Correlations of CSF Biomarkers of Alzheimer’s Disease with Cognitive Measures in MCI and AD Dementia
Gabriel Bitar1, Sierra Alban1, Kassu Mehari Beyene, PhD2, Boris Decourt, PhD3, Marwan Sabbagh, MD2
1School of Medicine, Creighton University, 2Barrow Neurological Institute, 3Texas Tech University
Objective:
Examine the relationship between cerebrospinal fluid (CSF) Aβ₁₋₄₂, t-tau, p-tau-181, and cognition in the Alzheimer’s Disease Neuroimaging Initiative (ADNI 1, 2, and GO) dataset.
Background:
Previous studies have examined longitudinal relationships between CSF biomarkers for AD and cognition. However, discordance exists in the strength of associations between CSF biomarkers and cognition at different disease stages. We examined this relationship in a large, cross-sectional ADNI dataset across many cognitive assessments of learning, memory, executive function, language, attention, visuospatial skills, and activities of daily living.
Design/Methods:
976 subjects (265 cognitively normal (CN); 518 mild cognitive impairment (MCI); and 193 AD) were included. Cognitive assessments, diagnoses, and specimen collection/processing were conducted per published ADNI protocols. Pearson correlations were performed between CSF biomarkers (Aβ₁₋₄₂, t-tau, p-tau-181) and the various cognitive measures.
Results:
In the MCI cohort, significant (p<0.05) negative correlations were observed between CSF Aβ₁₋₄₂ and ADAS-Cog11 (r=-0.33), ADAS-Cog13 (r=-0.374), CDR-SB (r=-0.181), Trails B (r=-0.23), and FAQ (r=-0.193). Positive correlations were between Aβ₁₋₄₂ and RAVLT immediate (r=0.333), MMSE (r=0.254), and Weschler Memory Scale (WMS) Delayed Recall (r=0.294).
Furthermore, significant correlations were observed between CSF t-tau, p-tau and the following cognitive assessments: CDR-SB (r=0.161 and 0.157, respectively), ADAS-Cog11 (r=0.212 and 0.218), ADAS-Cog13 (r=0.275 and 0.279), RAVLT forgetting (r=0.206 and 0.2), Trails B (r=0.117 each), MMSE (r=-0.217 and -0.224), RAVLT immediate (r=-0.235 and -0.242), and WMS Delayed Recall (r=-0.321; -0.324).
In the AD cohort, only Aβ₁₋₄₂ and MMSE (r=0.143) were correlated. No significant correlations were found between t-tau/p-tau and any cognitive scores.
Conclusions:
Our findings suggest that the relationship between CSF biomarkers and cognitive performance is most pronounced in MCI individuals. The lack of significant correlations in the AD cohort may indicate other pathophysiological changes dominating cognitive dysfunction at this disease stage. Further research is warranted to explore these biomarkers' longitudinal impacts and predictive value across different stages of disease.
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