Microstructural alterations of the amygdala in neurodegenerative and neuroinflammatory disorders: insights from diffusion tensor imaging
Clinical Snapshot
PICO Framework
| P — Population | Patients with neurodegenerative and neuroinflammatory disorders (Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, dementia with Lewy bodies, multiple sclerosis) compared to healthy controls |
| I — Intervention | Diffusion tensor imaging (DTI) assessment of amygdala microstructure |
| C — Comparator | Healthy controls or baseline measurements |
| O — Outcomes | DTI metrics including mean diffusivity (MD), fractional anisotropy (FA), radial diffusivity (RD), and free water (FW) in amygdala tissue |
Bottom Line
This systematic review of 13 studies involving 2,558 participants demonstrates that DTI can detect microstructural amygdala changes across multiple neurodegenerative conditions. Elevated mean diffusivity emerged as the most consistent finding, present in all Alzheimer's disease patients and observed across Parkinson's disease, ALS, dementia with Lewy bodies, and multiple sclerosis. Reduced fractional anisotropy was the second most common alteration. These microstructural changes often preceded volumetric atrophy and correlated with clinical severity. However, the inability to perform meta-analysis due to study heterogeneity limits the strength of conclusions. While DTI shows promise as a sensitive biomarker for early detection and monitoring of neurodegeneration, more standardized research is needed before routine clinical implementation. Australian clinicians should consider DTI as a complementary tool in specialist neurological assessment, particularly for early-stage disease detection and differential diagnosis.
Key Findings
P Value: Not reported in abstract
Effect Size: 100% of AD patients showed elevated MD
Primary Outcome: Mean diffusivity (MD) elevation in amygdala across neurodegenerative disorders
Nnt Or Sensitivity: 36.6% of AD patients showed reduced fractional anisotropy
Confidence Interval: Not reported due to lack of meta-analysis
Clinical Application
DTI widely available in Australian tertiary hospitals and specialist neuroimaging centres Relevant to neurologists and radiologists in Australian practice; DTI covered under Medicare for appropriate indications; aligns with RACGP guidelines for dementia assessment Patients with suspected or confirmed neurodegenerative disorders requiring neuroimaging assessment
Abstract
Diffusion tensor imaging (DTI) is a valuable method for evaluating microstructural changes in the amygdala associated with neurodegenerative and neuroinflammatory disorders. This systematic review examines amygdala microstructural alterations in Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), dementia with Lewy bodies (DLB), and multiple sclerosis (MS) using DTI metrics. Following PRISMA 2020 guidelines, we searched PubMed, Scopus, and Web of Science databases through August 2025, identifying 4,442 records. After screening and eligibility assessment, 13 studies were included, comprising 1,412 patients and 1,146 healthy controls. Due to sample heterogeneity and lack of standardized effect size measures, meta-analysis was not performed. Across disorders, elevated mean diffusivity (MD) emerged as the most consistent finding, present in 100 % of AD patients and observed in all examined conditions. Reduced fractional anisotropy (FA) was the second most frequent alteration, with 36.6 % of AD patients showing decreased FA. In MS, increased radial diffusivity (RD) was prominent, while longitudinal DLB studies revealed progressive free water (FW) increases. These DTI-based microstructural changes often preceded volumetric atrophy and correlated with clinical severity. Our findings demonstrate that DTI metrics, particularly MD and FA, serve as sensitive markers of amygdala pathology across neurodegenerative diseases and may facilitate early diagnosis, disease monitoring, and differential diagnosis of these conditions.
References
- 1.Falahati, M., Orangi, K., Shaabanpoor Haghighi, A., Pouroushaninia, N., Niknam, N., Soltani, S., Radnia, P., Arab Bafrani, M., Shirdel, S., & Aarabi, M. H. (2026). Microstructural alterations of the amygdala in neurodegenerative and neuroinflammatory disorders: insights from diffusion tensor imaging. Reviews in the Neurosciences. https://doi.org/10.2147/ndt.s84602
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