Longitudinal Patterns of Brain Parenchymal Damage Associated With the ALPS Index in a Community‐Based Cohort

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AIMS: To better comprehend relationships between the analysis along the perivascular space (ALPS) index and glymphatic dysfunction, we assessed the spatiotemporal patterns of structural brain injury related to the ALPS index in a longitudinal study. METHODS: We performed voxel/vertex-wise analysis to explore the relationship between lower ALPS index and brain parenchymal injury. We also performed brain network connectivity analysis to investigate the relationship between white matter disruption and cortical atrophy. RESULTS: The lower baseline ALPS index showed an association with drastic progression of disruption of white matter microstructural integrity, primarily located in the subcortical regions where association fibers are distributed. Brain network connectivity analysis revealed an association of the lower ALPS index with a disconnected sub-network in the midline and right frontal lobe, where association fibers are widely distributed. The lower ALPS index also displayed a correlation with cortical atrophy in the projection areas of both association and projection fibers in cross-sectional analysis. However, this correlation was nonsignificant in longitudinal analysis. CONCLUSION: The ALPS index could be considered a composite marker of perivascular dynamics and white matter microstructural integrity, shedding light on the spatial pattern of disruption of white matter integrity in community-dwelling populations.