Cognitive Heterogeneity and Risk of Progression in Data-Driven Subtle Cognitive Decline Phenotypes

Kelsey R Thomas; Katherine J Bangen; Alexandra J Weigand; Gema Ortiz; Kayla S Walker; David P Salmon; Mark W Bondi; Emily C Edmonds

doi:10.3233/JAD-220684

Cognitive Heterogeneity and Risk of Progression in Data-Driven Subtle Cognitive Decline Phenotypes

J Alzheimers Dis. 2022;90(1):323-331. doi: 10.3233/JAD-220684.

Authors

Kelsey R Thomas^{1

2}, Katherine J Bangen^{1

2}, Alexandra J Weigand³, Gema Ortiz¹, Kayla S Walker^{1

4}, David P Salmon⁵, Mark W Bondi^{2

6}, Emily C Edmonds^{7

8}

Affiliations

¹ Research Service, VA San Diego Healthcare System, San Diego, CA, USA.
² Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA.
³ San Diego State University/University of California, San Diego Joint Doctoral Program in Clinical Psychology, San Diego, CA, USA.
⁴ San Diego State University, San Diego, CA, USA.
⁵ Department of Neurosciences, University of California, San Diego, La Jolla, CA, USA.
⁶ Psychology Service, VA San Diego Healthcare System, San Diego, CA, USA.
⁷ Banner Alzheimer's Institute, Tucson, AZ, USA.
⁸ Department of Psychology, University of Arizona, Tucson, AZ, USA.

Abstract

Background: There is increasing recognition of cognitive and pathological heterogeneity in early-stage Alzheimer's disease and other dementias. Data-driven approaches have demonstrated cognitive heterogeneity in those with mild cognitive impairment (MCI), but few studies have examined this heterogeneity and its association with progression to MCI/dementia in cognitively unimpaired (CU) older adults.

Objective: We identified cluster-derived subgroups of CU participants based on comprehensive neuropsychological data and compared baseline characteristics and rates of progression to MCI/dementia or a Dementia Rating Scale (DRS) of ≤129 across subgroups.

Methods: Hierarchical cluster analysis was conducted on individual baseline neuropsychological test scores from 365 CU participants in the UCSD Shiley-Marcos Alzheimer's Disease Research Center longitudinal cohort. Cox regressions examined the risk of progression to consensus diagnosis of MCI or dementia, or to DRS score ≤129, by cluster group.

Results: Cluster analysis identified 5 groups: All-Average (n = 139), Low-Visuospatial (n = 46), Low-Executive (n = 51), Low-Memory/Language (n = 83), and Low-All Domains (n = 46). Subgroups had unique demographic and clinical characteristics. Rates of progression to MCI/dementia or to DRS ≤129 were faster for all subgroups (Low-All Domains progressed the fastest > Low Memory/Language≥Low-Visuospatial and Low-Executive) relative to the All-Average subgroup.

Conclusion: Faster progression in the Low-Visuospatial, Low-Executive, and Low-Memory/Language groups compared to the All-Average group suggests that there are multiple pathways and/or unique subtle cognitive decline profiles that ultimately lead to a diagnosis of MCI/dementia. Use of comprehensive neuropsychological test batteries that assess several domains may be a key first step toward an individualized approach to early detection and fewer missed opportunities for early intervention.

Keywords: Alzheimer’s disease; cognitive phenotypes; heterogeneity; subtle cognitive decline.

Publication types

Research Support, U.S. Gov't, Non-P.H.S.
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural

MeSH terms

Alzheimer Disease* / diagnosis
Cognition
Cognitive Dysfunction* / psychology
Disease Progression
Humans
Neuropsychological Tests
Phenotype

Abstract

Publication types

MeSH terms

Grants and funding