Subjective Memory Complaints, Cortical Thinning, and Cognitive Dysfunction in Middle-Aged Adults at Risk for AD

Alzheimers Dement (Amst). 2015 Mar 1;1(1):33-40. doi: 10.1016/j.dadm.2014.11.010.


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: Participants were 261 middle-aged adults (mean age=54.30 years) enrolled in the Wisconsin Registry for Alzheimer's Prevention, a registry of cognitively normal adults at risk for AD. They answered a question pertaining to subjective memory, completed a comprehensive neuropsychological exam, and subsequently underwent a volumetric MRI scan. Cortical thickness measurements were derived from 10 a priori regions of interest involved in AD. Analyses of covariance were conducted to investigate group differences in cortical thickness and neuropsychological measures.

Results: Compared with individuals without SMCs, individuals with SMCs had significant cortical thinning in the entorhinal, fusiform, posterior cingulate, and inferior parietal cortices, as well as 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).

Conclusions: At-risk, cognitively healthy individuals with SMCs exhibit cortical thinning in brain regions affected by AD as well as poorer performance on objective memory tests. These findings suggest that, in some individuals, SMCs might represent the earliest stages of AD.

Keywords: Cognition; Cortical thickness; Preclinical AD; Subjective memory complaints.