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Clinical Manifestations.

Caitlin S Latimer1, Rod L Walker2, Marika Bogdani1

  • 1University of Washington, Seattle, WA, USA.

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

Alzheimer's disease (AD) dementia shows varied neuropathology across cognitive subgroups. Memory and language-impaired AD dementia subgroups had higher LATE and hippocampal sclerosis, while visuospatial-impaired subgroups had lower Thal phases.

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Area of Science:

  • Neuropathology
  • Neuroscience
  • Gerontology

Background:

  • Alzheimer's disease (AD) dementia is recognized as a heterogeneous condition.
  • Subgrouping AD dementia based on cognitive test performance at diagnosis may reveal distinct underlying pathologies.

Purpose of the Study:

  • To compare neuropathological findings across different subgroups of Alzheimer's disease dementia.
  • To investigate if cognitive profiles at diagnosis correlate with specific neuropathological markers.

Main Methods:

  • Utilized data from the Adult Changes in Thought (ACT) prospective cohort study.
  • Classified participants with probable or possible AD dementia into subgroups based on cognitive performance (memory, executive function, language, visuospatial).
  • Analyzed postmortem neuropathological data, including Alzheimer's type pathology, LATE, Lewy bodies, and hippocampal sclerosis, using ordinal logistic regression.

Main Results:

  • Examined 358 individuals with AD dementia, categorized into subgroups such as AD-Memory, AD-Language, AD-Visuospatial, and AD-Executive.
  • Found distinct patterns of neuropathology across subgroups: Thal phases were highest in AD-Memory and lowest in AD-Visuospatial.
  • Observed higher LATE stage and hippocampal sclerosis in AD-Language and AD-Memory subgroups compared to AD-Visuospatial.

Conclusions:

  • Neuropathological patterns differ significantly across cognitively defined subgroups of Alzheimer's disease dementia.
  • These findings support the heterogeneity of AD dementia at a neuropathological level.
  • Further research is needed to explore differences in natural history and other characteristics across these subgroups.