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Clinical Manifestations.

Jacob Ziontz1, Piyush Maiti2, Jiaxiuxiu Zhang2

  • 1Memory and Aging Center, Weill Institute for Neurosciences, 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.

Asymmetric neuroimaging patterns are common in early-onset Alzheimer's disease (EOAD) and linked to specific cognitive deficits. Analyzing this asymmetry may help predict early cognitive decline in diverse EOAD presentations.

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Area of Science:

  • Neuroimaging
  • Alzheimer's Disease Research
  • Cognitive Neuroscience

Background:

  • Asymmetrical neuroimaging findings are noted in Alzheimer's disease (AD).
  • The prevalence and impact of asymmetry in early-onset AD (EOAD) phenotypes remain unclear.

Purpose of the Study:

  • To investigate the prevalence and clinical correlations of neuroimaging asymmetry in early-onset Alzheimer's disease (EOAD).
  • To explore the relationship between asymmetry patterns and specific cognitive deficits in heterogeneous EOAD presentations.

Main Methods:

  • Analyzed PET (florbetaben, flortaucipir) and MRI data from 373 amyloid-PET-positive EOAD patients (MCI or mild dementia).
  • Calculated global and voxelwise asymmetry indices using Freesurfer segmentation.
  • Correlated imaging asymmetry with clinical phenotypes (amnestic/nonamnestic EOAD, PPA, PCA) and cognitive performance.

Main Results:

  • Global asymmetry was observed across imaging modalities, particularly with flortaucipir tau PET.
  • Asymmetry patterns varied by clinical phenotype (e.g., left-lateralized in PPA, right-lateralized in PCA).
  • Flortaucipir asymmetry robustly correlated with worse cognitive performance, especially verbal fluency, working memory, and visuospatial recall.

Conclusions:

  • Asymmetric neuroimaging is prevalent in EOAD and associated with clinical presentation.
  • Specific patterns of asymmetry may predict early cognitive deficits in diverse EOAD subtypes.
  • Neuroimaging asymmetry offers potential for predicting cognitive manifestations in early-onset Alzheimer's disease.