Free Water Fraction Predicts Cognitive Decline for Individuals with Idiopathic Parkinson's disease


      • Free water fraction (FWF) is a metric of microstructural integrity.
      • FWF in cognitive ROIs reliably categorizes individuals with Parkinson's disease.
      • Individuals with higher FWF display lower executive function and memory.
      • High FWF at baseline predicts cognitive decline in multiple domains over two years.



      Free water fraction (FWF) is considered a metric of microstructural integrity and may be useful in predicting cognitive decline in idiopathic Parkinson's Disease (PD). We sought to determine if higher FWF within the dorsal portion of the caudate nucleus and basal nucleus of Meynert, two regions associated with cognitive decline in PD, predict change in cognition over a two-year span. Due to the existence of cognitive and neurophysiological subgroups within PD, we statistically categorized participants based on FWF in these regions.


      At baseline, participants completed a research cognitive protocol followed by MRI structural and diffusion metrics. We used k-means cluster analysis with average FWF values from bilateral basal nucleus of Meynert and dorsal caudate to create data-driven FWF clusters for baseline. Two-year reliable change indices were calculated for metrics of language, visuospatial, memory, cognitive flexibility, and reasoning domains. Reliable change scores were compared between the clusters and non-PD peers.


      Baseline participants included 174 participants (112 PD, 62 non-PD). Cluster analysis yielded three clusters: low FWF in both regions of interest (ROIs), high FWF in both ROIs, and moderate FWF in both ROIs. Reliable change analyses were completed on 93 participants (67 PD, 26 non-PD). After controlling for age and education, the High FWF cluster declined more than non-PD peers in every domain except memory.


      Individuals with high FWF in regions associated with cognitive decline in PD show significant decline across several cognitive domains compared to non-PD peers. Future research should include FWF in additional cortical regions.
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