# Frontal Lobe and Subregional Volumetric Alterations Across Alzheimer’s Disease, Amnestic Mild Cognitive Impairment, and Vascular Dementia: An MRI Volumetry Study

**Authors:** Stefan Stojanoski, Katarina Karher, Duško Kozić, Siniša S. Babović, Miloš Vuković, Katarina Koprivšek

PMC · DOI: 10.3390/brainsci16030317 · Brain Sciences · 2026-03-16

## TL;DR

This study used MRI scans to find that Alzheimer’s disease is linked to reduced overall frontal lobe volume, but not specific subregions, while vascular dementia showed no clear frontal volume patterns.

## Contribution

The study provides new insights into global frontal lobe volume changes in Alzheimer’s disease using automated MRI volumetry.

## Key findings

- Alzheimer’s disease patients had significantly lower total frontal lobe volume compared to controls and aMCI.
- Subregional frontal volume differences were observed but did not survive multiple testing corrections.
- Vascular dementia did not show consistent frontal volumetric patterns.

## Abstract

Background: Frontal lobe involvement represents an important but heterogeneously expressed feature across neurodegenerative and vascular cognitive disorders. While frontal atrophy has been described in Alzheimer’s disease (AD), detailed volumetric assessment of frontal subregions across Alzheimer’s disease, amnestic mild cognitive impairment (aMCI), and vascular dementia (VaD) remains insufficiently characterized. The aim of this study was to evaluate frontal lobe and frontal subregional volumetric alterations across these diagnostic groups using automated MRI-based volumetry. Methods: This cross-sectional study included 120 participants divided into four groups: AD, VaD, aMCI, and cognitively healthy controls (n = 30 per group). All participants underwent standardized neuropsychological assessment and 3T brain MRI. Automated volumetric analysis of the frontal lobe and its subregions was performed using the Vol2Brain pipeline. Group differences in total intracranial volume–adjusted frontal volumes were assessed using analysis of covariance, controlling for age and sex, followed by Bonferroni-corrected post hoc comparisons. False discovery rate (FDR) correction was applied across subregional comparisons. Results: A significant main effect of diagnostic group was observed for total frontal lobe volume, with lower adjusted volumes in patients with AD compared with aMCI and cognitively healthy controls. After correction for multiple comparisons, only total frontal lobe volume remained statistically significant. At the nominal level, group differences were observed in several frontal subregions, predominantly involving prefrontal and orbitofrontal areas. However, these findings did not survive FDR correction and should be interpreted as exploratory. No consistent frontal volumetric pattern was observed in VaD. Receiver operating characteristic analysis demonstrated moderate discriminatory ability of total frontal lobe volume for distinguishing AD from cognitively healthy controls. Conclusions: Automated MRI-based volumetry revealed global frontal lobe reduction in Alzheimer’s disease, whereas subregional findings were exploratory after correction for multiple testing. Frontal volumetric measures did not demonstrate a characteristic pattern in VaD. Global frontal volume may provide complementary structural information within clinically define cognitive disorders.

## Linked entities

- **Diseases:** Alzheimer’s disease (MONDO:0004975), vascular dementia (MONDO:0004648)

## Full-text entities

- **Genes:** MAPT (microtubule associated protein tau) [NCBI Gene 4137] {aka DDPAC, FTD1, FTDP-17, MAPTL, MSTD, MTBT1}
- **Diseases:** Cognitive Impairment (MESH:D003072), small vessel disease (MESH:D059345), neurodegeneration (MESH:D019636), lacunar infarcts (MESH:D059409), Stroke (MESH:D020521), Amnestic Mild Cognitive Impairment (MESH:D060825), White matter hyperintensities (MESH:D056784), injury to (MESH:D014947), Orbitofrontal atrophy (MESH:D001284), Depression (MESH:D003866), Neurological Disorders (MESH:D009461), AD (MESH:D000544), VaD (MESH:D015140), cortical degeneration (MESH:D009410), head trauma (MESH:D006259), vascular lesion (MESH:D014652), prefrontal degeneration (MESH:C536329), Dementia (MESH:D003704), frontal dysfunction (MESH:D001927), brain atrophy (MESH:C566985)
- **Chemicals:** Vol2Brain (-)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

2 figures with captions in the complete paper: https://tomesphere.com/paper/PMC13024419/full.md

## References

60 references — full list in the complete paper: https://tomesphere.com/paper/PMC13024419/full.md

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Source: https://tomesphere.com/paper/PMC13024419