Persistent cognitive slowing in post-COVID patients: longitudinal study over 6 months.

BACKGROUND: Fatigue is a frequent and one of the most debilitating symptoms in post-COVID syndrome (PCS). Recently, we proposed that fatigue is caused by hypoactivity of the brain's arousal network and reflected by a reduction of cognitive processing speed. However, it is unclear whether cognitive slowing is revealed by standard neuropsychological tests, represents a selective deficit, and how it develops over time. OBJECTIVES: This prospective study assesses whether PCS patients show deficits particularly in tests relying on processing speed and provides the first longitudinal assessment focusing on processing speed in PCS patients. METHODS: Eighty-eight PCS patients with cognitive complaints and 50 matched healthy controls underwent neuropsychological assessment. Seventy-seven patients were subsequently assessed at 6-month follow-up. The Test for Attentional Performance measured tonic alertness as primary study outcome and additional attentional functions. The Neuropsychological Assessment Battery evaluated all key cognitive domains. RESULTS: Patients showed cognitive slowing indicated by longer reaction times compared to control participants (r = 0.51, p < 0.001) in a simple-response tonic alertness task and in all more complex tasks requiring speeded performance. Reduced alertness correlated with higher fatigue (r = - 0.408, p < 0.001). Alertness dysfunction remained unchanged at 6-month follow-up (p = 0.240) and the same was true for most attention tasks and cognitive domains. CONCLUSION: Hypoarousal is a core deficit in PCS which becomes evident as a selective decrease of processing speed observed in standard neuropsychological tests. This core deficit persists without any signs of amelioration over a 6-month period of time.

Impact of an online guided physical activity training on cognition and gut-brain axis interactions in older adults: protocol of a randomized controlled trial.

Introduction: By 2050, the worldwide percentage of people 65 years and older is assumed to have doubled compared to current numbers. Therefore, finding ways of promoting healthy (cognitive) aging is crucial. Physical activity is considered an effective approach to counteract not only physical but also cognitive decline. However, the underlying mechanisms that drive the benefits of regular physical activity on cognitive function are not fully understood. This randomized controlled trial aims to analyze the effect of an eight-week standardized physical activity training program in older humans on cognitive, brain, and gut-barrier function as well as the relationship between the resulting changes. Methods and analysis: One-hundred healthy participants aged 60 to 75 years will be recruited. First, participants will undergo an extensive baseline assessment consisting of neurocognitive tests, functional and structural brain imaging, physical fitness tests, and gut-microbiome profiling. Next, participants will be randomized into either a multi-component physical activity group (experimental condition) or a relaxation group (active control condition), with each training lasting 8 weeks and including an equal number and duration of exercises. The whole intervention will be online-based, i.e., participants will find their intervention schedule and all materials needed on the study website. After the intervention phase, participants will have their post-intervention assessment, which consists of the same measures and tests as the baseline assessment. The primary outcome of this study is the change in the cognitive parameter of visual processing speed from baseline to post-measurement, which will on average take place 10 weeks after the randomization. Secondary outcomes related to cognitive, brain, and microbiome data will be analyzed exploratory. Clinical trial registration: https://drks.de/search/de/trial/DRKS00028022.

A hypoarousal model of neurological post-COVID syndrome: the relation between mental fatigue, the level of central nervous activation and cognitive processing speed.

BACKGROUND: Knowledge on the nature of post-COVID neurological sequelae often manifesting as cognitive dysfunction and fatigue is still unsatisfactory. OBJECTIVES: We assumed that cognitive dysfunction and fatigue in post-COVID syndrome are critically linked via hypoarousal of the brain. Thus, we assessed whether tonic alertness as a neurocognitive index of arousal is reduced in these patients and how this relates to the level of central nervous activation and subjective mental fatigue as further indices of arousal. METHODS: 40 post-COVID patients with subjective cognitive dysfunction and 40 matched healthy controls underwent a whole-report paradigm of briefly presented letter arrays. Based on report performance and computational modelling according to the theory of visual attention, the parameter visual processing speed (VPS) was quantified as a proxy of tonic alertness. Pupillary unrest was assessed as a measure of central nervous activation. The Fatigue Assessment Scale was applied to assess subjective mental fatigue using the corresponding subscale. RESULTS: VPS was reduced in post-COVID patients compared to controls (p = 0.005). In these patients, pupillary unrest (p = 0.029) and mental fatigue (p = 0.001) predicted VPS, explaining 34% of the variance and yielding a large effect with f2 = 0.51. CONCLUSION: In post-COVID patients with subjective cognitive dysfunction, hypoarousal of the brain is reflected in decreased processing speed which is explained by a reduced level of central nervous activation and a higher level of mental fatigue. In turn, reduced processing speed objectifies mental fatigue as a core subjective clinical complaint in post-COVID patients.