Cerebrospinal Fluid Biomarkers, Education, Brain Volume, and Future Cognition

Knight Alzheimer’s Disease Research Center, St Louis, MO, USA.
Archives of neurology (Impact Factor: 7.01). 09/2011; 68(9):1145-51. DOI: 10.1001/archneurol.2011.192
Source: PubMed

ABSTRACT Cross-sectional studies suggest that the cognitive impact of Alzheimer disease pathology varies depending on education and brain size.
To evaluate the combination of cerebrospinal fluid biomarkers of β-amyloid(42) (Aβ(42)), tau, and phosphorylated tau (ptau(181)) with education and normalized whole-brain volume (nWBV) to predict incident cognitive impairment.
Longitudinal cohort study.
Charles F. and Joanne Knight Alzheimer's Disease Research Center, Washington University, St Louis, Missouri.
A convenience sample of 197 individuals 50 years and older with normal cognition (Clinical Dementia Rating of 0) at baseline observed for a mean of 3.3 years.
Time to Clinical Dementia Rating ≥ 0.5.
Three-factor interactions among the baseline biomarker values, education, and nWBV were found for Cox proportional hazards regression models testing tau (P = .02) and ptau (P = .008). In those with lower tau values, nWBV (hazard ratio [HR], 0.54; 95% confidence interval [CI], 0.31-0.91; P = .02), but not education, was related to time to cognitive impairment. For participants with higher tau values, education interacted with nWBV to predict incident impairment (P = .01). For individuals with lower ptau values, there was no effect of education or nWBV. Education interacted with nWBV to predict incident cognitive impairment in those with higher ptau values (P = .02).
In individuals with normal cognition and higher levels of cerebrospinal fluid tau and ptau at baseline, time to incident cognitive impairment is moderated by education and brain volume as predicted by the cognitive/brain reserve hypothesis.


Available from: Catherine M Roe, May 30, 2015
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Alzheimer disease (AD) is a complex neurodegenerative disorder, whose prevalence will dramatically rise by 2050. Despite numerous clinical trials investigating this disease, there is still no effective treatment. Many trials showed negative or inconclusive results, possibly because they recruited only patients with severe disease, who had not undergone disease-modifying therapies in preclinical stages of AD before severe degeneration occurred. Detection of AD in asymptomatic at risk individuals (and a few presymptomatic individuals who carry an autosomal dominant monogenic AD mutation) remains impractical in many of clinical situations and is possible only with reliable biomarkers. In addition to early diagnosis of AD, biomarkers should serve for monitoring disease progression and response to therapy. To date, the most promising biomarkers are cerebrospinal fluid (CSF) and neuroimaging biomarkers. Core CSF biomarkers (amyloid β1-42, total tau, and phosphorylated tau) showed a high diagnostic accuracy but were still unreliable for preclinical detection of AD. Hence, there is an urgent need for detection and validation of novel CSF biomarkers that would enable early diagnosis of AD in asymptomatic individuals. This article reviews recent research advances on biomarkers for AD, focusing mainly on the CSF biomarkers. In addition to core CSF biomarkers, the potential usefulness of novel CSF biomarkers is discussed.
    Croatian Medical Journal 08/2014; 55(4):347-365. DOI:10.3325/cmj.2014.55.347 · 1.37 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: As the field begins to test the concept of a “preclinical” stage of neurodegenerative disease, when the pathophysiological process has begun in the brain, but clinical symptoms are not yet manifest, a number of intriguing questions have already arisen. In particular, in preclinical Alzheimer’s disease (AD), the temporal relationship of amyloid markers to markers of neurodegeneration and their relative utility in the prediction of cognitive decline among clinically normal older individuals remains to be fully elucidated. Secondary prevention trials in AD have already begun in both genetic at-risk and amyloid at-risk cohorts, with several more trials in the planning stages, and should provide critical answers about whether intervention at this very early stage of disease can truly bend the curve of clinical progression. This review will highlight recent progress in cognitive, imaging, and biomarker outcomes in the field of preclinical AD, and the remaining gaps in knowledge.
    Neuron 11/2014; 84(3). DOI:10.1016/j.neuron.2014.10.038 · 15.98 Impact Factor
  • JAMA Neurology 12/2014; 72(2). DOI:10.1001/jamaneurol.2014.3832 · 7.01 Impact Factor