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Magnitude of Cognitive Dysfunction in Adults with Type 2 Diabetes: A Meta-analysis of Six Cognitive Domains and the Most Frequently Reported Neuropsychological Tests Within Domains
The objectives were to conduct a meta-analysis in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standards to determine effect sizes (Cohen's d) for cognitive dysfunction in adults with type 2 diabetes, relative to nondiabetic controls, and to obtain effect sizes for the most commonly reported neuropsychological tests within domains. Twenty-four studies, totaling 26,137 patients (n = 3351 with diabetes), met study inclusion criteria. Small to moderate effect sizes were obtained for five of six domains: motor function (3 studies, n = 2374; d = −0.36), executive function (12 studies, n = 1784; d = −0.33), processing speed (16 studies, n = 3076; d = −0.33), verbal memory (15 studies, n = 4,608; d = −0.28), and visual memory (6 studies, n = 1754; d = −0.26). Effect size was smallest for attention/concentration (14 studies, n = 23,143; d = −0.19). The following tests demonstrated the most notable performance decrements in diabetes samples: Grooved Pegboard (dominant hand) (d = −0.60), Rey Auditory Verbal Learning Test (immediate) (d = −0.40), Trails B (d = −0.39), Rey-Osterreith Complex Figure (delayed) (d = −0.38), Trails A (d = −0.34), and Stroop Part I (d = −0.28). This study provides effect sizes to power future epidemiological and clinical diabetes research studies examining cognitive function and to help inform the selection of neuropsychological tests. (JINS, 2014, 20, 1–14)
Journal Article
Prevalence of Self-Reported Head Injury in the United States
In a survey of adults 40 years of age or older from the 2011–2014 National Health and Nutrition Examination Survey (NHANES) cohort, the prevalence of recalled head injury was 15.7%.
Journal Article
Methods for stroke severity assessment by chart review in the Atherosclerosis Risk in Communities study
Stroke severity is the most important predictor of post-stroke outcome. Most longitudinal cohort studies do not include direct and validated measures of stroke severity, yet these indicators may provide valuable information about post-stroke outcomes, as well as risk factor associations. In the Atherosclerosis Risk in Communities (ARIC) study, stroke severity data were retrospectively collected, and this paper outlines the procedures used and shares them as a model for assessment of stroke severity in other large epidemiologic studies. Trained physician abstractors, who were blinded to other clinical events, reviewed hospital charts of all definite/probable stroke events occurring in ARIC. In this analysis we included 1,198 ischemic stroke events occurring from ARIC baseline (1987–1989) through December 31, 2009. Stroke severity was categorized according to the National Institutes of Health Stroke Scale (NIHSS) score and classified into 5 levels: NIHSS ≤ 5 (minor), NIHSS 6–10 (mild), NIHSS 11–15 (moderate), NIHSS 16–20 (severe), and NIHSS > 20 (very severe). We assessed interrater reliability in a subgroup of 180 stroke events, reviewed independently by the lead abstraction physician and one of the four secondary physician abstractors. Interrater correlation coefficients for continuous NIHSS score as well as percentage of absolute agreement and Cohen Kappa Statistic for NIHSS categories were presented. Determination of stroke severity by the NIHSS, based on data abstracted from hospital charts, was possible for 97% of all ischemic stroke events. Median (25%-75%) NIHSS score was 5 (2–8). The distribution of NIHSS category was NIHSS ≤ 5 = 58.3%, NIHSS 6–10 = 24.5%, NIHSS 11–15 = 8.9%, NIHSS 16–20 = 4.7%, NIHSS > 20 = 3.6%. Overall agreement in the classification of severity by NIHSS category was present in 145/180 events (80.56%). Cohen’s simple Kappa statistic (95% CI) was 0.64 (0.55–0.74) and weighted Kappa was 0.79 (0.72–0.86). Mean (SD) NIHSS score was 5.84 (5.88), with a median score of 4 and range 0–31 for the lead reviewer (rater 1) and mean (SD) 6.16 (6.10), median 4.5 and range 0–36 in the second independent assessment (rater 2). There was a very high correlation between the scores reported in both assessments (Pearson r = 0.90). Based on our findings, we conclude that hospital chart-based retrospective assessment of stroke severity using the NIHSS is feasible and reliable.
Journal Article
Sex differences in the extent of acute axonal pathologies after experimental concussion
Although human females appear be at a higher risk of concussion and suffer worse outcomes than males, underlying mechanisms remain unclear. With increasing recognition that damage to white matter axons is a key pathologic substrate of concussion, we used a clinically relevant swine model of concussion to explore potential sex differences in the extent of axonal pathologies. At 24 h post-injury, female swine displayed a greater number of swollen axonal profiles and more widespread loss of axonal sodium channels than males. Axon degeneration for both sexes appeared to be related to individual axon architecture, reflected by a selective loss of small caliber axons after concussion. However, female brains had a higher percentage of small caliber axons, leading to more extensive axon loss after injury compared to males. Accordingly, sexual dimorphism in axonal size is associated with more extensive axonal pathology in females after concussion, which may contribute to worse outcomes.
Journal Article
Olfactory Dysfunction Following Moderate to Severe Traumatic Brain Injury: A Systematic Review and Meta-Analysis
ObjectiveReports of smell loss following traumatic brain injury (TBI) are a well-documented but understudied phenomenon. Given the broad consequences of olfactory loss, we characterized psychophysical olfactory dysfunction in individuals with moderate to severe TBI using systematic review and meta-analytic methods.MethodsFollowing Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) protocol, five databases (PubMed, EMBASE, Cochrane Library, Web of Science, Scopus) were reviewed for studies investigating olfactory dysfunction in persons with moderate to severe TBI. Of the 5,223 studies reviewed, 19 met our inclusion criteria for the systematic review and 11 met inclusion criteria for meta-analysis. We calculated effect sizes (Hedges’ g) to characterize the degree of olfactory dysfunction between patients with moderate to severe TBI and controls.ResultsA total of 951 moderate-severe TBI patients from 19 studies were included in the systematic review, which largely demonstrated poorer olfactory psychophysical performances in this patient population. Meta-analysis demonstrated a large effect size for olfactory dysfunction in moderate-severe TBI relative to healthy controls (g=-2.43, 95%CI: -3.16 < δ<-1.69). The magnitude of the effect was moderated by age and patient sex, with larger effect sizes associated with older age (following exclusion of a pediatric population) and larger compositions of women in the patient group.ConclusionModerate to severe TBI is associated with prominent olfactory dysfunction. Significant research gaps remain regarding the mechanism, recovery and natural history of olfactory dysfunction following moderate to severe TBI, which has significant clinical implications for the identification and treatment for those with post-traumatic olfactory dysfunction.
Journal Article
Sleep apnea, hypoxia, and late-onset epilepsy: the Atherosclerosis Risk in Communities study
Abstract
Study Objective
Sleep apnea is associated with unexplained epilepsy in older adults in small studies. We sought to determine the relationship between sleep apnea and additional sleep characteristics and late-onset epilepsy (LOE), adjusting for comorbidities, using data from the large, prospective Atherosclerosis Risk in Communities (ARIC) Study cohort.
Methods
We used Medicare claims to identify cases of LOE in ARIC participants. We used polysomnography data from 1309 ARIC participants who also participated in the Sleep Heart Health Study in 1995–1998, and demographic and comorbidity data from ARIC. Later risk of LOE was evaluated using survival analysis with a competing risk of death. We also used survival analysis in 2672 ARIC participants to identify the association between self-reported obstructive sleep apnea (2011–2013), and the risk of subsequent LOE.
Results
Late-midlife oxygen desaturation to less than 80% during sleep was associated with subsequent development of LOE, adjusted subhazard ratio 3.28 (1.18–9.08), but the apnea–hypopnea index was not related. Participant report of diagnosis of sleep apnea in 2011–2013 was also associated with subsequent LOE, adjusted subhazard ratio 2.59 (1.24–5.39).
Conclusions
Sleep apnea and oxygen saturation nadir during sleep are associated with LOE, independently of hypertension and other comorbidities. These potentially modifiable risk factors could have large clinical implications for LOE.
Graphical Abstract
Graphical Abstract
Journal Article
Mild cognitive impairment and dementia prevalence: The Atherosclerosis Risk in Communities Neurocognitive Study
Abstract Introduction We examined prevalence of mild cognitive impairment (MCI) and dementia in the Atherosclerosis Risk in Communities (ARIC) Neurocognitive study. Methods Beginning in June, 2011, we invited all surviving ARIC participants to undergo cognitive, neurologic, and brain imaging assessments to diagnose MCI or dementia and assign an etiology for the cognitive disorder. Results Of 10,713 surviving ARIC participants (age range, 69–88 years), we ascertained cognitive diagnoses in 6471 in person, 1966 by telephone interviews (participant or informant), and the remainder by medical record review. The prevalence of dementia was 9.0% and MCI 21%. Alzheimer's disease (AD) was the primary or secondary etiology in 76% of dementia and 75% of MCI participants. Cerebrovascular disease was the primary or secondary etiology in 46% of dementia and 32% of MCI participants. Discussion MCI and dementia were common among survivors from the original ARIC cohort. Nearly 30% of the ARIC cohort received diagnoses of either dementia or MCI, and for the majority of these individuals, the etiologic basis was attributed to AD.
Journal Article
Diabetes and Risk of Fracture-Related Hospitalization: The Atherosclerosis Risk in Communities Study
To examine the association between diabetes, glycemic control, and risk of fracture-related hospitalization in the Atherosclerosis Risk in Communities (ARIC) Study.
Fracture-related hospitalization was defined using International Classification of Diseases, 9th revision, codes (733.1-733.19, 733.93-733.98, or 800-829). We calculated the incidence rate of fracture-related hospitalization by age and used Cox proportional hazards models to investigate the association of diabetes with risk of fracture after adjustment for demographic, lifestyle, and behavioral risk factors.
There were 1,078 incident fracture-related hospitalizations among 15,140 participants during a median of 20 years of follow-up. The overall incidence rate was 4.0 per 1,000 person-years (95% confidence interval [CI], 3.8-4.3). Diagnosed diabetes was significantly and independently associated with an increased risk of fracture (adjusted hazard ratio [HR], 1.74; 95% CI, 1.42-2.14). There also was a significantly increased risk of fracture among persons with diagnosed diabetes who were treated with insulin (HR, 1.87; 95% CI, 1.15-3.05) and among persons with diagnosed diabetes with hemoglobin A1c (HbA1c) ≥8% (1.63; 1.09-2.44) compared with those with HbA1c <8%. Undiagnosed diabetes was not significantly associated with risk of fracture (HR, 1.12; 95% CI, 0.82-1.53).
This study supports recommendations from the American Diabetes Association for assessment of fracture risk and implementation of prevention strategies in persons with type 2 diabetes, particularly those persons with poor glucose control.
Journal Article
Traumatic brain injury, changes in plasma amyloid, tau, and neurodegenerative biomarkers, and dementia risk
INTRODUCTION Long‐term trajectories of plasma biomarkers in relation to incident traumatic brain injury (TBI) and whether TBI modifies associations of biomarkers with dementia risk are unknown. METHODS One thousand fifty Atherosclerosis Risk in Communities (ARIC) study participants without prior TBI had amyloid beta (Aβ42/Aβ40), phosphorylated‐tau181 (pTau181), neurofilament light (NfL), and glial fibrillary acidic protein (GFAP) measured from plasma collected in 1993 to 1995, 2011 to 2013, and 2016 to 2019. Linear mixed‐effects models estimated biomarker trajectories associated with TBI and Cox proportional hazards models determined if TBI modified associations of biomarkers with incident dementia through December 31, 2020. RESULTS After the median time of incident TBI, Aβ42/Aβ40 levels remained lower for 9.3 years, and pTau181, NfL, and GFAP remained elevated for 8.5, >13.8, and 12.7 years, respectively. There was evidence of additive interaction by TBI in associations of log2NfL with incident dementia (p = 0.024). DISCUSSION TBI alters trajectories of plasma biomarkers of neurodegeneration for approximately a decade after the injury and modifies associations of NfL with dementia risk. Highlights Our findings provide evidence that TBI fundamentally alters trajectories of plasma biomarkers of AD‐related pathology, neuronal degeneration, and astrogliosis for approximately a decade after the injury. Further, our findings also suggest that an incident TBI event adds to and interacts with ongoing neurodegenerative processes to increase the risk of later life dementia. These results suggest that the pathologic processes underlying post‐TBI dementia are heterogeneous, that individuals with preclinical changes in neurodegenerative biomarkers may be more susceptible to TBI (i.e., that associations are bidirectional), or a combination thereof.
Journal Article