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.
Tanaka et al. (Thu,) studied this question.
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