Voxel-based morphometry reveals extra-nigral atrophy patterns associated with dopamine refractory cognitive and motor impairment in parkinsonism

Parkinsonism Relat Disord. 2009 Mar;15(3):187-95. doi: 10.1016/j.parkreldis.2008.05.002. Epub 2008 Jun 24.

Abstract

Objectives: To determine overall patterns of brain atrophy associated with memory, executive function (EF) and dopamine non-responsive motor measures in older parkinsonian patients.

Design: Forty-three older PD patients (>or=65 years) and matched controls underwent a neurological examination (Unified Parkinson's Disease Rating Scale, separated into dopamine responsive and dopamine non-responsive signs) and neuropsychological testing (memory: California Verbal Learning Test (CVLT)) and a composite of index of executive function (EF): Stroop Interference, Trail Making Test Part B, and digit ordering. All underwent volumetric MRI scans analyzed using voxel-based morphometry (VBM). Group comparisons, and the correlations between MRI gray and white matter volume and motor and cognitive measures were controlled for age, sex and intracranial volume. Cerebellar volume was independently measured using a validated extraction method.

Results: Patients and controls were matched for demographics and global cognitive measures. VBM indicated significant gray matter (GM) atrophy in the cerebellum in PD and was confirmed independently. Poor memory was associated with GM atrophy in the left (uncus, middle temporal and fusiform gyri) and right temporal lobes and left putamen. Dopamine non-responsive motor signs and EF were associated with caudate atrophy. EF was also associated with GM atrophy in the middle temporal gyri, the left precuneus and cerebellum.

Conclusions: Cortical and striatal atrophy were associated with dopamine non-responsive motor signs and cognitive impairment and provide a morphologic correlate for progression of PD. Cerebellar atrophy was found in older PD patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Analysis of Variance
  • Atrophy / etiology
  • Brain Mapping
  • Case-Control Studies
  • Cognition Disorders / etiology*
  • Cognition Disorders / pathology
  • Dopamine / metabolism*
  • Dopamine Agents / therapeutic use
  • Female
  • Humans
  • Magnetic Resonance Imaging / methods
  • Male
  • Movement Disorders / etiology*
  • Movement Disorders / pathology
  • Neurologic Examination / methods
  • Neuropsychological Tests
  • Parkinsonian Disorders / complications*
  • Parkinsonian Disorders / drug therapy
  • Statistics as Topic
  • Substantia Nigra / drug effects
  • Substantia Nigra / pathology*

Substances

  • Dopamine Agents
  • Dopamine