Abstract Body

Several papers show that the core AD pathophysiologies amyloid deposition (A), tau pathology (T), neurodegeneration (N), as well as glial activation (G) can accurately be identified and monitored using CSF and blood tests. For amyloid deposition, the Ab42/40 ratio, shows high concordance (AUCs of 80-90%) with brain amyloidosis evaluated by PET, but despite high AUCs, the fold change in PET positive cases is lower in plasma than in CSF. Several plasma P-tau species (181, 217, and 231), show a specific increase in plasma in AD, high concordance with tau PET, and increase also in elderly people with PET evidence of brain amyloidosis but with negative tau PET scans. Recent studies show high correlations between these P-tau species in both CSF and plasma, suggesting that differences are minor.

To implement the blood biomarkers in clinical routine diagnostics, full analytical validation of the analytical methods is needed, and optimally also Reference Measurement Procedures and Certified Reference Materials to assure batch-to-batch stability and comparable results across laboratories. In addition, data on the robustness, defined as the difference between the biomarker variability [combined effects of patient-related, biological, pre-analytical, analytical, and longitudinal bias] and the fold change [percent difference between patients and controls]. For a biomarker to be robust and clinically useful, the variability needs to be substantially lower than the fold change. In summary, although more data on assay performance and the certainty of classification into normal/abnormal is needed, blood tests show great promise as easily accessible screening tools for AD in the clinic.

Aims

Patients with COVID-19 often report and present with a wide range of neurological symptoms, but the underlying mechanisms have only scarcely been characterised. The Sahlgrenska NeuroCOVID Study aims to map neurological sequelae in COVID-19 patients longitudinally with a focus on multi-domain cognitive impairment and associated processes using an array of modalities.

Methods

We will recruit 20 hospitalised COVID-19 patients (Group 1) who have either been treated with high-flow oxygen, several of which at the ICU (severe disease severity), or with oxygen (moderate), 20 convalescent patients (Group 2) with persisting neurological or cognitive symptoms and 20 age-matched healthy controls (HC). All subjects undergo comprehensive structural and functional MRI and [¹⁸F]FDG PET brain imaging, lumbar puncture, blood sampling and thorough neuropsychological examination including testing of olfactory and gustatory function. Group 1 will be examined on four occasions, Group 2 on two and HC on one over the 12-months course of the study.

Results

Preliminary findings from the hitherto recruited 19 patients from Group 1 (mean age 53.6 y, 7 females), 15 from Group 2 (mean age 46.9 y, 8 females) and 20 HC (mean age 53.7 y, 14 females) highlight the prevalence of subjective (subjective cognitive impairment and mental fatigue) and objectively assessed cognitive and psychological sequelae of COVID-19 affecting predominantly executive function, attention and speed domains.

Conclusions

There is a great need to understand the mechanisms underlying the multi-faceted long-term neurological consequences of COVID-19. We will present detailed 6-months data focusing on the relationship between cognitive performance and bodily fluid- and neuroimaging-derived biomarkers.