Minor hallucinations reflect early gray matter loss and predict subjective cognitive decline in Parkinson's disease

Background and purpose: Well-structured hallucinations in Parkinson's disease (PD) are associated with poor prognosis and dementia. However, the predictive value of minor psychotic phenomena in cognitive deterioration is not well known. Cross-sectional studies have shown that PD patients with minor hallucinations have more severe cortical atrophy than non-hallucinators, but baseline and longitudinal studies addressing the evolution of these brain differences are lacking. The impact of developing minor hallucinations on cognitive impairment and cortical atrophy progression in early PD was explored. Methods: One hundred and thirty-one de novo PD patients from the Parkinson's Progression Marker Initiative for whom brain magnetic resonance imaging scans were available were included. Cognitive outcome at 5 years was compared between patients with and without minor hallucinations during follow-up. Additionally, using gray matter volume (GMV) voxel-based morphometry, cross-sectional (at baseline) and longitudinal (1- and 2-year GMV loss) structural brain differences between groups were studied. Results: During follow-up, 35.1% of patients developed minor hallucinations. At 5 years, these patients showed an increased prevalence of subjective cognitive decline compared to non-hallucinators (44.1% vs. 13.9%; p < 0.001), but not formal cognitive impairment. Additionally, compared to non-hallucinators, they exhibited reduced GMV at baseline in visuoperceptive areas and increased GMV loss in left temporal areas (p < 0.05 corrected). Conclusions: Minor hallucinations seem to be an early clinical marker of increased neurodegeneration and are associated with mid-term subjective cognitive decline. Longer follow-up analyses would be needed to further define if these findings could reflect a higher risk of future cognitive deterioration.