Abstract
Subjective cognitive decline (SCD), a self-reported worsening in cognition concurrent with normal performance on standardized neuropsychological tests, has gained much attention due to its high risks in the development of mild cognitive impairments or Alzheimer’s disease. The existing cross-sectional diffusion tensor imaging (DTI) studies in SCD have shown extremely controversial findings. Furthermore, all of these studies investigated diffusion properties within the voxel, such as fractional anisotropy, mean diffusivity, or axial diffusivity (DA). However, it remains unclear whether individuals with SCD demonstrate alterations of diffusion profile between voxels and their neighbors, as indexed by local diffusion homogeneity (LDH). We selected 30 healthy controls (HCs) and 23 SCD subjects to acquire their whole-brain DTI. Diffusion images were compared using the tract-based spatial statistics method. Diffusion indices with significant between-group tract clusters were extracted from each individual for further region-of-interest (ROI)-based comparisons. Our results showed that subjects with SCD demonstrated reduced LDH in the left superior frontal gyrus (SFG) and DA in the right anterior cingulate cortex compared with the HC group. In contrast, the SCD group showed higher LDH values in the left lingual gyrus (LG) compared with the HC group. Notably, LDH in the left SFG was significantly and negatively correlated with LDH in the left LG. In conclusion, white matter (WM) integrity in the left SFG, right ACC, and left LG is altered in SCD, suggesting that individuals with SCD exhibit detectable changes in WM tracts before they demonstrate objective cognitive deficits.
Highlights
There is a consensus that amnestic mild cognitive impairment stands in an intermediate stage between normal aging and Alzheimer’s disease (AD), several lines of evidence from large-cohort follow-up studies have suggested subjective cognitive decline (SCD) as a pre-MCI stage in the AD spectrum (Jessen et al, 2010; Albert et al, 2011; Molinuevo et al, 2017)
The voxel-wise TBSS analysis showed that compared with healthy controls (HCs), Subjective cognitive decline (SCD) had significantly lower DA values of the right anterior cingulate cortex (ACC, cluster size = 4) and lower local diffusion homogeneity (LDH) values of left superior frontal gyrus (SFG, cluster size = 6)
Considering the whole-brain diffusion tensor imaging (DTI) analysis and ROI-based analysis, our results showed that individuals with SCD demonstrated reduced LDH in the left SFG and DA in the right ACC as compared with the HC group
Summary
There is a consensus that amnestic mild cognitive impairment (aMCI) stands in an intermediate stage between normal aging and Alzheimer’s disease (AD), several lines of evidence from large-cohort follow-up studies have suggested subjective cognitive decline (SCD) as a pre-MCI stage in the AD spectrum (Jessen et al, 2010; Albert et al, 2011; Molinuevo et al, 2017). SCD is defined as a self-reported cognitive decline, relevant for the memory domain, concurrent with normal performance (adjusted by age and education) in the assessments of objective neuropsychological functions; the identification of SCD cannot be explained by other neurological diseases (e.g., MCI and AD), psychiatric diseases (e.g., anxiety disorder and depressive disorder), medication, or substance use (Jessen et al, 2014, 2020). Since neuropsychological assessments are not sensitive enough to distinguish individuals with SCD from those without SCD, neuroimaging technology provides a promising window to study the neural basis of SCD
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