Subjective memory complaints, cortical thinning, and cognitive dysfunction in middle‐age adults at risk of AD

Abstract Background Subjective memory complaints (SMCs) represent an individual's perception of subtle changes in memory in the absence of objective impairment in memory. However, it is not fully known whether persons with SMCs harbor brain alterations related to Alzheimer's disease (AD) or whether they indeed demonstrate poorer cognitive performance. Methods The participants were 261 middle‐age adults (mean age 54.30 years) enrolled in the Wisconsin Registry for Alzheimer's Prevention, a registry of cognitively normal adults at risk of AD. They answered a question pertaining to subjective memory, completed a comprehensive neuropsychological examination, and subsequently underwent a volumetric magnetic resonance imaging scan. Cortical thickness measurements were derived from 10 a priori regions of interest involved in AD. Analyses of covariance were conducted to investigate the group differences in cortical thickness and neuropsychological measures. Results Compared with individuals without SMCs, those with SMCs had significant cortical thinning in the entorhinal, fusiform, posterior cingulate, and inferior parietal cortices and significantly reduced amygdala volume. Similarly, those with SMCs had significantly lower test scores on measures of Immediate Memory, Verbal Learning & Memory, and Verbal Ability. Additional adjustment for depressive symptoms (which differed between the groups) attenuated only the findings for the entorhinal cortex (P = .061) and Verbal Ability (P = .076). Conclusion At‐risk, cognitively healthy individuals with SMCs exhibit cortical thinning in brain regions affected by AD and poorer performance on objective memory tests. These findings suggest that, in some individuals, SMCs might represent the earliest stages of AD.