title: Relationship of cognitive reserve and cerebrospinal fluid biomarkers to the emergence of clinical symptoms in preclinical Alzheimer's disease.
abstract: The levels of β-amyloid (Aβ) and phosphorylated tau (p-tau), as measured in cerebrospinal fluid, have been associated with the risk of progressing from normal cognition to onset of clinical symptoms during preclinical Alzheimer's disease. We examined whether cognitive reserve (CR) modifies this association. Cerebrospinal fluid was obtained at baseline from 239 participants (mean age, 57.2 years) who had been followed for up to 17 years with clinical and cognitive assessments (mean follow-up, 8 years). A composite score based on the National Adult Reading Test, vocabulary, and years of education at baseline was used as an index of CR. Cox regression models showed that the increased risk of progressing from normal cognition to symptom onset was associated with lower CR, lower baseline Aβ, and higher baseline p-tau. There was no interaction between CR and Aβ, suggesting that the protective effects of higher CR are equivalent across the observed range of amyloid levels. In contrast, both tau and p-tau interacted with CR, indicating that CR was more protective at lower levels of tau and p-tau.
authors.affiliation: Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Anja
authors.initials: A
authors.lastname: Soldan
authors.forename: Corinne
authors.initials: C
authors.lastname: Pettigrew
authors.forename: Shanshan
authors.initials: S
authors.lastname: Li
authors.forename: Mei-Cheng
authors.initials: MC
authors.lastname: Wang
authors.forename: Abhay
authors.initials: A
authors.lastname: Moghekar
authors.forename: Ola A
authors.initials: OA
authors.lastname: Selnes
authors.forename: Marilyn
authors.initials: M
authors.lastname: Albert
authors.forename: Richard
authors.initials: R
authors.lastname: O'Brien
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000175:diagnosis* / Q000523:psychology*; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid*; D015415:Biomarkers / Q000134:cerebrospinal fluid; D003071:Cognition; D060825:Cognitive Dysfunction / Q000175:diagnosis / Q000523:psychology; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D012306:Risk; D013997:Time Factors; D016875:tau Proteins / Q000134:cerebrospinal fluid*
chemical_list: D016229:Amyloid beta-Peptides; D015415:Biomarkers; D016875:tau Proteins
keywords: Amyloid; Biomarkers; Cerebrospinal fluid; Cognitive reserve; Cohort studies; Mild cognitive impairment; Preclinical Alzheimer's disease; Tau
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