Long COVID is associated with neurological and neuropsychiatric manifestations. We conducted an observational study on 97 patients with prior SARS-CoV-2 infection and persisting cognitive complaints that presented to the University Health Network Memory Clinic between October 2020 and December 2021. We assessed the main effects of sex, age, and their interaction on COVID-19 symptoms and outcomes. We also examined the relative contribution of demographics and acute COVID-19 presentation (assessed retrospectively) on persistent neurological symptoms and cognition. Among our cohort, males had higher hospitalization rates than females during the acute COVID-19 illness (18/35 (51%) vs. 15/62 (24%); P = .009). Abnormal scores on cognitive assessments post-COVID were associated with older age (AOR = 0.84; 95% CI 0.74–0.93) and brain fog during initial illness (AOR = 8.80; 95% CI 1.76–65.13). Female sex (ARR = 1.42; 95% CI 1.09–1.87) and acute shortness of breath (ARR = 1.41; 95% CI 1.09–1.84) were associated with a higher risk of experiencing more persistent short-term memory symptoms. Female sex was the only predictor associated with persistent executive dysfunction (ARR = 1.39; 95% CI 1.12–1.76) and neurological symptoms (ARR = 1.66; 95% CI 1.19–2.36). Sex differences were evident in presentations and cognitive outcomes in patients with long COVID.

BackgroundMild traumatic brain injury (mTBI) in former contact sports athletes is a risk factor for dementia. However, it is unknown why only some individuals with mTBI develop dementia, suggesting that head injury exposure alone is not sufficient to produce the condition. We hypothesize that mTBI could be associated with neurodegenerative processes that target specific brain structures and connectivity networks and increase vulnerability to dementia.Method46 male former professional athletes with a history of multiple concussions were recruited. To compare participants with evidence of underlying pathology versus participants without any evidence, the sample was divided into neurodegenerative biomarker positive (N+, n = 25) and negative (N‐, n = 21) groups. The division was based on the positivity in at least one of these biomarkers: cerebrospinal fluid total tau (> 300 pg/ml), cortical positron emission tomography tau standardized uptake value ratio (>1.30) and serum neurofilament light‐chain (> 12.5 pg/ml). Groups were matched for age and number of concussions. Cognitive profiles were assessed by comparing the following scores between groups: Trail Making Test ratio, Digit Span Backwards, Paced Auditory Serial Addition Test, verbal fluency, and Rey Auditory Verbal Learning Test (RAVLT). Grey matter volume was calculated by voxel‐based morphometry and compared between groups. Functional connectivity differences were evaluated for the default mode (DMN), the salience (SN) and the dorsal attention (DAN) networks.Results(N+) presented more number of intrusions at immediate (p = 0.04, FDR corrected) and short delay recall (p = 0.02, FDR corrected) and worse recognition discrimination index (p = 0.02, FDR corrected) in the RAVLT in comparison to (N‐). In addition, (N+) displayed more atrophy in the left frontal superior and middle gyrus (p < 0.001, extended threshold = 50 voxels) and disconnection of the DAN (p < 0.001, FWE cluster correction) versus (N‐). No significant differences were obtained for the DMN and SN.ConclusionFrontal atrophy and DAN abnormal connectivity may underlie cognitive deficits in the (N+) group. Biomarkers of neurodegeneration provide a sensitive tool to detect participants with structural and functional changes and may associate with higher risk to develop dementia after mTBI.