# Differences in Glucose Metabolism Between Single Memory Domain and Multidomain Subjective Cognitive Decline: A Longitudinal Study From SILCODE

## TL;DR

This study finds that multidomain subjective cognitive decline is linked to lower glucose metabolism in specific brain regions and higher risk of cognitive decline compared to single memory domain cases.

## Contribution

The study identifies distinct glucose metabolism patterns and biomarker correlations in multidomain versus single memory domain subjective cognitive decline.

## Key findings

- Multidomain SCD shows lower glucose metabolism in brain regions like the anterior cingulate and middle temporal gyri compared to single memory domain SCD.
- SUVR in multidomain SCD correlates with plasma Aβ42/40 and cognitive scores, but not in single memory domain SCD.
- SCD individuals with positive biomarkers or in the multidomain group have a higher risk of cognitive decline conversion.

## Abstract

Glucose metabolism and plasma biomarkers have emerged as important early markers in Alzheimer's disease. Different subtypes (single memory domain, multidomain) of subjective cognitive decline (SCD) may represent distinct stages of disease progression, but the differences in glucose metabolism remain unclear. This study focused on exploring the differences in glucose metabolism between different SCD subtypes and the correlation with plasma biomarkers based on 18F‐FDG PET.

In this study, thirty‐three normal controls (NCs), thirty‐five individuals with single memory domain SCD (sd‐SCD), thirty‐nine individuals with multidomain SCD (md‐SCD), and twenty‐one cognitively impaired (CI) individuals were involved. We investigated the standardized uptake value ratio (SUVR) and voxel differences between the sd‐SCD and md‐SCD groups followed by FDR and GRF corrections, with an average follow‐up time of 44.98 ± 16.49 months. Correlation analyses were employed to assess relationships between FDG‐PET SUVR and neuropsychological scales as well as plasma biomarkers. Finally, Kaplan–Meier survival analysis was used to investigate the risk of cognitive decline conversion among SCD subgroups.

After controlling for the effects of covariates, the following brain regions showed voxel differences and lower SUVR in md‐SCD groups, including right anterior cingulate and paracingulate gyri (ACG.R, p = 0.003), left anterior cingulate and paracingulate gyri (ACG.L, p = 0.003), right middle temporal gyrus (MTG.R, p = 0.004), and right inferior temporal gyrus (ITG.R, p = 0.001), compared to the sd‐SCD group. SUVR of ACG.R was correlated with plasma Aβ42/40 (r = 0.435, p = 0.006) and AVLT‐N7 score (r = 0.347, p = 0.031) in the md‐SCD group while none of the correlations existed in the sd‐SCD group. SUVR of MTG.R was also correlated with the AVLT‐N7 score (r = 0.246, p = 0.035) across SCD individuals. The SCD individuals with positive plasma Aβ42/40, p‐tau181, and glucose metabolism in above four regions, or those in the md‐SCD group showed an elevated risk of cognitive conversion in comparison to the controls.

Differences in glucose metabolism could be observed between the md‐SCD and sd‐SCD groups. SCD participants in the md‐SCD group, or those with positive biomarkers, might represent a higher risk of cognitive decline conversion.

The study highlights differences in glucose metabolism between two SCD subtypes, indicating that md‐SCD individuals or SCD individuals with high‐risk factors including positive plasma Aβ42/40, p‐tau181, and glucose metabolism biomarkers, might exhibit an increased risk of cognitive decline. This provides a new valuable clinical biomarker for timely diagnosis, identifying high‐risk individuals, and predicting cognitive conversion.