Visual dysfunction predicts cognitive impairment and white matter degeneration in Parkinson's disease

Visual dysfunction predicts dementia in Parkinsons disease (PD), but whether this translates to structural change is not known. We aimed to identify longitudinal white matter changes in patients with Parkinsons disease and low visual function and also in those who developed mild cognitive impairment (MCI). We used fixel-based analysis to examine longitudinal white matter change in PD. Diffusion MRI and clinical assessments were performed in 77 patients at baseline (22 low visual function /55 intact vision; and 13 MCI, 13 MCI converters /51 normal cognition) and 25 controls and again after 18 months. We compared micro-structural changes in fibre density, macro-structural changes in fibre bundle cross-section (FC) and combined fibre density and cross-section across white matter, adjusting for age, gender and intracranial volume. Patients with Parkinsons and visual dysfunction showed worse cognitive performance at follow up and were more likely to develop MCI compared with those with normal vision (p=0.008). Parkinsons with poor visual function showed diffuse micro-structural and macro-structural changes at baseline, whereas those with MCI showed fewer baseline changes. At follow-up, Parkinsons with low visual function showed widespread macrostructural changes, involving the fronto-occipital fasciculi, external capsules, and middle cerebellar peduncles bilaterally. No longitudinal change was seen in baseline MCI or in MCI converters, even when the two groups were combined. Parkinsons patients with poor visual function show increased white matter damage over time, providing further evidence for visual function as a marker of imminent cognitive decline.