Linking CSF and cognition in Alzheimer's disease: Reanalysis of clinical data

Michael Guhra; Christine Thomas; Sebastian Boedeker; Stefan Kreisel; Martin Driessen; Thomas Beblo; Patricia Ohrmann; Max Toepper

doi:10.1016/j.exger.2015.11.008

Linking CSF and cognition in Alzheimer's disease: Reanalysis of clinical data

Exp Gerontol. 2016 Jan:73:107-13. doi: 10.1016/j.exger.2015.11.008. Epub 2015 Nov 14.

Authors

Michael Guhra¹, Christine Thomas², Sebastian Boedeker³, Stefan Kreisel³, Martin Driessen³, Thomas Beblo³, Patricia Ohrmann⁴, Max Toepper³

Affiliations

¹ Evangelisches Krankenhaus Bielefeld, Department of Psychiatry and Psychotherapy Bethel, Remterweg 69-71, D-33617 Bielefeld, Germany. Electronic address: Michael.Guhra@evkb.de.
² Clinical Centre Stuttgart, Clinic for Psychiatry and Psychotherapy for the Elderly, Prießnitzweg 24, D-70374 Stuttgart, Germany.
³ Evangelisches Krankenhaus Bielefeld, Department of Psychiatry and Psychotherapy Bethel, Remterweg 69-71, D-33617 Bielefeld, Germany.
⁴ University of Muenster, Department of Psychiatry, Albert-Schweitzer-Campus 1, A9, D-48149 Muenster, Germany.

PMID: 26585048
DOI: 10.1016/j.exger.2015.11.008

Abstract

Objectives: Memory and executive deficits are important cognitive markers of Alzheimer's disease (AD). Moreover, in the past decade, cerebrospinal fluid (CSF) biomarkers have been increasingly utilized in clinical practice. Both cognitive and CSF markers can be used to differentiate between AD patients and healthy seniors with high diagnostic accuracy. However, the extent to which performance on specific mnemonic or executive tasks enables reliable estimations of the concentrations of different CSF markers and their ratios remains unclear.

Methods: To address the above issues, we examined the association between neuropsychological data and CSF biomarkers in 51 AD patients using hierarchical multiple regression analyses. In the first step of these analyses, age, education and sex were entered as predictors to control for possible confounding effects. In the second step, data from a neuropsychological test battery assessing episodic memory, semantic memory and executive functioning were included to determine whether these variables significantly increased (compared to step 1) the explained variance in Aβ42 concentration, p-tau concentration, t-tau concentration, Aβ42/t-tau ratio, and Aβ42/Aβ40 ratio.

Results: The different models explained 52% of the variance in Aβ42/t-tau ratio, 27% of the variance in Aβ42 concentration, and 28% of the variance in t-tau concentration. In particular, Aβ42/t-tau ratio was associated with verbal recognition and code shifting, with Aβ42 being related to verbal recognition and t-tau being related to code shifting. By contrast, the inclusion of neuropsychological data did not allow reliable estimations of Aβ42/Aβ40 ratio or p-tau concentration.

Conclusion: Our results showed that strong associations exist between the cognitive key symptoms of AD and the concentrations and ratios of specific CSF markers. In addition, we revealed a specific combination of neuropsychological tests that may facilitate reliable estimations of CSF concentrations, thereby providing important diagnostic information for non-invasive early AD detection.

Keywords: Alzheimer's disease; Amyloid beta; Biomarkers; Cerebrospinal fluid; Cognition; Executive function; Memory; Tau.

MeSH terms

Aged
Aged, 80 and over
Alzheimer Disease / diagnosis*
Alzheimer Disease / psychology
Amyloid beta-Peptides / cerebrospinal fluid
Biomarkers / cerebrospinal fluid*
Cognition*
Educational Status
Executive Function
Female
Humans
Male
Memory
Middle Aged
Neuropsychological Tests
Peptide Fragments / cerebrospinal fluid
tau Proteins / cerebrospinal fluid

Substances

Amyloid beta-Peptides
Biomarkers
Peptide Fragments
amyloid beta-protein (1-42)
tau Proteins