia in 2.5 years, with evidence for associated posterior cortical atrophy and
hypometabolism. However, since the incidence of visual hallucinations is low, additional sensitive regional
markers of visuoperceptual dysfunction may potentially serve as cardinal signs of pathologic density and
distribution. The long-term objective of this application is the study of the predictive validity of early cognitive
deficits in PD, and identification of functional neuroimaging markers signaling more rapid conversion to
dementia. Our hypothesis, based on models of pathologic staging, is that earlier involvement of posterior
cortical regions and the dorsal and ventral visual pathways (with or without the presence of visual
hallucinations) are reliable signals for cognitive progression. We will pursue the following specific aims: (1) To
utilize a prospective longitudinal cohort to evaluate the prognostic value of PD-MCI subtypes in predicting risk
for progression to dementia. Serial neuropsychological evaluations will be given across 4 years to mild PD
patients to determine if visuoperceptual deficits predict cognitive progression. An exploratory genetic analysis
of how SNCA (α-synuclein), MAPT (microtubule associated tau) and APOE (apolipoprotein E) might influence
cognitive progression will be conducted. (2) To evaluate the utility of task-activated fMRI as a probe for
cognitive progression by investigating altered posterior cortical networks prior to clinical manifestation. An
event-related fMRI paradigm of object recognition memory will measure BOLD response in dorsolateral
prefrontal, medial temporal and occipito-parieto-temporal regions in PD patients (with and without MCI) at
baseline. (3) To determine the anatomical and regional brain activation patterns predictive of cognitive
progression. Structural and functional MRI at baseline and annually for 4 years will characterize anatomical
and neural network changes predictive of progression. Identification of bioma...

## Key facts

- **NIH application ID:** 10165841
- **Project number:** 5R01NS098249-05
- **Recipient organization:** UNIVERSITY OF MARYLAND BALTIMORE
- **Principal Investigator:** Brenda Hanna-Pladdy
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $473,603
- **Award type:** 5
- **Project period:** 2017-08-15 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10165841

## Citation

> US National Institutes of Health, RePORTER application 10165841, Functional MRI Biomarkers Predicting Cognitive Progression in PD (5R01NS098249-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10165841. Licensed CC0.

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