RESUMO
INTRODUCTION: Patients with subjective memory complaints (SMC) may include subgroups with different neuropsychological profiles and risks of cognitive impairment. METHODS: Cluster analysis was performed on two datasets (n: 630 and 734) comprising demographic and neuropsychological data from SMC and healthy controls (HC). Survival analyses were conducted on clusters. Bayesian model averaging assessed the predictive utility of clusters and other biomarkers. RESULTS: Two clusters with higher and lower than average cognitive performance were detected in SMC and HC. Assignment to the lower performance cluster increased the risk of cognitive impairment in both datasets (hazard ratios: 1.78 and 2.96; Plog-rank: 0.04 and <0.001) and was associated with lower hippocampal volumes and higher tau/amyloid beta 42 ratios in cerebrospinal fluid. The effect of SMC was small and confounded by mood. DISCUSSION: This study provides evidence of the presence of cognitive clusters that hold biological significance and predictive value for cognitive decline in SMC and HC. HIGHLIGHTS: Patients with subjective memory complaints include two cognitive clusters. Assignment to the lower performance cluster increases risk of cognitive impairment. This cluster shows a pattern of biomarkers consistent with incipient Alzheimer's disease pathology. The same cognitive cluster structure is found in healthy controls. The effect of memory complaints on risk of cognitive decline is small and confounded.
RESUMO
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.