CSF Biomarkers of Neurodegeneration May Predict Progression in Mild Cognitive Impairment

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.

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.