Differential effects of neurodegeneration biomarkers on subclinical cognitive decline

Merluzzi AP, Vogt NM, Norton D, Jonaitis E, Clark LR, Carlsson CM, Johnson SC, Asthana S, Blennow K, Zetterberg H, Bendlin BB.

Alzheimers Dement (N Y). 2019 Apr 12;5:129-138. doi: 10.1016/j.trci.2019.02.004. eCollection 2019.


Introduction: Neurodegeneration appears to be the biological mechanism most proximate to cognitive decline in Alzheimer's disease. We test whether t-tau and alternative biomarkers of neurodegeneration-neurogranin and neurofilament light protein (NFL)-add value in predicting subclinical cognitive decline. Methods: One hundred fifty cognitively unimpaired participants received a lumbar puncture for cerebrospinal fluid and at least two neuropsychological examinations (mean age at first visit = 59.3 ± 6.3 years; 67% female). Linear mixed effects models were used with cognitive composite scores as outcomes. Neurodegeneration interactions terms were the primary predictors of interest: age × NFL or age × neurogranin or age × t-tau. Models were compared using likelihood ratio tests. Results: Age × NFL accounted for a significant amount of variation in longitudinal change on preclinical Alzheimer's cognitive composite scores, memory composite scores, and learning scores, whereas age × neurogranin and age × t-tau did not. Discussion: These data suggest that NFL may be more sensitive to subclinical cognitive decline compared to other proposed biomarkers for neurodegeneration.


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