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Clinical Manifestations.

Yu Chen1, Electra Chatzidimitriou1,2, Howard J Rosen1

  • 1Department of Neurology, Memory and Aging Center, University of California San Francisco, San Francisco, CA, USA.

Alzheimer'S & Dementia : the Journal of the Alzheimer'S Association
|December 25, 2025
PubMed
Summary
This summary is machine-generated.

Early-stage behavioral variant frontotemporal dementia (bvFTD) shows significant social cognitive deficits linked to cerebellar degeneration. Cerebellar changes interact with brain networks, impacting social cognition more than previously thought.

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Area of Science:

  • Neuroscience
  • Cognitive Neurology
  • Neuroimaging

Background:

  • Social cognitive dysfunction is an early hallmark of behavioral variant frontotemporal dementia (bvFTD), causing caregiver distress.
  • Research traditionally focused on cortical networks, but emerging evidence suggests early cerebellar changes in bvFTD are linked to cognitive and neuropsychiatric symptoms.
  • The specific impact of cerebellar degeneration on social cognition and its relationship with cortical networks in bvFTD remains unclear.

Purpose of the Study:

  • To investigate the role of cerebellar subregion volumes in social cognitive deficits in early-stage bvFTD.
  • To examine the relationship between cerebellar degeneration and cortical networks involved in social cognition.
  • To determine if cerebellar measures improve prediction of social cognitive dysfunction in bvFTD.

Main Methods:

  • Evaluated 109 bvFTD individuals and 100 controls on Theory of Mind (ToM), emotion reading, and real-life empathy.
  • Extracted cerebellar subregion volumes from early structural MRIs using a precision cerebellar mapping atlas.
  • Utilized region-of-interest-based partial least squares correlation and voxel-wise structural covariance network analyses.

Main Results:

  • Individuals with early bvFTD performed significantly worse on all social cognition assessments compared to controls.
  • Significant volume loss in cerebellar subregions (Crus I, Crus II, lobules VIIb) correlated with deficits in all social domains, especially ToM and emotion reading.
  • Key cerebellar subregions showed increased covariance with cortical social cognition networks (e.g., salience network), and incorporating cerebellar measures improved predictive models.

Conclusions:

  • Cerebellar involvement and its interaction with cerebral networks play a significant role in early-stage bvFTD social cognition.
  • Posterior cerebellar subregions are critical contributors to social cognitive dysfunction in bvFTD.
  • Morphological covariance between cerebellar and cortical regions highlights the cerebellum's integrated role in brain networks governing social cognition.