Comparisons of hippocampal volume and glymphatic-related MRI markers for assessing disease status in Alzheimer’s Disease

Glymphatic imaging markers have emerged as promising biomarkers in Alzheimer’s disease (AD). However, few studies have directly compared their ability to discriminate disease status with that of hippocampal volume. This study aimed to assess the diagnostic value of hippocampal atrophy and glymphatic imaging markers in distinguishing disease status among cognitively normal (CN), mild cognitive impairment (MCI), and AD groups. This retrospective study used data from the Alzheimer’s Disease Neuroimaging Initiative, including 223 participants categorized as CN (n = 58), MCI (n = 118), and AD (n = 47). Group comparisons were performed for hippocampal volume ratio (HPVR), choroid plexus volume ratio (CPVR), and the diffusion tensor imaging along the perivascular space (DTI-ALPS) index. Logistic regression and ordered random forest models were applied to identify significant discriminative factors and evaluate classification performance using 5-fold stratified cross-validation. Model discrimination was assessed using the area under the receiver operating characteristic curve (AUC). HPVR was significantly reduced in the AD group compared with CN and MCI (both p < 0.05). CPVR was significantly increased in AD compared with CN and MCI (both p < 0.05), while DTI-ALPS index was also significantly lower in AD compared with CN (p < 0.05). HPVR was consistently identified as the strongest discriminative imaging marker of disease status across all classification models, with the highest discriminative performance observed in the CN vs. AD comparison (AUC, 0.86; SD = 0.11). Hippocampal atrophy is a superior biomarker for disease classification in AD, whereas glymphatic MRI markers show limited discriminative performance.