Affiliations: [a] Municipal Hospital of Bremen-Mitte, Department of Neurology, Stroke Unit, FRG, Bremen, Germany | [b] University of Oldenburg, Neuropsychology, FRG, Oldenburg, Germany | [c] Radboud University of Nijmegen, Donders Institute for Brain, Cognition and Behaviour, Nijmegen, The Netherlands | [d] Municipal Hospital of Bremen-Ost, Department of Neurology, FRG, Bremen, Germany
Correspondence:
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Correspondence to: Helmut Hildebrandt, Ph.D., Klinikum Bremen Ost, Department of Neurology, Züricher Str. 40, 28325 Bremen, Germany. Tel.: +49 421 408 1599; Fax: +49 421 408 2599; E-mail: [email protected].
Abstract: Decreased delayed recall, decreased amyloid-β peptides (Aβ1–42), and increased tau protein concentration in cerebrospinal fluid (CSF) are generally regarded to be valid neuropsychological and biological markers for Alzheimer's disease (AD). Previous studies failed to demonstrate clear-cut correlations between neuropsychological impairment and CSF markers. In this study we test recent models of disease progression, that propose that changes in CSF biomarkers already reach a plateau in a preclinical phase, before cognitive decline begins, that is, even before MCI can be diagnosed. We recruited 73 patients with probable AD (n = 36) and mild cognitive impairment (MCI) (amnesic MCI = 25; non-amnesic MCI = 12). We used the CERAD-NP, a widely used neuropsychological battery with norms for different age and education groups, and additional neuropsychological tests for assessing the cognitive profile of these patient groups. We found a significant correlation between Aβ1–42 in the CSF and memory performance for amnesic MCI patients, but not for non-amnesic MCI and AD patients. All other correlations between cognitive tasks and Aβ1–42 were not significant. Tau protein concentration in the CSF was not correlated with any neuropsychological marker in any of the patients groups. We conclude that the decrease of Aβ1–42 in the CSF mirrors disease progression during the early stages up into AD and therefore is not restricted to the preclinical phase. The decrease of Aβ1–42 reaches a plateau only in the full blown demented syndrome and further functional disease progression is then related to neurodegeneration without further reduction of Aβ1–42 in the CSF.
Keywords: Aβ1–42, Alzheimer's disease, cognitive speed, MCI, memory, total tau
