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

Abstract

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.

Fig. 1

Venn Diagram representing the overlap of subjective cognitive decline (SCD) diagnosis between the four definitions of SCD. There was a total of 273 participants in the sample, 91/273 (33%) were SCD− with all definitions. The remaining 182 participants are shown in the Venn Diagram with the number of participants, the percentage of the overall SCD+ sample, and the fraction of the sample that was amyloid positive. Overall, there were 72/182 (40%) SCD participants that were amyloid positive. For the four SCD definitions, there were 97 SCD+ subjects defined by CCI, 143 SCD+ defined by ECog, 96 SCD+ defined by ECog &Worry, and 124 defined by Worry only. Finally, only 39% (n = 71) of the 182 SCD+ subjects are common between the four definitions.

Fig. 2

Significant t-statistic values obtained for regions of interest for each definition of subjective cognitive decline. Significant t-statistic values obtained for the categorical diagnosis variable (Subjective Cognitive Decline; SCD+ and SCD−) for the four definitions of SCD for the six regions tested (left/right hippocampus, amygdala, and superior temporal gyrus). Green regions indicate ROIs that were examined but were not significantly different between the groups. Colder blue colors indicate lower DBM values in SCD+ compared to SCD−. A) Cognitive Change Index analysis – smaller left hippocampal grading in SCD+ vs. SCD−. B) Everyday Cognition Scale analysis – smaller right hippocampal grading, right amygdala, and right and left superior temporal regions in SCD+ vs. SCD−. C) Everyday Cognition Scale + Worry analysis – smaller left hippocampal grading in SCD+ vs. SCD−. D) Worry analysis – smaller left hippocampal grading in SCD+ vs. SCD−. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)

Fig. 3

Longitudinal cognitive change by group for ADAS and MoCA. This figure shows the only significant differences in cognitive score for each definition. Longitudinal clinical change of each participant group as well as the group change over time is presented in each image. Red lines = SCD+; Blue lines = SCD−. A) Longitudinal change of ADAS scores when defining SCD− and SCD+ based on the CCI. B) Longitudinal change of Montreal Cognitive Assessment (MoCA) scores when defining SCD− and SCD+ based on ECog; C) Longitudinal change of MoCA scores when defining SCD− and SCD+ based on ECog + Worry; (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)