Related amyloid burden and cortical atrophy in individuals with subtle cognitive decline

Abstract Background Subtle cognitive decline represents a stage of subclinical cognitive deterioration in which pathological biomarkers, particularly for Alzheimer’s disease may be present, including early cortical atrophy and amyloid deposition. Using individual items from the Montreal Cognitive Assessment (MoCA) and k‐modes cluster analysis, we previously identified three distinct cognitive clusters of individuals without overt cognitive impairment, which comprised a High Performing cluster (no deficits in performance), a Memory Deficits cluster (lower memory performance), and a Compound Deficits cluster (lower memory and executive function performance). In this study, we sought to understand the different relationships found in our clusters between cortical atrophy on MRI and B‐amyloid burden on PET. Methods Data was derived from the Alzheimer’s Disease Neuroimaging Initiative and comprised individuals with Clinical Dementia Rating of 0 with available MRI and 18‐Florbetapir B‐amyloid PET data (n = 272). Using multiple group structural equation modeling, we regressed amyloid standardized uptake value ratio (PET) on volumetric regions (MRI). Models were constrained to test significance of associations across groups defined by cognitive clusters. Results In our Compound Deficits cluster, greater whole cerebral B‐amyloid burden was significantly related to atrophy of the right entorhinal cortex and left hippocampus, with regression coefficients of ‐0.412 (p = 0.005) and ‐0.304 (p = 0.049), respectively. Within this cluster, right entorhinal cortical atrophy was significantly related to greater amyloid burden within multiple frontal lobe regions. Conclusions The Compound Deficits cluster, which represents a group at higher risk of decline with deficits in both memory and executive function, was observed to have significantly more cortical atrophy, particularly within the entorhinal cortex and hippocampus, associated with whole brain and frontal lobe B‐amyloid burden. These findings, which are consistent with the neuropsychological deficits observed on the MoCA in this cluster, point to a pattern of early pathological deterioration that may place these individuals at risk for future decline.