The influence of ADHD on recovery from sport concussion among collegiate athletes in the United States: LIMBIC MATARS consortium investigation.

OBJECTIVE: The present study aimed to assess the potential influence of a diagnosis of ADHD on concussion recovery among collegiate athletes. DESIGN: Retrospective and cross-sectional. METHODS: Data were extracted retrospectively from medical records across LIMBIC MATARS member institutions (n = 11), representing 1,044 concussion cases among collegiate athletes. After exclusions, 406 concussions were included in our analysis (ADHD: n = 38, age = 20.2 ± 1.67 years, 18.4% female; No ADHD: n = 368, age = 19.8 ± 1.39 years, 40.1% female). Mann-Whitney U tests were used to compare days from injury to diagnosis, symptom resolution, and return to sport among athletes with and without ADHD. RESULTS: No differences were observed for days from concussion until diagnosis (z = -0.33, p = 0.74), until days to symptom resolution (z = -1.30, p = 0.19), or days until return to sport (z = -0.68, p = 0.49); among concussion cases with or without a previously reported diagnosis of ADHD. CONCLUSION: Our findings further expand the literature that suggests ADHD is not strongly associated with recovery trajectory following sport concussion in collegiate athletes. Future research should extend these findings to be inclusive of additional preexisting health conditions and moderating effects related to medication usage among diverse athlete levels.

CARE4Kids Study: Endophenotypes of Persistent Post-Concussive Symptoms in Adolescents: Study Rationale and Protocol.

Treatment of youth concussion during the acute phase continues to evolve, and this has led to the emergence of guidelines to direct care. While symptoms after concussion typically resolve in 14-28 days, a portion (∼20%) of adolescents endorse persistent post-concussive symptoms (PPCS) beyond normal resolution. This report outlines a study implemented in response to the National Institute of Neurological Diseases and Stroke call for the development and initial clinical validation of objective biological measures to predict risk of PPCS in adolescents. We describe our plans for recruitment of a Development cohort of 11- to 17-year-old youth with concussion, and collection of autonomic, neurocognitive, biofluid, and imaging biomarkers. The most promising of these measures will then be validated in a separate Validation cohort of youth with concussion, and a final, clinically useful algorithm will be developed and disseminated. Upon completion of this study, we will have generated a battery of measures predictive of high risk for PPCS, which will allow for identification and testing of interventions to prevent PPCS in the most high-risk youth.

CSF-Derived CD4+ T-Cell Diversity Is Reduced in Patients With Alzheimer Clinical Syndrome.

BACKGROUND AND OBJECTIVES: Patients with Alzheimer dementia display evidence of amyloid-related neurodegeneration. Our focus was to determine whether such patients also display evidence of a disease-targeting adaptive immune response mediated by CD4+ T cells. To test this hypothesis, we evaluated the CSF immune profiles of patients with Alzheimer clinical syndrome (ACS), who display clinically defined dementia. METHODS: Innate and adaptive immune profiles of patients with ACS were measured using multicolor flow cytometry. CSF-derived CD4+ and CD8+ T-cell receptor repertoire genetics were measured using next-generation sequencing. Brain-specific autoantibody signatures of CSF-derived antibody pools were measured using array technology or ELISA. CSF from similar-age healthy controls (HCs) was used as a comparator cohort. RESULTS: Innate cells were expanded in the CSF of patients with ACS in comparison to HCs, and innate cell expansion increased with age in the patients with ACS, but not HCs. Despite innate cell expansion in the CSF, the frequency of total CD4+ T cells reduced with age in the patients with ACS. T-cell receptor repertoire genetics indicated that T-cell clonal expansion is enhanced, and diversity is reduced in the patients with ACS compared with similar-age HCs. DISCUSSION: Examination of CSF indicates that CD4+ T cell-mediated adaptive immune responses are altered in patients with ACS. Understanding the underlying mechanisms affecting adaptive immunity will help move us toward the goal of slowing cognitive decline.

Using local rather than general anesthesia for inguinal hernia repair is associated with shorter operative time and enhanced postoperative recovery.

BACKGROUND: Inguinal hernia repair is the most common general surgery procedure and can be performed under local or general anesthesia. We hypothesized that using local rather than general anesthesia would improve outcomes, especially for older adults. METHODS: This is a retrospective review of 97,437 patients in the Veterans Affairs Surgical Quality Improvement Program who had open inguinal hernia surgery under local or general anesthesia. Outcomes included 30-day postoperative complications, operative time, and recovery time. RESULTS: Our cohort included 22,333 (23%) Veterans who received local and 75,104 (77%) who received general anesthesia. Mean age was 62 years. Local anesthesia was associated with a 37% decrease in the odds of postoperative complications (95% CI 0.54-0.73), a 13% decrease in operative time (95% CI 17.5-7.5), and a 27% shorter recovery room stay (95% CI 27.5-25.5), regardless of age. CONCLUSIONS: Using local rather than general anesthesia is associated with a profound decrease in complications (equivalent to "de-aging" patients by 30 years) and could significantly reduce costs for this common procedure.

Using Local Anesthesia for Inguinal Hernia Repair Reduces Complications in Older Patients.

BACKGROUND: Inguinal hernia repair is the most common general surgery operation in the United States. Nearly 80% of inguinal hernia operations are performed under general anesthesia versus 15%-20% using local anesthesia, despite the absence of evidence for the superiority of the former. Although patients aged 65 y and older are expected to benefit from avoiding general anesthesia, this presumed benefit has not been adequately studied. We hypothesized that the benefits of local over general anesthesia for inguinal hernia repair would increase with age. MATERIALS AND METHODS: We analyzed 87,794 patients in the American College of Surgeons National Surgical Quality Improvement Project who had elective inguinal hernia repair under local or general anesthesia from 2014 to 2018, and we used propensity scores to adjust for known confounding. We compared postoperative complications, 30-day readmissions, and operative time for patients aged <55 y, 55-64 y, 65-74 y, and ≥75 y. RESULTS: Using local rather than general anesthesia was associated with a 0.6% reduction in postoperative complications in patients aged 75+ y (95% CI -0.11 to -1.13) but not in younger patients. Local anesthesia was associated with faster operative time (2.5 min - 4.7 min) in patients <75 y but not in patients aged 75+ y. Readmissions did not differ by anesthesia modality in any age group. Projected national cost savings for greater use of local anesthesia ranged from $9 million to $45 million annually. CONCLUSIONS: Surgeons should strongly consider using local anesthesia for inguinal hernia repair in older patients and in younger patients because it is associated with significantly reduced complications and substantial cost savings.

Baseline Prevalence of Polypharmacy in Older Hypertensive Study Subjects with Elevated Dementia Risk: Findings from the Risk Reduction for Alzheimer's Disease Study (rrAD).

BACKGROUND: Little is known about the prevalence of polypharmacy, the taking of five or more medications a day, in older adults with specific dementia risk factors. OBJECTIVE: To examine the prevalence of polypharmacy in participants at baseline in a vascular risk reduction focused Alzheimer's disease (rrAD) trial targeting older patients with hypertension and elevated dementia risk. METHODS: We conducted a detailed review of medications in a cross-sectional study of community-dwelling older adults with hypertension and elevated dementia risk. Medications were identified in a structured interview process with an onsite pharmacist or qualified designee. Polypharmacy was defined as use of five or more medications on a regular basis. Descriptive analyses were conducted on the sample as well as direct comparisons of subgroups of individuals with hypertension, diabetes, and hyperlipidemia. RESULTS: The 514 rrAD participants, mean age 68.8 (standard deviation [sd] 6), reported taking different combinations of 472 unique medications at their baseline visit. The median number of medications taken by participants was eight [Range 0-21], with 79.2% exhibiting polypharmacy (n = 407). Sites differed in their prevalence of polypharmacy, χ2(3) = 56.0, p < 0.001. A nearly identical percentage of the 2,077 prescribed (51.8%) and over the counter (48.2%) medications were present in the overall medication profile. The presence of diabetes (87.5%), hyperlipidemia (88.2%), or both (97.7%) was associated with a higher prevalence of polypharmacy than participants who exhibited hypertension in the absence of either of these conditions (63.2%), χ2(3) = 35.8, p < 0.001. CONCLUSION: Participants in a dementia risk study had high levels of polypharmacy, with the co-existence of diabetes or hyperlipidemia associated with a greater prevalence of polypharmacy as compared to having hypertension alone.

Comparison of psychiatric comorbidities and impact on quality of life in patients with epilepsy or psychogenic nonepileptic spells.

OBJECTIVES: Psychiatric comorbidity is common in people with epilepsy (PWE) and psychogenic nonepileptic spells (PNES). These comorbidities can be detrimental to quality of life (QOL) and are often underdiagnosed and undertreated. Some types of epilepsy, such as focal temporal lobe epilepsy (TLE), have been associated with higher rates of psychiatric comorbidity. This study examined the impact of psychiatric comorbidity on QOL in patients admitted to two level 4 epilepsy monitoring units (EMUs). METHODS: In this prospective observational study, 200 patients admitted to two level 4 EMUs completed standardized surveys including the Quality of Life in Epilepsy (QOLIE-31-P), Generalized Anxiety Disorder 7-item (GAD-7), Patient Health Questionnaire (PHQ-9), and Beck Depression Inventory-II (BDI-II). Hierarchal multiple regression was performed to assess impact on QOL. RESULTS: Of the 200 participants, 113 had a diagnosis of epilepsy, 36 had a diagnosis of PNES, and 51 were excluded for nondiagnostic evaluation or dual diagnosis. Of those with epilepsy, 65 had TLE, 28 had focal extratemporal lobe epilepsy (ETLE), and 20 had nonfocal epilepsy. Patients with PNES had higher self-reported anxiety and depression levels (GAD-7: p = 0.04, PHQ-9: p < 0.01; BDI-II: p < 0.01) but similar QOL to PWE (p = 0.78). Using hierarchal multiple regression, symptoms of anxiety and depression were significant predictors of lower QOL in PWE but not in patients with PNES. There was no difference in QOL in those with ETLE and TLE. CONCLUSIONS: Our findings suggest that self-reported anxiety and depression symptoms are common in patients admitted to level 4 EMUs regardless of diagnosis and play an important role in predicting QOL in PWE. Our findings emphasize the importance of routinely screening all EMU patients for psychiatric comorbidity.

Ventriculoperitoneal Shunt Outcomes of Normal Pressure Hydrocephalus: A Case Series of 116 Patients.

Background Permanent cerebrospinal fluid (CSF) diversion with a ventriculoperitoneal shunt (VPS) is a treatment option for patients with normal pressure hydrocephalus (NPH). Objectives Herein, we examine the outcomes, complication rates, and associations between predictors and outcomes after VPS in patients with NPH. Methods This was a retrospective review of 116 patients (68 males, 48 females) with NPH who underwent VPS placement from March 2008 to September 2017 after demonstrating objective and/or subjective improvement after a lumbar drain trial. The Chi-square test of independence was used to examine associations between predictors and clinical improvement after shunting. Complications associated with the VPS procedure were recorded. Results The mean age was 77 years (range 52-93). The mean duration of disturbance in gait, cognition, and continence were 29, 32, and 28 months, respectively. Of the 116 patients, 111 followed up at two weeks; of these, improvement in gait, incontinence, and cognition were reported in 72, 20, and 23 patients, respectively. Gait improved more than incontinence or cognition. A shorter duration of gait disturbance predicted an improvement in gait after shunting (p<0.01). Being on a cognition-enhancing medication predicted an improvement in cognition and/or incontinence after shunting (p<0.05). Complications included misplaced proximal catheters (n=6), asymptomatic catheter tract hemorrhages (n=3), bilateral hygromas (n=7), subdural hematomas (SDH) (n=5), and CSF leak (n=1). Conclusion VPS placement in patients with NPH is well-tolerated and associated with improved outcomes at least in the short-term follow-up (<6 months). A shorter duration of gait disturbance and being on a cognition-enhancing medication are associated with greater improvement after VPS.

Reduced global brain metabolism but maintained vascular function in amnestic mild cognitive impairment.

Amnestic mild cognitive impairment represents an early stage of Alzheimer's disease, and characterization of physiological alterations in mild cognitive impairment is an important step toward accurate diagnosis and intervention of this condition. To investigate the extent of neurodegeneration in patients with mild cognitive impairment, whole-brain cerebral metabolic rate of oxygen in absolute units of µmol O2/min/100 g was quantified in 44 amnestic mild cognitive impairment and 28 elderly controls using a novel, non-invasive magnetic resonance imaging method. We found a 12.9% reduction ( p = 0.004) in cerebral metabolic rate of oxygen in mild cognitive impairment, which was primarily attributed to a reduction in the oxygen extraction fraction, by 10% ( p = 0.016). Global cerebral blood flow was not found to be different between groups. Another aspect of vascular function, cerebrovascular reactivity, was measured by CO2-inhalation magnetic resonance imaging and was found to be equivalent between groups. Therefore, there seems to be a global, diffuse diminishment in neural function in mild cognitive impairment, while their vascular function did not show a significant reduction.

Cognitive endophenotypes of psychosis within dimension and diagnosis.

This study sought to characterize the psychosis phenotype, contrasting cognitive features within traditional diagnosis and psychosis dimension in a family sample containing both schizophrenia and psychotic bipolar I disorder. Seventy-six probands with psychosis [44 probands with schizophrenia, 32 probands with psychotic bipolar I disorder] and 55 first-degree relatives [30 relatives of schizophrenia probands, 25 relatives of bipolar probands] were recruited. Standardized clinical and neuropsychological measures were administered. No differences in cognitive performance emerged between probands with schizophrenia and probands with psychotic bipolar disorder, or between relatives of probands with schizophrenia and relatives of probands with bipolar disorder in the domains of working and declarative memory, executive function and attention. Relatives overall showed higher cognitive performance compared to probands, as expected. However, when we segmented the probands and relatives along a psychosis dimension, independent of diagnostic groups, results revealed lower cognitive performance in probands compared to relatives without psychosis spectrum disorders, whereas relatives with psychosis spectrum disorders showed an intermediate level of performance across all cognitive domains. In this study, cognitive performance did not distinguish either probands or their first-degree relatives within traditional diagnostic groups (schizophrenia and psychotic bipolar disorder), but distinguished probands and relatives with and without lifetime psychosis manifestations independent of diagnostic categories. These data support the notion that schizophrenia and psychotic bipolar disorder present a clinical continuum with overlapping cognitive features defining the psychosis phenotype.

Evaluation of the Effects of Severe Depression on Global Cognitive Function and Memory.

INTRODUCTION: Major depressive disorder (MDD) is thought to negatively impact cognitive function; however, the relationship has not been well explored. OBJECTIVE: This study examined the association between depression severity and global cognitive function and memory in subjects with severe, treatment-resistant MDD. METHODS: We enrolled 66 subjects with Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition diagnosed unipolar MDD in a multicenter trial to assess the efficacy and neurocognitive effects of electroconvulsive therapy (ECT). We measured depression severity with the 24 item Hamilton Rating Scale for Depression (HRSD(24)). Neuropsychologic measures included the Mini Mental State Examination (MMSE), Rey Auditory Verbal Learning Test (RAVLT), and the Complex Figure Test (CFT). Correlational and regression analyses were conducted to explore associations between depression severity and cognitive function. RESULTS: The mean age of the subjects was 53.6 years (SD=15.8), 65% were female, and mean HRSD(24) was 33.9 (SD=6.7). Mean demographic-corrected T-scores for each neurocognitive measure were in the average to borderline range, and HRSD(24) values were unrelated to performance on the MMSE, RAVLT immediate and delayed recall, and CFT immediate and delayed recall. CONCLUSION: In this sample of severely depressed subjects referred for ECT, depression severity was unrelated to global cognitive function or memory. Future research should examine the interactions between other depressive characteristics and neurocognitive function.

Altered neural cholinergic receptor systems in cocaine-addicted subjects.

Changes in the brain's cholinergic receptor systems underlie several neuropsychiatric disorders, including Alzheimer's disease, schizophrenia, and depression. An emerging preclinical literature also reveals that acetylcoholine may have an important function in addictive processes, including reward, learning, and memory. This study was designed to assess alterations in cholinergic receptor systems in limbic regions of abstinent cocaine-addicted subjects compared with healthy controls. On three separate days, 23 1- to 6-week abstinent, cocaine- (and mostly nicotine-) addicted subjects and 22 sex-, age-, and race-matched control subjects were administered the muscarinic and nicotinic cholinergic agonist physostigmine, the muscarinic antagonist scopolamine, and saline. Regional cerebral blood flow (rCBF) after each infusion was determined using single photon emission-computed tomography. Both cholinergic probes induced rCBF changes (p<0.005) in relatively distinct, cholinergic-rich, limbic brain regions. After physostigmine, cocaine-addicted subjects showed altered rCBF, relative to controls, in limbic regions, including the left hippocampus, left amygdala, and right insula. Group differences in the right dorsolateral prefrontal cortex, posterior cingulate, and middle temporal gyrus were also evident. Scopolamine also revealed group differences in the left hippocampus and right insula as well as the posterior cingulate and middle temporal gyrus. Cocaine addicted and controls differ in their subcortical, limbic, and cortical response to cholinergic probes in areas relevant to craving, learning, and memory. Cholinergic systems may offer a pharmacologic target for cocaine addiction treatment.

Bifrontal, bitemporal and right unilateral electrode placement in ECT: randomised trial.

BACKGROUND: Electroconvulsive therapy (ECT) is an effective treatment for major depression. Optimising efficacy and minimising cognitive impairment are goals of ongoing technical refinements. AIMS: To compare the efficacy and cognitive effects of a novel electrode placement, bifrontal, with two standard electrode placements, bitemporal and right unilateral in ECT. METHOD: This multicentre randomised, double-blind, controlled trial (NCT00069407) was carried out from 2001 to 2006. A total of 230 individuals with major depression, bipolar and unipolar, were randomly assigned to one of three electrode placements during a course of ECT: bifrontal at one and a half times seizure threshold, bitemporal at one and a half times seizure threshold and right unilateral at six times seizure threshold. RESULTS: All three electrode placements resulted in both clinically and statistically significant antidepressant outcomes. Remission rates were 55% (95% CI 43-66%) with right unilateral, 61% with bifrontal (95% CI 50-71%) and 64% (95% CI 53-75%) with bitemporal. Bitemporal resulted in a more rapid decline in symptom ratings over the early course of treatment. Cognitive data revealed few differences between the electrode placements on a variety of neuropsychological instruments. CONCLUSIONS: Each electrode placement is a very effective antidepressant treatment when given with appropriate electrical dosing. Bitemporal leads to more rapid symptom reduction and should be considered the preferred placement for urgent clinical situations. The cognitive profile of bifrontal is not substantially different from that of bitemporal.

Insight and frontal cortical function in schizophrenia: a review.

Insight into illness has been identified as a clinically important phenomenon, in no small part due to an association with treatment-adherence. An increasing number of studies, but not all, have observed poor insight to be a reflection of cognitive dysfunction in schizophrenia. A review of 34 published English-language studies found a significant number (i.e., 21) reporting a relationship between insight deficits and impaired performance on cognitive tasks primarily mediated by frontal cortex. A significant number of reviewed studies examined insight function in more than one psychiatric population, including bipolar and schizoaffective disorder. The most replicated findings from these studies were the correlations between insight deficits and impaired performance on the Wisconsin Card Sorting Test (WCST). More specifically, WCST perseverative errors correlated positively and the number of categories completed correlated negatively with poor insight, suggesting that impaired insight may be mediated by deficiencies in conceptual organization and flexibility in abstract thinking. Since the WCST requires the ability to demonstrate conceptual flexibility through the generation, maintenance and switching of mental sets along with the capacity to use verbal feedback to correct errors, it would appear that such 'executive' functions are most related to insight. In addition, recently identified structural correlates of poor insight in schizophrenia show some association with anosognosia in neurological patients. This review will discuss the implications of these findings and directions for future research.