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O1‐11‐01: OBSTRUCTIVE SLEEP APNEA, BRAIN BETA‐AMYLOID MEASURES AND TIME‐TO‐PROGRESSION FROM MILD COGNITIVE IMPAIRMENT TO ALZHEIMER'S DISEASE
Author(s) -
Bubu Omonigho Michael,
Birckbichler Maddie,
Mukhtar Fahad,
Hogan Megan,
Shim Amanda,
Umasabor-Bubu Ogie Queen,
Sharma Ram A.,
Jean-Louis Girardin,
deLeon Mony J.,
Osorio Ricardo S.
Publication year - 2018
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2018.06.2390
Subject(s) - obstructive sleep apnea , medicine , dementia , hazard ratio , amyloid beta , proportional hazards model , alzheimer's disease neuroimaging initiative , neuroimaging , amyloid (mycology) , cohort , oncology , disease , pathology , psychiatry , confidence interval
disorders such as Alzheimer’s disease (AD) and Parkinson’s disease (PD). Independent proteomics studies have revealed that levels of the synaptic and axonal proteins contactin-1 and -2 were increased in cerebrospinal fluid (CSF) of DLB and AD respectively compared to non-demented controls, highlighting their potential as diagnostic markers. Here, we analyzed the potential value of contactin-1 and -2 as CSF biomarkers, as such and in combination with more established biomarkers, in discriminating DLB from AD, PD and non-demented controls. Methods:Contactin-1 and -2 were measured in CSF from DLB (n1⁄472), AD (n1⁄440), PD (n1⁄458) and non-demented control subjects (n1⁄490) (age 63-68 years, female:male1⁄473:187) from the Amsterdam Dementia Cohort and VUmc movement disorder outpatient clinic using commercial ELISAs. Differences in biomarker concentrations between the diagnostic groups were analyzed by general linear model adjusting for age and sex. The correlations between contactins and established AD biomarkers (amyloid beta-42 (Ab42), total Tau (tTau) and PhosphoTau (pTau)) and total alpha-synuclein (t-a-syn) were analyzed. Logistic regression analysis and receiver operating characteristic (ROC) were performed to analyze the diagnostic performance of contactin-1 and -2 for discrimination of DLB from AD, PD and controls. Results: CSF contactin-1 was higher in DLB compared to PD patients (p1⁄40.003, Figure 1). The levels were similar in DLB, AD and control groups. Contactin-2 levels were comparable across the diagnostic groups. Within the DLB group, correlations of both contactin-1 and -2 with CSF tTau and pTau (r1⁄40.50-0.60, p<0.0001), but not Ab42 were observed. Contactin-1 also correlated with t-a-syn in DLB as well as in PD patients (both r 1⁄40.4-0.5, p<0.001).The combination of contactin-1, tTau and t-a-syn accurately discriminated DLB from AD (AUC[CI]1⁄40.94[0.88-0.99]; sensitivity1⁄489%, specificity1⁄483%). The combination of contactin1 and Ab42 distinguished DLB from PD (AUC[CI]1⁄40.84[0.770.91]; sensitivity 1⁄479%, specificity1⁄472%)(Figure 2). These models performed better than classical AD biomarkers in discriminating DLB from AD (c1⁄48.4, p1⁄40.015) and DLB from PD (c1⁄48.4, p1⁄40.004) . Conclusions: Contactin-1 appears useful in a biomarker panel to optimize the discrimination of DLB from AD and PD.