Regional brain atrophy and cognitive decline depend on definition of subjective cognitive decline

Neuroimage Clin. 2022;33:102923. doi: 10.1016/j.nicl.2021.102923. Epub 2021 Dec 21.


Background: People with subjective cognitive decline (SCD) may be at increased risk for Alzheimer's disease (AD). However, not all studies have observed this increased risk. This project examined whether four common methods of defining SCD yields different patterns of atrophy and future cognitive decline between cognitively normal older adults with (SCD+ ) and without SCD (SCD-).

Methods: Data from 273 Alzheimer's Disease Neuroimaging Initiative cognitively normal older adults were examined. To operationalize SCD we used four common methods: Cognitive Change Index (CCI), Everyday Cognition Scale (ECog), ECog + Worry, and Worry. Voxel-based logistic regressions were applied to deformation-based morphology results to determine if regional atrophy between SCD- and SCD+ differed by SCD definition. Linear mixed-effects models were used to evaluate differences in future cognitive decline.

Results: Results varied between the four methods of defining SCD. Left hippocampal grading was more similar to AD in SCD+ than SCD- when using the CCI (p = .041) and Worry (p = .021) definitions. The right (p=.008) and left (p=.003) superior temporal regions had smaller volumes in SCD+ than SCD-, but only with the ECog. SCD+ was associated with greater future cognitive decline measured by Alzheimer's Disease Assessment Scale, but only with the CCI definition. In contrast, only the ECog definition of SCD was associated with future decline on the Montreal Cognitive Assessment.

Conclusion: These findings suggest that the various methods used to differentiate between SCD- and SCD+ influence whether volume differences and findings of cognitive decline are observed between groups in this retrospective analysis.

Keywords: Alzheimer’s disease; Cognitive decline; Deformation based morphometry; Magnetic resonance imaging; Regional atrophy; Subjective cognitive decline.

Publication types

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

MeSH terms

  • Aged
  • Alzheimer Disease* / diagnostic imaging
  • Alzheimer Disease* / pathology
  • Atrophy / pathology
  • Brain / diagnostic imaging
  • Brain / pathology
  • Cognitive Dysfunction* / pathology
  • Hippocampus
  • Humans
  • Magnetic Resonance Imaging / methods
  • Neuropsychological Tests
  • Retrospective Studies