Correlation between cognitive impairment and CSF biomarkers in amnesic MCI, non-amnesic MCI, and Alzheimer's disease.
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.
Haldenwanger
Andreas
A
Municipal Hospital of Bremen-Mitte, Department of Neurology, Stroke Unit, FRG, Bremen, Germany.
Eling
Paul
P
Kastrup
Andreas
A
Hildebrandt
Helmut
H
D000368:Aged; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000523:psychology; D000647:Amnesia / Q000134:cerebrospinal fluid* / Q000150:complications* / Q000523:psychology; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid*; D015415:Biomarkers / Q000134:cerebrospinal fluid; D003072:Cognition Disorders / Q000134:cerebrospinal fluid* / Q000150:complications* / Q000523:psychology; D006801:Humans; D008875:Middle Aged; D009483:Neuropsychological Tests; D010446:Peptide Fragments / Q000134:cerebrospinal fluid*; D016875:tau Proteins / Q000134:cerebrospinal fluid
D016229:Amyloid beta-Peptides; D015415:Biomarkers; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D016875:tau Proteins