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Peer-reviewedCC BY 4.0Alzheimer's & Dementia

Neuropathologic features of cognitively defined Alzheimer's disease subgroups in the Adult Changes in Thought study

  • Caitlin S. Latimer1
  • Rod L. Walker2
  • Marika Bogdani1
  • C. Dirk Keene3
  • Amber L. Nolan1
  • Daniel D. Child3
  • Shubhabrata Mukherjee4
  • Seo‐Eun Choi2
  • Michael L. Lee2
  • Connie Nakano2
  • Kelly Ehrlich2
  • Linda K. McEvoy2
1 more authors
  • Paul K. Crane4
4 affiliations
  1. 1Department of Laboratory Medicine and Pathology University of Washington Seattle Washington USA
  2. 2Kaiser Permanente Washington Health Research Institute Seattle Washington USA
  3. 3Department of Pathology University of California, San Diego San Diego California USA
  4. 4Department of Medicine University of Washington Seattle Washington USA
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Abstract

BACKGROUND: Individuals with Alzheimer's disease (AD) dementia can be subgrouped based on cognitive performance at diagnosis. We compared neuropathology across cognitively defined AD subgroups in the Adult Changes in Thought study.

METHODS: Scores for memory, executive functioning, language, and visuospatial abilities were derived from the Cognitive Abilities Screening Instrument and a neurocognitive battery. Subgroups were defined by relative performance within domains. Standardized neuropathologic evaluation was performed post mortem. Associations were estimated using ordinal logistic regression, with odds ratios (OR) and 95% confidence intervals (CIs) comparing neuropathology between the AD subgroups and relative to individuals without dementia.

RESULTS: Of 885 participants with post mortem neuropathology, 370 had AD dementia: 54% AD–no domain, 15% AD–memory, 15% AD–visuospatial, 8% AD–language, and 7% AD–executive. Among AD subgroups, associations were detected for limbic‐predominant age‐related transactive response DNA binding protein 43 kDa encephalopathy neuropathologic change (LATE‐NC; P = 0.019) and hippocampal sclerosis (HS; P = 0.006), with highest levels in AD–language (LATE‐NC OR 2.37, 95% CI 1.03–5.46 and HS OR 2.19, 95% CI 0.88–5.50) and AD–memory (LATE‐NC OR 1.88, 95% CI 1.02–3.46 and HS OR 3.11, 95% CI 1.56–6.20) relative to AD–no domain, and lowest levels in AD–visuospatial. AD–visuospatial tended to have lowest estimated Alzheimer's disease neuropathologic change (ADNC) burden across AD subgroups. Relative to participants without dementia, all AD subgroups expectedly had higher ADNC burden, and several AD subgroups had higher odds of Lewy body pathology (P = 0.017) and gross infarcts (P = 0.004), with broadly similar estimates across multiple AD subgroups.

DISCUSSION: Neuropathologic patterns of ADNC and co‐pathologies across AD dementia subgroups suggest cognitive phenotyping may inform clinicopathologic studies of AD dementia.

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Cite

BibTeXRIS
BibTeX
@article{latimer2026neuropathologic,
  title = {{Neuropathologic features of cognitively defined Alzheimer's disease subgroups in the Adult Changes in Thought study}},
  author = {Caitlin S. Latimer and Rod L. Walker and Marika Bogdani and C. Dirk Keene and Amber L. Nolan and Daniel D. Child and Shubhabrata Mukherjee and Seo‐Eun Choi and Michael L. Lee and Connie Nakano and Kelly Ehrlich and Linda K. McEvoy and Paul K. Crane},
  journal = {Alzheimer's \& Dementia},
  year = {2026},
  month = oct,
  doi = {10.1002/alz.71938},
  url = {https://doi.org/10.1002/alz.71938},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Neuropathologic features of cognitively defined Alzheimer's disease subgroups in the Adult Changes in Thought study
AU  - Caitlin S. Latimer
AU  - Rod L. Walker
AU  - Marika Bogdani
AU  - C. Dirk Keene
AU  - Amber L. Nolan
AU  - Daniel D. Child
AU  - Shubhabrata Mukherjee
AU  - Seo‐Eun Choi
AU  - Michael L. Lee
AU  - Connie Nakano
AU  - Kelly Ehrlich
AU  - Linda K. McEvoy
AU  - Paul K. Crane
PY  - 2026
DA  - 2026/10/01
JO  - Alzheimer's & Dementia
DO  - 10.1002/alz.71938
UR  - https://doi.org/10.1002/alz.71938
AB  - BACKGROUND: Individuals with Alzheimer's disease (AD) dementia can be subgrouped based on cognitive performance at diagnosis. We compared neuropathology across cognitively defined AD subgroups in the Adult Changes in Thought study.  METHODS: Scores for memory, executive functioning, language, and visuospatial abilities were derived from the Cognitive Abilities Screening Instrument and a neurocognitive battery. Subgroups were defined by relative performance within domains. Standardized neuropathologic evaluation was performed post mortem. Associations were estimated using ordinal logistic regression, with odds ratios (OR) and 95% confidence intervals (CIs) comparing neuropathology between the AD subgroups and relative to individuals without dementia.  RESULTS: Of 885 participants with post mortem neuropathology, 370 had AD dementia: 54% AD–no domain, 15% AD–memory, 15% AD–visuospatial, 8% AD–language, and 7% AD–executive. Among AD subgroups, associations were detected for limbic‐predominant age‐related transactive response DNA binding protein 43 kDa encephalopathy neuropathologic change (LATE‐NC; P = 0.019) and hippocampal sclerosis (HS; P = 0.006), with highest levels in AD–language (LATE‐NC OR 2.37, 95% CI 1.03–5.46 and HS OR 2.19, 95% CI 0.88–5.50) and AD–memory (LATE‐NC OR 1.88, 95% CI 1.02–3.46 and HS OR 3.11, 95% CI 1.56–6.20) relative to AD–no domain, and lowest levels in AD–visuospatial. AD–visuospatial tended to have lowest estimated Alzheimer's disease neuropathologic change (ADNC) burden across AD subgroups. Relative to participants without dementia, all AD subgroups expectedly had higher ADNC burden, and several AD subgroups had higher odds of Lewy body pathology (P = 0.017) and gross infarcts (P = 0.004), with broadly similar estimates across multiple AD subgroups.  DISCUSSION: Neuropathologic patterns of ADNC and co‐pathologies across AD dementia subgroups suggest cognitive phenotyping may inform clinicopathologic studies of AD dementia.
SN  - 1552-5260
SN  - 1552-5279
ER  -