Differential atrophy along the longitudinal axis of the hippocampus in Alzheimer’s disease and suspected non-Alzheimer’s disease pathophysiology (SNAP)
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Purpose
Cerebrospinal fluid (CSF) biomarkers are increasingly used to support Alzheimer’s disease (AD) diagnosis: Alzheimer’s Disease continuum (ADc) is defined by abnormal amyloid-beta (Aβ), while Suspected Non-AD Pathophysiology (SNAP) refers to normal Aβ with elevated tau. Given the differential properties along the hippocampal longitudinal axis, this study aimed to evaluate anterior-posterior subregional hippocampal volume differences among ADc, SNAP, and biomarker-negative participants, and their associations with CSF biomarkers and clinical presentation.
Methods
Data from 1242 participants in the Alzheimer’s Disease Neuroimaging Initiative were analyzed. Biomarker-negative participants ( n = 234) had normal CSF Aβ42 (≥ 192 pg/ml), total tau (< 93 pg/ml), and phosphorylated tau at threonine 181 (< 23 pg/ml). ADc individuals ( n = 784) had abnormal Aβ42, and SNAP ( n = 224) showed normal Aβ42 with elevated tau. T1-weighted MRI scans were used to segment the hippocampus into anterior, intermediate, and posterior subregions. Controlling for age, sex, and multiple comparisons, groups were compared using one-way ANOVA, and Pearson correlation coefficients were calculated to assess the relationships between volumetric variables and age, CSF biomarkers, or neuropsychological scores.
Results
ADc individuals showed significantly lower total and subregional hippocampal volumes compared with SNAP and biomarker-negative participants ( P < 0.001). Normalized volumes to total ipsilateral hippocampal volume revealed greater posterior atrophy ( P < 0.001) and relatively higher anterior volume ( P < 0.01) in ADc. SNAP and biomarker-negative participants showed stronger correlations between hippocampal volumes and age. Several subregional hippocampal volumes correlated with CSF biomarkers, cognitive performance, neuropsychiatric symptoms, and functional impairment.
Conclusion
This study reveals distinct patterns of hippocampal atrophy in ADc and SNAP, enhancing our understanding of their differential pathophysiology and associated clinical features.
