Abstract

To investigate the structural changes of the brain that correlate with physical frailty and cognitive impairments in Parkinson's disease (PD) patients. Sixty-one PD patients and 59 age- and sex-matched healthy controls were enrolled. For each participant, a frailty assessment using Fried's criteria and comprehensive neuropsychological testing using the Wechsler Adult Intelligence Scale-III and Cognitive Ability Screening Instrument were conducted, and structural brain MR images were acquired for voxel-based morphometric analysis. The neuropsychological testing includes various tests in these five domains: attention, executive, memory, speech and language, and visuospatial functions. Exploratory group-wise comparisons of gray matter volume (GMV) in the PD patients and controls were conducted. Voxel-wise multiple linear regression analyses were conducted for physical frailty-related and cognitive impairment-related GMV changes in the PD patients. Voxel-wise multiple linear regressions were also performed with the five cognitive domains separated using the same model. The PD patients exhibited diffuse GMV reductions in comparison to the controls. In the PD patients, physical frailty-related decreases in GMV were observed in the bilateral frontal and occipital cortices, while cognitive impairment-related decreases in GMV were observed in the bilateral frontal, occipital, and temporal cortices. These regions overlap in the lateral occipital cortex. After the five domains of cognitive functions were analyzed separately, physical frailty-related decreases in GMV still overlap in lateral occipital cortices with every domain of cognitive impairment-related decreases in GMV. Reduced GMV in the lateral occipital cortex is associated with cognitive impairment and physical frailty in PD patients. • Physical frailty in PD was associated with decreased GMV in the frontal and occipital cortices, while cognitive impairment was associated with decreased GMV in the frontal, temporal, and occipital cortices. • Physical frailty and cognitive impairment were both associated with decreased GMV in the lateral occipital cortex, which is part of the ventral object-based visual pathway. • Decreased GMV in the lateral occipital cortex may serve as a potential imaging biomarker for physical frailty and cognitive impairment in PD.

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