Functional connectivity underlying cognitive and psychiatric symptoms in post-COVID-19 syndrome: is anosognosia a key determinant?

Abstract

Lack of awareness of cognitive impairment (i.e., anosognosia) could be a key factor for distinguishing between neuropsychological post-COVID-19 condition phenotypes. In this context, the twofold aim of the present study was to i) establish the prevalence of anosognosia for memory impairment, according to the severity of the infection in the acute phase, and ii) determine whether anosognosic patients with post-COVID syndrome have a different cognitive and psychiatric profile from nosognosic patients, with associated differences in brain functional connectivity. A battery of neuropsychological, psychiatric, olfactory, dyspnea, fatigue and quality-of-life tests was administered 227.07 ± 42.69 days post-SARS-CoV-2 infection to 102 patients (mean age: 56.35 years, 65 men, no history of neurological, psychiatric, neuro-oncological or neurodevelopmental disorder prior to infection) who had experienced either a mild (not hospitalized; n = 45), moderate (conventional hospitalization; n = 34) or severe (hospitalization with intensive care unit stay and mechanical ventilation; n = 23) presentation in the acute phase. Patients were first divided into two groups according to the presence or absence of anosognosia for memory deficits (26 anosognosic patients and 76 nosognosic patients). Of these, 49 patients underwent an MRI. Structural images were visually analyzed, and statistical intergroup analyses were then performed on behavioral and functional connectivity measures. Only 15.6% of patients who presented mild disease displayed anosognosia for memory dysfunction, compared with 32.4% of patients with moderate presentation and 34.8% of patients with severe disease. Compared with nosognosic patients, those with anosognosia for memory dysfunction performed significantly more poorly on objective cognitive and olfactory measures. By contrast, they gave significantly more positive subjective assessments of their quality of life, psychiatric status, and fatigue. Interestingly, the proportion of patients exhibiting a lack of consciousness of olfactory deficits was significantly higher in the anosognosic group. Functional connectivity analyses revealed significant decrease in connectivity, in the anosognosic group as compared to the nosognosic group, within and between the following networks: the left default mode, the bilateral somatosensory motor, the right executive control, the right salient ventral attention and the bilateral dorsal attention networks, as well as the right Lobules IV and V of the cerebellum. Lack of awareness of cognitive disorders and, to a broader extent, impairment of the self-monitoring brain system, may be a key factor for distinguishing between the clinical phenotypes of post-COVID syndrome with neuropsychological deficits.

Correlations between Persistent Olfactory and Semantic Memory Disorders after SARS-CoV-2 Infection

“…Several studies have also shown an impairment of executive functions [ 20 , 25 , 28 , 29 , 30 , 31 , 32 , 33 ] attention [ 20 , 26 , 28 , 30 , 32 , 33 ] and memory [ 24 , 27 , 30 , 32 , 33 ] following COVID-19. In our study, we found that for the 40–59 age group, generative naming time was correlated with PPTT scores: the longer the generative naming time, the better the PPTT scores.…”

“…A recent study using pre- and post-infection imaging data identified a reduction in grey matter thickness, especially in the left hemisphere, and tissue-contrast in the orbitofrontal cortex and parahippocampal gyrus, which are highly connected to the olfactory system [ 26 ]. The damage to certain brain regions as a result of SARS-CoV-2 infection seems to lead to cognitive dysfunction [ 20 , 24 , 25 , 26 , 27 , 28 , 29 , 30 ]. Indeed, the percentage of post COVID-19 patients with global cognitive impairment varies from 15 to 80% [ 31 ].…”

“…Indeed, the percentage of post COVID-19 patients with global cognitive impairment varies from 15 to 80% [ 31 ]. This cognitive dysfunction results in executive disorders [ 20 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 ], attentional disorders [ 20 , 26 , 28 , 30 , 32 , 33 ], memory disorders [ 24 , 27 , 28 , 30 , 32 , 33 ], and sometimes language disorders regarding semantic and phonological verbal fluency [ 25 , 30 , 32 , 33 ].…”

Frequency of Abnormally Low Neuropsychological Scores in Post-COVID-19 Syndrome: the Geneva COVID-COG Cohort

“…This suggests that post-ICU effects are not the sole cause of long-term neuropsychological deficits ( Sakusic et al., 2018 ), given the high cumulative percentages of memory, executive, perceptual, and logical reasoning deficits in the moderate subgroup. Moreover, this highlights central nervous system involvement, either directly via SARS-CoV-2 neuroinvasive mechanisms, or indirectly via an immunological and/or inflammatory response to SARS-CoV-2 ( Bougakov, Podell, & Goldberg, 2021 ), which is supported by PET-FDG ( Guedj et al., 2021 ), functional connectivity ( Voruz et al., 2022b ), and structural ( Douaud et al., 2022 ) neuroimaging. Another hypothesis, which could explain the greater number of cumulative deficits in moderate patients, concerns the level of hypoxemia, for according to the literature, this is a predictor of cognitive deficits ( Herridge et al., 2016 ; Mikkelsen et al., 2012 ).…”

Acute and long-term neurological disorders in patients with coronavirus infection

“…Показано, что в среднем через 8 мес после COVID-19 16% пациентов с легкой формой заболевания, 33% со среднетяжелой формой и 35% с тяжелой формой игнорируют нарушения памяти и другие КН, которые ассоциируются с изменениями на МРТ [52].…”