Objective: To investigate the pattern of grey matter (GM) atrophy associated with cognitive decline in PD by use of voxel-based morphometry (VBM) analysis.

Background: Loss of GM volume has been previously demonstrated in PD-patients with cognitive deficits. However, patient neuropsychological assessment with a structured battery specifically designed to assess PD-related cognitive decline has been never comprised in any previous VBM study. Parkinson’s disease-Cognitive Rating scale (PD-CRS) is a battery targeted to assess cognitive domains particularly affected in PD, including items sensitive to both fronto-subcortical and posterior-cortical dysfunction.

Methods: T1-weighted brain MRIs were obtained from 63 PD-patients with varying degrees of cognitive impairment. All patients underwent examination with PD-CRS. Prior to application PD-CRS was adapted into the Greek language. Clinical and medication data were also acquired. Structural data were analyzed with an optimized VBM protocol carried out with FSL tools. Multiple regression models were used to investigate the association of GM volume with total PD-CRS score and sub-scores, including age and educational level as covariates.The level of significance was set to 0.05 corrected for multiple comparisons.

Results: The basic patient characteristics are described in Table1.

Patient characteristics

	Mean	Median	Range
Age (years)	69.2	70	55-79
Hoehn & Yahr Stage	2.3	2	1-4
Disease duration (years)	6.9	5	1-25
Total levodopa equivalent dose (mg/day)	814.4	609.8	0-2292
Total PD-CRS score	71.2	74	19-126
Posterior-cortical PD-CRS score	24	25	7-30
Frontal-subcortical PD-CRS score	47.3	47	11-99
MMSE score	26.1	27	18-30
Hamilton Depression Rating Scale score	4.4	3	0-16

The total PD-CRS score demonstrated a significant positive association with GM volume in multiple regions including extended cortical areas, along with thalamus, caudate, putamen, pallidum, hippocampus, amygdala and nucleus accumbens bilaterally. The volume of widespread GM areas was positively associated with posterior-cortical PD-CRS score, while a more spatially restricted pattern of GM atrophy has observed in association with frontal-subcortical PD-CRS score. Poor performance in immediate and delayed recall, confrontation naming, clock-drawing and working memory tasks was also associated with atrophy in specific GM regions.

Conclusions: Degenerative changes in neural circuits linking cortical, limbic, thalamic, striatal and pallidal structures are significantly implicated in the progression of PD-related cognitive impairment. Neural correlates of changes in cognitive domains particularly affected in PD are revealed by use of disease-specific cognitive assessment instruments.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/grey-matter-atrophy-associated-with-the-progression-of-cognitive-decline-in-parkinsons-disease-pd/