Value of CSF Biomarkers in Predicting Risk of Progression from aMCI to ADD in a 5-Year Follow-Up Cohort
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MEDICINE
Value of CSF Biomarkers in Predicting Risk of Progression from aMCI to ADD in a 5-Year Follow-Up Cohort Liara Rizzi 1,2
&
Luciane Missiaggia 1,2 & Ida Vanessa Doederlein Schwartz 2,3 & Matheus Roriz-Cruz 1,2
Accepted: 28 July 2020 # Springer Nature Switzerland AG 2020
Abstract The aim of this study is to approach cerebrospinal fluid (CSF) Aβ1-42 and p-Tau181 as risks factors in predicting progression from amnestic mild cognitive impairment (aMCI) to Alzheimer’s disease dementia (ADD) in a 5-year follow-up. Forty-two individuals diagnosed as aMCI or subjective cognitive impairment (SCI) were evaluated in 2013 and reevaluated in 2018. CSF Aβ1–42 and p-Tau181 were measured by immunoenzymatic assay. Differences in cognitive performance between endpoint and baseline were verified by neuropsychological tests. Of the aMCI individuals, 45.2% progressed to ADD in 5 years. The relative risk to develop ADD in individuals with aMCI and Aβ1–42 < 618.5 pg/mL was 5.8 times higher than in those whose levels were above this cutoff (P = 0.0011). Moreover, the relative risk among those in which the p-Tau181/Aβ1–42 ratio was higher than 0.135 was 3.83 times greater (P = 0.0001). Both Aβ1–42 and p-Tau181 levels explained 47.5% of ΔCERADs variance (P < 0.001), whereas Aβ1–42 alone explained 38.6% (P < 0.001). Aβ1–42 provided 5.8 times higher cumulative risk to the progression from aMCI to ADD in a 5-year follow-up. The p-Tau181/Aβ1–42 ratio was no better than Aβ1–42 alone. However, p-Tau181 levels helped to explain an extra 9% of ΔCERADs variance. Keywords Alzheimer’s disease . Amyloid protein . CSF biomarkers . MCI . Tau
Introduction The new research framework, proposed by the National Institute on Aging and Alzheimer’s Association (NIA-AA), This article is part of the Topical Collection on Medicine * Liara Rizzi [email protected] Luciane Missiaggia [email protected] Ida Vanessa Doederlein Schwartz [email protected] Matheus Roriz-Cruz [email protected] 1
Division of Geriatric Neurology, Neurology Service, Hospital de Clínicas de Porto Alegre, Rua Ramiro Barcelos, 2350, Porto Alegre, RS 90035-903, Brazil
2
School of Medicine, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil
3
Medical Genetics Service, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil
defined that Alzheimer’s disease (AD) underlying pathologic processes can be acknowledged by postmortem examination or in vivo by biomarkers [1]. Especially, cerebrospinal fluid (CSF) concentrations of Aβ1–42 and p-Tau181 proteins seem to be the most promising biomarkers related to AD and can be early identified in the disease continuum [2]. Therefore, it is extreme important to estimate the added value of these biomarkers to identify the real risk of progression to the dementia phase of this disease. Longitudinal researches on mild cognitive impairment (MCI) individuals represent an opportunity to investigate the underlying biological processes and their relevance in the progression to AD. However, MCI remains a largel
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