Cerebrospinal Fluid Biomarkers and Clinical Progression in Patients with Subjective Cognitive Decline and Mild Cognitive Impairment

Article type: Research Article

Authors: Wolfsgruber, Steffen^{a; b; 1; *} | Polcher, Alexandra^{a; b; 1} | Koppara, Alexander^{a; b} | Kleineidam, Luca^{a; b} | Frölich, Lutz^c | Peters, Oliver^d | Hüll, Michael^e | Rüther, Eckart^f | Wiltfang, Jens^f | Maier, Wolfgang^{a; b} | Kornhuber, Johannes^g | Lewczuk, Piotr^{g; h} | Jessen, Frank^{b; i} | Wagner, Michael^{a; b}

Affiliations: [a] Department of Psychiatry and Psychotherapy, University of Bonn, Germany | [b] German Center for Neurodegenerative Diseases, Bonn, Germany | [c] Department of Gerontopsychiatry, Central Institute of Mental Health, Mannheim, Germany | [d] Department of Psychiatry, Charité Berlin, Campus Benjamin Franklin, Berlin, Germany | [e] Center for Geriatric Medicine and Gerontology, University of Freiburg, Germany | [f] Department ofPsychiatry and Psychotherapy, University of Göttingen, Germany | [g] Department of Psychiatry and Psychotherapy, Universitätsklinikum Erlangen, and Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany | [h] Department of Neurodegeneration Diagnostics, Medical University of Biasłystok, and Departmentof Biochemical Diagnostics, University Hospital of Bialystok, Bialystok, Poland | [i] Department of Psychiatry, University of Cologne, Germany

Correspondence: [*] Correspondence to: Dr. phil. Steffen Wolfsgruber, Dipl.-Psych., German Center for Neurodegenerative Diseases, Sigmund-Freud-Straße 27, D-53105, Bonn, Germany. Tel.: +49 228 43302 816; E-mail: [email protected].

Note: [1] These authors contributed equally to this work.

Abstract: Background: There is very limited data on the prevalence of abnormal cerebrospinal fluid (CSF) biomarkers of Alzheimer’s disease (AD) and their predictive value for clinical progression in memory clinic patients with subjective cognitive decline (SCD). Objective: To assess the frequency of abnormal CSF biomarkers of AD and their predictive value for clinical progression in memory clinic patients with SCD in comparison to patients with mild cognitive impairment (MCI) from the same cohort. Methods: We analyzed prospective data from memory clinic patients of the German Competence Network Dementia cohort with a baseline diagnosis of SCD (n = 82) or MCI (n = 134), distinguished by actuarial neuropsychological MCI criteria (“Jak-Bondi criteria”). Risk of clinical progression during 3-year follow-up was evaluated with Cox-Proportional-Hazard models. Results: Prevalence of abnormal values in CSF markers of tau-mediated neurodegeneration (67.8% versus 46.3%) but not of amyloid deposition (40.3% versus 35.4%) was significantly higher in MCI compared to SCD. The rate of incident AD dementia (26.1% versus 12.2%) was also significantly higher in MCI. In SCD, additional 22% progressed to MCI during follow-up. Combined amyloid/tau abnormality was the strongest predictor of clinical progression in both groups. Conclusion: High prevalence of biomarker abnormality and clinical progression, together with the predictive value of CSF biomarkers, in memory clinic patients with SCD support the validity and usefulness of this condition as a “pre-MCI” at risk stage of AD.

Keywords: Alzheimer’s disease, cerebrospinal fluid, mild cognitive impairment, subjective cognitive decline

DOI: 10.3233/JAD-161252

Journal: Journal of Alzheimer's Disease, vol. 58, no. 3, pp. 939-950, 2017