Differential atrophy along the longitudinal hippocampal axis in Alzheimer's disease

• Published in: The European journal of neuroscience Vol. 59; no. 12; pp. 3376 - 3388
• Main Authors: Morais‐Ribeiro, Rafaela, Almeida, Francisco C., Coelho, Ana, Oliveira, Tiago Gil
• Format: Journal Article
• Language: English
• Published: Chichester Wiley Subscription Services, Inc 01.06.2024
• Subjects: ADNI; Age; Alzheimer's disease; Atrophy; Hippocampus; longitudinal axis; Magnetic resonance imaging; mild cognitive impairment; Neurodegenerative diseases; Neuroimaging
• ISSN: 0953-816X; 1460-9568
• DOI: 10.1111/ejn.16361

Alzheimer's disease (AD) is a progressive neurodegenerative disorder that primarily affects the hippocampus. Since hippocampal studies have highlighted a differential subregional regulation along its longitudinal axis, a more detailed analysis addressing subregional changes along the longitudinal hippocampal axis has the potential to provide new relevant biomarkers. This study included structural brain MRI data of 583 participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Cognitively normal (CN) subjects, mild cognitively impaired (MCI) subjects and AD patients were conveniently selected considering the age and sex match between clinical groups. Structural MRI acquisitions were pre‐processed and analysed with a new longitudinal axis segmentation method, dividing the hippocampus in three subdivisions (anterior, intermediate, and posterior). When normalizing the volume of hippocampal sub‐divisions to total hippocampus, the posterior hippocampus negatively correlates with age only in CN subjects (r = −.31). The longitudinal ratio of hippocampal atrophy (anterior sub‐division divided by the posterior one) shows a significant increase with age only in CN (r = .25). Overall, in AD, the posterior hippocampus is predominantly atrophied early on. Consequently, the anterior/posterior hippocampal ratio is an AD differentiating metric at early disease stages with potential for diagnostic and prognostic applications. The hippocampus, a brain structure importantly involved in Alzheimer's disease, is differentially regulated over its longitudinal axis. Across age, the anterior–posterior volume ratio on MRI varies differently in cognitively normal subjects, mild cognitive impairment and Alzheimer's disease. These findings suggest the longitudinal ratio might be a differentiating MRI metric with potential pathophysiological and diagnostic implications.