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Clinical Manifestations.

Daliah Ross1,2, Molly Split1,2, Zachary J Kunicki1,2

  • 1Brown University, Providence, RI, USA.

Alzheimer'S & Dementia : the Journal of the Alzheimer'S Association
|December 24, 2025
PubMed
Summary
This summary is machine-generated.

Comorbid Alzheimer's disease neuropathologic change (ADNC) and frontotemporal lobar degeneration (FTLD) show distinct neuropsychiatric symptoms. These findings aid in diagnosing mixed neurodegenerative diseases and personalizing treatment strategies.

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Area of Science:

  • Neurology
  • Neuroscience
  • Pathology

Background:

  • Neurodegenerative diseases frequently co-occur, yet the clinical presentation of comorbid Alzheimer's disease neuropathologic change (ADNC) and frontotemporal lobar degeneration (FTLD) is poorly understood.
  • This study investigates neuropsychiatric symptoms in individuals with coexisting ADNC and FTLD neuropathology, compared to those with single pathologies.

Purpose of the Study:

  • To examine the association between comorbid ADNC and FTLD neuropathology and specific neuropsychiatric symptoms.
  • To compare the neuropsychiatric profiles of individuals with comorbid ADNC and FTLD against those with ADNC alone and FTLD alone.

Main Methods:

  • Utilized data from the National Alzheimer's Coordinating Center, analyzing neuropsychiatric symptoms in 919 individuals with varying ADNC and FTLD neuropathology.
  • Employed logistic regression to assess the odds of specific neuropsychiatric symptoms (apathy, delusions, disinhibition, etc.) based on neuropathology, controlling for demographic and clinical factors.

Main Results:

  • Individuals with FTLD-only pathology were less likely to exhibit delusions, irritability, and anxiety compared to those with comorbid ADNC and FTLD.
  • The ADNC-only group showed lower odds of disinhibition and personality change compared to the comorbid group.
  • Apathy, depression, hallucinations, agitation, and REM sleep behavior disorder did not significantly differ between the comorbid and single-pathology groups.

Conclusions:

  • Comorbid ADNC and FTLD neuropathology is linked to a higher likelihood of neuropsychiatric symptoms characteristic of each individual disease.
  • Specific symptoms like disinhibition and personality change differentiate comorbid ADNC/FTLD from ADNC alone, while delusions, irritability, and anxiety differentiate it from FTLD alone.
  • Recognizing these distinct behavioral symptoms is crucial for accurate diagnosis and precision medicine approaches in patients with mixed neurodegenerative pathologies.