Neuropsychiatric complications of coronavirus disease 2019: Mount Sinai Health System cohort study.

OBJECTIVE: To describe the frequency of neuropsychiatric complications among hospitalized patients with coronavirus disease 2019 (COVID-19) and their association with pre-existing comorbidities and clinical outcomes. METHODS: We retrospectively identified all patients hospitalized with COVID-19 within a large multicenter New York City health system between March 15, 2020 and May 17, 2021 and randomly selected a representative cohort for detailed chart review. Clinical data, including the occurrence of neuropsychiatric complications (categorized as either altered mental status [AMS] or other neuropsychiatric complications) and in-hospital mortality, were extracted using an electronic medical record database and individual chart review. Associations between neuropsychiatric complications, comorbidities, laboratory findings, and in-hospital mortality were assessed using multivariate logistic regression. RESULTS: Our study cohort consisted of 974 patients, the majority were admitted during the first wave of the pandemic. Patients were treated with anticoagulation (88.4%), glucocorticoids (24.8%), and remdesivir (10.5%); 18.6% experienced severe COVID-19 pneumonia (evidenced by ventilator requirement). Neuropsychiatric complications occurred in 58.8% of patients; 39.8% experienced AMS; and 19.0% experienced at least one other complication (seizures in 1.4%, ischemic stroke in 1.6%, hemorrhagic stroke in 1.0%) or symptom (headache in 11.4%, anxiety in 6.8%, ataxia in 6.3%). Higher odds of mortality, which occurred in 22.0%, were associated with AMS, ventilator support, increasing age, and higher serum inflammatory marker levels. Anticoagulant therapy was associated with lower odds of mortality and AMS. CONCLUSION: Neuropsychiatric complications of COVID-19, especially AMS, were common, varied, and associated with in-hospital mortality in a diverse multicenter cohort at an epicenter of the COVID-19 pandemic.

Greater executive dysfunction in patients post-COVID-19 compared to those not infected.

BACKGROUND: A number of patients post-coronavirus disease-19 (COVID-19) report cognitive impairment (CI), even months after acute infection. We aimed to assess if COVID-19 is associated with increased incidence of CI in comparison to controls. METHODS: We analyzed data from the Mount Sinai Health System Post-COVID-19 Registry in New York City, a prospective cohort of patients post-COVID-19 ≥18 years of age and non-infected controls. CI was defined by scores ≥ 1.0 standard deviation below population norms, and was assessed using well-validated measures of attention, working memory, processing speed, executive functioning/cognitive flexibility, language, learning, and memory. Logistic regression models assessed odds for CI in each domain in patients post-COVID-19 vs. controls after adjusting for potential confounders. In exploratory analyses, we assessed odds for CI by site of acute COVID-19 care as a proxy for disease severity. FINDINGS: 417 patients post-COVID-19 and 151 controls (mean age 49 years, 63% female, 21% Black, 17% Latinx) were included. In adjusted analyses, patients were significantly more likely than controls to have CI in executive functioning (odds ratio [OR]: 2.19; 95% confidence interval [CI]: 1.03 to 4.67), particularly those treated in outpatient (OR: 2.22; 95% CI: 1.02 to 4.82) and inpatient hospital (OR: 3.59; 95% CI: 1.27 to 10.16) settings. There were no significant associations between CI in other domains and history of COVID-19 or site of acute care. INTERPRETATION: Patients post-COVID-19 have greater odds of executive dysfunction, suggesting that focused cognitive screening may be prudent, even in those with mild to moderate disease. Studies should explore the pathophysiology and potential treatments for CI in this population. FUNDING: This work was funded by the Icahn School of Medicine at Mount Sinai.

Cognition predicts days-alive-out-of-hospital after LVAD implantation.

OBJECTIVE: Cognition influences hospitalization rates for a variety of patient groups but this association has not been examined in heart failure (HF) patients undergoing left ventricular assist device (LVAD) implantation. We used cognition to predict days-alive-out-of-hospital (DAOH) in patients after LVAD surgery. METHODS: We retrospectively identified 59 HF patients with cognitive assessment prior to LVAD. Cognitive tests of attention, memory, language, and visual motor speed were averaged into one score. DAOH was converted to a percentage based on total days from LVAD surgery to either heart transplant or 900 days post-LVAD. Variables significantly associated with DAOH in univariate analyses were included in a linear regression model to predict DAOH. RESULTS: A linear regression model including LVAD type (continuous or pulsatile flow) and cognition significantly predicted DAOH (F(2,54) = 6.44, p = 0.003, R2 = .19). Inspection of each variable revealed that cognition was a significant predictor in the model (ß = .11, SE = .04, p = 0.007) but LVAD type was not (p = 0.08). CONCLUSIONS: Cognitive performance assessed prior to LVAD implantation predicted how much time patients spent out of the hospital following surgery. Further studies are warranted to identify the impact of pre-LVAD cognition on post-LVAD hospitalization.

Predicting post-LVAD outcome: Is there a role for cognition?

BACKGROUND: Cognition has been found to influence risk of stroke and death for a variety of patient groups but this association has not been examined in heart failure (HF) patients undergoing left ventricular assist device (LVAD) implant. We aimed to study the relationship between cognition, stroke, and death in a cohort of patients who received LVAD therapy. It was hypothesized that cognitive test results obtained prior to LVAD placement would predict stroke and death after surgery. METHODS: We retrospectively identified 59 HF patients who had cognitive assessment prior to LVAD placement. Cognitive assessment included measures of attention, memory, language, and visualmotor speed and were averaged to produce one z-score variable per patient. Survival analyses, censored for transplant, evaluated predictors for stroke and death within a follow-up period of 900 days. RESULTS: For patients with stroke or death during the follow up period, the average cognitive z-score predicted post-LVAD stroke (HR = 0.513, 95% CI = 0.31-0.86, p = 0.012) and death (HR = 0.166, 95% CI = 0.06-0.47, p = 0.001). Cognitive performances were worse in the patients who suffered stroke or died. No other variable predicted stroke and death within the follow up period when the cognitive variable was in the model. CONCLUSION: Cognitive performance was predictive of post-LVAD risk of stroke and death. Results are consistent with findings from other studies in non-LVAD samples and may reflect early signs of neurologic vulnerability. Further studies are needed to clarify the relationship between cognition and LVAD outcomes in order to optimize patient selection, management, and advanced care planning.

Cognition and Quality of Life in Symptomatic Carotid Occlusion.

PURPOSE: Carotid occlusion may result in stroke, TIA, and cognitive reductions. Whether cognition predicts quality of life (QOL) for patients with carotid occlusion is unknown. Depression is also known to affect QOL. We examined whether cognition and depression predicted QOL in patients with carotid occlusive disease who have not had revascularization. METHODS: Patients with unilateral carotid occlusion and history of TIA or a remote history of minor stroke were included. Patients underwent exam of memory, language, motor, and executive function skills and completed depression and QOL questionnaires (Center for Epidemiological Studies-Depression [CES-D], Stroke Specific QOL [SSQOL]). Deficits from remote stroke were assessed with the NIH Stroke Scale (NIHSS). Z-scores for cognitive tests were averaged (Cog-Z). The SSQOL scores were averaged across subgroup domains. Analyses of patients with all depression levels were followed by subgroup analyses for patients with minimal depression. Correlation findings were used to select the variables in a regression model to predict SSQOL. RESULTS: Among 37 patients with all depression levels, QOL was predicted by deficits from remote stroke and depression (F(3, 36) = 21.15, P<.0005; NIHSS Beta = -.392, P = .001; CES-D Beta = -.577, P < .0005). Among 22 patients with minimal depression, QOL was predicted by cognitive and depression scores, (F(2,21) = 7.88, P = .003; Cog-Z Beta = .364, P = .05; CES-D Beta = -.495, P = .01). CONCLUSIONS: In patients with carotid occlusive disease without major stroke and without revascularization, cognitive and depression scores independently predicted QOL. These data demonstrate the clinical relevance of cognitive and mood decline among patients with carotid occlusion.

Introduction to the Special Issue on Neuropsychology Practices in Integrated Care Teams.

This special issue on neuropsychology practices in integrated healthcare teams demonstrates how neuropsychologists have transformed their practices in an evolving healthcare landscape. These contributions are an overview of the many ways in which neuropsychologists function in integrated care teams. The experiences of integrated neuropsychologists serve as a model for those seeking new practice opportunities by providing highly practical, clinically relevant information. Included in this volume are articles on education and reimbursement issues, information about clinical practices that address diagnostic issues, prognostics and clinical management, as well as surgical treatment planning and outcome prediction. Authors highlight the value of their services, their contribution to improving team and patient communication, as well as the biopsychosocial understanding of the patient. Several unexpected challenges are detailed among the pearls and pitfalls of these practices.

The Times They Are a Changin': Neuropsychology and Integrated Care Teams.

OBJECTIVE: To gather illustrative data from clinical neuropsychologists who are working in integrated care settings in order to provide an initial blueprint for moving forward in this new era of health care. METHOD: A survey was designed to illustrate the ways in which neuropsychologists are participating in integrated care teams and distributed on major neuropsychology listservs. The survey evaluated the settings, roles, services provided, practice issues, remuneration, and impact of neuropsychologists' participation in integrated care teams with respect to patient care and health outcomes. Frequencies were used to summarize the findings as well as qualitative coding of narrative responses. RESULTS: There were 412 respondents to the survey and 261 of those indicated that they worked in at least one integrated care setting. Neuropsychologists work in a variety of integrated care settings and provide diverse services which contribute to improved patient care and outcomes. CONCLUSIONS: Three primary themes emerge from the findings with regard to the engagement and teams: advocacy, collaboration, and communication. We argue for the need for more easily accessible outcome studies illustrating the clinical benefits and cost-savings associated with inclusion of neuropsychologists in integrated care teams. In addition, educational and training initiatives are needed to better equip current and future clinical neuropsychologists to function effectively in integrated care settings.

Randomized Evaluation of Carotid Occlusion and Neurocognition (RECON) trial: main results.

OBJECTIVE: To determine whether extracranial-intracranial (EC-IC) bypass can improve cognition over 2 years compared to best medical therapy alone in patients with symptomatic internal carotid artery (ICA) occlusion and increased oxygen extraction fraction (OEF) on PET. METHODS: Patients underwent (15)O PET and were randomized if OEF ratio was >1.13 on the occluded side. Using blinded baseline and 2-year cognitive assessments, age-adjusted composite z scores were generated from subtests sensitive to right/left hemisphere plus global cognitive functioning. Multiple regression predicted 2-year cognitive change. RESULTS: Eighty-nine patients were enrolled; 41 had increased OEF and were randomized. Two died, 2 were lost to follow-up, and 2 refused 2-year testing. Of the 35 remaining, 6 had ipsilateral stroke or death, leaving 13 surgical and 16 medical patients. Controlling for age, education, and depression, there was no difference in 2-year cognitive change between the medical and surgical arms (95% confidence interval -0.5 to 0.5, p = 0.9). In post hoc analysis of 26 patients with no stroke in the follow-up period, cognitive improvement was associated with less impaired PET OEF at baseline (p = 0.045). CONCLUSION: Cognitive improvement following bypass surgery was not superior to medical therapy among patients with recently symptomatic carotid occlusion and increased OEF. Among those with no recurrent stroke, less hemodynamic impairment at baseline was associated with greater cognitive gain in both groups. Reversing cognitive impairment in hemodynamic failure remains an open challenge. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that for patients with symptomatic ICA occlusion and increased OEF on PET, EC-IC bypass compared to no bypass does not improve cognitive function after 2 years.

Association of low ejection fraction with impaired verbal memory in older patients with heart failure.

BACKGROUND: Cognitive dysfunction has a major role in health outcomes for cardiac patients. The association of cognitive dysfunction with heart failure is well established, but the cardiac variables that contribute to cognition are not well understood. OBJECTIVES: To investigate the relationships among age, memory, and left ventricular ejection fraction (EF) in patients with heart failure. DESIGN: Retrospective study. SETTING: Academic medical center. PARTICIPANTS: A total of 207 patients with heart failure underwent neuropsychological assessment of memory on standardized tests. MAIN OUTCOME MEASURES: Patients were grouped by age quartiles, and memory function was compared in those with an EF below 30% vs those with an EF of 30% or higher. RESULTS: Demographic, cognitive, and medical variables having a significant association with a memory composite score were identified in a univariate linear regression analysis. In a multivariate linear model that adjusted for significant covariates, there was a significant interaction between age and EF for memory function. Patients younger than 63 years maintained stable memory function across EF levels, but patients 63 years or older showed a significant decline in memory performance when EF dropped below 30% (P < .02). Post hoc multivariate analysis showed that verbal delayed recall and recognition were the components of memory most affected by low EF. CONCLUSION: The effect of EF on memory differs by age such that older patients with lower EFs have significantly reduced verbal memory function.

Improvement in aphasia scores after stroke is well predicted by initial severity.

BACKGROUND AND PURPOSE: Most improvement from poststroke aphasia occurs within the first 3 months, but there remains unexplained variability in recovery. Recently, we reported a strong correlation between initial impairment and change scores in motor recovery at 90 days. We wanted to determine whether aphasia recovery (defined as a change from baseline to 90 days) shows a comparably strong correlation and whether the relation was similar to that in motor recovery. METHODS: Twenty-one stroke patients had aphasia scores on the Western Aphasia Battery (WAB) obtained on stroke admission (WAB(initial)) and at 90 days (WAB(3 mo)). The relation between actual change (Delta) scores (defined as WAB(3 mo)- WAB(initial)) and WAB(initial) was calculated in multiple-regression analysis. RESULTS: Regression analysis demonstrated that WAB(initial) was highly correlated with DeltaWAB (R(2)=0.81, P<0.001) and that, in addition, the relation between WAB(initial) and DeltaWAB was proportional, such that patients recovered 0.73 of maximal potential recovery (WAB(maximum)-WAB(initial)). CONCLUSIONS: We show that, like motor recovery, there is a highly predictable relation between aphasia recovery and initial impairment, which is also proportional in nature. The comparability of recovery from motor and language impairment suggests that common mechanisms may govern reduction of poststroke neurologic impairment across different functional domains and that they could be the focus of therapeutic intervention.

GABAergic but not anti-cholinergic agents re-induce clinical deficits after stroke.

Our goal was to determine whether the excitatory (i.e., GABA) neurotransmitter system was important in human stroke recovery. We hypothesized that giving midazolam, a GABA(A) agonist, to patients would re-induce clinical deficits to a greater extent than the anti-cholinergic scopolamine. Twelve patients (7 M) who had recovered from hemiparesis and/or aphasia after first-time stroke and 10 age-matched, healthy controls underwent double-blinded drug challenge with midazolam and 90 days later with scopolamine, or vice versa. Language was scored for comprehension, naming and repetition, and motor function was tested with the 9-Hole Peg Test (9HPT) in each hand. The drugs were administered intravenously in small aliquots until mild awake sedation was achieved. The primary outcome was the change scores from baseline to the two drug conditions, with higher scores denoting greater loss of function. Ten of the 12 patients had recovered from hemiparesis and 7 from aphasia. The median time from stroke to participation was 9.3 months (range=0.3-77.9 months). For motor function, analysis of variance showed that change scores on the 9HPT were significantly greater in patients using the previously paretic hand during the drug state with midazolam (p=0.001). Similarly, language change scores were significantly greater among recovered aphasics during the midazolam challenge (p=0.01). In our study, patients demonstrated transient re-emergence of former stroke deficits during midazolam but not scopolamine. These data provide beginning clinical evidence for the specificity of GABA-sensitive pathways for stroke recovery.

The politics of technicians.

An unintended consequence of the New York psychology Scope of Practice legislation led to a restriction in the use of testing technicians that has yet to be reversed after 4 years. The misperception of neuropsychology by state legislators and psychology colleagues was a key obstacle to achieving a timely solution. We discuss how the political agenda and practice philosophies of New York neuropsychologists were at odds with those of our psychology colleagues, and how that brought about a protracted struggle affecting both patient care and the practice of clinical neuropsychology. Neuropsychologists must maintain an active role in professional and political organizations with equal attention at the local, state, and national levels to avoid similar restrictions to their clinical practice.

Neurocognitive dysfunction in adult moyamoya disease.

We wanted to determine the neurocognitive profile of adult patients with moyamoya disease prior to neurosurgical intervention. The experience of three United States medical centers, Columbia University, University of Illinois at Chicago, and the University of Texas Southwestern Medical Center at Dallas, were combined. Clinical data from adult patients (N = 29) referred for neuropsychological evaluation from 1996 to 2008 were reviewed. Neurocognitive functioning was assessed using standardized neuropsychological tests and all data were converted to z-scores. Memory, attention, processing speed, verbal memory, visuo-spatial, language, and executive functions were examined. Cognitive dysfunction was defined as performance in two or more cognitive domains 1.5 standard deviations below age-corrected normative means OR one or more cognitive domains two standard deviations below age-corrected normative means. Manual strength and dexterity, as well as depressive symptoms, were also assessed. Two-thirds of patients demonstrated neurocognitive dysfunction. A large proportion of patients were found to have pronounced cognitive dysfunction (>2 SD below the mean) on tests of processing speed (29%), verbal memory (31%), verbal fluency (26%) and executive function (25%). Manual strength and dexterity were also affected in many patients, with impairment found in 36-58% of patients. Twenty-eight percent of patients reported moderate to severe depression, but depressive symptoms did not correlate with neurocognitive findings. A large proportion of adults with moyamoya disease demonstrate disruption of neurocognition in a broad range of functions, particularly those mediated by subcortical and frontal regions. The pattern of deficits suggests a mechanism of diffuse small vessel disease possibly caused by chronic hypoperfusion.

Acute confusional syndrome from a dural arteriovenous fistula.

OBJECTIVE: We describe a case of an acute confusional state associated with a right parietal dural arteriovenous fistula. CLINICAL PRESENTATION: A 67-year-old man in his usual state of health experienced an acute confusion episode preceded by a valsalva maneuver. The episode lasted approximately 60 minutes. Afterward he was able to remember everything that occurred. A magnetic resonance imaging scan suggested a right parietal dural arteriovenous fistula, which was confirmed by angiography. A seizure was ruled out by clinical examination and an electroencephalogram. INTERVENTION: The patient underwent therapeutic embolization and surgical ligation of the fistula. Feeding vessels to the malformation were cauterized within the leaves of the falx, and the draining vein was clipped with a titanium aneurysm clip and divided. An intraoperative angiogram was then performed, which showed obliteration of the fistula. There was no demonstrable confusion or memory loss noted postoperatively. CONCLUSION: We propose that venous hypertension from the dural arteriovenous fistula in combination with a valsalva maneuver caused ischemia in the right parietal lobe, eliciting a deficit in attention.

Clinical features, surgical treatment, and long-term outcome in adult patients with moyamoya disease. Clinical article.

OBJECT: The object of this study was to report the clinical features, surgical treatment, and long-term outcomes in adults with moyamoya phenomenon treated at a single institution in the US. METHODS: Forty-three adult patients with moyamoya disease (mean age 40 +/- 11 years [SD], range 18-69 years) were treated with encephaloduroarteriosynangiosis (EDAS). Neurologists examined patients pre- and postoperatively. Follow-up was obtained in person or by structured telephone interview (median 41 months, range 4-126 months). The following outcomes were collected: transient ischemic attack (TIA), infarction, graft collateralization, change in cerebral perfusion, and functional level according to the modified Rankin scale (mRS). Kaplan-Meier estimates of infarction risk were calculated for comparison of surgically treated and contralateral hemispheres. RESULTS: The majority of patients were women (65%), were Caucasian (65%), presented with ischemic symptoms (98%), and had bilateral disease (86%). Nineteen patients underwent unilateral and 24 patients bilateral EDAS (67 treated hemispheres). Collateral vessels developed in 50 (98%) of 52 hemispheres for which imaging was available and there was evidence of increased perfusion on SPECT scans in 41 (82%) of the 50 hemispheres evaluated. Periprocedural infarction (< 48 hours) occurred in 3% of the hemispheres treated. In the follow-up period patients experienced 10 TIAs, 6 infarctions, and 1 intracranial hemorrhage. Although the hemisphere selected for surgery was based upon patients' symptoms and severity of pathology, the 5-year infarction-free survival rate was 94% in the surgically treated hemispheres versus < 36% in the untreated hemispheres (p = 0.007). After controlling for age and sex, infarction was 89% less likely to occur in the surgically treated hemispheres than in the contralateral hemispheres (hazard ratio 0.11, 95% CI 0.02-0.56). Thirty-eight (88%) of 43 patients had preserved or improved mRS scores, relative to baseline status. CONCLUSIONS: In this mixed-race population of North American patients, indirect bypass promoted adequate pial collateral development and increased perfusion in the majority of adult patients with moyamoya disease. Patients had low rates of postoperative TIAs, infarction, and hemorrhage, and the majority of patients had preserved or improved functional status.

White matter hyperintensities and subclinical infarction: associations with psychomotor speed and cognitive flexibility.

BACKGROUND AND PURPOSE: We examined white matter hyperintensity volume (WMHV) and subclinical infarction (no history of clinical stroke; SI) in relation to performance on tests of sequencing, cognitive flexibility, and sensorimotor ability. METHODS: The Northern Manhattan Study includes a stroke-free community-based sample of Hispanic, Black, and White participants. A subsample (n=656) has undergone measurement of WMHV, SI, and neuropsychological testing. Linear regression was used to examine WMHV and SI in relation to performance on tests of sequencing as measured by Color Trails 1, cognitive flexibility as measured by Color Trails 2, and sensorimotor ability as measured by Grooved Pegboard, using generalized estimating equations (GEE) to account for the correlation among the cognitive tests and other covariates. RESULTS: Considering performance on the tests of sequencing, cognitive flexibility, and sensorimotor ability simultaneously using GEE, WMHV and subclinical infarction were each associated with worse cognitive performance globally. There was a threshold effect for WMHV with those in the upper quartile performing significantly worse on the tests of cognitive flexibility and sensorimotor ability. Those with frontal SI performed worse on the test of cognitive flexibility and those with deep SI, worse on the test of sequencing. CONCLUSIONS: Both SI and WMHV were associated with globally worse cognitive performance. Participants with WMH affecting more than 0.75% of cranial volume had significantly slower performance on a task of cognitive flexibility and sensorimotor ability than those in the lowest quartile. The effects of SI on cognitive performance varied by location.

Multitasking disorder from right temporoparietal stroke.

Acute behavioral syndromes after right hemisphere stroke (eg, hemi-inattention) resolve in most patients by 6 months. Less is known about the nature of chronic disorders after these lesions when the initial deficits are no longer apparent. We report the case of a woman who suffered a cerebral infarct in the right temporoparietal region and who, after the resolution of neglect, demonstrated a significant disorder of multitasking in her everyday life. Neuropsychologic tests failed to reveal the extent of disruption in her daily functioning. A journal of daily activities elucidates the nature of her deficits and demonstrates, from the patient's perspective, the impact of the lesion on her ability to multitask. Our findings are consistent with the concept of a right frontoparietal attentional axis that governs the ability to hold several tasks in working memory at the same time. We conclude that right hemisphere lesions can disrupt the cognitive system of multitasking through disruption of the attentional matrix.

Chronic ischemia and neurocognition.

Cognitive impairment from a major stroke as a consequence of carotid disease is an acknowledged clinical outcome; however, cognitive impairment without major stroke is open to discussion. The three recognized mechanisms for cognitive dysfunction from internal carotid artery are microembolization, white-matter disease, and hypoperfusion. The last has been most difficult to characterize physiologically. In this article, the authors review evidence supporting the existence of chronic ischemia in the brain and its direct impact on cognitive functions. By incorporating the pathophysiology of chronic ischemia into the algorithm of the management of carotid artery disease, we may be able to extend the goals of carotid artery revascularization beyond merely preventing stroke to include preventing or reversing cognitive decline.

Dural arteriovenous fistula presents like an ischemic stroke.

OBJECTIVE: We report the case of a patient with a dural arteriovenous fistula whose neurobehavioral syndrome was indistinguishable from that of an ischemic stroke. BACKGROUND: Case studies of dural arteriovenous fistulas primarily describe global cognitive changes like dementia, but detailed neurocognitive evaluations of dural arteriovenous fistula patients are rarely reported. METHOD: We provide a dural arteriovenous fistula case of a patient who presented with aphasia and other symptoms of stroke. Background history, serial neuropsychological data, and angiographic images are presented. RESULTS AND CONCLUSIONS: Serial neurocognitive data show the extent to which cognitive deficits are reversed with embolization. The case demonstrates that the mechanisms underlying neurocognitive deficits are specific to the fistula's unique hemodynamic features in addition to the location of the dural arteriovenous fistula.