Cognitively Preserved Subjects with Transitional Cerebrospinal Fluid β-Amyloid 1-42 Values Have Thicker Cortex in Alzheimer's Disease Vulnerable Areas

Background: Establishing the relationship between cerebrospinal fluid (CSF) beta-amyloid 1-42 (A beta) and cortical thickness (CTh) would represent a major step forward in the understanding of the Alzheimer's disease (AD) process. We studied this relationship in a group of healthy control subjects and subjects with subjective memory complaints with preserved cognitive function at neuropsychological testing. Methods: In this cross-sectional study, 33 individuals (17 healthy control subjects and 16 subjects with subjective memory complaints) underwent structural 3-Tesla magnetic resonance image scanning and a spinal tap. Cerebrospinal fluid A beta was measured by enzyme-linked immunosorbent assay. The relationship between CSF A beta values and CTh in several regions of interest, both susceptible and unrelated to AD pathology, was analyzed with a curve fit analysis and CTh difference maps were derived from group comparisons. Results: Dichotomizing the whole sample according to A beta values (cutoff 500 pg/mL), we found the expected cortical thinning in A beta positive subjects in temporoparietal areas (p < .05 corrected). When analyzing the relationship between CSF A beta and CTh in AD-susceptible regions, we found a significant inverted U-shaped relationship (quadratic). Therefore, the sample was further divided into tertiles (according to CSF A beta values) to perform subsequent subgroup comparisons. Increased CTh in temporoparietal areas and precuneus (p < .05 corrected) was found in the middle A beta tertile (CSF A beta between 416 and 597 pg/mL) when compared with the high A beta tertile (616-881 pg/mL). Conclusions: The relationship between A beta and CTh in preclinical stages may not be linear. Cortical thickness in temporoparietal and precuneus regions is greater in subjects with transitional CSF A beta values.