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Clinical Manifestations.

Douglas Teixeira Leffa1, Guilherme Povala1, Pamela C L Ferreira1

  • 1University of Pittsburgh, Pittsburgh, PA, USA.

Alzheimer'S & Dementia : the Journal of the Alzheimer'S Association
|December 26, 2025
PubMed
Summary
This summary is machine-generated.

Lewy body (LB) pathology in Alzheimer's disease (AD) is linked to increased neuropsychiatric symptoms like anxiety and psychosis. Detecting LB pathology in vivo may help identify individuals at higher risk for these symptoms.

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Area of Science:

  • Neurology
  • Neuroscience
  • Geriatrics

Background:

  • Co-pathology, including Lewy body (LB) pathology, is common in Alzheimer's disease (AD) dementia.
  • Previous studies suggest a link between AD and LB co-pathology and neuropsychiatric symptoms (NPS).
  • The impact of in vivo measured LB pathology on NPS in AD remains underexplored.

Purpose of the Study:

  • To evaluate the cross-sectional and longitudinal effects of in vivo measured LB pathology on NPS in individuals across the AD continuum.
  • To investigate the association between LB pathology and specific NPS, including anxiety, apathy, motor disturbances, appetite disturbances, and psychosis.
  • To determine if LB pathology's effects on NPS are independent of amyloid-beta (Aβ) and tau pathologies.

Main Methods:

  • Analysis of data from 1,169 participants in the Alzheimer's Disease Neuroimaging Initiative (ADNI).
  • In vivo LB pathology was measured using CSF alpha-synuclein seed amplification assays.
  • Neuropsychiatric assessments were conducted using the NPI-Q, with longitudinal follow-up up to 10 years. Logistic and Cox proportional hazard regression models were used.

Main Results:

  • Cross-sectionally, LB pathology was associated with higher rates of anxiety, apathy, motor disturbances, and appetite disturbances.
  • Longitudinally, LB pathology increased the risk of developing psychosis and anxiety.
  • These associations remained significant and independent of Aβ and tau levels.

Conclusions:

  • In vivo detected LB pathology is associated with a higher frequency of NPS in individuals with AD.
  • Apathy, motor disturbances, appetite changes, anxiety, and psychosis may be early manifestations of LB pathology in AD.
  • In vivo LB detection can serve as a valuable marker for identifying individuals at elevated risk of NPS in clinical trials and practice.