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Updated: Jan 20, 2026

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Cognitive function and neuropathological outcomes: a forward-looking approach.

Elizabeth Munoz1,2, Teresa Filshtein3, Brianne M Bettcher4

  • 1Department of Human Development and Family Sciences, University of Texas at Austin, Austin, TX, 78712, USA. Elizabeth.Munoz@austin.utexas.edu.

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PubMed
Summary
This summary is machine-generated.

Cognitive decline in older adults may indicate a higher risk of Alzheimer's disease (AD) neuropathology. Lower cognitive scores increase the likelihood of advanced AD-related brain changes found at autopsy.

Keywords:
Alzheimer’s diseaseCognitionMulti-state modelNeuropathology

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Area of Science:

  • Neuropathology
  • Cognitive Neuroscience
  • Gerontology

Background:

  • Alzheimer's disease (AD) is a progressive neurodegenerative disorder.
  • Assessing neuropathological burden in living individuals is challenging.
  • Cognitive function is a key indicator of brain health in aging populations.

Purpose of the Study:

  • To evaluate the association between cognitive status and Alzheimer's disease-related neuropathology.
  • To determine the risk of neuropathological burden at autopsy based on current cognitive performance.
  • To explore the utility of cognitive assessments in predicting AD pathology.

Main Methods:

  • Utilized multi-state Cox proportional hazard models on data from the Religious Orders Study (ROS) and Rush Memory and Aging Project (MAP).
  • Analyzed cognitive status (global cognition, episodic memory) and autopsy-confirmed neuropathological data (Braak Stages, CERAD, TDP-43).
  • Included 1,303 ROS and 1,789 MAP participants, with approximately 50% deceased at the time of analysis.

Main Results:

  • A cognitive test score one standard deviation below average was associated with up to a threefold increased risk of high-level neuropathology (Braak Stages 5-6, CERAD 3, TDP-43 3) at autopsy.
  • This association remained significant after adjusting for demographic and clinical factors including sex, APOE-e4 status, smoking, education, and vascular health.
  • Cognitive performance is a strong predictor of underlying AD-related brain changes.

Conclusions:

  • Multi-state modeling effectively identifies individuals at risk for specific neuropathological burdens based on cognitive test results.
  • Current cognitive status offers a valuable, non-invasive method for estimating the risk of significant Alzheimer's disease neuropathology.
  • This approach holds promise for improving early diagnosis and guiding treatment development for AD.