Fig. 3: Parkinson’s patients with LRRK2 pathogenic variants show a milder form of brain atrophy. | Communications Medicine

Fig. 3: Parkinson’s patients with LRRK2 pathogenic variants show a milder form of brain atrophy.

From: Carriers of LRRK2 pathogenic variants show a milder, anatomically distinct brain signature of Parkinson’s disease

Fig. 3: Parkinson’s patients with LRRK2 pathogenic variants show a milder form of brain atrophy.

a The infographic highlights the sPD and LRRK2 PD subgroups used to assess the extent of PD-related brain atrophy. b Selection of carefully matched groups of PD patients. Only 19 out of 293 sPD and 19 out of 77 LRRK2 participants were selected based on age, sex, disease duration, and site using propensity score matching. c Transferring the model of PD-related atrophy between cohort subgroups. We apply a PD atrophy model, trained on measures from sPD and HC subgroups, to estimate regional thickness and volume in LRRK2 PD and sPD patients. We then average these estimates to derive region-specific measures. d Model estimates reveal less atrophy in LRRK2 PD patients. The plot illustrates region-wise deviations between measured and estimated morphometry, with positive values indicating preserved structure and negative values reflecting greater degeneration. The p-value denotes a two-sample t-test of prediction differences. e LRRK2 pathogenic variants are associated with less cortical thinning in temporal and occipital regions. Region-wise differences between measured and estimated brain metrics are plotted on cortical and subcortical regions for LRRK2 PD participants. Orange indicates less thinning or volume loss; purple denotes increased atrophy. f Relationship of prediction difference with PD atrophy. The diagnosis-related beta coefficients are plotted against prediction differences for every brain region. g Linking predictions of brain structure to cognitive and genetic measures. The correlations quantify linear association strength across all sPD and LRRK2 PD patients between averaged structural predictions and MDS-UPDRS III, MoCA, and PRS. h Relating regional predictions to cognitive and genetic factors. Correlations with regional predictions are shown for MDS-UPDRS III, MoCA, and PRS. Overall, patients carrying LRRK2 pathogenic variants show less brain atrophy, with preservation especially in the temporal and occipital regions.

Back to article page