Diagnosis of delirium: a practical approach.

Delirium is an acute disorder of fluctuating attention and awareness with cardinal features that allow it to be positively distinguished from other causes of an acute confusional state. These features include fluctuations, prominent inattentiveness with other cognitive deficits, a change in awareness and visual hallucinations. We describe a framework for diagnosing delirium, noting the need to consider certain caveats and differential diagnoses. Delirium is a clinical diagnosis where a thorough history and clinical examination are much more helpful diagnostically than any single test or combination of tests.

Validation study of "Santé-Cerveau", a digital tool for early cognitive changes identification.

BACKGROUND: There is a need for a reliable, easy-to-use, widely available, and validated tool for timely cognitive impairment identification. We created a computerized cognitive screening tool (Santé-Cerveau digital tool (SCD-T)) including validated questionnaires and the following neuropsychological tests: 5 Word Test (5-WT) for episodic memory, Trail Making Test (TMT) for executive functions, and a number coding test (NCT) adapted from the Digit Symbol Substitution Test for global intellectual efficiency. This study aimed to evaluate the performance of SCD-T to identify cognitive deficit and to determine its usability. METHODS: Three groups were constituted including 65 elderly Controls, 64 patients with neurodegenerative diseases (NDG): 50 AD and 14 non-AD, and 20 post-COVID-19 patients. The minimum MMSE score for inclusion was 20. Association between computerized SCD-T cognitive tests and their standard equivalent was assessed using Pearson's correlation coefficients. Two algorithms (a simple clinician-guided algorithm involving the 5-WT and the NCT; and a machine learning classifier based on 8 scores from the SCD-T tests extracted from a multiple logistic regression model, and data from the SCD-T questionnaires) were evaluated. The acceptability of SCD-T was investigated through a questionnaire and scale. RESULTS: AD and non-AD participants were older (mean ± standard deviation (SD): 72.61 ± 6.79 vs 69.91 ± 4.86 years old, p = 0.011) and had a lower MMSE score (Mean difference estimate ± standard error: 1.74 ± 0.14, p < 0.001) than Controls; post-COVID-19 patients were younger than Controls (mean ± SD: 45.07 ± 11.36 years old, p < 0.001). All the computerized SCD-T cognitive tests were significantly associated with their reference version. In the pooled Controls and NDG group, the correlation coefficient was 0.84 for verbal memory, -0.60 for executive functions, and 0.72 for global intellectual efficiency. The clinician-guided algorithm demonstrated 94.4% ± 3.8% sensitivity and 80.5% ± 8.7% specificity, and the machine learning classifier 96.8% ± 3.9% sensitivity and 90.7% ± 5.8% specificity. The acceptability of SCD-T was good to excellent. CONCLUSIONS: We demonstrate the high accuracy of SCD-T in screening cognitive disorders and its good acceptance even in individuals with prodromal and mild dementia stages. SCD-T would be useful in primary care to faster refer subjects with significant cognitive impairment (and limit unnecessary referrals) to specialized consultation, improve the AD care pathway and the pre-screening in clinical trials.

COVID-19 severity is related to poor executive function in people with post-COVID conditions.

Patients with post-coronavirus disease 2019 (COVID-19) conditions typically experience cognitive problems. Some studies have linked COVID-19 severity with long-term cognitive damage, while others did not observe such associations. This discrepancy can be attributed to methodological and sample variations. We aimed to clarify the relationship between COVID-19 severity and long-term cognitive outcomes and determine whether the initial symptomatology can predict long-term cognitive problems. Cognitive evaluations were performed on 109 healthy controls and 319 post-COVID individuals categorized into three groups according to the WHO clinical progression scale: severe-critical (n = 77), moderate-hospitalized (n = 73), and outpatients (n = 169). Principal component analysis was used to identify factors associated with symptoms in the acute-phase and cognitive domains. Analyses of variance and regression linear models were used to study intergroup differences and the relationship between initial symptomatology and long-term cognitive problems. The severe-critical group performed significantly worse than the control group in general cognition (Montreal Cognitive Assessment), executive function (Digit symbol, Trail Making Test B, phonetic fluency), and social cognition (Reading the Mind in the Eyes test). Five components of symptoms emerged from the principal component analysis: the "Neurologic/Pain/Dermatologic" "Digestive/Headache", "Respiratory/Fever/Fatigue/Psychiatric" and "Smell/ Taste" components were predictors of Montreal Cognitive Assessment scores; the "Neurologic/Pain/Dermatologic" component predicted attention and working memory; the "Neurologic/Pain/Dermatologic" and "Respiratory/Fever/Fatigue/Psychiatric" components predicted verbal memory, and the "Respiratory/Fever/Fatigue/Psychiatric," "Neurologic/Pain/Dermatologic," and "Digestive/Headache" components predicted executive function. Patients with severe COVID-19 exhibited persistent deficits in executive function. Several initial symptoms were predictors of long-term sequelae, indicating the role of systemic inflammation and neuroinflammation in the acute-phase symptoms of COVID-19." Study Registration: www.ClinicalTrials.gov , identifier NCT05307549 and NCT05307575.

Cognitive deficit in post-acute COVID-19: an opportunity for EEG evaluation?

BACKGROUND AND PURPOSE: Among the most common post-COVID symptoms, many patients experienced subjective cognitive deficit, commonly named "brain fog," that might be present also in those individuals without severe acute COVID-19 respiratory involvement. Some studies have investigated some of the mechanisms that might be associated with the brain fog with objective techniques including transcranial magnetic stimulation and neuroimaging. METHODS: The aim of this study was to investigate the presence of electroencephalographic (EEG) alterations in people with post-COVID self-reported cognitive deficit. RESULTS: Out of the 90 patients attending the post-COVID neurology ambulatory service, twenty patients presenting brain fog at least 4 weeks after acute non-severe COVID-19 infection, and without previous history of epilepsy, were investigated with 19-channel EEG, Montreal Cognitive Assessment (MoCA), and magnetic resonance imaging (MRI). EEG was found altered in 65% of the sample, among which 69% presented a slowing activity and 31% were characterized by epileptic discharges principally in the frontal areas. None of the patients showed DWI MRI lesions. CONCLUSIONS: These findings highlight the usefulness of EEG analysis to objectively describe possible neurophysiological abnormalities in post-COVID patients presenting subjective cognitive deficit.

Functional cognitive disorders: clinical presentations and treatment approaches.

Functional cognitive disorders (FCDs) are a common cause of subjective and mild cognitive impairment. Isolated FCDs commonly present to the cognitive clinic, but examination of the nature of the symptoms suggests that they can also be understood as a transdiagnostic feature of many other conditions. This article examines methods of formulating the cognitive difficulties in order to identify treatment targets in people with FCDs.

[Cognitive consequences of COVID-19]. / Kognitivnaya disfunktsiya pri COVID-19.

An analysis of foreign publications illustrates changes in ideas about the etiology, pathogenesis, target organs, leading pathophysiological syndromes and clinical manifestations of nervous system damage in COVID-19 over 2.5 years of the pandemic. It has been demonstrated that, according to modern concepts, COVID-19 is considered as a pathology with a tendency to multiple organ damage, where the symptoms of damage to the nervous system not only determine the severity of the course of the disease, but also indirectly affect the development of severe somatic manifestations, such as distress syndrome. Particular attention is paid to the analysis of publications summarizing the available data on the frequency of cognitive deficit in the acute period of COVID-19 and in the post-COVID period, risk factors, recovery prospects. Putative mechanisms underlying cognitive deficit in COVID-19 are considered. Despite a significant number of observations and publications, many mechanisms of nervous system damage in COVID-19 and the selectivity of the cognitive deficit pattern remain unexplored. In modern publications, there is no information and long term forecast of the cognitive state dynamics, which is an important argument in favor of the need to continue research.

Cognitive phenotyping of post-infectious SARS-CoV-2 patients.

BACKGROUND: SARS-CoV-2 infection entails neuroinvasive, neuroinflammatory, and treatment-related features accounting for cognitive deficits in COVID-19-recovered patients. Although screening for such dysfunctions in this population is considered clinically relevant, contributions to cognitive phenotyping including premorbid and disease-related confounders are scarcely represented. This study thus aimed at describing the cognitive outcome at the function-/domain-level of post-infectious SARS-CoV-2 patients being already at risk (RCD +) or not (RCD -) for cognitive decline. METHODS: Fifty-four COVID-19-recovered individuals were classified as either RCD + or RCD - according to medical records. The Mini-Mental State Examination (MMSE), Addebrooke Cognitive Examination-Revised (ACE-R), Frontal Assessment Battery (FAB), and Attentive Matrices (AM) were administered (N = 54, 34, 28, and 28 patients, respectively). RESULTS: Prevalence of defective (cutoff = 24.89) MMSE scores was 24.3% in RCD + patients and 5.9% in the RCD - group. ACE-R-total below cutoff scores were less frequent (RCD + : 5.4%; RCD - : 5.9%). Abnormal performances at the FAB an AM were respectively detected in 18.9% and 8.1% of RCD + patients and 0% and 11.8% of the RCD - group. Within the ACE-R subtests, those assessing orientation, attention, and fluency were the most frequently impaired in both groups. Disease-related variables were mostly unassociated with cognitive measures. DISCUSSION: Both RCD + and RCD - COVID-19-recovered individuals might show cognitive deficits within the dysexecutive-inattentive and amnesic spectrum. Non-instrumental, executive/attentive dysfunctions are predominant in this population and can be detected by both screening and domain-specific psychometric tests-although the latter might be more sensitive in RCD - patients.

Predicting daily functioning with the modified Telephone Interview for Cognitive Status.

BACKGROUND: The modified Telephone Interview for Cognitive Status (mTICS) is a frequently used telephone-based cognitive screening measure that can distinguish between normal aging, mild cognitive impairment (MCI), and dementia. Although it has been used to predict current and future cognitive function in older adults, no studies have examined if the mTICS can predict daily functioning. AIMS: The current study sought to examine the relationship between the mTICS and a performance-based measure of daily functioning. METHODS: The mTICS and demographic information (age, sex, education) were collected during a telephone screening visit for 149 older adults (65-91 years in age) with amnestic MCI. Three subscales of the Independent Living Scales (ILS; Managing Money, Managing Home and Transportation, Health and Safety) were collected during a baseline visit and during a 16 month follow-up visit in a subsample of 93 individuals. RESULTS: Using simple hierarchical regression, baseline mTICS total score combined with demographic variables significantly predicted 19-22% of baseline ILS subscale scores. Similarly, in a subsample of 93 participants with 16 month follow-up data, baseline mTICS and demographic information predicted 9-31% of ILS subscale scores at follow-up. CONCLUSIONS: The mTICS appears able to predict daily functioning in older individuals with MCI. Remote tracking of cognition and daily functioning in this at-risk group seems particularly beneficial to geriatricians and other providers, especially during COVID-19.

Outcomes in post-acute sequelae of COVID-19 (PASC) at 6 months post-infection Part 1: Cognitive functioning.

OBJECTIVE: Long-term cognitive sequelae of COVID-19 have not been extensively studied. This study provides initial results on cognitive outcomes in Post-Acute Sequelae of COVID-19 (PASC).Participants and Methods: This study examined 53 consecutive outpatients diagnosed with COVID-19. Four participants were excluded due to performance validity test failure. All participants had positive COVID-19 tests, reported cognitive concerns, and completed neuropsychological tests to assess performance validity, attention/working memory, processing speed, memory, language, visual-spatial, executive functioning, motor, and emotional functioning. The sample was mostly white (89.8%), female (83.7%), and never hospitalized (69.4%) for COVID-19. RESULTS: Analyses indicated no mean scores in the Impaired range (>2 standard deviations [SD] below normative mean) on objective cognitive testing and a low base rate of Impaired test scores. Higher (>20%) base rates of Borderline performance (1-2 SDs below normative mean) were found on some measures. There was also evidence for frequently elevated mean scores on mood measures which correlated with some cognitive measures and the number of Borderline scores per participants. CONCLUSIONS: The results were noteworthy for infrequent Impaired scores, and significant correlations between cognition and mood/anxiety measures, but not between cognitive performance and premorbid vascular risk factors, psychiatric diagnoses, or COVID-19 disease severity. Results suggest that psychological distress was prominent in PASC and related to objective cognitive performance, but objective cognitive performance was unrelated to cognitive complaints. Other contributing factors may include fatigue/sleep issues. Neurologically based cognitive deficits were not suggested by the results.

Long-term consequences of COVID-19 on cognitive functioning up to 6 months after discharge: role of depression and impact on quality of life.

Neurologic and psychiatric symptoms have been reported in the months following the infection with COVID-19. A low-grade inflammation has been associated both with depression and cognitive symptoms, suggesting a link between these disorders. The aim of the study is to investigate cognitive functioning 6 months following hospital discharge for COVID-19, the impact of depression, and the consequences on quality of life. Ninety-two COVID-19 survivors evaluated at 1-month follow-up, 122 evaluated at 3 months and 98 evaluated at 6 months performed neuropsychological and psychiatric evaluations and were compared with a healthy comparison group (HC) of 165 subjects and 165 patients with major depression (MDD). Cognitive performances were adjusted for age, sex, and education. Seventy-nine percent of COVID-19 survivors at 1 month and 75% at 3- and 6-month follow-up showed cognitive impairment in at least one cognitive function. No significant difference in cognitive performances was observed between 1-, 3-, and 6-months follow-up. COVID-19 patients performed worse than HC but better than MDD in psychomotor coordination and speed of information processing. No difference between COVID-19 survivors and MDD was observed for verbal fluency, and executive functions, which were lower than in HC. Finally, COVID-19 survivors performed the same as HC in working memory and verbal memory. The factor that most affected cognitive performance was depressive psychopathology which, in turn, interact with cognitive functions in determining quality of life. Our results confirm that COVID-19 sequelae include signs of cognitive impairment which persist up to 6 months after hospital discharge and affect quality of life.

Neurocognitive Outcome Following Recovery from Severe Acute Respiratory Syndrome - Coronavirus-1 (SARS-CoV-1).

OBJECTIVE: Severe acute respiratory syndrome (SARS) is a highly contagious viral respiratory illness associated with hypoxia and dyspnea. Many of those who contracted and recovered from SARS during the 2002-2003 outbreak reported persistent physical, psychological, and cognitive difficulties. Here, we investigated the residual influences of SARS on cognition for a subset of healthcare professionals who recovered and were referred for neuropsychological evaluation through their workplace insurance. METHOD: Twenty-eight healthcare professionals were evaluated on neuropsychological and mood functioning approximately 1.5 years post-recovery from a severe respiratory illness. Test scores were compared with age-matched normative data, and correlations were examined between mood, self-report memory scales, subjective complaints (e.g., poor concentration, pain, fatigue), illness severity (i.e., length of hospitalization, oxygen use during hospital stay), and cognitive performance. RESULTS: Participants performed within age expectations on the majority of cognitive measures including overall memory ability. Although processing speed was generally within normal limits, 43% showed significant speed-accuracy trade-offs favoring accuracy over maintaining speed. Deficits were observed on measures of complex attention, such as working memory and the ability to sustain attention under conditions of distraction. Participants endorsed poorer memory ability than same-age peers on a meta-memory measure and mild to moderate depression and anxiety symptoms. Objective test performance was largely uncorrelated with self-reports, mood, or illness severity, except for moderate correlations between complex attention and participants' subjective ratings of Everyday Task-Oriented Memory. CONCLUSIONS: These findings demonstrate specific long-term cognitive deficits associated with SARS and provide further evidence of the cognitive effects of hypoxic illnesses.

Cognitive Stabilization Intervention during the Era of COVID-19.

As COVID-19 halted traditional neuropsychological assessment due to infection risk, neuropsychologists considered alternative practice models. Cognitive stabilization intervention (CSI) via telehealth, was developed to stabilize cognition in advance of neuropsychological assessment. It incorporates elements of evidence-based treatments, including cognitive training, sleep training, and medication adherence training within a motivational interview framework. Two case vignettes are described. One vignette describes an elder man who received CSI to manage sleep difficulties, forgetfulness, and mood symptoms. Another vignette describes a woman who completed CSI following an autoimmune disorder episode to improve sleep, organization, and attention. The benefits and limitations of CSI are discussed.

Diagnostic accuracy of virtual cognitive assessment and testing: Systematic review and meta-analysis.

BACKGROUND/OBJECTIVES: Virtual (i.e., telephone or videoconference) care was broadly implemented because of the COVID-19 pandemic. Our objectives were to compare the diagnostic accuracy of virtual to in-person cognitive assessments and tests and barriers to virtual cognitive assessment implementation. DESIGN: Systematic review and meta-analysis. SETTING: MEDLINE, EMBASE, CDSR, CENTRAL, PsycINFO, and gray literature (inception to April 1, 2020). PARTICIPANTS AND INTERVENTIONS: Studies describing the accuracy or reliability of virtual compared with in-person cognitive assessments (i.e., reference standard) for diagnosing dementia or mild cognitive impairment (MCI), identifying virtual cognitive test cutoffs suggestive of dementia or MCI, or describing correlations between virtual and in-person cognitive test scores in adults. MEASUREMENTS: Reviewer pairs independently conducted study screening, data abstraction, and risk of bias appraisal. RESULTS: Our systematic review included 121 studies (15,832 patients). Two studies demonstrated that virtual cognitive assessments could diagnose dementia with good reliability compared with in-person cognitive assessments: weighted kappa 0.51 (95% confidence interval [CI] 0.41-0.62) and 0.63 (95% CI 0.4-0.9), respectively. Videoconference-based cognitive assessments were 100% sensitive and specific for diagnosing dementia compared with in-person cognitive assessments in a third study. No studies compared telephone with in-person cognitive assessment accuracy. The Telephone Interview for Cognitive Status (TICS; maximum score 41) and modified TICS (maximum score 50) were the only virtual cognitive tests compared with in-person cognitive assessments in >2 studies with extractable data for meta-analysis. The optimal TICS cutoff suggestive of dementia ranged from 22 to 33, but it was 28 or 30 when testing was conducted in English (10 studies; 1673 patients). Optimal modified TICS cutoffs suggestive of MCI ranged from 28 to 31 (3 studies; 525 patients). Sensory impairment was the most often voiced condition affecting assessment. CONCLUSION: Although there is substantial evidence supporting virtual cognitive assessment and testing, we identified critical gaps in diagnostic certainty.

Effects of COVID-19 Home Confinement on Mental Health in Individuals with Increased Risk of Alzheimer's Disease.

We explored the impact of the Spanish COVID-19 strict home confinement on mental health and cognition in non-infected subjects (N = 16, 60-80 years) diagnosed with subjective cognitive decline and APOEɛ3/ɛ4 carriers. Mental health was monitored for 2 months on a daily, weekly, or monthly basis, and compared to pre-confinement values. Emotional distress, anxiety, and depression scores increased to pathological threshold values during and after confinement. Those with lower mood during confinement experienced a decline in their mood after confinement. Cognition did not change. These preliminary results suggest that mental health consequences of corona measures in preclinical stages of Alzheimer's disease should be further evaluated.

Neurocognitive deficits in severe COVID-19 infection: Case series and proposed model.

Objective: To date, very few studies investigating neurocognitive deficits in COVID-19 have been published. This case series addresses cognition in post-COVID-19 patient by describing three patients in acute rehabilitation to inform a model of cognitive sequelae of COVID-19. Methods: Three English-speaking inpatients with severe symptoms and long-term intensive care unit (ICU) treatment are described. All patients had a premorbid history of hypertension and hyperlipidemia and experienced delirium and hypoxemia when hospitalized. Patient 1 is a 62-year-old male with 15 years of education with additional history of obstructive sleep apnea and type 2 diabetes. Patient 2 is a 73-year-old female with 12 years of education with a premorbid medical history of alcohol use disorder and Guillain-Barre syndrome. Patient 3 is a 75-year-old male with 14 years of education. No patients had premorbid psychiatric histories. Results: The three patients demonstrated deficits on formal neuropsychological testing, particularly with encoding and verbal fluency. Memory measures improved with a more structured story memory task compared to a less-structured verbal list-learning task, suggesting executive dysfunction impacted learning. None of the patients demonstrated rapid forgetting of information. Two patients endorsed new depressive and/or anxiety symptoms. Conclusions: The results suggest evidence for neurocognitive deficits after severe COVID-19 infection, particularly in encoding and verbal fluency. These results were interpreted with caution given the limited number of patients and the telephone-based battery. The specific mechanism that caused these cognitive deficits in these individuals remains unclear. A proposed three-stage model of cognitive dysfunction is described to help guide future research.

Assessment of Prorated Scoring of an Abbreviated Protocol for the National Institutes of Health Toolbox Cognition Battery.

OBJECTIVE: To evaluate an abbreviated NIH Toolbox Cognition Battery (NIHTB-CB) protocol that can be administered remotely without any in-person assessments, and explore the agreement between prorated scores from the abbreviated protocol and standard scores from the full protocol. METHODS: Participant-level age-corrected NIHTB-CB data were extracted from six studies in individuals with a history of stroke, mild traumatic brain injury (mTBI), treatment-resistant psychosis, and healthy controls, with testing administered under standard conditions. Prorated fluid and total cognition scores were estimated using regression equations that excluded the three fluid cognition NIHTB-CB instruments which cannot be administered remotely. Paired t tests and intraclass correlations (ICCs) were used to compare the standard and prorated scores. RESULTS: Data were available for 245 participants. For fluid cognition, overall prorated scores were higher than standard scores (mean difference = +4.5, SD = 14.3; p < 0.001; ICC = 0.86). For total cognition, overall prorated scores were higher than standard scores (mean difference = +2.7, SD = 8.3; p < 0.001; ICC = 0.88). These differences were significant in the stroke and mTBI groups, but not in the healthy control or psychosis groups. CONCLUSIONS: Prorated scores from an abbreviated NIHTB-CB protocol are not a valid replacement for the scores from the standard protocol. Alternative approaches to administering the full protocol, or corrections to scoring of the abbreviated protocol, require further study and validation.