Category: Cognitive Dysfunction

Cognitive impairments among patients in a long-COVID clinic: Prevalence, pattern and relation to illness severity, work function and quality of life

Abstract:

Background: A considerable proportion of people experience lingering symptoms after Coronavirus Disease 2019 (COVID-19). The aim of this study was to investigate the frequency, pattern and functional implications of cognitive impairments in patients at a long-COVID clinic who were referred after hospitalisation with COVID-19 or by their general practitioner.

Methods: Patients underwent cognitive screening and completed questionnaires regarding subjective cognition, work function and quality of life. Patients’ cognitive performance was compared with that of 150 age-, sex-, and education-matched healthy controls (HC) and with their individually expected performance calculated based on their age, sex and education.

Results: In total, 194 patients were assessed, on average 7 months (standard deviation: 4) after acute COVID-19.44-53 % of the patients displayed clinically relevant cognitive impairments compared to HC and to their expected performance, respectively. Moderate to large impairments were seen in global cognition and in working memory and executive function, while mild to moderate impairments occurred in verbal fluency, verbal learning and memory. Hospitalised (n = 91) and non-hospitalised (n = 103) patients showed similar degree of cognitive impairments in analyses adjusted for age and time since illness. Patients in the cognitively impaired group were older, more often hospitalised, had a higher BMI and more frequent asthma, and were more often female. More objective cognitive impairment was associated with more subjective cognitive difficulties, poorer work function and lower quality of life.

Limitations: The study was cross-sectional, which precludes causality inferences.

Conclusions: These findings underscore the need to assess and treat cognitive impairments in patients at long-COVID clinics.

Source: Miskowiak KW, Pedersen JK, Gunnarsson DV, Roikjer TK, Podlekareva D, Hansen H, Dall CH, Johnsen S. Cognitive impairments among patients in a long-COVID clinic: Prevalence, pattern and relation to illness severity, work function and quality of life. J Affect Disord. 2022 Dec 28;324:162-169. doi: 10.1016/j.jad.2022.12.122. Epub ahead of print. PMID: 36586593; PMCID: PMC9795797. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9795797/ (Full text)

Brain correlates of subjective cognitive complaints in COVID-19 survivors: A multimodal magnetic resonance imaging study

Abstract:

Cognitive impairment represents a leading residual symptom of COVID-19 infection, which lasts for months after the virus clearance. Up-to-date scientific reports documented a wide spectrum of brain changes in COVID-19 survivors following the illness’s resolution, mainly related to neurological and neuropsychiatric consequences.

Preliminary insights suggest abnormal brain metabolism, microstructure, and functionality as neural under-layer of post-acute cognitive dysfunction. While previous works focused on brain correlates of impaired cognition as objectively assessed, herein we investigated long-term neural correlates of subjective cognitive decline in a sample of 58 COVID-19 survivors with a multimodal imaging approach.

Diffusion Tensor Imaging (DTI) analyses revealed widespread white matter disruption in the sub-group of cognitive complainers compared to the non-complainer one, as indexed by increased axial, radial, and mean diffusivity in several commissural, projection and associative fibres. Likewise, the Multivoxel Pattern Connectivity analysis (MVPA) revealed highly discriminant patterns of functional connectivity in resting-state among the two groups in the right frontal pole and in the middle temporal gyrus, suggestive of inefficient dynamic modulation of frontal brain activity and possible metacognitive dysfunction at rest.

Beyond COVID-19 actual pathophysiological brain processes, our findings point toward brain connectome disruption conceivably translating into clinical post-COVID cognitive symptomatology. Our results could pave the way for a potential brain signature of cognitive complaints experienced by COVID-19 survivors, possibly leading to identify early therapeutic targets and thus mitigating its detrimental long-term impact on quality of life in the post-COVID-19 stages.

Source: Paolini M, Palladini M, Mazza MG, Colombo F, Vai B, Rovere-Querini P, Falini A, Poletti S, Benedetti F. Brain correlates of subjective cognitive complaints in COVID-19 survivors: A multimodal magnetic resonance imaging study. Eur Neuropsychopharmacol. 2022 Dec 12;68:1-10. doi: 10.1016/j.euroneuro.2022.12.002. Epub ahead of print. PMID: 36640728. https://www.sciencedirect.com/science/article/pii/S0924977X22009130 (Full study)

Brain fog of post-COVID-19 condition and Chronic Fatigue Syndrome, same medical disorder?

Abstract:

Background: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is characterized by persistent physical and mental fatigue. The post-COVID-19 condition patients refer physical fatigue and cognitive impairment sequelae. Given the similarity between both conditions, could it be the same pathology with a different precipitating factor?

Objective: To describe the cognitive impairment, neuropsychiatric symptoms, and general symptomatology in both groups, to find out if it is the same pathology. As well as verify if the affectation of smell is related to cognitive deterioration in patients with post-COVID-19 condition.

Methods: The sample included 42 ME/CFS and 73 post-COVID-19 condition patients. Fatigue, sleep quality, anxiety and depressive symptoms, the frequency and severity of different symptoms, olfactory function and a wide range of cognitive domains were evaluated.

Results: Both syndromes are characterized by excessive physical fatigue, sleep problems and myalgia. Sustained attention and processing speed were impaired in 83.3% and 52.4% of ME/CFS patients while in post-COVID-19 condition were impaired in 56.2% and 41.4% of patients, respectively. Statistically significant differences were found in sustained attention and visuospatial ability, being the ME/CFS group who presented the worst performance. Physical problems and mood issues were the main variables correlating with cognitive performance in post-COVID-19 patients, while in ME/CFS it was anxiety symptoms and physical fatigue.

Conclusions: The symptomatology and cognitive patterns were similar in both groups, with greater impairment in ME/CFS. This disease is characterized by greater physical and neuropsychiatric problems compared to post-COVID-19 condition. Likewise, we also propose the relevance of prolonged hyposmia as a possible marker of cognitive deterioration in patients with post-COVID-19.

Source: Azcue N, Gómez-Esteban JC, Acera M, Tijero B, Fernandez T, Ayo-Mentxakatorre N, Pérez-Concha T, Murueta-Goyena A, Lafuente JV, Prada Á, López de Munain A, Ruiz-Irastorza G, Ribacoba L, Gabilondo I, Del Pino R. Brain fog of post-COVID-19 condition and Chronic Fatigue Syndrome, same medical disorder? J Transl Med. 2022 Dec 6;20(1):569. doi: 10.1186/s12967-022-03764-2. PMID: 36474290. https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-022-03764-2 (Full text)

Effects of SARS-CoV-2 Infection on Attention, Memory, and Sensorimotor Performance

Abstract:

Background: Recovery after SARS-CoV-2 infection is extremely variable, with some individuals recovering quickly, and others experiencing persistent long-term symptoms or developing new symptoms after the acute phase of infection, including fatigue, poor concentration, impaired attention, or memory deficits. Many existing studies reporting cognitive deficits associated with SARS-CoV-2 infection are limited by the exclusive use of self-reported measures or a lack of adequate comparison groups.

Methods: Forty-five participants, ages 18-70, (11 Long-COVID, 14 COVID, and 20 No-COVID) underwent behavioral testing with the NIH Toolbox Neuro-Quality of Life survey and selected psychometric tests, including a flanker interference task and the d2 Test of Attention.

Results: We found greater self-reported anxiety, apathy, fatigue, emotional dyscontrol, sleep disturbance and cognitive dysfunction in COVID compared No-COVID groups. After categorizing COVID patients according to self-reported concentration problems, we observed declining performance patterns in multiple attention measures across No-COVID controls, COVID and Long-COVID groups. COVID participants, compared to No-COVID controls, exhibited worse performance on NIH Toolbox assessments, including the Eriksen Flanker, Nine-Hole Pegboard and Auditory Verbal Learning tests.

Conclusion: This study provides convergent evidence that previous SARS-CoV-2 infection is associated with impairments in sustained attention, processing speed, self-reported fatigue and concentration. The finding that some patients have cognitive and visuomotor dysfunction in the absence of self-reported problems suggests that SARS-CoV-2 infection can have unexpected and persistent subclinical consequences.

Source: O’Connor EE, Rednam N, O’Brien R, O’Brien S, Rock P, Levine A, Zeffiro TA. Effects of SARS-CoV-2 Infection on Attention, Memory, and Sensorimotor Performance. medRxiv [Preprint]. 2022 Sep 23:2022.09.22.22280222. doi: 10.1101/2022.09.22.22280222. PMID: 36172134; PMCID: PMC9516858. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9516858/ (Full text)

Memory alterations after COVID-19 infection: a systematic review

Abstract:

SARS-CoV-2 infection has a wide range of both acute and long-term symptoms. Memory alterations have been frequently reported in studies that explore cognition. The main objective of the systematic review is to update and further analyze the existing evidence of objective memory impairments in long-COVID-19 considering sample and study design characteristics, as well as to explore associations between memory performance and their epidemiological, clinical, and pathological features.

A total of 13 studies were identified by searching in PubMed, Web of Science, and PsycInfo databases up to May 6, 2022. Most studies evaluated verbal component of memory in the short-term and long-term recall up to 30 min and mainly performed a single assessment completed at 4-6 months after the infection. The samples mainly consisted of middle-aged adults that required hospitalization. Samples were not stratified by sex, age, and severity.

Poor verbal learning was reported in most cases (6-58%), followed by deficits in long-term (4-58%) and short-term (4-37%) verbal memory. Visuospatial component of memory was studied less than verbal component, showing impairment of long-term retention of visual items (10-49%). COVID-19 severity in the acute stage was not systematically associated with poor memory performance. Verbal memory deficits were associated with anxiety and depression.

The existing literature on objective memory assessment in long-COVID suggests further research is warranted to confirm memory dysfunction in association with epidemiological, pathological, and clinical factors, using both verbal and visuospatial tests, and exploring in deep long-term memory deficits.

Source: Llana T, Zorzo C, Mendez-Lopez M, Mendez M. Memory alterations after COVID-19 infection: a systematic review. Appl Neuropsychol Adult. 2022 Sep 15:1-14. doi: 10.1080/23279095.2022.2123739. Epub ahead of print. PMID: 36108666.  https://pubmed.ncbi.nlm.nih.gov/36108666/

Cognitive task performance and subjective cognitive symptoms in individuals with Chronic Fatigue Syndrome or Fibromyalgia: A cross-sectional analysis of the Lifelines cohort study

Abstract:

Objective: This study examined cognitive task performance and self-reported cognitive functioning in individuals with chronic fatigue syndrome (CFS) and fibromyalgia (FM) in a population-based sample and investigated the role of mood and anxiety disorders as well as severity of the physical symptoms.

Methods: This study was performed in 79,966 participants (Mean age: 52.9, SD = ±12.6 years, 59.2% women) from the Lifelines general-population. Symptoms consistent with the diagnostic criteria for CFS and FM were assessed using questionnaires. Two comparison groups were used: participants with self-reported medical disorders with well-defined pathophysiology (i.e., multiple sclerosis and rheumatic arthritis) and controls without these diseases. Objective task-performance was based on the computerized CogState cognitive battery and subjective cognitive symptoms using the concentration subscale of the Checklist Individual Strength.

Results: Cognitive task performance was poorer in individuals with CFS vs. controls without disease and controls with a medical disorder, although the severity of cognitive dysfunction was mild. Participants meeting criteria for CFS (n = 2,461) or FM (n = 4,295) reported more subjective cognitive symptoms compared to controls without a medical disorder (d = 1.53, 95%CI = 1.49-1.57 for CFS; d = 1.25, 95%CI = 1.22-1.29 for FM) and participants with a medical disease (d = 0.62, 95%CI = 0.46-0.79 for CFS; d = 0.75, 95%CI = 0.70-0.80 for FM). These differences remained essentially the same when excluding participants with comorbid mood or anxiety disorders or adjusting for physical symptom severity.

Conclusions: Subjective cognitive symptoms and to a lesser extent suboptimal cognitive task performance are more prevalent in individuals with CFS or FM compared to controls without these conditions.

Source: Joustra ML, Hartman CA, Bakker SJL, Rosmalen JGM. Cognitive task performance and subjective cognitive symptoms in individuals with Chronic Fatigue Syndrome or Fibromyalgia: A cross-sectional analysis of the Lifelines cohort study. Psychosom Med. 2022 Aug 2. doi: 10.1097/PSY.0000000000001117. Epub ahead of print. PMID: 35980775.  https://pubmed.ncbi.nlm.nih.gov/35980775/

COVID fog demystified

Abstract:

Acute mild respiratory SARS-CoV-2 infection can lead to a more chronic cognitive syndrome known as “COVID fog.” New findings from Fernández-Castañeda et al. reveal how glial dysregulation and consequent neural circuit dysfunction may contribute to cognitive impairments in long COVID.

Source: Kao J, Frankland PW. COVID fog demystified. Cell. 2022 Jul 7;185(14):2391-2393. doi: 10.1016/j.cell.2022.06.020. Epub 2022 Jun 15. PMID: 35768007; PMCID: PMC9197953. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9197953/ (Full text)

Mild respiratory SARS-CoV-2 infection can cause multi-lineage cellular dysregulation and myelin loss in the brain

Abstract:

Survivors of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection frequently experience lingering neurological symptoms, including impairment in attention, concentration, speed of information processing and memory. This long-COVID cognitive syndrome shares many features with the syndrome of cancer therapy-related cognitive impairment (CRCI). Neuroinflammation, particularly microglial reactivity and consequent dysregulation of hippocampal neurogenesis and oligodendrocyte lineage cells, is central to CRCI. We hypothesized that similar cellular mechanisms may contribute to the persistent neurological symptoms associated with even mild SARS-CoV-2 respiratory infection.

Here, we explored neuroinflammation caused by mild respiratory SARS-CoV-2 infection – without neuroinvasion – and effects on hippocampal neurogenesis and the oligodendroglial lineage. Using a mouse model of mild respiratory SARS-CoV-2 infection induced by intranasal SARS-CoV-2 delivery, we found white matter-selective microglial reactivity, a pattern observed in CRCI. Human brain tissue from 9 individuals with COVID-19 or SARS-CoV-2 infection exhibits the same pattern of prominent white matter-selective microglial reactivity. In mice, pro-inflammatory CSF cytokines/chemokines were elevated for at least 7-weeks post-infection; among the chemokines demonstrating persistent elevation is CCL11, which is associated with impairments in neurogenesis and cognitive function.

Humans experiencing long-COVID with cognitive symptoms (48 subjects) similarly demonstrate elevated CCL11 levels compared to those with long-COVID who lack cognitive symptoms (15 subjects). Impaired hippocampal neurogenesis, decreased oligodendrocytes and myelin loss in subcortical white matter were evident at 1 week, and persisted until at least 7 weeks, following mild respiratory SARS-CoV-2 infection in mice. Taken together, the findings presented here illustrate striking similarities between neuropathophysiology after cancer therapy and after SARS-CoV-2 infection, and elucidate cellular deficits that may contribute to lasting neurological symptoms following even mild SARS-CoV-2 infection.

Source: Fernández-Castañeda A, Lu P, Geraghty AC, Song E, Lee MH, Wood J, Yalçın B, Taylor KR, Dutton S, Acosta-Alvarez L, Ni L, Contreras-Esquivel D, Gehlhausen JR, Klein J, Lucas C, Mao T, Silva J, Peña-Hernández MA, Tabachnikova A, Takahashi T, Tabacof L, Tosto-Mancuso J, Breyman E, Kontorovich A, McCarthy D, Quezado M, Hefti M, Perl D, Folkerth R, Putrino D, Nath A, Iwasaki A, Monje M. Mild respiratory SARS-CoV-2 infection can cause multi-lineage cellular dysregulation and myelin loss in the brain. bioRxiv [Preprint]. 2022 Jan 10:2022.01.07.475453. doi: 10.1101/2022.01.07.475453. PMID: 35043113; PMCID: PMC8764721.  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8764721/ (Full text)

Orthostatic Challenge Causes Distinctive Symptomatic, Hemodynamic and Cognitive Responses in Long COVID and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Abstract:

Background: Some patients with acute COVID-19 are left with persistent, debilitating fatigue, cognitive impairment (“brain fog”), orthostatic intolerance (OI) and other symptoms (“Long COVID”). Many of the symptoms are like those of other post-infectious fatigue syndromes and may meet criteria for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Common diagnostic laboratory tests are often unrevealing.

Methods: We evaluated whether a simple, standardized, office-based test of OI, the 10-min NASA Lean Test (NLT), would aggravate symptoms and produce objective hemodynamic and cognitive abnormalities, the latter being evaluated by a simple smart phone-based app.

Participants: People with Long COVID (N = 42), ME/CFS (N = 26) and healthy control subjects (N = 20) were studied just before, during, immediately after, 2 and 7 days following completion of the NLT.

Results: The NLT provoked a worsening of symptoms in the two patient groups but not in healthy control subjects, and the severity of all symptoms was similar and significantly worse in the two patient groups than in the control subjects (p < 0.001). In the two patient groups, particularly those with Long COVID, the NLT provoked a marked and progressive narrowing in the pulse pressure. All three cognitive measures of reaction time worsened in the two patient groups immediately following the NLT, compared to the healthy control subjects, particularly in the Procedural Reaction Time (p < 0.01).

Conclusions: A test of orthostatic stress easily performed in an office setting reveals different symptomatic, hemodynamic and cognitive abnormalities in people with Long COVID and ME/CFS, compared to healthy control subjects. Thus, an orthostatic challenge easily performed in an office setting, and the use of a smart phone app to assess cognition, can provide objective confirmation of the orthostatic intolerance and brain fog reported by patients with Long COVID and ME/CFS.

Source: Vernon SD, Funk S, Bateman L, Stoddard GJ, Hammer S, Sullivan K, Bell J, Abbaszadeh S, Lipkin WI, Komaroff AL. Orthostatic Challenge Causes Distinctive Symptomatic, Hemodynamic and Cognitive Responses in Long COVID and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Front Med (Lausanne). 2022 Jun 23;9:917019. doi: 10.3389/fmed.2022.917019. PMID: 35847821; PMCID: PMC9285104. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9285104/ (Full text)

Memory impairments in chronic fatigue syndrome patients

Abstract:

Background: Chronic Fatigue Syndrome (CFS) patients often report memory problems. Prior research has produced conflicting results on this topic. Episodic memory impairments appear to be robust, but tasks assessing other aspects of memory (e.g., working and semantic memory) show slower speed but no decrease in accuracy. This study examined whether the memory problems of CFS patients reflect slower responses. Methods: CFS patients were recruited from a specialist clinic. Sixty-seven patients carried out tasks measuring immediate recall, delayed recognition memory, logical reasoning and semantic processing. The control group were 126 healthy volunteers recruited from the general population.

Results: The CFS patients recalled fewer words and had poorer delayed recognition. The other tasks showed slower speed but no effect on accuracy.

Conclusions: CFS patients have poorer immediate recall and delayed recognition memory. The delayed recognition memory probably reflected the poorer immediate recall. Slower responding was present in three of the tasks, and it is possible that this also accounted for the reduced immediate recall.

Source:  Smith, Andrew. Memory impairments in chronic fatigue syndrome patients. wjpmr, 2022, 8(6), 50-54. ISSN 2455-3301 https://orca.cardiff.ac.uk/id/eprint/150176/1/article_1654063780_pub.pdf (Full text)