Preprint ASSESSMENT AND CHARACTERIZATION OF COVID-19 RELATED COGNITIVE DECLINE: RESULTS FROM A NATURAL EXPERIMENT, 2023, Clouston et al

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ASSESSMENT AND CHARACTERIZATION OF COVID-19 RELATED COGNITIVE DECLINE: RESULTS FROM A NATURAL EXPERIMENT

Background: Cognitive impairment is the most common and disabling manifestation of post-acute sequelae of SARS-CoV-2. There is an urgent need for the application of more stringent methods for evaluating cognitive outcomes in research studies.

Objective: To determine whether cognitive decline emerges with the onset of COVID-19 and whether it is more pronounced in patients with Post-Acute Sequelae of SARS-CoV-2 or severe COVID-19.

Methods: This longitudinal cohort study compared the cognitive performance of 276 patients with COVID-19 to that of 217 controls across four neuroinflammation or vascular disease-sensitive domains of cognition using data collected both before and after the pandemic starting in 2015.

Results: The mean age of the COVID-19 group was 56.04 (SD=6.6) years, while that of the control group was 58.1 (SD=7.3) years. Longitudinal models indicated a significant decline in cognitive throughput ((B=-0.168, P=.001) following COVID-19, after adjustment for pre-COVID-19 functioning, demographics, and medical factors. The effect sizes were large; the observed changes in throughput were equivalent to 10.6 years of normal aging and a 59.8% increase in the burden of mild cognitive impairment. Cognitive decline worsened with coronavirus disease 2019 severity and was concentrated in participants reporting post-acute sequelae of SARS-CoV-2.

Conclusion: COVID-19 was most likely associated with the observed cognitive decline, which was worse among patients with PASC or severe COVID-19. Monitoring patients with post-acute sequelae of SARS-CoV-2 for declines in the domains of processing speed and visual working memory and determining the long-term prognosis of this decline are therefore warranted.

https://www.medrxiv.org/content/10.1101/2023.11.06.23298101v1

 

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The ultra-sensitive Cog State Brief Battery, a computerized neuropsychological examination, was used to assess cognition. The test was used to measure four metrics that are sensitive to neuroinflammation or vascular disease and influence executive function: response speed, processing speed, cognitive throughput, and visual working memory.

After the application of the inclusion and exclusion criteria, we analyzed data from a total of 493 eligible participants (Figure 1). As shown in Table 1, the infected and uninfected groups had similar demographics and health conditions before infection, though those who reported infections were somewhat younger (mean age=58.1 years) as compared to 56.0 years in the COVID-19 group (P=.001)

(this sentence structure is a bit confusing to me, what they are saying is that the infected COVID-19 group is younger at 56.04 years compared to the uninfected controls with 58.1 years)

The massive caviat is that this study is extremely focused on the male population with only 7.8% of controls and even only 4.7% of the Covid-19 group being females. This raises the question with which accuracy they were able to meaningfully determine PASC since half of the patients having PASC following a Covid-19 infection is an absurdely high ratio, especially in a male dominated cohort and even more so once one considers that more than 1/3 of participants had PASC for longer than one year.

Longitudinal results comparing functioning after the onset of COVID-19 to pre-COVID-19 levels (Table 7) suggested cognitive deficits concentrated in PASC cases. While only reaction speed was associated with the onset of acute COVID-19, in participants with PASC, we found significant decrements across all four domains of cognitive performance after the onset of COVID-19, with the largest decrements involving cognitive throughput and response speed.