Role of cerebrospinal fluid biomarkers to predict conversion to dementia in patients with mild cognitive impairment: a clinical cohort study

Manuela Tondelli; Roberta Bedin; Annalisa Chiari; Maria Angela Molinari; Guendalina Bonifacio; Nicoletta Lelli; Tommaso Trenti; Paolo Nichelli

doi:10.1515/cclm-2014-0414

Article

Role of cerebrospinal fluid biomarkers to predict conversion to dementia in patients with mild cognitive impairment: a clinical cohort study

Manuela Tondelli , Roberta Bedin , Annalisa Chiari , Maria Angela Molinari , Guendalina Bonifacio , Nicoletta Lelli , Tommaso Trenti and Paolo Nichelli

Published/Copyright: October 2, 2014

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From the journal Clinical Chemistry and Laboratory Medicine (CCLM) Volume 53 Issue 3

Abstract

Background: Cerebrospinal fluid (CSF) levels assessment of Aβ_1-42 and Tau proteins may be accurate diagnostic biomarkers for the differentiation of preclinical Alzheimer’s disease (AD) from age-associated memory impairment, depression and other forms of dementia in patients with mild cognitive impairment (MCI). The aim of our study was to explore the utility of CSF biomarkers in combination with common cognitive markers as predictors for the risk of AD development, and other forms of dementia, and the time to conversion in community patients with MCI.

Methods: A group of 71 MCI patients underwent neurological assessment, extended neuropsychological evaluation, routine blood tests, ApoE determination, and lumbar puncture to dose t-tau, p-tau₁₈₁, Aβ_1-42. We investigated baseline CSF and neuropsychological biomarker patterns according to groups stratified with later diagnoses of AD conversion (MCI-AD), other dementia (MCI-NAD) conversion, or clinical stability (sMCI).

Results: Baseline Aβ_1-42 CSF levels were significantly lower in MCI-AD patients compared to both sMCI and MCI-NAD. Additionally, p-tau₁₈₁ was higher in the MCI-AD group compared to sMCI. The MCI-AD subgroup analysis confirmed the role of Aβ_1-42 in its predictive role of time to conversion: rapid converters had lower Aβ_1-42 levels compared to slow converters. Logistic regression and survival analysis further supported the key predictive role of baseline Aβ_1-42 for incipient AD and dementia-free survival.

Conclusions: Our results confirm the key role of CSF biomarkers in predicting patient conversion from MCI to dementia. The study suggests that CSF biomarkers may also be reliable in a real world clinical setting.

Keywords: Alzheimer’s disease; biomarkers; cerebrospinal fluid; mild cognitive impairment

Corresponding author: Manuela Tondelli, MD, PhD, Biomedical, Metabolic, and Neural Sciences Department, University of Modena and Reggio Emilia, S. Agostino-Estense Hospital, Via Giardini 1355, Baggiovara, Modena, Italy, Phone: +39 059 3961677, E-mail: manuela.tondelli@unimore.it

Acknowledgments

The authors would like to thank Johanna Chester for her critical revision and editorial assistance.

Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

Financial support: None declared.

Employment or leadership: None declared.

Honorarium: None declared.

Competing interests: None declared.

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Received: 2014-4-15

Accepted: 2014-8-24

Published Online: 2014-10-2

Published in Print: 2015-2-1

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Articles in the same Issue

https://doi.org/10.1515/cclm-2014-0414

Keywords for this article

Alzheimer’s disease; biomarkers; cerebrospinal fluid; mild cognitive impairment