Mapping the clinical correlates of brain hypoperfusion in behavioral variant frontotemporal dementia: insights from a...

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.