CSF Biomarkers of Neurodegeneration May Predict Progression in Mild Cognitive Impairment

Douglas Galasko, MD, of the Shiley-Marcos Alzheimers Disease Research Center

Douglas Galasko, MD

Cerebrospinal fluid (CSF) biomarkers related to neurodegeneration may provide value beyond Aβ_1-42/tau in predicting progression in mild cognitive impairment and in cognitively normal controls.

The results were presented at the 2019 Alzheimer’s Association International Conference, July 14­—18, in Los Angeles, California.

Based on a recent finding that CSF synaptic biomarkers and neurofilament light, together with Aβ_1-42 and total tau, predict cognitive progression, Douglas Galasko, MD, of the Shiley-Marcos Alzheimer’s Disease Research Center in La Jolla, California, and colleagues sought to evaluate this in elderly controls.

The investigators analyzed 2 datasets: participants from University of California San Diego Alzheimer’s Disease Research Center (UCSD) who received standardized clinical and cognitive assessment, CSF collection and annual follow-up, and participants from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) who had CSF analyses. Those with normal cognition and a Clinical Dementia Rating (CDR) of 0 at baseline, available CSF biomarkers, and long-term follow-up were analyzed.

In both datasets, investigators found that in patients with mild cognitive impairment, longitudinal decline on memory scores and CDR-sum of boxes (CDR-sb) was predicted by CSF NPTX2, neurogranin, SNAP25, and neurofilament light after controlling for Aβ_1-42, tau, APOE, and demographic values. When analyzing the combined ADRC and ADNI datasets, healthy controls with a high Aβ_1-42/tau ratio (n=133) had a greater decline throughout the 36 month follow-up than those with a low Aβ_1-42/tau ratio (n=33) on memory acquisition (P =.02), with trends for delayed recall (P =.06) and CDR-sb (P =.06).

When investigators added NPTX2 to the model, participants with high CSF Aβ_1-42/tau and lower NPTX2 levels experienced greater decline throughout the 36 months than all other subgroups on memory acquisition (P =.08), delayed recall (P =.018) and CDR-sb (P =.033).

Galasko and colleagues concluded that CSF biomarkers related to neurodegeneration may provide value in predicting progression in mild cognitive impairment and in cognitively normal, healthy elderly controls.

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REFERENCE

Galasko D, Smirnov D, Edland S, et al. CSF Biomarkers related to neurodegeneration as predictors of cognitive progression in MCI and elderly controls. Presented at: 2019 Alzheimer’s Association International Conference. July 14-18, 2019; Los Angeles, CA.