Abstract

BackgroundSubjective cognitive decline (SCD) is characterized by self-reported cognitive deficits without measurable cognitive impairment. It has been suggested that individuals with SCD exhibited brain structural alterations in widespread cortical thinning or gray matter loss in the medial temporal and frontotemporal regions. Apolipoprotein E (APOE) ε4 allele is thought to be a genetic marker associated with risk of SCD. Neuropsychiatric symptoms may provide insight in detecting higher-risk elders for early Alzheimer’s disease as well. Therefore, we aim to explore the characteristics of brain morphology in SCD and to determine whether it is influenced by APOE ε4 as well as neuropsychiatric symptoms in SCD.MethodsA total of 138 cognitively normal older individuals from the SILCODE cohort underwent a clinical interview, neuropsychological assessments, a blood test, and MRI. A two-sample t-test was used to examine the cortex volume and bilateral cortical surface area alterations between SCD (n = 65) and controls (n = 73). A general linear model analysis was used to test for both main and interaction effects of clinical phenotype (SCD vs. controls) and APOE on global and regional cortex volume and bilateral cortical surface area and thickness. A multiple linear regression analysis was conducted to determine the effects of the APOE genotype on the relationships between morphometric features and neuropsychiatric symptoms in SCD.ResultsCompared with controls, individuals with SCD showed decreased total cortical volumes and cortical surface area. SCD APOE ε4 carriers showed additive reduction in the right cortical surface area. The evaluation scores of anxiety symptoms were negatively associated with the right cortical surface area in SCD APOE 4 non-carriers.ConclusionsIndividuals with SCD had an altered cortical surface area, and APOE genotype and anxiety symptoms are modified factors on the cortical surface area decrease in SCD.Trial registrationClinicalTrials.gov (Identifier: NCT03370744). Registered 15 March 2017.

Highlights

  • Subjective cognitive decline (SCD) is characterized by self-reported cognitive deficits without measurable cognitive impairment

  • Individuals with SCD may show a higher risk for biomarker patterns indicative of Alzheimer’s disease (AD) pathology, suggesting that SCD are at an increased risk for progressing to mild cognitive impairment (MCI) or AD [1,2,3,4]

  • We aim to investigate the characteristics of the cortical surface area in individuals with SCD compared to controls, and whether Apolipoprotein E (APOE) ε4 statue and neuropsychiatric symptoms influenced the cortical surface area, which may help improve the sensitivity of structural imaging studies to provide a separate morphologic index of SCD with genetic and neuropsychiatric risk factors

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Summary

Introduction

Subjective cognitive decline (SCD) is characterized by self-reported cognitive deficits without measurable cognitive impairment. It has been suggested that individuals with SCD exhibited brain structural alterations in widespread cortical thinning or gray matter loss in the medial temporal and frontotemporal regions. Subjective cognitive decline (SCD) is a clinical state characterized by subjective cognitive deficits without measurable cognitive impairment. Previous studies have identified that individuals with SCD showed structural gray matter volume reductions and cortical thinning in the bilateral entorhinal cortex [5], medial temporal, and frontotemporal regions [6] compared to cognitively normal elders without cognitive complaints. SCD has known associations with an AD-like pattern of gray matter atrophy [7], and the widespread cortical thinning is associated with faster subsequent decline in memory [8]. In this study, we employed surface-based analysis to detect cortical morphology which would be better suitable to manifest the subtle structural changes under early stages

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