# Mapping the clinical correlates of brain hypoperfusion in behavioral variant frontotemporal dementia: insights from a SPECT imaging study

**Authors:** Electra Chatzidimitriou, Chrissa Sioka, Eleni Aretouli, Ioannis Iakovou, Panagiotis Ioannidis, Despina Moraitou

PMC · DOI: 10.3389/fnins.2026.1737054 · Frontiers in Neuroscience · 2026-02-04

## TL;DR

This study uses SPECT imaging to show how reduced blood flow in specific brain regions is linked to cognitive, behavioral, and personality changes in early-stage behavioral variant frontotemporal dementia.

## Contribution

The study identifies specific brain regions whose hypoperfusion correlates with distinct clinical features of bvFTD, offering new insights into brain-behavior relationships in this disorder.

## Key findings

- Reduced perfusion in right prefrontal regions correlates with increased behavioral disturbances and disease severity.
- Hypoperfusion in frontotemporal and limbic areas is associated with declines in personality traits like conscientiousness and extraversion.
- Distinct patterns of hypoperfusion in frontal, temporal, and limbic regions are linked to specific cognitive deficits such as memory and executive functions.

## Abstract

Behavioral variant frontotemporal dementia (bvFTD) is characterized by heterogeneous cognitive, behavioral, and personality changes, reflecting underlying disruptions in brain structure and function. Neuroimaging, particularly single-photon emission computed tomography (SPECT) assessment of regional cerebral blood flow (rCBF), provides a valuable functional window into these alterations. Despite advances in mapping perfusion abnormalities in bvFTD, the precise relationship between region-specific brain hypoperfusion and the full spectrum of clinical manifestations remains incompletely understood. The present study aims to systematically explore these associations to clarify the neurofunctional underpinnings of bvFTD and to delineate brain-behavior relationships across cognitive, behavioral, and personality domains.

rCBF was assessed in 25 individuals with early-stage bvFTD using 99mTc-HMPAO SPECT imaging, with analysis of lobar and Brodmann area (BA) perfusion performed via NeuroGam™ software. Participants underwent a comprehensive neuropsychological evaluation to assess cognitive functions, while behavioral disturbances and personality traits were evaluated through informant-based measures. Relationships between rCBF and clinical variables were examined using non-parametric correlation analyses, with correction for multiple comparisons.

Reduced perfusion in right prefrontal regions correlated with heightened behavioral disturbances (BAs 8 and 46) and overall disease severity (BA 8). In addition, greater hypoperfusion in frontotemporal and limbic areas was linked to more pronounced declines in personality traits, including conscientiousness (left BAs 6, 31) and extraversion (right BAs 8, 32; left BA 37). A pattern of statistically significant associations also emerged between rCBF in frontal, temporal, limbic, and parietal regions and domain-specific cognitive performances, including visuoconstructional abilities (right BA 5), memory skills (left BAs 28 and 31), executive functions (left BAs 6, 31; right BAs 5, 8), and social cognition (left BA 37; right BAs 11, 32, 40, 46). In contrast, global cognitive measures showed no significant association with regional perfusion.

These findings reveal that distinct patterns of regional hypoperfusion are selectively linked to specific cognitive, behavioral, and personality alterations in early-stage bvFTD, highlighting the neural substrates underlying its core clinical features. Identifying discrete brain regions associated with key symptoms may inform the development of more targeted therapeutic interventions, ultimately enhancing personalized management and care for individuals affected by this complex and highly disabling syndrome.

## Linked entities

- **Chemicals:** 99mTc-HMPAO (PubChem CID 11954234)
- **Diseases:** bvFTD (MONDO:0017160)

## Full-text entities

- **Genes:** C9orf72 (C9orf72-SMCR8 complex subunit) [NCBI Gene 203228] {aka ALSFTD, DENND9, DENNL72, FTDALS, FTDALS1}
- **Diseases:** impulsivity (MESH:D007174), Dementia (MESH:D003704), personality alterations (MESH:D010554), executive dysfunction (MESH:D006331), eating disorders (MESH:D001068), bipolar disorder (MESH:D001714), inhibitory control (MESH:C536209), multiple sclerosis (MESH:D009103), blunted affect (MESH:D014949), Behavioral variant frontotemporal dementia (MESH:D057180), Memory impairments (MESH:D008569), behavioral and/or cognitive deterioration (MESH:D003072), perfusion (MESH:D001480), epilepsy (MESH:D004827), abnormalities (MESH:D000014), emotional flatness (MESH:D005413), Brain perfusion abnormalities (MESH:D001927), impaired emotional regulation (MESH:C565631), FTLD (MESH:D057174), structural degeneration (MESH:D020914), neurodegenerative syndrome (MESH:D020271), language deficits (MESH:D007806), stroke (MESH:D020521), fatigue (MESH:D005221), major depressive disorder (MESH:D003865), executive and motivational deficits (MESH:D009461), behavioral dysregulation (MESH:D021081), impaired interpersonal processing (MESH:D001308), loss of (MESH:D016388), neurodegeneration (MESH:D019636), Parkinson's disease (MESH:D010300), vascular lesions (MESH:D014652), AD (MESH:D000544), Behavioral disturbances (MESH:D001523), social inappropriateness (MESH:D007177), DM (MESH:D009223), schizophrenia (MESH:D012559), atrophy (MESH:D001284), traumatic brain injury (MESH:D000070642)
- **Chemicals:** alcohol (MESH:D000438), BA (-), caffeine (MESH:D002110), 99mTc-HMPAO (MESH:D019690), FDG (MESH:D019788)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

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## References

75 references — full list in the complete paper: https://tomesphere.com/paper/PMC12913503/full.md

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Source: https://tomesphere.com/paper/PMC12913503