Structural neuroimaging changes associated with subjective cognitive decline from a clinical sample

Abstract

Background: Alzheimer's disease (AD) is characterized by progressive deterioration of cognitive functions. Some individuals with subjective cognitive decline (SCD) are in the early phase of the disease and subsequently progress through the AD continuum. Although neuroimaging biomarkers could be used for the accurate and early diagnosis of preclinical AD, the findings in SCD samples have been heterogeneous. This study established the morphological differences in brain magnetic resonance imaging (MRI) findings between individuals with SCD and those without cognitive impairment based on a clinical sample of patients defined according to SCD-Initiative recommendations. Moreover, we investigated baseline structural changes in the brains of participants who remained stable or progressed to mild cognitive impairment or dementia.

Methods: This study included 309 participants with SCD and 43 healthy controls (HCs) with high-quality brain MRI at baseline. Among the 99 subjects in the SCD group who were followed clinically, 32 progressed (SCDp) and 67 remained stable (SCDnp). A voxel-wise statistical comparison of gray and white matter (WM) volume was performed between the HC and SCD groups and between the HC, SCDp, and SCDnp groups. XTRACT ATLAS was used to define the anatomical location of WM tract damage. Region-of-interest (ROI) analyses were performed to determine brain volumetric differences. White matter lesion (WML) burden was established in each group.

Results: Voxel-based morphometry (VBM) analysis revealed that the SCD group exhibited gray matter atrophy in the middle frontal gyri, superior orbital gyri, superior frontal gyri, right rectal gyrus, whole occipital lobule, and both thalami and precunei. Meanwhile, ROI analysis revealed decreased volume in the left rectal gyrus, bilateral medial orbital gyri, middle frontal gyri, superior frontal gyri, calcarine fissure, and left thalamus. The SCDp group exhibited greater hippocampal atrophy (p < 0.001) than the SCDnp and HC groups on ROI analyses. On VBM analysis, however, the SCDp group exhibited increased hippocampal atrophy only when compared to the SCDnp group (p < 0.001). The SCD group demonstrated lower WM volume in the uncinate fasciculus, cingulum, inferior fronto-occipital fasciculus, anterior thalamic radiation, and callosum forceps than the HC group. However, no significant differences in WML number (p = 0.345) or volume (p = 0.156) were observed between the SCD and HC groups.

Conclusions: The SCD group showed brain atrophy mainly in the frontal and occipital lobes. However, only the SCDp group demonstrated atrophy in the medial temporal lobe at baseline. Structural damage in the brain regions was anatomically connected, which may contribute to early memory decline.

Keywords: Alzheimer’s disease; Magnetic resonance imaging; Region-of-interest; Subjective cognitive decline; Voxel-based morphometry; White matter lesions.

Fig. 1

Gray matter (GM) changes in participants with subjective cognitive decline (SCD) and healthy controls (HCs). SPM maps showing regions of decreased GM volume in the SCD group compared with the control group (P < 0.05 FWE cluster corrected) overlaid on anatomical T1-weighted images. Age, sex, education level, scanner type, and intracranial volume were included as covariates in the statistical model. Color scale shows the T-values. L = Left, R = Right.

Fig. 2

Gray matter (GM) changes among participants with subjective cognitive decline who did (SCDp) and did not exhibit clinical progression (SCDnp). SPM maps overlaid on anatomical T1-weighted images comparing the regions in which GM volume decreased between (a) the SCDnp and control groups (P < 0.05 FWE cluster corrected), (b) the SCDp and control groups (P < 0.05 FWE cluster corrected), and (c) the SCDp and SCDnp groups (P < 0.001 FWE uncorrected). Age, sex, education level, scanner type, and intracranial volume were included as covariates in the statistical model. Color scale shows the T-values. L = Left, R = Right.

Fig. 3

White matter (WM) changes in subjective cognitive decline (SCD) and healthy control (HC) groups. SPM maps overlaid on anatomical images and XTRACT atlas comparing the regions in which WM volume decreased between the SCD and control groups (P < 0.05 FWE cluster corrected). Age, sex, education level, scanner type, and intracranial volume were included as covariates in the statistical model. Map color definitions: cyan = forceps minor; dark blue = cinguli; dark green = forceps major; light blue = uncinate fasciculi; light green = both anterior thalamic radiations; purple = inferior fronto-occipital fasciculi. L = Left, R = Right. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)

Supplementary Fig. 1

Supplementary Fig. 2