Anxiety is very common in Parkinson’s disease (PD) where according to a systematic review, the average prevalence is 31%, surprisingly higher than the average 17% of depressive disorders found in PD. Only a few studies have investigated the impact of anxiety on cognitive performance and brain morphology in PD. They demonstrated anxiety to be a significant predictor of cognitive impairment, where PD patients with anxiety have shown to be twice more likely to have deficits in the memory domain compared to those without anxiety. Furthermore, poorer cognitive performance in all cognitive domains was reported to be a significant risk factor for increased anxiety the following year. Anxiety in PD has also shown reduced volume/thinning in the fronto-cingulate, anterior cingulate cortex, left parietal cortices and the precuneus, despite the scant number of studies on this topic. Hence, the objective of this study aims to determine the evolution of cognitive performance and brain morphology in PD patients with and without anxiety over a three-year span.

We analyzed the baseline and three-year follow-up Parkinson’s Progression Markers Initiative (PPMI) data of 58 PD patients. MRI 3T was processed with FreeSurfer 7.1.1 on the Compute Canada cluster “Cedar” and we extracted cortical (Desikan-atlas-based volumes, thickness, area, folding index, curvature) and volumes of subcortical structures. Additionally, anxiety subscores from the State-trait anxiety inventory as well as neuropsychological tests were analyzed. PD patients were classified in two groups: PD-no-anxiety (n=46) and PD-anxiety (n=12) (subscore of > 40 on the State anxiety scale). Two-way mixed ANOVA models were established with presence/absence of anxiety as a between-subjects factor, time (baseline and three year) as a within-subjects factor and neuropsychological and MRI data were regarded as dependent variables.

Mixed ANOVA revealed that PD-anxiety saw a significantly greater decline in performance on the Montreal Cognitive Assessment test compared to PD-no-anxiety. In addition, PD-anxiety saw their performance decline over time in the Hopkins Verbal Learning test (HVLT) immediate recall, HVLT retention and HVLT delayed recall while PD-no-anxiety saw an increase in performance. In terms of brain morphology, over the three years, PD-anxiety had a greater decrease in the frontal precentral thickness, cingulate isthmus area and thickness, and temporal regions (transverse area and inferior folding) all in the left hemisphere compared to PD-no-anxiety. In subcortical regions, PD-anxiety had a greater decrease in volume of the hippocampal cornu ammonis-1 and pallidum compared to PD-no-anxiety. By contrast, PD-anxiety showed a greater increase in curvature of the frontal middle rostral, frontal pole, parietal supramarginal, and insula cortex as well as in the folding of the parietal superior and occipital pericalcarine of the right hemisphere in comparison to PD-no-anxiety.

This study highlights the importance of taking into consideration anxiety symptoms in PD, as they contribute to poorer cognitive performance and frontal, parietal and temporal differences over time. More studies with a larger sample size are needed in order to confirm these results.