In a recent study published in Healthcare, researchers evaluated the association between cognitive impairment and clinical-functional variables in the coronavirus disease 2019 (COVID-19) post-acute period.
Cognitive impairment includes difficulties in performing routine activities that involve attention, speed processing, and memory, significantly impacting the emotional and functional aspects of a patient’s quality of life (QOL). It has been established as a post-COVID 19 effect with associated neurological manifestations such as headache, myalgia, hyposmia, stroke, seizures, etc.
Previous studies have reported long-term behavioral and psychological symptoms among hospitalized COVID-19 patients, encompassing muscle weakness, depression, non-restorative sleep, anxiety, post-traumatic stress disorder (PTSD), etc. Autonomic dysregulations such as hypertension and circadian rhythm alterations have been associated with cognitive dysfunction. However, large-scale studies assessing the impact and mechanisms of functional and clinical alterations on cognitive function post-COVID-19 remission have not been conducted. Moreover, it is unclear whether cognitive decline is a direct effect of COVID-19 or an indirect effect secondary to mechanical ventilation, hypoxia, etc.
About the study
The researchers of the present observational study investigated the neuropsychological impact of COVID-19 in patients without relevant premorbid diseases at a multidisciplinary rehabilitation unit.
They consequently screened for convalescent COVID-19 patients suffering from moderate to severe pneumonia and who were referred to a multidisciplinary rehabilitation center in two months of test swab negativizing. The pulmonary rehabilitation (PR) scheme comprised everyday sessions (six sessions per week), psychological and dietary counseling, and physical exercises based on the American Thoracic Society/European Respiratory Society(ATS/ERS) recommendations.
Patients in the age range of 18-65 years who had received primary school education without prior history of neurological, pulmonary, or cardiovascular disorders were included in the study. Clinical and demographic data were obtained along with interviews and assessment of past medical records. Pulmonary function tests including one-second forced expiratory volume (FEV1), forced vital capacity (FVC), FEV1/FVC ratios, arterial blood gas [partial pressures of oxygen (PaO2) as well as carbon dioxide (PaCO2)] were performed.
Circadian rhythms and blood pressure (BP) variations were assessed. Based on nocturnal BP decrease, patients were categorized as dippers (≥ 10%) fall in nocturnal BP) and non-dippers (< 10% nocturnal BP fall). Venous blood samples were collected from all patients for D-Dimer and C-reactive protein (CRP) evaluation.
All participants responded to the questionnaires such as hospital anxiety and depression scale (HADS), state-trait anxiety inventory-form Y2 (STAI-Y2), the impact of event scale-revised (IES-R), and European Quality of Life Scale (EuroQOL). The various tests included a verbal fluency test (FAS), trail making test (TMT), Rey auditory verbal learning task, Corsi block-tapping test, Supra-span learning on Corsi’s test, and frontal assessment battery (FAB). Higher scores represented better cognitive functioning.
The neurological assessment was conducted by an expert neuropsychologist in the morning before physiotherapy. All patients completed the assessment during two sessions, two days apart, within a week from admission.
A total of 193 patients were screened of which 65 patients were enrolled for the study. Of these, two patients chose to withdraw before study completion. Thus, 63 (32.6%) convalescent COVID-19 patients (47 men, average age 60 years) were included in the final study.
Over 44% of patients were classified as reduced cognitive efficiency (RCE). The participants demonstrated high anxiety (55.5%), depressive symptoms (76.2%), and PTSD symptoms (44.4%). About 50% of the patients had RCE related to long-term spatial and verbal executive and memory functions. HADS scores revealed depression and anxiety in 76% and 55% of patients, respectively. STAI Y2 denoted moderate trait anxiety in six patients, and PTSD symptoms were observed in 44% of patients. Cronbach alpha values of the internal consistency of self-reported measures analysis were 0.82, 0.87, 0.92, and 0.85 for HADS-D, HADS-A STAI-Y2, and IES-R, respectively.
RCE patients more frequently showed alterations in circadian rhythm and BP (significantly higher proportion of non-dippers), elevated D-dimer levels, more PTSD symptoms, greater anxiety, and lower EuroQOL scores. They also were severely ill and had a longer disease duration and more frequent cognitive complaints in daily life activities such as poor concentration, difficulty in retrieving words during the speech, and reduced ability to remember and learn new information than subjects with normal cognitive efficiency (NCE).
The study findings highlight the association of autonomic dysfunctions such as BP and circadian rhythm changes with cognitive impairment in convalescent COVID-19 patients.
However, future studies with larger and heterogeneous samples, involving sleep study and cerebral neuroimaging with regular follow-ups are required to better elucidate the mechanisms of neuropsychological COVID-19 sequalae and validate the current study findings.