Morphometric analysis of medial temporal lobe subregions in Alzheimer's disease using high-resolution MRI
Emre Hari1,2,3, Elif Kurt4,5, Cigdem Ulasoglu-Yildiz4,5
1Graduate School of Health Sciences, Istanbul University, Bozdogan Kemeri Caddesi No:8 Vezneciler Hamami Sokagi, Vezneciler, 34216, Fatih, Istanbul, Turkey. emrehr@hotmail.com.
Abstract:
The spread pattern of progressive degeneration seen in Alzheimer's disease (AD) to small-scale medial temporal lobe subregions is critical for early diagnosis. In this context, it was aimed to examine the morphometric changes of the hippocampal subfields, amygdala nuclei, entorhinal cortex (ERC), and parahippocampal cortex (PHC) using MRI. MRI data of patients diagnosed with 20 Alzheimer's disease dementia (ADD), 30 amnestic mild cognitive impairment (aMCI), and 30 subjective cognitive impairment (SCI) without demographic differences were used. Segmentation and parcellation were performed using FreeSurfer. The segmentation process obtained volume values of 12 hippocampal subfields and 9 amygdala nuclei. Thickness values of ERC and PHC were calculated with the parcellation process. ANCOVA was performed using age, education and gender as covariates to evaluate the intergroup differences. Linear discriminant analysis was used to investigate whether atrophy predicted groups at an early stage. ERC and PHC thickness decreased significantly throughout the disease continuum, while only ERC was affected in the early stage. When the hippocampal and amygdala subfields were compared volumetrically, significant differences were found in the amygdala between the SCI and aMCI groups. In the early period, only volume reduction in the anterior amygdaloid area of the amygdala nuclei exceeded the significance threshold. Research on AD primarily focuses on original hippocampocentric structures and their main function which is episodic memory. Our results emphasized the significance of so far relatively neglected olfactocentric structures and their functions, such as smell and social cognition in the pre-dementia stages of the AD process.
Insights
Early Alzheimer's disease (AD) diagnosis can be improved by examining changes in the entorhinal cortex (ERC) and amygdala, even before significant memory loss.
Area of Science:
- Neuroimaging and Neurodegeneration
- Alzheimer's Disease Research
- Cognitive Impairment Studies
Background:
- Alzheimer's disease (AD) progression involves degeneration in medial temporal lobe subregions, crucial for early diagnosis.
- Current AD research often focuses on hippocampocentric structures, potentially overlooking early changes in other brain regions.
Purpose of the Study:
- To investigate morphometric changes in hippocampal subfields, amygdala nuclei, entorhinal cortex (ERC), and parahippocampal cortex (PHC) in Alzheimer's disease dementia (ADD), amnestic mild cognitive impairment (aMCI), and subjective cognitive impairment (SCI) using MRI.
- To identify early structural changes indicative of pre-dementia stages of AD.
Main Methods:
- Utilized MRI data from 20 ADD, 30 aMCI, and 30 SCI patients.
- Employed FreeSurfer for segmentation and parcellation to obtain volumes of 12 hippocampal subfields and 9 amygdala nuclei, and thickness of ERC and PHC.
- Applied ANCOVA and linear discriminant analysis to assess intergroup differences and predictive value of atrophy.
Main Results:
- Significant decreases in ERC and PHC thickness were observed across the disease continuum, with ERC affected early.
- Volumetric differences in amygdala subfields were found between SCI and aMCI groups, with anterior amygdaloid area reduction being significant in early stages.
- Findings highlight the importance of olfactocentric structures (e.g., amygdala) in pre-dementia stages, beyond hippocampocentric structures.
Conclusions:
- Morphometric analysis of ERC, PHC, and amygdala provides critical insights into early AD progression.
- Early structural changes in the entorhinal cortex and amygdala are significant indicators in pre-dementia stages.
- The study emphasizes the role of olfactocentric structures in early AD, suggesting a broader diagnostic focus beyond memory-related regions.


