Data-driven classification of cognitively normal and mild cognitive impairment subtypes predicts progression in the NACC dataset

Emily C Edmonds; Kelsey R Thomas; Steven Z Rapcsak; Shannon L Lindemer; Lisa Delano-Wood; David P Salmon; Mark W Bondi

doi:10.1002/alz.13793

Data-driven classification of cognitively normal and mild cognitive impairment subtypes predicts progression in the NACC dataset

Alzheimers Dement. 2024 Apr 4. doi: 10.1002/alz.13793. Online ahead of print.

Authors

Emily C Edmonds^{1

2}, Kelsey R Thomas^{3

4}, Steven Z Rapcsak^{1

2

5}, Shannon L Lindemer¹, Lisa Delano-Wood^{4

6}, David P Salmon⁷, Mark W Bondi^{4

6}

Affiliations

¹ Banner Alzheimer's Institute, Tucson, Arizona, USA.
² Departments of Neurology and Psychology, University of Arizona, Tucson, Arizona, USA.
³ Research Service, Veterans Affairs San Diego Healthcare System, San Diego, California, USA.
⁴ Department of Psychiatry, University of California, San Diego, La Jolla, California, USA.
⁵ Department of Speech, Language, & Hearing Sciences, University of Arizona, Tucson, Arizona, USA.
⁶ Psychology Service, Veterans Affairs San Diego Healthcare System, San Diego, California, USA.
⁷ Department of Neurosciences, University of California, San Diego, La Jolla, California, USA.

PMID: 38574399
DOI: 10.1002/alz.13793

Abstract

Introduction: Data-driven neuropsychological methods can identify mild cognitive impairment (MCI) subtypes with stronger associations to dementia risk factors than conventional diagnostic methods.

Methods: Cluster analysis used neuropsychological data from participants without dementia (mean age = 71.6 years) in the National Alzheimer's Coordinating Center (NACC) Uniform Data Set (n = 26,255) and the "normal cognition" subsample (n = 16,005). Survival analyses examined MCI or dementia progression.

Results: Five clusters were identified: "Optimal" cognitively normal (oCN; 13.2%), "Typical" CN (tCN; 28.0%), Amnestic MCI (aMCI; 25.3%), Mixed MCI-Mild (mMCI-Mild; 20.4%), and Mixed MCI-Severe (mMCI-Severe; 13.0%). Progression to dementia differed across clusters (oCN < tCN < aMCI < mMCI-Mild < mMCI-Severe). Cluster analysis identified more MCI cases than consensus diagnosis. In the "normal cognition" subsample, five clusters emerged: High-All Domains (High-All; 16.7%), Low-Attention/Working Memory (Low-WM; 22.1%), Low-Memory (36.3%), Amnestic MCI (16.7%), and Non-amnestic MCI (naMCI; 8.3%), with differing progression rates (High-All < Low-WM = Low-Memory < aMCI < naMCI).

Discussion: Our data-driven methods outperformed consensus diagnosis by providing more precise information about progression risk and revealing heterogeneity in cognition and progression risk within the NACC "normal cognition" group.

Keywords: Alzheimer's disease; cluster analysis; cognitive subtypes; dementia; mild cognitive impairment; neuropsychology; preclinical Alzheimer's disease; subtle cognitive decline.

Abstract

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