Clusters of cognitive performance predict long-term cognitive impairment in elderly patients with subjective memory complaints and healthy controls

Alzheimers Dement. 2024 Jul;20(7):4702-4716. doi: 10.1002/alz.13903. Epub 2024 May 23.

Abstract

Introduction: Patients with subjective memory complaints (SMC) may include subgroups with different neuropsychological profiles and risks of cognitive impairment.

Methods: Cluster analysis was performed on two datasets (n: 630 and 734) comprising demographic and neuropsychological data from SMC and healthy controls (HC). Survival analyses were conducted on clusters. Bayesian model averaging assessed the predictive utility of clusters and other biomarkers.

Results: Two clusters with higher and lower than average cognitive performance were detected in SMC and HC. Assignment to the lower performance cluster increased the risk of cognitive impairment in both datasets (hazard ratios: 1.78 and 2.96; Plog-rank: 0.04 and <0.001) and was associated with lower hippocampal volumes and higher tau/amyloid beta 42 ratios in cerebrospinal fluid. The effect of SMC was small and confounded by mood.

Discussion: This study provides evidence of the presence of cognitive clusters that hold biological significance and predictive value for cognitive decline in SMC and HC.

Highlights: Patients with subjective memory complaints include two cognitive clusters. Assignment to the lower performance cluster increases risk of cognitive impairment. This cluster shows a pattern of biomarkers consistent with incipient Alzheimer's disease pathology. The same cognitive cluster structure is found in healthy controls. The effect of memory complaints on risk of cognitive decline is small and confounded.

Keywords: Alzheimer's disease; Bayesian model averaging; biomarkers; cluster analysis; cognitive impairment; neuropsychological profiles; subjective memory complaints.

Publication types

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

MeSH terms

  • Aged
  • Amyloid beta-Peptides / cerebrospinal fluid
  • Bayes Theorem
  • Biomarkers / cerebrospinal fluid
  • Cluster Analysis
  • Cognitive Dysfunction* / cerebrospinal fluid
  • Female
  • Hippocampus / pathology
  • Humans
  • Male
  • Memory Disorders*
  • Middle Aged
  • Neuropsychological Tests* / statistics & numerical data
  • Peptide Fragments / cerebrospinal fluid
  • tau Proteins / cerebrospinal fluid

Substances

  • Amyloid beta-Peptides
  • tau Proteins
  • Biomarkers
  • Peptide Fragments