Changes in network activity with the progression of Parkinson's disease.

Changes in network activity with the progression of Parkinson's disease. Research Abstract Details 

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Changes in network activity with the progression of Parkinson's disease. Abstract Text:

Chaorui Huang,Chengke Tang,Andrew Feigin,Martin Lesser,Yilong Ma,Michael Pourfar,Vijay Dhawan,David Eidelberg,

Parkinson's disease (PD) is associated with abnormal activity in spatially distributed neural systems mediating the motor and cognitive manifestations of this disorder. Metabolic PET studies have demonstrated that this illness is characterized by a set of reproducible functional brain networks that correlate with these clinical features. The time at which these abnormalities appear is unknown, as is their relationship to concurrent clinical and dopaminergic indices of disease progression. In this longitudinal study, 15 early stage PD patients (age 58.0 +/- 10.2 years; Hoehn and Yahr Stage 1.2 +/- 0.3) were enrolled within 2 years of diagnosis. The subjects underwent multitracer PET imaging at baseline, 24 and 48 months. At each timepoint they were scanned with [18F]-fluorodeoxyglucose (FDG) to assess longitudinal changes in regional glucose utilization and in the expression of the PD-related motor (PDRP) and cognitive metabolic covariance patterns (PDCP). At each timepoint the subjects also underwent PET imaging with [18F]-fluoropropyl betaCIT (FP-CIT) to quantify longitudinal changes in caudate and putamen dopamine transporter (DAT) binding. Regional metabolic changes across the three timepoints were localized using statistical parametric mapping (SPM). Longitudinal changes in regional metabolism and network activity, caudate/putamen DAT binding, and Unified Parkinson's Disease Rating Scale (UPDRS) motor ratings were assessed using repeated measures analysis of variance (RMANOVA). Relationships between these measures of disease progression were assessed by computing within-subject correlation coefficients. We found that disease progression was associated with increasing metabolism in the subthalamic nucleus (STN) and internal globus pallidus (GPi) (P < 0.001), as well as in the dorsal pons and primary motor cortex (P < 0.0001). Advancing disease was also associated with declining metabolism in the prefrontal and inferior parietal regions (P < 0.001). PDRP expression was elevated at baseline relative to healthy control subjects (P < 0.04), and increased progressively over time (P < 0.0001). PDCP activity also increased with time (P < 0.0001). However, these changes in network activity were slower than for the PDRP (P < 0.04), reaching abnormal levels only at the final timepoint. Changes in PDRP activity, but not PDCP activity, correlated with concurrent declines in striatal DAT binding (P < 0.01) and increases in motor ratings (P < 0.005). Significant within-subject correlations (P < 0.01) were also evident between the latter two progression indices. The early stages of PD are associated with progressive increases and decreases in regional metabolism at key nodes of the motor and cognitive networks that characterize the illness. Potential disease-modifying therapies may alter the time course of one or both of these abnormal networks.

Changes in network activity with the progression of Parkinson's disease. Publishing Authors By Initials

C Huang,C Tang,A Feigin,M Lesser,Y Ma,M Pourfar,V Dhawan,D Eidelberg,

For similar investigative techniques: epidemiologic methods: data collection: health surveys: health status indicators: severity of illness index research abstracts see: investigative techniques: epidemiologic methods: data collection: health surveys: health status indicators: severity of illness index research

PUBMED ID PMID:

MEDLINE DATE:

Changes in network activity with the progression of Parkinson's disease. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: Brain : a journal of neurology

VOLUME: 130

Page Numbers: 1834-46

Journal Abbreviation: Brain

ISSN: 1460-2156

DAY: 30

MONTH: 04

YEAR: 2007

Changes in network activity with the progression of Parkinson's disease. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 372537

Changes in network activity with the progression of Parkinson's disease. Keywords Mesh Terms:

KEYWORDS: Severity of Illness Index

MESH TERMS: diagnostic use

Chemical & Substance for Abstract: Changes in network activity with the progression of Parkinson's disease. Information

Substance Name: Fluorodeoxyglucose F18

Registry Number: 63503-12-8

Grant and Affiliation Information for Changes in network activity with the progression of Parkinson's disease.

AFFILIATION: Center for Neurosciences, Feinstein Institute for Medical Research, North Shore-Long Island Jewish Health System, 350 Community Drive, Manhasset, NY 11030, USA.

Country: England

AGENCY: United States PHS

GRANT: R01 35069

ACRONYM: NS

MEDLINETA: Brain

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