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Atrophy patterns of deep gray matter nuclei in Alzheimer's disease and frontotemporal dementia
Arit Banerjee, Fan Yang, Joyita Dutta, Alberto Cacciola, Michael Hornberger, Manojkumar Saranathan. Journal of Alzheimer s Disease, 2025-10-29
Topic: Amyloid, tau and blood-test diagnosis
Plain-language summary
BackgroundWhile cortical atrophy has been widely studied in dementia, emerging evidence highlights the role of subcortical degeneration, particularly in deep gray matter structures such as the thalamus, claustrum, and basal nuclei, in both Alzheimer's disease (AD) and frontotemporal dementia (FTD). However, disease-specific subcortical patterns remain undercharacterized.ObjectiveTo quantify deep gray matter atrophy across the AD continuum (mild cognitive impairment and AD) and three FTD subtypes (bvFTD, svFTD, PNFA), and to assess longitudinal atrophy, cognitive associations, and diagnostic classification.MethodsWe applied a novel segmentation pipeline (sTHOMAS) to T1-weighted MRI data from 380 participants in the ADNI cohort and 274 participants in the FTLDNI cohort, with longitudinal follow-up available for 237 participants. Group differences were assessed using ANCOVA (adjusted for age and sex), followed by post hoc comparisons and effect size estimation (Cohen's d). Neuropsychological associations were examined using partial correlations. A hierarchical Random Forest model was trained to classify diagnostic groups.ResultsPronounced atrophy was observed in the mediodorsal, anteroventral, pulvinar thalamic nuclei, and nucleus accumbens, and claustrum in both AD and FTD, but was significantly greater in bvFTD. Longitudinal analysis revealed the fastest progression in bvFTD. Classification achieved 96.8% accuracy (AUC = 0.99) for AD versus FTD and 77.7% accuracy (AUC = 0.83) for PNFA versus svFTD. Subcortical atrophy correlated to executive, language, and semantic deficits.ConclusionsAtrophy in the mediodorsal, pulvinar, anteroventral thalamic nuclei, nucleus accumbens, and claustrum distinguishes AD from FTD and differentiates FTD subtypes. These subcortical structures represent promising biomarkers for diagnosis and monitoring of neurodegeneration.
What this study adds
Evidence grade: Moderate
This is a follow-up (cohort) study of 380 participants. Deep gray matter structures such as the thalamus, nucleus accumbens, and claustrum showed atrophy in both Alzheimer's disease and frontotemporal dementia, with greater and faster atrophy in behavioral variant frontotemporal dementia. Reported effect size: 96.8%; AUC = 0.99; 77.7%.
Taken from this record’s own fields, not from reading the paper. The grade is assigned from the abstract’s wording; what that means.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Banerjee, A., Yang, F., Dutta, J., Cacciola, A., Hornberger, M., & Saranathan, M. (2025). Atrophy patterns of deep gray matter nuclei in Alzheimer's disease and frontotemporal dementia. Journal of Alzheimer s Disease. https://doi.org/10.1177/13872877251390386
Vancouver
Banerjee A, Yang F, Dutta J, Cacciola A, Hornberger M, Saranathan M. Atrophy patterns of deep gray matter nuclei in Alzheimer's disease and frontotemporal dementia. Journal of Alzheimer s Disease. 2025. doi:10.1177/13872877251390386. PMID: 41160467.
BibTeX
@article{banerjee2025-41160467,
author = {Banerjee, Arit and Yang, Fan and Dutta, Joyita and Cacciola, Alberto and Hornberger, Michael and Saranathan, Manojkumar},
title = {{Atrophy patterns of deep gray matter nuclei in Alzheimer's disease and frontotemporal dementia}},
journal = {Journal of Alzheimer s Disease},
year = {2025},
doi = {10.1177/13872877251390386},
pmid = {41160467},
url = {https://doi.org/10.1177/13872877251390386}
}
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Key findings
- A hierarchical Random Forest model was trained to classify diagnostic groups.ResultsPronounced atrophy was observed in the mediodorsal, anteroventral, pulvinar thalamic nuclei, and nucleus accumbens, and claustrum in both AD and FTD, but was significantly greater in bvFTD.
- Longitudinal analysis revealed the fastest progression in bvFTD.
- Classification achieved 96.8% accuracy (AUC = 0.99) for AD versus FTD and 77.7% accuracy (AUC = 0.83) for PNFA versus svFTD.
Why it matters
Deep gray matter structures such as the thalamus, nucleus accumbens, and claustrum showed atrophy in both Alzheimer's disease and frontotemporal dementia, with greater and faster atrophy in behavioral variant frontotemporal dementia. A classification model distinguished the diseases with high accuracy, which is relevant to diagnosis rather than treatment.
Study details
- Study designlongitudinal study
- Participants380
- Effect size96.8%; AUC = 0.99; 77.7%
- Evidence strengthModerate
How this study scored 55/100
Published in a peer-reviewed journal, and it is a longitudinal study following the same people over time. Scored zero for randomized / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Journal of Alzheimer s Disease) |
| Journal's citation record | 2 / 4 | Journal of Alzheimer s Disease: journal h-index 218 (OpenAlex, 2026-10-29) |
| Study design | 7 / 12 | A longitudinal study following the same people over time |
| Strength of evidence | 3 / 5 | Rated “moderate” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 4 / 5 | 2025 — within 3 year(s) of the newest study here |
| Sample size | 2 / 4 | 380 participants |
| Effect reported | 3 / 3 | Effect reported with a statistic (interval, p-value, ratio or similar) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomized / blinded | 0 / 2 | No randomization or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 2 / 7 | Cited 8 times (OpenAlex, 2026-10-10) |
| Citations per year | 1 / 5 | 2.7 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 3 / 6 | Cited 5.1× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 0 / 6 | No other study in this library cites it |
| Still being cited | 1 / 4 | Cited 8 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Manojkumar Saranathan: h-index 31 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | University of Massachusetts Chan Medical School: institution h-index 990 (OpenAlex) |
| Multicenter collaboration | 2 / 3 | OpenAlex lists 5 institution(s) in 3 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 41160467) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 55 / 100 | — |
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