Associations of Cognitive Impairment with Putative Glymphatic-Related Imaging Indices and Cortical Atrophy in Cerebral Amyloid Angiopathy.

Purpose: The aim of this study was to compare the contributions of putative glymphatic-related imaging indices-diffusion-weighted image analysis along the perivascular space (DWI-ALPS) index and choroid plexus volume (CPV)-and total cortical gray matter volume (TCGMV) to cognitive function in cerebral amyloid angiopathy (CAA). Methods: Forty-four CAA patients and 22 controls underwent 3.0T MRI. Cognitive function was assessed by the Mini-Mental State Examination (MMSE). The mean DWI-ALPS index, CPV/intracranial volume (ICV), and TCGMV/ICV were compared between groups; hierarchical multivariable regression and mediation analyses evaluated MMSE correlates. Results: Compared with controls, CAA showed a lower mean DWI-ALPS index and TCGMV/ICV (both adjusted p < 0.05), whereas CPV/ICV did not differ significantly after adjustment. In hierarchical multivariable regression analysis, mean DWI-ALPS index was associated with MMSE before adjustment for TCGMV/ICV (p = 0.022), but this association was attenuated after TCGMV/ICV was added to the model (p = 0.665). CPV/ICV was not associated with MMSE in either model, whereas TCGMV/ICV was independently associated with MMSE (p = 0.013). Exploratory mediation analysis suggested an indirect association between mean DWI-ALPS and MMSE via TCGMV/ICV (indirect: p = 0.023; direct: p = 0.720). Conclusions: Cortical atrophy appeared to be the strongest imaging correlate of cognitive impairment in CAA, while the association between DWI-ALPS and MMSE in multivariable models was attenuated after accounting for cortical gray matter volume. The ALPS index may provide indirect information on glymphatic-related pathways, but its biological specificity in CAA requires cautious interpretation because ALPS measurements may be influenced by underlying microstructural alterations in white matter.