Associations between normal cognitive aging and neurodegeneration

Abstract

AbstractBackgroundMultiple cognitive domains, including learning, memory and psychomotor speed, show significant reductions with age. These changes are thought to reflect normal cognitive aging. However, since cerebrospinal fluid (CSF) neurodegenerative biomarkers, such as total‐tau (t‐tau) and Neurofilament light chain (NfL), also show age‐related increases in normal aging, we aimed to investigate whether age‐associated cognitive decline may be mediated by age‐associated neurodegenerative changes.MethodWe included 114 cognitively healthy participants aged 40‐80 years from The Norwegian Dementia Disease Initiation Study. All had normal concentrations of CSF Aβ42/40 ratio. Cognitively healthy was defined as demographically adjusted T‐scores ≥35 on standardized cognitive tests. We fitted mediation models using structural equation modelling (SEM), with either CSF NfL or t‐tau as a mediator between age and CERAD learning, CERAD recall, TMT‐A and TMT‐B. All variables were standardized prior to analyses; in addition, both t‐tau and NfL were log transformed due to skewness.ResultsSee table 1 for demographic and clinical characteristics. Whilst neither NfL nor t‐tau showed statistically significant mediation of age‐related cognitive decline, our results nevertheless suggest a partial mediation of NfL on age‐related cognitive decline. Here, relationships between age and CERAD learning, CERAD Recall, and TMT‐A performance were weakened whereas higher NfL was associated with worse performance, in particular for delayed memory recall. This was not observed for t‐tau in any models. See figure 1‐2.ConclusionAge‐related decline in verbal learning, memory and psychomotor speed may be partially attributable to NfL‐associated neurodegenerative changes in cognitively healthy adults. As NfL reflects axonal degeneration, these results may reflect white matter neurodegeneration in aging.