Screening for neurodegeneration in an elderly cohort from the community

Neurodegenerative dementias, presently untreatable, are associated with a high social and familial burden, for which national health systems are not prepared for. Reducing the burden and costs associated with the late-stages of dementia implies preventing the progressive decline, symptomatic of the irreversible neurodegenerative process. A hint from the interventional field in neurodegenerative dementias is that any effective preventive or disease-modifying treatment must be started very early in the disease process, stressing the importance of an early diagnosis based on biomarkers. Current biomarker modalities in this field, neuroimaging and cerebrospinal fluid (CSF) analysis, are not suitable for large scale population screening and only available in specialized memory clinics. Recent developments of ultrasensitive techniques have allowed for the accurate measurement of brain-derived proteins in blood, with the possibility of tracking down neurodegeneration in a more accessible fluid. Currently, the most robust blood-based biomarker to reliably reflect neurodegeneration is Neurofilament light chain (NfL). In the past five years, data on clinical cohorts has emerged showing that blood NfL can reliably detect neuronal loss and is therefore regarded as a sensitive but nonspecific marker of axonal injury, with potential to rule-in or out neurodegeneration. However, the potential for blood NfL as a first-line screening tools for neurodegeneration at early stages is still largely unknown. In this pilot study, using Single Molecule Array (SiMoA), an ultrasensitive immunoassay technology, pioneer in our country, we will measure serum levels of NfL in a elderly non- demented cohort (n=100). This cohort is part of a larger longitudinal community-cohort (ESCUDO.: Aging and Cognitive Decline in the Portuguese Population: Incidence, profiles, risk and protective factors” (FCT/IF/01325/2015)), that has, during the last three months, under project “COVID-19: Impacto do isolamento social na saúde mental de adultos e idosos” (079_596650513/Research4COVID19/FCT), undergone a reassessment using a comprehensive neuropsychological battery addressing depressive symptoms, anxiety, stress, quality of life, functional and cognitive status and memory complaints. Within this population we will, based on their last neuropsychological assessment results, divide participants into 3 different cognitive profiles (cognitive impairment, normal performers and high-cognitive performers) and evaluate if NfL serum levels differ between these subgroups. We will also look for correlations between NfL serum levels and scores in the different assessed neuropsychological domains, with particular attention to memory, attention and executive domains. Moreover, the ability of current NfL levels to reflect individuals’ cognitive trajectories during the pandemic will also be assessed. This will allow us to look into the value of this blood marker in detecting subtle differences in cognitive performance within non-demented individuals, and how this has been influenced by the current pandemic. We believe that this study will pave the way for the establishment of a primary care based-cohort with blood-biomarker determination and long-time prospective neuropsychological follow-up, allowing us to truly assess the value of this marker in predicting future cognitive impairment and dementia.