Structural brain MRI and cognition in newly diagnosed Parkinson’s disease

Background:
Parkinson’s disease (PD) is a common progressive neurodegenerative disorder
mainly affecting the elderly. Previously regarded a pure motor disease, PD is now
considered a multisystem brain disease with various nonmotor aspects, including
cognitive dysfunction. Mild cognitive impairment (MCI) is currently explored as a
possible pre-dementia stage in patients with PD. Little is known about the pathology
underlying MCI in PD. A full characterization of the various aspects of MCI in PD
would be of great value in the search for prognostic factors and potential preventive
treatments for disabling dementia in patients with PD.
Volumetric brain magnetic resonance imaging (MRI) is increasingly used in research
aiming to find the biological basis for various neurodegenerative diseases, atrophy
regarded as the end stage of neurodegeneration. In PD, studies have shown brain
atrophy in patients presenting with dementia. A few studies reported loss of brain
tissue of midbrain and mesocortex in advanced stage patients with PD and MCI, but
no previous study has investigated possible brain atrophy in newly diagnosed patients
with PD and MCI.
White matter hyperintensities (WMH) are high signal changes in T2- weighted brain
MRI scans as a consequence of vascular damage. WMH has been linked to cognitive
dysfunction in both normal aging and neurodegenerative disease, e.g. Alzheimer’s
disease. Controlling vascular risk factors resulting in WMH might thus protect against dementia and other forms of cognitive impairments. Earlier works on WMH
in PD are conflicting, but a previous study indicated that WMH load is increased in
demented patients with advanced PD. The role of WMH in patients with early PD
and MCI is unknown. Objective:
The primary aim of this thesis was to test the hypothesis that cognitive impairment in
newly diagnosed PD is related to atrophy and/or WMH changes in the brain.
Methods:
Included subjects are all part of the Norwegian ParkWest study. The ParkWest study
is a prospective multicentre cohort study of patients with incident PD from western
and southern Norway, caregivers and a control group consisting of age and sex
matched normal controls. An MRI examination was part of the baseline study
evaluation and was conducted in 182 patients with PD and 109 controls.
By widely used and validated quantitative MRI analysing methods, we performed
volumetric global and regional brain segmentation and WMH quantification.
WMH load was estimated by a semi-automated local threshold technique. Total
volume and regional distribution of WMH in patients with newly diagnosed PD were
compared with findings in age-matched controls. The impact of WMH on cognitive test performance was investigated both in the unselected PD sample and according to
MCI classification.
Global brain MRI atrophy measures were whole brain and total
gray/white/cerebrospinal fluid volumes calculated using SIENAX software. Regional
atrophy was investigated in a subgroup of patients from one centre using voxel-based
morphometry (VBM) and the FreeSurfer software. Ventricular volumes were also
calculated.
Neuropsychological tests were chosen to minimize the impact of impaired motor
skills and assessed memory, visuospatial and attention-executive domains. Nondemented
patients with an observed age-and education corrected z-score deviating
more than -1.5 standard deviations from the expected z-score (based on the test
performance of controls) in at least one cognitive domain, were classified as having
MCI. Results:
Our investigations of global brain MRI atrophy parameters (whole brain, total gray
and white matter volume) did not show any significant difference between newly
diagnosed patients with PD and controls and were not significant predictors of
cognitive performance. Furthermore, neither total WMH volume nor regional
distribution of WMH was significantly different between patients and controls,
irrespectively if patients were presenting MCI. Regional gray matter atrophy analyses, volume of subcortical gray matter structures and ventricular volume
measures may indicate enlargement of fourth, third and left inferior lateral ventricles,
but no cortical atrophy, as a sign of MCI in early PD.
Conclusion:
Based on these studies, WMH do not seem to play a significant role as a
neurobiological factor in the cognitive dysfunctions of incident patients with PD.
Volume studies could indicate a possible role of atrophy in brainstem, midbrain and
temporal regions, but this needs to be explored further in future larger studies