Objective: This study was designed to clarify the relationship between early cognitive decline and functional connectivity changes in non-demented Parkinson’s disease (PD) patients.

Background: Cognitive impairment in PD is one of the most important non-motor symptoms. However, previous studies have yet to reveal the patterns of early cognitive decline and brain network changes.

Methods: We enrolled 72 non-demented PD patients and age- and gender- matched 72 healthy control subjects (HC). All participants underwent the Addenbrooke’s Cognitive Examination-Revised (ACE-R) which consists of 5 sub-scores (attention/orientation, memory, fluency, language and visuospatial ability). Based on ACE-R subscores, we classified PD patients who had all subscores ≥ average – 1.5SD of HC as PD-Cognitively Normal (PD-CN). Furthermore, we conducted hierarchical cluster analysis to the others who had at least one of subscores < -1.5SD to clarify the characteristic of early cognitive changes in PD. T1WI, T2WI, and resting-state functional MRI (rsfMRI) were obtained with a 3T MRI scanner.

Results: 28 PD patients was classified as PD-CN. Cluster analysis divided 44 PD patients who had at least one of subscores < -1.5SD into two groups: 20 PD patients who had predominantly decrease in memory (PD-Amnestic; PD-A) and 24 those who had good memory but decrease in other subscores in particular fluency and visuospatial ability (PD-Non Amnestic; PD-NA). In VBM study, PD-A showed significant atrophy of gray matter in the left amygdala, right rectal gyrus and middle occipital gyrus compared with HC (FWEc p<0.05). As for rsfMRI findings using independent component analysis, PD-A showed significant decreased functional connectivity in the ventral default mode network compared with all other groups and in the visuospatial network compared with HC. In contrast, PD-NA showed decreased connectivity in the visual network compared with HC and PD-CN as well in the cerebellum-brainstem network compared with HC and PD-A (FWE p<0.05).

Conclusions: PD patients showed distinct phenotypes of early cognitive impairment. RsfMRI study showed the different patterns of resting state network involvement depending on the phenotype.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/early-cognitive-impairment-phenotype-and-functional-connectivity-in-non-demented-parkinsons-disease-patients/