title: Cognitive reserve and cortical thickness in preclinical Alzheimer's disease.
abstract: This study examined whether cognitive reserve (CR) alters the relationship between magnetic resonance imaging (MRI) measures of cortical thickness and risk of progression from normal cognition to the onset of clinical symptoms associated with mild cognitive impairment (MCI). The analyses included 232 participants from the BIOCARD study. Participants were cognitively normal and largely middle aged (M age = 56.5) at their baseline MRI scan. After an average of 11.8 years of longitudinal follow-up, 48 have developed clinical symptoms of MCI or dementia (M time from baseline to clinical symptom onset = 7.0 years). Mean thickness was measured over eight 'AD vulnerable' cortical regions, and cognitive reserve was indexed by a composite score consisting of years of education, reading, and vocabulary measures. Using Cox regression models, CR and cortical thickness were each independently associated with risk of clinical symptom onset within 7 years of baseline, suggesting that the neuronal injury occurring proximal to symptom onset has a direct association with clinical outcomes, regardless of CR. In contrast, there was a significant interaction between CR and mean cortical thickness for risk of progression more than 7 years from baseline, suggesting that individuals with high CR are better able to compensate for cortical thinning that is beginning to occur at the very earliest phase of AD.
authors.affiliation: Department of Neurology, School of Medicine, Johns Hopkins University, Baltimore, MD, 21205, USA. cpettigrew@jhmi.edu.
authors.forename: Corinne
authors.initials: C
authors.lastname: Pettigrew
authors.affiliation: Department of Neurology, School of Medicine, Johns Hopkins University, Baltimore, MD, 21205, USA.
authors.forename: Anja
authors.initials: A
authors.lastname: Soldan
authors.affiliation: Department of Biostatistics, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, 21205, USA.
authors.forename: Yuxin
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Department of Biostatistics, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, 21205, USA.
authors.forename: Mei-Cheng
authors.initials: MC
authors.lastname: Wang
authors.affiliation: Center for Imaging Science, Johns Hopkins University, Baltimore, MD, 21218, USA.
authors.forename: Timothy
authors.initials: T
authors.lastname: Brown
authors.affiliation: Center for Imaging Science, Johns Hopkins University, Baltimore, MD, 21218, USA.|Institute for Computational Medicine, Johns Hopkins University, Baltimore, MD, 21218, USA.|Department of Biomedical Engineering, Whiting School of Engineering, Johns Hopkins University, Baltimore, MD, 21218, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Miller
authors.affiliation: Department of Neurology, School of Medicine, Johns Hopkins University, Baltimore, MD, 21205, USA.
authors.forename: Marilyn
authors.initials: M
authors.lastname: Albert
mesh_terms: D000375:Aging / Q000473:pathology*; D000544:Alzheimer Disease / Q000150:complications / Q000473:pathology* / Q000503:physiopathology*; D058070:Asymptomatic Diseases; D001931:Brain Mapping; D002540:Cerebral Cortex / Q000473:pathology* / Q000503:physiopathology*; D060825:Cognitive Dysfunction / Q000150:complications / Q000473:pathology / Q000503:physiopathology*; D058245:Cognitive Reserve; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D009929:Organ Size
keywords: Alzheimer’s disease; Cognitive reserve; Cortical thickness; Magnetic resonance imaging; Preclinical AD