Differential effects of neurodegeneration biomarkers on subclinical cognitive decline. Merluzzi AP1, Vogt NM1, Norton D2, Jonaitis E2, Clark LR1,3, Carlsson CM1,3, Johnson SC1,3, Asthana S1,3, Blennow K4,5, Zetterberg H4,5,6,7, Bendlin BB1. Author information 1 Wisconsin Alzheimer's Disease Research Center, University of Wisconsin-Madison, Madison, WI, USA. 2 Department of Biostatistics and Medical Informatics, University of Wisconsin-Madison, Madison, WI, USA. 3 Geriatric Research Education and Clinical Center, William S. Middleton Memorial Veteran's Hospital, Madison, WI, USA. 4 Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden. 5 Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden. 6 Institute of Neurology, University College London, Queen Square, London, UK. 7 UK Dementia Research Institute, London, UK. Abstract 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.
