Cognitively preserved subjects with transitional cerebrospinal fluid ß-amyloid 1-42 values have thicker cortex in Alzheimer's disease vulnerable areas

Abstract

Background: Establishing the relationship between cerebrospinal fluid (CSF) ß-amyloid 1-42 (Aß) 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 Aß was measured by enzyme-linked immunosorbent assay. The relationship between CSF Aß 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 Aß values (cutoff 500 pg/mL), we found the expected cortical thinning in Aß positive subjects in temporoparietal areas (p < .05 corrected). When analyzing the relationship between CSF Aß 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 Aß values) to perform subsequent subgroup comparisons. Increased CTh in temporoparietal areas and precuneus (p < .05 corrected) was found in the middle Aß tertile (CSF Aß between 416 and 597 pg/mL) when compared with the high Aß tertile (616-881 pg/mL).

Conclusions: The relationship between Aß and CTh in preclinical stages may not be linear. Cortical thickness in temporoparietal and precuneus regions is greater in subjects with transitional CSF Aß values.