Neuropsychological Predictors of Fatigue in Post-COVID Syndrome

Abstract

Fatigue is one of the most disabling symptoms in several neurological disorders and has an important cognitive component. However, the relationship between self-reported cognitive fatigue and objective cognitive assessment results remains elusive. Patients with post-COVID syndrome often report fatigue and cognitive issues several months after the acute infection. We aimed to develop predictive models of fatigue using neuropsychological assessments to evaluate the relationship between cognitive fatigue and objective neuropsychological assessment results. We conducted a cross-sectional study of 113 patients with post-COVID syndrome, assessing them with the Modified Fatigue Impact Scale (MFIS) and a comprehensive neuropsychological battery including standardized and computerized cognitive tests. Several machine learning algorithms were developed to predict MFIS scores (total score and cognitive fatigue score) based on neuropsychological test scores. MFIS showed moderate correlations only with the Stroop Color–Word Interference Test. Classification models obtained modest F1-scores for classification between fatigue and non-fatigued or between 3 or 4 degrees of fatigue severity. Regression models to estimate the MFIS score did not achieve adequate R2 metrics. Our study did not find reliable neuropsychological predictors of cognitive fatigue in the post-COVID syndrome. This has important implications for the interpretation of fatigue and cognitive assessment. Specifically, MFIS cognitive domain could not properly capture actual cognitive fatigue. In addition, our findings suggest different pathophysiological mechanisms of fatigue and cognitive dysfunction in post-COVID syndrome.

Fatigue and Cognitive Dysfunction Are Associated with Occupational Status in Post-COVID Syndrome

“…However, the questionnaire responses revealed a wide variety of symptoms potentially interfering with work capacity, and a careful, individualized assessment of each symptom would be needed in these patients. Regarding cognitive function, the Stroop test was the most associated test, which is in accordance with previous studies in which the Stroop test is one of the most impaired tests in PCS and more associated with fatigue [ 12 , 22 , 23 , 24 ]. The results remained significant even after excluding those patients requiring ICU admission or ventilatory assistance.…”

Transcranial direct current stimulation for post-COVID fatigue: a randomized, double-blind, controlled pilot study

“…Fatigue usually has a physical and a cognitive dimension, which may have different pathophysiological mechanisms. 5 , 6 The detection of brain damage in neuroimaging studies in patients with post-COVID syndrome and in histopathological studies in individuals who died due to COVID-19 supports the hypothesis of central nervous system dysfunction in patients with this condition. 7-10 Furthermore, research with transcranial magnetic stimulation has found connectivity changes potentially associated with gamma-aminobutyric acid (GABA)-ergic neurotransmission dysfunction.…”

“…Although some studies suggest that dorsolateral prefrontal tDCS could enhance cognitive performance, especially attention function and working memory, recent meta-analyses have shown conflicting results. 42 , 43 In a recent study into post-COVID syndrome, we found that the Stroop test was the test that most strongly correlated with subjective fatigue, 6 although this test is also associated with other cognitive functions. Thus, our results suggest that short-term prefrontal tDCS has no significant effects on cognitive fatigue as measured by subjective and objective tests.…”

“…We used the Stroop Color-Word Interference test, 31 as previous works by our research group have found that this test is the tool that most frequently detects abnormal results in patients with post-COVID syndrome and is best correlated with fatigue severity. 6 , 32 The Stroop test is a measure of cognitive flexibility, selective attention, inhibition, and processing speed. It comprises three tasks: (i) reading the names of colours printed in blank ink (W); (ii) naming different colour patches (C); and (iii) naming the colour of the ink in colour words printed in an incongruent colour ink (e.g.…”

An exploration of the definitions and measures that have been used when investigating fatigue in adults with Long COVID: a scoping review protocol

“…Physical fatigue can be measured using a variety of physiological measures, such as those obtained from heart rate, nerve conduction studies, and electrophysiological examinations 13 . Cognitive fatigue, also called brain fog, 5 is typically measured by self-report or by a decline in performance of a cognitively demanding task 22 …”