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Relationship of cognitive reserve and cerebrospinal fluid biomarkers to the emergence of clinical symptoms in preclinical Alzheimer's disease.

ABSTRACT: The levels of ?-amyloid (A?) 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 A?, and higher baseline p-tau. There was no interaction between CR and A?, 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.

SUBMITTER: Soldan A

PROVIDER: S-EPMC3823238 | biostudies-literature | 2013 Dec

REPOSITORIES: biostudies-literature

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Relationship of cognitive reserve and cerebrospinal fluid biomarkers to the emergence of clinical symptoms in preclinical Alzheimer's disease.

Soldan Anja A Pettigrew Corinne C Li Shanshan S Wang Mei-Cheng MC Moghekar Abhay A Selnes Ola A OA Albert Marilyn M O'Brien Richard R

Neurobiology of aging 20130801 12

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 y ...[more]

PMID: 23916061

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Project description:African Americans have been reported to have a higher prevalence of Alzheimer's disease (AD) than Caucasians, but etiology-specific AD biomarkers have not been systematically analyzed in older African Americans. Coexisting cerebrovascular disease may also contribute to this increased prevalence. We hypothesized that cerebrospinal fluid (CSF) biomarkers of amyloid, neurodegeneration, and endothelial dysfunction would differ between older African Americans and Caucasians with normal cognition and cognitive impairment associated with AD.We prospectively recruited 135 older Americans to undergo detailed clinical, neuropsychological, genetic, magnetic resonance imaging (MRI), and CSF analysis from 2013 to 2015 at Emory University (Atlanta, GA, USA). We compared levels of CSF markers for ?-amyloid (A?42, A?40), total and phosphorylated tau (t-tau and p-tau181, respectively), endothelial dysfunction (soluble vascular cell adhesion molecule 1, soluble intercellular adhesion molecule 1), ?-synuclein, and neurodegeneration (neurofilament light chain [NfL]), as well as MRI markers, for hippocampal atrophy and cerebrovascular disease (white matter hyperintensity [WMH] volume).Sixty-five older African Americans (average age, 69.1 years) and 70 older Caucasians (average age, 70.8 years) were included. After adjusting for demographic variables, AD risk alleles, and cognitive function, older African Americans had lower CSF levels of p-tau181 (difference of 7.4 pg/ml; 95% CI, 3.7-11.2 pg/ml; p?<?0.001), t-tau (difference of 23.6 pg/ml; 95% CI, 9.5-37.7; p?=?0.001), and A?40 (difference of 1.35 ng/ml; 95% CI, 0.29-2.42 ng/ml; p?=?0.013) despite similar levels of A?42, NfL, WMH volume, and hippocampal volume. Cognitively impaired African Americans also had lower CSF t-tau/A?42 (difference of 0.255 per 1-SD change in composite cognition; 95% CI, 0.100-0.409; p?=?0.001) and p-tau181/A?42 (difference of 0.076 per 1-SD change in composite cognition; 95% CI, 0.031-0.122; p?=?0.001). These could not be explained by measured biomarkers of non-AD processes, but African Americans may be more susceptible than Caucasians to the cognitive effects of WMH.Despite comparable levels of CSF A?42 and A?42/A?40, cognitive impairment in African Americans is associated with smaller changes in CSF tau markers but greater impact from similar WMH burden than Caucasians. Race-associated differences in CSF tau markers and ratios may lead to underdiagnosis of AD in African Americans.ClinicalTrials.gov, NCT02089555 . Retrospectively registered on 14 March 2014.

Dataset Information

Relationship of cognitive reserve and cerebrospinal fluid biomarkers to the emergence of clinical symptoms in preclinical Alzheimer's disease.

Publications

Relationship of cognitive reserve and cerebrospinal fluid biomarkers to the emergence of clinical symptoms in preclinical Alzheimer's disease.

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