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Article ; Online: Improved executive function in patients with systemic lupus erythematosus following interactive digital training.

Kozora, Elizabeth / Zell, JoAnn L / Baraghoshi, David / Smith, Rebecca M / Strand, Matthew

2022 Volume 31, Issue 8, Page(s) 910–920

Abstract: Objective: This study aimed to evaluate the sensitivity of a digital platform to assess attentional and executive function in systemic lupus erythematosus (SLE) patients, and to evaluate the impact of an at-home interactive digital treatment to improve ... ...

Abstract	Objective: This study aimed to evaluate the sensitivity of a digital platform to assess attentional and executive function in systemic lupus erythematosus (SLE) patients, and to evaluate the impact of an at-home interactive digital treatment to improve cognitive dysfunction in this clinical population. Background: Deficits in attention and executive function are common in patients with SLE. Despite these cognitive difficulties, there are limited brief assessment techniques and few treatment options to improve cognitive abilities in patients with SLE. Interactive digital treatment approaches (use of video game-based software) have been successful in identifying and improving cognition in other clinical populations. Methods: Sixty SLE patients completed baseline neuropsychological tests (of attention, psychomotor speed, and executive function), a tablet-based digital platform (EVO Results: Systemic lupus erythematosus patients demonstrated impairment in visuomotor and processing speed, visual attention, and cognitive flexibility/sequencing skills at baseline. The video game-like treatment group (AKL-T01) had significant improvement in visuomotor speed (Trail Making A) and cognitive flexibility/sequencing (Trail Making B) compared to the control group at 4-week follow-up. The treatment group also demonstrated significant improvement in EVO Monitor multitasking at follow-up (with no change in controls). At baseline, a multitasking metric from EVO Monitor was associated with performance on tasks of cognitive flexibility (Trail Making B) and psychomotor speed (WAIS-IV Coding). Conclusions: These findings provide evidence that SLE patients who participated in a 4-week interactive digital video game-like activity had significant improvement in motor speed and executive functions, and would benefit from participation in digital interventions designed to target frontoparietal networks of the brain. Preliminary findings also suggest specific metrics from EVO Monitor may also be useful to detect cognitive impairment and cognitive changes in patients with SLE.
MeSH term(s)	Cognition ; Cognition Disorders/psychology ; Executive Function ; Humans ; Lupus Erythematosus, Systemic/complications ; Lupus Erythematosus, Systemic/therapy ; Neuropsychological Tests
Language	English
Publishing date	2022-05-18
Publishing country	England
Document type	Journal Article ; Randomized Controlled Trial
ZDB-ID	1154407-7
ISSN	1477-0962 ; 0961-2033
ISSN (online)	1477-0962
ISSN	0961-2033
DOI	10.1177/09612033221098534
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Article ; Online: Review: Nervous System Disease in Systemic Lupus Erythematosus: Current Status and Future Directions.

Hanly, John G / Kozora, Elizabeth / Beyea, Steven D / Birnbaum, Julius

Arthritis & rheumatology (Hoboken, N.J.)

2018 Volume 71, Issue 1, Page(s) 33–42

Abstract: The American College of Rheumatology's case definitions for 19 neuropsychiatric syndromes in systemic lupus erythematosus (SLE) constitute a comprehensive classification of nervous system events in this disease. However, additional strategies are needed ... ...

Abstract	The American College of Rheumatology's case definitions for 19 neuropsychiatric syndromes in systemic lupus erythematosus (SLE) constitute a comprehensive classification of nervous system events in this disease. However, additional strategies are needed to determine whether a neuropsychiatric syndrome is attributable to SLE versus a competing comorbidity. Cognitive function is a clinical surrogate of overall brain health, with applications in both diagnosis and determination of clinical outcomes. Ischemic and inflammatory mechanisms are both key components of the immunopathogenesis of neuropsychiatric SLE (NPSLE), including abnormalities of the blood-brain barrier and autoantibody-mediated production of proinflammatory cytokines. Advances in neuroimaging provide a platform to assess novel disease mechanisms in a noninvasive way. The convergence of more rigorous clinical characterization, validation of biomarkers, and brain neuroimaging provides opportunities to determine the efficacy of novel targeted therapies in the treatment of NPSLE.
MeSH term(s)	Autoantibodies/immunology ; Blood-Brain Barrier/metabolism ; Brain/diagnostic imaging ; Brain/immunology ; Brain/physiopathology ; Brain Ischemia/physiopathology ; Cognitive Dysfunction/immunology ; Cognitive Dysfunction/physiopathology ; Cognitive Dysfunction/therapy ; Cytokines/immunology ; Humans ; Inflammation/immunology ; Lupus Vasculitis, Central Nervous System/diagnostic imaging ; Lupus Vasculitis, Central Nervous System/immunology ; Lupus Vasculitis, Central Nervous System/physiopathology ; Lupus Vasculitis, Central Nervous System/therapy ; Magnetic Resonance Imaging ; Positron-Emission Tomography
Chemical Substances	Autoantibodies ; Cytokines
Language	English
Publishing date	2018-11-24
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2756371-6
ISSN	2326-5205 ; 2326-5191
ISSN (online)	2326-5205
ISSN	2326-5191
DOI	10.1002/art.40591
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Article ; Online: Non-stroke Central Neurologic Manifestations in Antiphospholipid Syndrome.

Yelnik, Cécile M / Kozora, Elizabeth / Appenzeller, Simone

Current rheumatology reports

2016 Volume 18, Issue 2, Page(s) 11

Abstract: Thrombotic manifestations of antiphospholipid syndrome (APS) are well known, and various non-stroke neuro-psychiatric manifestations (NPMs) have also been consistently described, but their place in APS remains unclear. Some syndromes, such as migraine or ...

Abstract	Thrombotic manifestations of antiphospholipid syndrome (APS) are well known, and various non-stroke neuro-psychiatric manifestations (NPMs) have also been consistently described, but their place in APS remains unclear. Some syndromes, such as migraine or cognitive dysfunction, are frequently described in APS, whereas others, like seizure, multiple sclerosis-like symptoms, transverse myelitis, movement disorders, or psychiatric symptoms, are rarely found. Overlap with other autoimmune diseases, in particular with systemic lupus erythematosus, the lack of large sample size prospective studies, and discrepancies in antiphospholipid antibody (aPL) determinations complicate the study of the relationship between those disorders and aPL/APS. This review article aimed to summarize updated data on pathophysiologic, epidemiologic, and radiologic findings about non-stroke NPM described in primary APS and aPL-positive patients without overlap of other autoimmune diseases.
MeSH term(s)	Antiphospholipid Syndrome/complications ; Antiphospholipid Syndrome/physiopathology ; Central Nervous System Diseases/etiology ; Cognition Disorders/etiology ; Humans ; Lupus Erythematosus, Systemic/complications ; Mental Disorders/etiology ; Movement Disorders/etiology ; Multiple Sclerosis/etiology
Language	English
Publishing date	2016-02
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2057357-1
ISSN	1534-6307 ; 1523-3774
ISSN (online)	1534-6307
ISSN	1523-3774
DOI	10.1007/s11926-016-0568-x
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Article ; Online: Cognitive disorders and antiphospholipid antibodies.

Yelnik, Cécile M / Kozora, Elizabeth / Appenzeller, Simone

Autoimmunity reviews

2016 Volume 15, Issue 12, Page(s) 1193–1198

Abstract: Cognitive disorders have frequently been described in the field of antiphospholipid syndrome (APS) and systemic lupus erythematosus (SLE). Nevertheless, the relationship between those disorders and antiphospholipid antibodies (aPL) remains unclear and ... ...

Abstract	Cognitive disorders have frequently been described in the field of antiphospholipid syndrome (APS) and systemic lupus erythematosus (SLE). Nevertheless, the relationship between those disorders and antiphospholipid antibodies (aPL) remains unclear and seems to involve various mechanisms. Overlap with systemic lupus erythematosus, the small sample size of studies, and discrepancies in antiphospholipid antibodies and cognitive impairment determinations complicate analyses of the literature data. In this paper, we summarize current knowledge on epidemiologic, clinical data, imaging findings and treatment of cognitive dysfunction associated with aPL. We separately analyzed data on aPL-positive carriers without history of clinical feature of APS, APS patients without overlaps autoimmune disease, and SLE-associated aPL patients.
MeSH term(s)	Antibodies, Antiphospholipid/immunology ; Antiphospholipid Syndrome/complications ; Antiphospholipid Syndrome/immunology ; Cognition Disorders/complications ; Cognition Disorders/etiology ; Humans ; Lupus Erythematosus, Systemic/complications ; Lupus Erythematosus, Systemic/immunology
Chemical Substances	Antibodies, Antiphospholipid
Language	English
Publishing date	2016-12
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	2144145-5
ISSN	1873-0183 ; 1568-9972
ISSN (online)	1873-0183
ISSN	1568-9972
DOI	10.1016/j.autrev.2016.09.002
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Zs.A 5913: Show issues

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Article ; Online: Cognitive dysfunction and white matter abnormalities in systemic lupus erythematosus.

Kozora, Elizabeth / Filley, Christopher M

Journal of the International Neuropsychological Society : JINS

2011 Volume 17, Issue 3, Page(s) 385–392

Abstract: Brain abnormalities have been documented by neuropsychological assessment as well as a variety of neuroimaging techniques in patients with systemic lupus erythematosus (SLE). Conventional neuroimaging in patients with neuropsychiatric disease (NPSLE) ... ...

Abstract	Brain abnormalities have been documented by neuropsychological assessment as well as a variety of neuroimaging techniques in patients with systemic lupus erythematosus (SLE). Conventional neuroimaging in patients with neuropsychiatric disease (NPSLE) typically discloses periventricular white matter (WM) hyperintensities, infarcts, hemorrhages, and cerebral atrophy. In SLE patients with none of these findings, sophisticated neuroimaging techniques have recently supported associations between microstructural WM abnormalities and abnormal attention, executive function, and processing speed. This mild cognitive dysfunction in SLE (MCD-SLE), which may result from early myelinopathy, precedes the more severe cognitive dysfunction of NPSLE, related to more obvious WM and neuronal damage.
MeSH term(s)	Cognition Disorders/diagnosis ; Cognition Disorders/etiology ; Humans ; Leukoencephalopathies/diagnosis ; Leukoencephalopathies/etiology ; Lupus Erythematosus, Systemic/complications ; Neuroimaging ; Neuropsychological Tests
Language	English
Publishing date	2011-05
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	1230632-0
ISSN	1469-7661 ; 1355-6177
ISSN (online)	1469-7661
ISSN	1355-6177
DOI	10.1017/S1355617711000191
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Article ; Online: Cognitive performance is lower among individuals with overlap syndrome than in individuals with COPD or obstructive sleep apnea alone: association with carotid artery stiffness.

Luehrs, Rachel E / Moreau, Kerrie L / Pierce, Gary L / Wamboldt, Frederick / Aloia, Mark / Weinberger, Howard D / Make, Barry / Bowler, Russell / Crapo, James D / Meschede, Kimberly / Kozora, Elizabeth / Moser, David J / Hoth, Karin F

Journal of applied physiology (Bethesda, Md. : 1985)

2021 Volume 131, Issue 1, Page(s) 131–141

Abstract: Chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA) are both independently associated with increased cardiovascular disease (CVD) risk and impaired cognitive function. It is unknown if individuals with both COPD and OSA (i.e., ... ...

Abstract	Chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA) are both independently associated with increased cardiovascular disease (CVD) risk and impaired cognitive function. It is unknown if individuals with both COPD and OSA (i.e., overlap syndrome) have greater common carotid artery (CCA) stiffness, an independent predictor of CVD risk, and lower cognitive performance than either COPD or OSA alone. Elevated CCA stiffness is associated with cognitive impairment in former smokers with and without COPD in past studies. We compared CCA stiffness and cognitive performance between former smokers with overlap syndrome, COPD only, OSA only and former smoker controls using analysis of covariance (ANCOVA) tests to adjust for age, sex, body mass index (BMI), pack years, and postbronchodilator FEV
MeSH term(s)	Carotid Arteries ; Carotid Artery, Common ; Cognition ; Humans ; Pulmonary Disease, Chronic Obstructive ; Sleep Apnea, Obstructive
Language	English
Publishing date	2021-05-13
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	219139-8
ISSN	1522-1601 ; 0021-8987 ; 0161-7567 ; 8750-7587
ISSN (online)	1522-1601
ISSN	0021-8987 ; 0161-7567 ; 8750-7587
DOI	10.1152/japplphysiol.00477.2020
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Article ; Online: Daily Activities: The Impact of COPD and Cognitive Dysfunction.

Brunette, Amanda M / Warner, Kelsey / Holm, Kristen E / Meschede, Kimberly / Wamboldt, Frederick S / Kozora, Elizabeth / Moser, David J / Make, Barry J / Crapo, James D / Moreau, Kerrie L / Weinberger, Howard D / Bowler, Russell / Hoth, Karin F

Archives of clinical neuropsychology : the official journal of the National Academy of Neuropsychologists

2020 Volume 36, Issue 5, Page(s) acaa090 767 779–767

Abstract: Objective: Chronic obstructive pulmonary disease (COPD) is characterized by airflow limitation; however, pulmonary function does not fully account for patients' functional difficulties. The primary aim of the study was to determine the association ... ...

Abstract	Objective: Chronic obstructive pulmonary disease (COPD) is characterized by airflow limitation; however, pulmonary function does not fully account for patients' functional difficulties. The primary aim of the study was to determine the association between several domains of cognition and daily activity among those with COPD. Method: Eighty-nine former smokers completed a neuropsychological battery including measures across multiple domains of cognition, pulmonary function measures, and daily activity questionnaires. Using a cross-sectional design, we compared daily activity between former smokers with and without COPD using two measures (St. George's Respiratory Questionnaire [SGRQ] Activity Subscale and Lawton Instrumental Activities of Daily Living [IADL] Scale) and examined the association between cognition and daily activity among those with COPD. Results: As expected, former smokers with COPD reported more difficulty than those without COPD on both activity measures (SGRQ Activity Subscale p < .001; Lawton IADL Scale p = .040). Among former smokers with COPD, poorer delayed recall was associated with more difficulty with daily activities (SGRQ Activity Subscale) (p = .038) while adjusting for severity of airflow limitation, exercise tolerance, oxygen use, dyspnea, and symptoms of anxiety and depression. Conclusion: The findings suggest that cognition is associated with daily activity in patients with COPD. Future research should examine whether cognitive interventions may help to maximize patients' engagement in daily activities.
MeSH term(s)	Activities of Daily Living ; Cognitive Dysfunction/etiology ; Cross-Sectional Studies ; Humans ; Neuropsychological Tests ; Pulmonary Disease, Chronic Obstructive/complications ; Quality of Life ; Surveys and Questionnaires
Language	English
Publishing date	2020-10-01
Publishing country	United States
Document type	Journal Article
ZDB-ID	632972-x
ISSN	1873-5843 ; 0887-6177
ISSN (online)	1873-5843
ISSN	0887-6177
DOI	10.1093/arclin/acaa090
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Article ; Online: Carotid Artery Stiffness is Associated With Cognitive Performance in Former Smokers With and Without Chronic Obstructive Pulmonary Disease.

Hoth, Karin F / Moreau, Kerrie L / Weinberger, Howard D / Holm, Kristen E / Meschede, Kimberly / Crapo, James D / Make, Barry J / Moser, David J / Kozora, Elizabeth / Bowler, Russell P / Pierce, Gary L / Ten Eyck, Patrick / Wamboldt, Frederick S

Journal of the American Heart Association

2020 Volume 9, Issue 9, Page(s) e014862

Abstract: Background Heavy smokers perform worse on neuropsychological assessment than age-matched peers. However, traditional pulmonary measures of airflow limitation and hypoxemia explain only a modest amount of variance in cognition. The current objective was ... ...

Abstract	Background Heavy smokers perform worse on neuropsychological assessment than age-matched peers. However, traditional pulmonary measures of airflow limitation and hypoxemia explain only a modest amount of variance in cognition. The current objective was to determine whether carotid artery stiffness is associated with cognition in former smokers beyond the effects of amount of smoking and pulmonary function. Methods and Results Eighty-four former smokers including individuals across a spectrum of airflow limitation severity were included: 30 without chronic obstructive pulmonary disease (Global Initiative for Chronic Obstructive Lung Disease [GOLD] 0 with normal spirometry and lung computed tomography), 31 with mild-moderate chronic obstructive pulmonary disease (GOLD 1-2), and 23 with severe-very severe chronic obstructive pulmonary disease (GOLD 3-4). Participants completed questionnaires, spirometry, carotid ultrasonography, and neuropsychological testing. Multiple linear regression was used to determine whether carotid artery stiffness is associated with neuropsychological performance in 4 cognitive domains after adjusting for age, sex, pack-years of smoking, estimated premorbid intellectual functioning, and airflow limitation. Higher carotid artery β-stiffness index was associated with reduced executive functioning-processing speed in the fully adjusted model (β=-0.49, SE=0.14;
MeSH term(s)	Aged ; Carotid Arteries/physiopathology ; Carotid Artery Diseases/diagnosis ; Carotid Artery Diseases/etiology ; Carotid Artery Diseases/physiopathology ; Cognition ; Cognitive Dysfunction/diagnosis ; Cognitive Dysfunction/etiology ; Cognitive Dysfunction/psychology ; Ex-Smokers ; Executive Function ; Female ; Humans ; Male ; Middle Aged ; Pulmonary Disease, Chronic Obstructive/diagnosis ; Pulmonary Disease, Chronic Obstructive/etiology ; Pulmonary Disease, Chronic Obstructive/physiopathology ; Risk Assessment ; Risk Factors ; Smoking/adverse effects ; Smoking/physiopathology ; Smoking/psychology ; Vascular Stiffness
Language	English
Publishing date	2020-04-26
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2653953-6
ISSN	2047-9980 ; 2047-9980
ISSN (online)	2047-9980
ISSN	2047-9980
DOI	10.1161/JAHA.119.014862
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Article: Cognitive dysfunction and white matter abnormalities in antiphospholipid syndrome.

Erkan, Doruk / Kozora, Elizabeth / Lockshin, Michael D

Pathophysiology : the official journal of the International Society for Pathophysiology

2010 Volume 18, Issue 1, Page(s) 93–102

Abstract: Diagnosis of the antiphospholipid syndrome (APS) requires that a patient have both a clinical event (thrombosis or pregnancy loss) and persistently positive antiphospholipid antibodies (aPL). Although stroke and transient ischemic attack are the most ... ...

Abstract	Diagnosis of the antiphospholipid syndrome (APS) requires that a patient have both a clinical event (thrombosis or pregnancy loss) and persistently positive antiphospholipid antibodies (aPL). Although stroke and transient ischemic attack are the most common neurologic manifestations of APS, both cognitive dysfunction and magnetic resonance imaging (MRI) white matter hyperintensities can occur in aPL-positive patients (with or without APS). Relatively little is known about the cognitive pattern in aPL-positive patients; MRI white matter hyperintensities may be related to underlying attentional and executive cognitive impairment. Studies with sophisticated neuroimaging techniques aimed to better understand MRI white matter hyperintensities may eventually facilitate our understanding of cognitive dysfunction in aPL-positive patients.
Language	English
Publishing date	2010-05-15
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	1212740-1
ISSN	0928-4680
ISSN	0928-4680
DOI	10.1016/j.pathophys.2010.04.010
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Article ; Online: Reduced Attention in Former Smokers with and without COPD.

Croghan, Anna / Brunette, Amanda / Holm, Kristen E / Kozora, Elizabeth / Moser, David J / Wamboldt, Frederick S / Meschede, Kimberly / Make, Barry J / Crapo, James D / Weinberger, Howard D / Moreau, Kerrie L / Bowler, Russell P / Hoth, Karin F

International journal of behavioral medicine

2019 Volume 26, Issue 6, Page(s) 600–607

Abstract: Background: Attention difficulties are often reported by patients with chronic obstructive pulmonary disease (COPD); however, limited research exists using objective tests designed specifically to measure attention in this population. This study aimed ... ...

Abstract	Background: Attention difficulties are often reported by patients with chronic obstructive pulmonary disease (COPD); however, limited research exists using objective tests designed specifically to measure attention in this population. This study aimed to (1) identify specific attention deficits in COPD and (2) determine which demographic/clinical characteristics are associated with reduced attention. Methods: Eighty-four former smokers (53 COPD, 31 no COPD) completed questionnaires, pulmonary function testing, and the Conner's Continuous Performance Test II (CPT-II). Participants with and without COPD were compared on CPT-II measures of inattention, impulsivity, and vigilance. CPT-II measures that differed significantly between the two groups were further examined using hierarchical regression modeling. Demographic/clinical characteristics were entered into models with attention as the dependent variable. Results: Participants with COPD performed worse than those without COPD on CPT measures of inattention and impulsivity (i.e., detectability [discrimination of target from non-target stimuli], perseverations [reaction time under 100 ms], omissions [target stimuli response failures], and commissions [responses to non-target stimuli]). More severe COPD (measured by greater airflow limitation) was associated with poorer ability to detect targets vs. foils and perseverative responding after adjusting for age and other covariates in the model. Conclusion: Former smokers with COPD experience problems with attention that go beyond slowed processing speed, including aspects of inattention and impulsivity. Clinicians should be aware that greater airflow limitation and older age are associated with attention difficulties, as this may impact functioning.
MeSH term(s)	Age Factors ; Aged ; Attention ; Female ; Humans ; Lung/physiopathology ; Male ; Middle Aged ; Pulmonary Disease, Chronic Obstructive/physiopathology ; Pulmonary Disease, Chronic Obstructive/psychology ; Respiratory Function Tests ; Severity of Illness Index ; Smokers/psychology ; Smoking/physiopathology ; Smoking/psychology
Language	English
Publishing date	2019-07-25
Publishing country	England
Document type	Journal Article
ZDB-ID	1187972-5
ISSN	1532-7558 ; 1070-5503
ISSN (online)	1532-7558
ISSN	1070-5503
DOI	10.1007/s12529-019-09826-y
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