Dataset Information

Amyloid imaging and CSF biomarkers in predicting cognitive impairment up to 7.5 years later.

ABSTRACT: We compared the ability of molecular biomarkers for Alzheimer disease (AD), including amyloid imaging and CSF biomarkers (A?42, tau, ptau181, tau/A?42, ptau181/A?42), to predict time to incident cognitive impairment among cognitively normal adults aged 45 to 88 years and followed for up to 7.5 years.Longitudinal data from Knight Alzheimer's Disease Research Center participants (N = 201) followed for a mean of 3.70 years (SD = 1.46 years) were used. Participants with amyloid imaging and CSF collection within 1 year of a clinical assessment indicating normal cognition were eligible. Cox proportional hazards models tested whether the individual biomarkers were related to time to incident cognitive impairment. "Expanded" models were developed using the biomarkers and participant demographic variables. The predictive values of the models were compared.Abnormal levels of all biomarkers were associated with faster time to cognitive impairment, and some participants with abnormal biomarker levels remained cognitively normal for up to 6.6 years. No differences in predictive value were found between the individual biomarkers (p > 0.074), nor did we find differences between the expanded biomarker models (p > 0.312). Each expanded model better predicted incident cognitive impairment than the model containing the biomarker alone (p < 0.005).Our results indicate that all AD biomarkers studied here predicted incident cognitive impairment, and support the hypothesis that biomarkers signal underlying AD pathology at least several years before the appearance of dementia symptoms.

SUBMITTER: Roe CM

PROVIDER: S-EPMC3719431 | biostudies-other | 2013 May

REPOSITORIES: biostudies-other

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Amyloid imaging and CSF biomarkers in predicting cognitive impairment up to 7.5 years later.

Roe Catherine M CM Fagan Anne M AM Grant Elizabeth A EA Hassenstab Jason J Moulder Krista L KL Maue Dreyfus Denise D Sutphen Courtney L CL Benzinger Tammie L S TL Mintun Mark A MA Holtzman David M DM Morris John C JC

Neurology 20130410 19

<h4>Objectives</h4>We compared the ability of molecular biomarkers for Alzheimer disease (AD), including amyloid imaging and CSF biomarkers (Aβ42, tau, ptau181, tau/Aβ42, ptau181/Aβ42), to predict time to incident cognitive impairment among cognitively normal adults aged 45 to 88 years and followed for up to 7.5 years.<h4>Methods</h4>Longitudinal data from Knight Alzheimer's Disease Research Center participants (N = 201) followed for a mean of 3.70 years (SD = 1.46 years) were used. Participants ...[more]

PMID: 23576620

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Project description:Research shows that late mild cognitive impairment (LMCI) has a high risk of turning into Alzheimer's disease (AD). Due to the invasion of detection methods and physical damage to the patients, it is not a convenient way to diagnose and detect early AD and LMCI by cerebrospinal fluid (CSF) data. So there is an urgent need to find the correlation between peripheral biological data and CSF data in the brain, and to find new diagnostic methods through changes in the peripheral biological data. Studies have shown that during the pathogenesis of LMCI and AD, peripheral immune cells specifically infiltrate into the brain through the blood-brain barrier, causing an imbalance in the brain's immune response and dysregulating the clearance of Aβ in CSF. Therefore, in this paper, canonical correlation analysis (CCA) algorithm is presented to derive the correlation between peripheral and CSF biomarkers based on LMCI peripheral gene expression data and plasma marker information. Firstly, to explore the influence of the infiltration of peripheral blood immune cells on the brain, the abundance of 28 immune cells were calculated by using the gene set enrichment analysis algorithm of LMCI samples. Then, to identify the correlation between biomarkers inside and outside of the brain, we performed CCA to calculate the relationship between CSF and peripheral biomarkers. Results of CCA showed significant correlations between the variable sets of 8 peripheral biomarkers and the variable sets of CSF biomarkers (at 0.794). Finally, according to Kyoto Encyclopedia of Genes and Genomes and Gene Ontology analysis, it was found that the obtained peripheral biomarkers are involved in many immune-related pathways and functions which can be activated in peripheral blood of LMCI patients. Most related genes enriched in immune-related pathways and functions were up-regulated. Through receiver operating characteristic curve (ROC) analysis, it was also found that FP40/FP42 and type 1 T helper can accurately predict the pathological changes of LMCI (at 0.747).

Dataset Information

Amyloid imaging and CSF biomarkers in predicting cognitive impairment up to 7.5 years later.

Publications

Amyloid imaging and CSF biomarkers in predicting cognitive impairment up to 7.5 years later.

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