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Article: Hypogammaglobulinemia secondary to B-cell depleting therapies in neuroimmunology: Comparing management strategies.

Kelly, Hannah / Vishnevetsky, Anastasia / Chibnik, Lori B / Levy, Michael

Multiple sclerosis journal - experimental, translational and clinical

2023 Volume 9, Issue 2, Page(s) 20552173231182534

Abstract: Background: Anti-CD20 agents are commonly used in MS, NMOSD, and MOGAD. Few studies have compared strategies to address hypogammaglobulinemia.: Objective: To compare strategies to manage secondary hypogammaglobulinemia in neuroimmunology patients, ... ...

Abstract	Background: Anti-CD20 agents are commonly used in MS, NMOSD, and MOGAD. Few studies have compared strategies to address hypogammaglobulinemia. Objective: To compare strategies to manage secondary hypogammaglobulinemia in neuroimmunology patients, including reducing anti-CD20 dose and dosing frequency, IVIG/SCIG, anti-CD20 cessation, and DMT switches. Methods: All MS, NMOSD, and MOGAD patients at our institution with hypogammaglobulinemia on anti-CD20 agents from 2001 to 2022 were analyzed. The median change in IgG, infection frequency, and infection severity before and after the treatment was calculated. Results: In total, 257 patients were screened, and 30 had a treatment for hypogammaglobulinemia. IVIG/SCIG yielded the largest increase in IgG per year (674.0 mg/dL), followed by B-cell therapy cessation (34.7 mg/dL), and DMT switch (5.9 mg/dL). Dose reduction had the largest decrease in yearly infection frequency (2.7 fewer infections), followed by IVIG/SCIG (2.5 fewer), DMT switch (2 fewer), and reduced dosing frequency (0.5 fewer). Infection grade decreased by 1.9 for reduced dosing frequency (less severe infections), by 1.3 for IVIG/SCIG, and by 0.6 for DMT switch. Conclusion: This data suggests that IVIG/SCIG may yield the greatest recovery in IgG while also reducing infection frequency and severity. Stopping anti-CD20 therapy and/or switching DMTs also increase IgG and may lower infection risk.
Language	English
Publishing date	2023-06-22
Publishing country	United States
Document type	Journal Article
ZDB-ID	2841884-0
ISSN	2055-2173 ; 2055-2173
ISSN (online)	2055-2173
ISSN	2055-2173
DOI	10.1177/20552173231182534
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Article ; Online: Chronotype, sleep, and sleepiness in Parkinson's disease.

Murphy, Samantha / Chibnik, Lori B / Videnovic, Aleksandar

Parkinsonism & related disorders

2022 Volume 106, Page(s) 105189

Abstract: We aimed to determine the distribution of chronotypes in a cohort of PD patients and to evaluate the relationships between chronotype and PD characteristics, and self-reported metrics of sleep and sleepiness. Chronotype was characterized using the Horne- ... ...

Abstract	We aimed to determine the distribution of chronotypes in a cohort of PD patients and to evaluate the relationships between chronotype and PD characteristics, and self-reported metrics of sleep and sleepiness. Chronotype was characterized using the Horne-Ostberg Morningness-Eveningness Questionnaire (MEQ). PD participants were categorized as Evening Types (ET), Neither Types (NT), or Morning Types (MT). Sleepiness was assessed by the Epworth Sleepiness Scale. Sleep metrics included self-reported sleep times and latency. 186 participants with PD, age 65.5 ± 9.8 yrs, disease duration 6.17 ± 6.7 yrs completed the MEQ. Most participants were classified as MT (63.4%). Participants in the ET group were younger than those in the NT and MT groups (57.6 ± 6.3 vs 67.3 ± 10.2 vs 64.9 ± 9.5). The mean disease duration was not different among chronotypes. No significant relationship between chronotype and sleepiness was found. MT participants woke up and went to bed significantly earlier than NT participants. There was no significant difference between chronotypes and PD medications. Further studies should examine if PD severity and progression affect the chronotype, and whether certain chronotype differentially affects the quality of life, symptom control, and medication effectiveness in the PD population.
MeSH term(s)	Humans ; Middle Aged ; Aged ; Circadian Rhythm ; Chronotype ; Sleepiness ; Parkinson Disease/complications ; Quality of Life ; Sleep ; Surveys and Questionnaires
Language	English
Publishing date	2022-10-13
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	1311489-x
ISSN	1873-5126 ; 1353-8020
ISSN (online)	1873-5126
ISSN	1353-8020
DOI	10.1016/j.parkreldis.2022.10.011
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Article ; Online: Polygenic risk for major depression, attention deficit hyperactivity disorder, neuroticism, and schizophrenia are correlated with experience of intimate partner violence.

Ratanatharathorn, Andrew / Quan, Luwei / Koenen, Karestan C / Chibnik, Lori B / Weisskopf, Marc G / Slopen, Natalie / Roberts, Andrea L

Translational psychiatry

2024 Volume 14, Issue 1, Page(s) 119

Abstract: Research has suggested that mental illness may be a risk factor for, as well as a sequela of, experiencing intimate partner violence (IPV). The association between IPV and mental illness may also be due in part to gene-environment correlations. Using ... ...

Abstract	Research has suggested that mental illness may be a risk factor for, as well as a sequela of, experiencing intimate partner violence (IPV). The association between IPV and mental illness may also be due in part to gene-environment correlations. Using polygenic risk scores for six psychiatric disorders - attention-deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD), bipolar disorder (BPD), major depressive disorder (MDD), neuroticism, and schizophrenia-and a combined measure of overall genetic risk for mental illness, we tested whether women's genetic risk for mental illness was associated with the experience of three types of intimate partner violence. In this cohort of women of European ancestry (N = 11,095), participants in the highest quintile of genetic risk for ADHD (OR range: 1.38-1.49), MDD (OR range: 1.28-1.43), neuroticism (OR range: (1.18-1.25), schizophrenia (OR range: 1.30-1.34), and overall genetic risk (OR range: 1.30-1.41) were at higher risk for experiencing more severe emotional and physical abuse, and, except schizophrenia, more severe sexual abuse, as well as more types of abuse and chronic abuse. In addition, participants in the highest quintile of genetic risk for neuroticism (OR = 1.43 95% CI: 1.18, 1.72), schizophrenia (OR = 1.33 95% CI: 1.10, 1.62), and the overall genetic risk (OR = 1.40 95% CI: 1.15, 1.71) were at higher risk for experiencing intimate partner intimidation and control. Participants in the highest quintile of genetic risk for ADHD, ASD, MDD, schizophrenia, and overall genetic risk, compared to the lowest quintile, were at increased risk for experiencing harassment from a partner (OR range: 1.22-1.92). No associations were found between genetic risk for BPD with IPV. A better understanding of the salience of the multiple possible pathways linking genetic risk for mental illness with risk for IPV may aid in preventing IPV victimization or re-victimization.
MeSH term(s)	Humans ; Female ; Attention Deficit Disorder with Hyperactivity/genetics ; Attention Deficit Disorder with Hyperactivity/psychology ; Depressive Disorder, Major/genetics ; Depression ; Schizophrenia/genetics ; Neuroticism ; Autism Spectrum Disorder ; Intimate Partner Violence/psychology ; Risk Factors
Language	English
Publishing date	2024-02-26
Publishing country	United States
Document type	Journal Article
ZDB-ID	2609311-X
ISSN	2158-3188 ; 2158-3188
ISSN (online)	2158-3188
ISSN	2158-3188
DOI	10.1038/s41398-024-02814-1
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Article ; Online: Functional dystonia: A case-control study and risk prediction algorithm.

Stephen, Christopher D / Perez, David L / Chibnik, Lori B / Sharma, Nutan

Annals of clinical and translational neurology

2021 Volume 8, Issue 4, Page(s) 732–748

Abstract: Objective: Functional dystonia (FD) is a disabling and diagnostically challenging functional movement disorder (FMD). We sought to identify historical predictors of FD vs. other primary dystonias (ODs) and develop a practical prediction algorithm to ... ...

Abstract	Objective: Functional dystonia (FD) is a disabling and diagnostically challenging functional movement disorder (FMD). We sought to identify historical predictors of FD vs. other primary dystonias (ODs) and develop a practical prediction algorithm to guide neurologists. Methods: 1475 consecutive new patient medical records were reviewed at an adult/pediatric tertiary-referral dystonia clinic from 2005 to 2017. Ninety-nine met criteria for clinically established FD (85 adults and 14 pediatric), paired with 99 age/dystonia distribution-matched OD. Univariate and multivariate regression analyses were performed to identify predictors of FD and disability. We formed a prediction algorithm, assessed using the area under the receiver operating curve (AUC). Results: Multivariate logistic regression analysis investigating independent predictors of FD (P < 0.001) followed by development of a prediction algorithm showed that the most robust predictors included abrupt onset, spontaneous resolution/recurrence, pain, cognitive complaints, being on or pursuing disability, lifetime mood/anxiety disorder, comorbid functional somatic disorders, and having ≥3 medication allergies. The prediction algorithm had utility for both adult and pediatric FD, with excellent sensitivity/specificity (89%/92%) and an area under the curve (AUC) 0.95 (0.92-0.98). Greater disability (modified Rankin Scale) independently correlated with a number of functional examination features, unemployment/not attending school, number of medication allergies, and younger age of presentation. FD patients were high health-care utilizers and were more frequently prescribed opiates/opioids and benzodiazepines (P < 0.003). Interpretation: This case-control study provides an algorithm to guide clinicians in gauging their index of suspicion for a FD, with diagnostic confirmation subsequently informed by neurological examination. While this algorithm requires prospective validation, health-care utilization data underscore the importance and need for more research in FD.
MeSH term(s)	Adolescent ; Adult ; Algorithms ; Case-Control Studies ; Cohort Studies ; Conversion Disorder/diagnosis ; Dystonic Disorders/diagnosis ; Female ; Humans ; Male ; Middle Aged ; Prognosis ; Risk Assessment ; Young Adult
Language	English
Publishing date	2021-03-16
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2740696-9
ISSN	2328-9503 ; 2328-9503
ISSN (online)	2328-9503
ISSN	2328-9503
DOI	10.1002/acn3.51307
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Article ; Online: Radiologically isolated syndrome: A single-center, retrospective cohort study.

George, Ilena C / Rice, Dylan R / Chibnik, Lori B / Mateen, Farrah J

Multiple sclerosis and related disorders

2021 Volume 55, Page(s) 103183

Abstract: Background: Radiologically Isolated Syndrome (RIS) likely represents the earliest detectable form of multiple sclerosis (MS). There are recognized risk factors for conversion of RIS to clinically definite central nervous system (CNS) demyelinating ... ...

Abstract	Background: Radiologically Isolated Syndrome (RIS) likely represents the earliest detectable form of multiple sclerosis (MS). There are recognized risk factors for conversion of RIS to clinically definite central nervous system (CNS) demyelinating disease. We aim to characterize a new clinical cohort with RIS and to analyze previously established risk factors for conversion to clinically definite disease. Methods: A medical records search was performed for patients who were diagnosed with RIS by their treating neurologist at our institution in Boston, USA, from January 2005 to April 2020. Demographic data, clinical outcomes, and treatment courses were analyzed. The time to first clinical event representing a demyelinating disease attack or last follow up without clinically definite disease was calculated for each person. Hazard ratios (HRs) for known risk factors for the conversion of RIS to clinically definite disease were calculated using Cox proportional hazards models. Results: Of 89 patients, the median age at RIS diagnosis was 41.0 years (76% female, 8% with a family history of MS and 16% of any autoimmune disorder, 66% never smokers, 40% BMI >30 kg/m Conclusion: We characterize a new cohort of RIS patients, demonstrating time to clinically evident demyelinating disease from RIS diagnosis of approximately 3.4 years. Our data suggest that early use of a DMT in RIS may mitigate the impact of recognized risk factors on the occurrence of clinically evident disease and reduce the likelihood of conversion to clinically definite CNS demyelinating disease in high-risk individuals.
MeSH term(s)	Adult ; Cohort Studies ; Demyelinating Diseases/diagnostic imaging ; Demyelinating Diseases/epidemiology ; Disease Progression ; Female ; Humans ; Magnetic Resonance Imaging ; Male ; Multiple Sclerosis/diagnostic imaging ; Multiple Sclerosis/epidemiology ; Retrospective Studies
Language	English
Publishing date	2021-08-02
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2645330-7
ISSN	2211-0356 ; 2211-0348
ISSN (online)	2211-0356
ISSN	2211-0348
DOI	10.1016/j.msard.2021.103183
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Article ; Online: Poverty, Cortical Structure, and Psychopathologic Characteristics in Adolescence.

Kim, Hannah H / McLaughlin, Katie A / Chibnik, Lori B / Koenen, Karestan C / Tiemeier, Henning

JAMA network open

2022 Volume 5, Issue 11, Page(s) e2244049

Abstract: Importance: Childhood poverty has been associated with increased internalizing and externalizing problems in adolescence, a period of peak onset for psychiatric problems. The underlying neural mechanisms remain unclear because longitudinal studies of ... ...

Abstract	Importance: Childhood poverty has been associated with increased internalizing and externalizing problems in adolescence, a period of peak onset for psychiatric problems. The underlying neural mechanisms remain unclear because longitudinal studies of poverty, brain structure, and changes in psychiatric symptoms are lacking. Objective: To examine whether structural differences in cortical regions mediate the association between household poverty and change in psychiatric symptoms in early adolescence. Design, setting, and participants: This longitudinal cohort study used baseline and 1-year follow-up data from the Adolescent Brain Cognitive Development Study. Children aged 9 to 10 years in the US were enrolled between September 1, 2016, and October 15, 2018. Data analysis was performed from August 13, 2021, to September 30, 2022. Exposures: Household poverty as measured by income-to-needs ratio, which incorporates family income and adjusts for family size as a percentage of the federal poverty level. Main outcomes and measures: Mediators were children's cortical surface area, thickness, and volume, obtained using magnetic resonance imaging. Internalizing and externalizing problems at 1-year follow-up were outcomes measured by maternal report using the Child Behavior Checklist. Analyses were adjusted for baseline psychiatric problems and sociodemographic variables, including sex, race and ethnicity, parental educational level, and study site. Results: Of the 7569 children (mean [SD] age, 9.91 [0.62] years; 3970 boys [52.5%]) included in the analysis, 1042 children (13.8%) lived below the poverty threshold between 2016 and 2018. Poverty was associated with increased externalizing symptoms score at 1-year follow-up (b = 1.57; 95% CI, 1.14-1.99), even after adjustment for baseline externalizing symptoms (b = 0.35; 95% CI, 0.06-0.64). The longitudinal associations of poverty with increases in externalizing problems over time were mediated by reductions in surface area in multiple cortical regions that support executive functioning (middle frontal gyrus), decision-making (lateral orbitofrontal cortex), visual processing (fusiform gyrus), auditory processing (transverse temporal gyrus), and emotion and language processing (superior temporal gyrus). Conclusions and relevance: The findings of this study suggest that childhood poverty is associated with increases in externalizing problems, but not internalizing problems, over time in early adolescence. This association is mediated by reductions in cortical surface area across numerous brain regions. These findings highlight potential neurobiological mechanisms underlying the link between poverty and the emergence of externalizing problems during early adolescence.
MeSH term(s)	Male ; Child ; Adolescent ; Humans ; Longitudinal Studies ; Psychopathology ; Poverty ; Income ; Family Characteristics
Language	English
Publishing date	2022-11-01
Publishing country	United States
Document type	Journal Article
ISSN	2574-3805
ISSN (online)	2574-3805
DOI	10.1001/jamanetworkopen.2022.44049
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Article ; Online: Rate of tau propagation is a heritable disease trait in genetically diverse mouse strains.

Welikovitch, Lindsay A / Dujardin, Simon / Dunn, Amy R / Fernandes, Analiese R / Khasnavis, Anita / Chibnik, Lori B / Kaczorowski, Catherine C / Hyman, Bradley T

iScience

2023 Volume 26, Issue 2, Page(s) 105983

Abstract: The speed and scope of cognitive deterioration in Alzheimer's disease is highly associated with the advancement of tau neurofibrillary lesions across brain networks. We tested whether the rate of tau propagation is a heritable disease trait in a large, ... ...

Abstract	The speed and scope of cognitive deterioration in Alzheimer's disease is highly associated with the advancement of tau neurofibrillary lesions across brain networks. We tested whether the rate of tau propagation is a heritable disease trait in a large, well-characterized cohort of genetically divergent mouse strains. Using an AAV-based model system, P301L-mutant human tau (hTau) was introduced into the entorhinal cortex of mice derived from 18 distinct lines. The extent of tau propagation was measured by distinguishing hTau-producing cells from neurons that were recipients of tau transfer. Heritability calculation revealed that 43% of the variability in tau spread was due to genetic variants segregating across background strains. Strain differences in glial markers were also observed, but did not correlate with tau propagation. Identifying unique genetic variants that influence the progression of pathological tau may uncover novel molecular targets to prevent or slow the pace of tau spread and cognitive decline.
Language	English
Publishing date	2023-01-14
Publishing country	United States
Document type	Journal Article
ISSN	2589-0042
ISSN (online)	2589-0042
DOI	10.1016/j.isci.2023.105983
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Article ; Online: Longitudinal Body Weight Change, Visit-To-Visit Body Weight Fluctuation, and Cognitive Decline Among Older Adults.

Lan, Yu-Tung / Blacker, Deborah / Yuan, Changzheng / Chibnik, Lori B / Hofman, Albert / Ma, Yuan

Journal of Alzheimer's disease : JAD

2021 Volume 84, Issue 2, Page(s) 777–786

Abstract: Background: The evidence regarding dementia and late-life weight change is inconsistent, and data on body weight fluctuation and dementia are limited.: Objective: To test the hypothesis that weight loss and substantial weight fluctuation predict ... ...

Abstract	Background: The evidence regarding dementia and late-life weight change is inconsistent, and data on body weight fluctuation and dementia are limited. Objective: To test the hypothesis that weight loss and substantial weight fluctuation predict cognitive decline independent of body weight and traditional risk factors of dementia. Methods: This study utilized longitudinal data from the National Alzheimer's Coordinating Center for 10,639 stroke- and dementia-free older adults (60.9%female, mean age 71.6 years, median follow-up 5.5 years). Trends in weight change and weight fluctuation were estimated for each individual by regressing repeated body weight measurements on time. Cognitive decline was examined as diagnostic progression from normal to mild cognitive impairment (MCI) or dementia and from MCI to dementia. Results: Compared to participants with stable weight, those with weight loss had increased odds of diagnostic progression (adjusted OR = 1.35, 95%CI [1.21, 1.51]). Also, large weight fluctuation was associated with increased odds of diagnostic progression (OR comparing the extreme quartiles = 1.20, 95%CI [1.04, 1.39]) after adjusting for traditional risk factors for dementia and body weight change. The magnitude of the association appeared larger among those older than 80 and those with 3 or more cardiometabolic risk factors at baseline (both p for interaction < 0.05). Conclusion: Weight loss and substantial weight fluctuation during late-life were associated with increased odds of cognitive decline independent of body weight and traditional risk factors of dementia. Our results suggested the linkage between late-life body weight instability and cognitive decline especially among those with greater age or higher cardiometabolic risk.
MeSH term(s)	Age Factors ; Aged ; Aged, 80 and over ; Body Weight/physiology ; Cardiometabolic Risk Factors ; Cognitive Dysfunction/physiopathology ; Dementia/epidemiology ; Female ; Humans ; Longitudinal Studies ; Male
Language	English
Publishing date	2021-10-14
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	1440127-7
ISSN	1875-8908 ; 1387-2877
ISSN (online)	1875-8908
ISSN	1387-2877
DOI	10.3233/JAD-210625
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Article ; Online: Association of Adverse Childhood Experiences With Poor Neuropsychiatric Health and Dementia Among Former Professional US Football Players.

Roberts, Andrea L / Zafonte, Ross / Chibnik, Lori B / Baggish, Aaron / Taylor, Herman / Baker, Jillian / Whittington, Alicia J / Weisskopf, Marc G

JAMA network open

2022 Volume 5, Issue 3, Page(s) e223299

Abstract: Importance: Childhood adversities, including neglect, abuse, and other indicators of family dysfunction, are associated in adulthood with risk factors for poor cognitive and mental health. However, the extent to which these experiences are associated ... ...

Abstract	Importance: Childhood adversities, including neglect, abuse, and other indicators of family dysfunction, are associated in adulthood with risk factors for poor cognitive and mental health. However, the extent to which these experiences are associated with adulthood cognition-related quality of life and risk for dementia is unknown. Objective: To determine the association of 10 adverse childhood experiences (ACEs) with neuropsychiatric outcomes among former National Football League (NFL) players. Design, setting, and participants: This cross-sectional analysis used data from the Football Player's Health Study at Harvard University, an ongoing longitudinal cohort study from January 30, 2015, to November 19, 2021, of former NFL players. Exposures: Ten ACEs were assessed using the Adverse Childhood Experiences Questionnaire. Main outcomes and measures: Dementia symptoms were assessed using the AD8: The Washington University Dementia Screening Test; cognition-related quality of life was assessed with the short form of the Quality of Life in Neurological Disorders; depression was assessed with the Patient Health Questionnaire-9; anxiety was assessed with the Generalized Anxiety Disorder-7; and pain intensity and pain interference in daily life were assessed with the Brief Pain Inventory. Risk ratios (RRs) assessing the association between ACEs and neuropsychiatric outcomes were estimated using generalized estimating equations, adjusted for age, race, and childhood socioeconomic status, and further adjusted for playing position, concussions incurred during football play, and number of seasons played in the NFL. Results: A total of 1755 men (mean [SD] age, 57.2 [13.5] years) who were former professional football players were included in the analysis. Five hundred twenty players (29.6%) identified as Black, 1160 (66.1%) identified as White, and 75 (4.3%) identified as other race or ethnicity. Players with 4 or more ACEs were at 48% greater risk of a positive screen for dementia (RR, 1.48 [95% CI, 1.22-1.79]), and at significantly greater risk of every other neuropsychiatric outcome except anxiety (RR range, 1.62 [95% CI, 1.09-2.39] to 1.74 [95% CI, 1.27-2.40]) compared with players with no ACEs. Further adjustment for concussions incurred during playing years attenuated these associations, although some were still significant (adjusted RR range, 1.32 [95% CI, 1.10-1.58] to 1.56 [95% CI, 1.15-2.11]). ACEs were also associated with concussion symptoms; players with 4 or more ACEs had a 60% increased risk of being in the top quartile of concussion symptoms (RR, 1.60; 95% CI, 1.12-2.28) compared with players with no ACEs. Conclusions and relevance: These findings suggest that ACEs may be associated with dementia symptoms among former NFL players. Moreover, ACEs should be investigated among professional football players and other populations as a prospective indicator of persons at high risk of concussion. These findings further suggest that treatment of psychological trauma in addition to treatment of physical injury may improve neuropsychiatric health in former NFL players.
MeSH term(s)	Adult ; Adverse Childhood Experiences ; Brain Concussion/complications ; Brain Concussion/epidemiology ; Child ; Cross-Sectional Studies ; Dementia/complications ; Dementia/epidemiology ; Football/injuries ; Humans ; Longitudinal Studies ; Male ; Middle Aged ; Pain/complications ; Prospective Studies ; Quality of Life
Language	English
Publishing date	2022-03-01
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	2574-3805
ISSN (online)	2574-3805
DOI	10.1001/jamanetworkopen.2022.3299
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Article: Sex Differences in People with Tourette Syndrome and Persistent Motor or Vocal Tic Disorder in the Tourette Association of America International Consortium for Genetics Database.

Dy-Hollins, Marisela E / Chibnik, Lori B / Tracy, Natasha A / Osiecki, Lisa / Budman, Cathy L / Cath, Danielle C / Grados, Marco A / King, Robert A / Gholson, Lyon / Rouleau, Guy A / Sandor, Paul / Singer, Harvey S / Sharma, Nutan / Mathews, Carol A / Scharf, Jeremiah

medRxiv : the preprint server for health sciences

2024

Abstract: Background and objective: Tourette Syndrome (TS) and Persistent Motor or Vocal Tic Disorders (PMVT) are more prevalent in males (vs. females). Females with TS may have a delay in diagnosis, and more complex tic features (vs. males). With respect to ... ...

Abstract	Background and objective: Tourette Syndrome (TS) and Persistent Motor or Vocal Tic Disorders (PMVT) are more prevalent in males (vs. females). Females with TS may have a delay in diagnosis, and more complex tic features (vs. males). With respect to comorbidities, obsessive-compulsive disorder (OCD) is more prevalent in females; attention-deficit hyperactivity disorder (ADHD) is more prevalent in males. Less is known about sex differences in PMVT. This study analyzes sex differences in outcomes among individuals with TS and PMVT in the Tourette Association of America International Consortium for Genetics dataset (TAAICG). Design/methods: Data from 2403 individuals (N=2109 TS; N=294 PMVT) from the TAAICG were analyzed to explore the relationship between sex and TS or PMVT outcomes: age at tic onset; age at diagnosis; time-to-diagnosis; tic severity; and comorbidity rates. Regression models were adjusted for age and family relationships to examine the impact of sex on outcomes. Results: Females with TS (25.5% of the sample) had a later age of symptom onset (6.5±2.8 vs. 6.0±2.7; p=0.001), later age at diagnosis (13.3±11.2 vs. 10.7±8.1; p=0.0001), and a longer time-to-diagnosis [3 (1,7) vs. 2 (1,5), p=0.01] than males. The total Yale-Global Tic Severity Scale (YGTSS) was lower in females with TS (28.4±9.1 vs. 30.7±8.7); p<0.0001); OCD was slightly more prevalent in females (55% vs. 48.7%; p=0.01) although OCD severity did not differ by sex; ADHD was more prevalent in males (55.7% vs 38.9%; p<0.001). Females with TS had 0.46 lower odds of being diagnosed with TS (p<0.00001). Females with PMVT (42.9% of the sample) had an earlier age of symptom onset (7.9±3.3 vs. 8.9±3.7; p=0.05). Motor or vocal tic severity (YGTSS) was not significantly different. OCD, but not ADHD, was more prevalent in females (OCD: 41.9% vs. 22.2%; p<0.001: ADHD:16.5% vs 21.0%; p=0.4). Conclusion: Females with TS are less likely to be formally diagnosed and have a later age of symptom onset, later age at diagnosis, longer time-to-diagnosis, higher prevalence of OCD, and lower prevalence of ADHD (vs. males). Females with PMVT have an earlier age of symptom onset, higher prevalence of OCD, but similar ADHD prevalence rates (vs. males). Females with TS and PMVT may be clinically different than males with TS. Future research is needed to understand differences longitudinally in TS and PMVT.
Language	English
Publishing date	2024-01-09
Publishing country	United States
Document type	Preprint
DOI	10.1101/2024.01.07.24300816
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