Childhood and Adulthood Trauma Associate With Cognitive Aging Among Black and White Older Adults.

Sociocontextual factors powerfully shape risk for age-related cognitive impairment, including excess risk burdening medically underserved populations. Lifecourse adversity associates with cognitive aging, but harms are likely mitigable. Understanding population-salient relationships and sensitive periods for exposure is crucial for targeting clinical interventions. OBJECTIVE: The authors examined childhood and adulthood traumatic events in relation to cognition among Black and White older adults in the Health and Retirement Study (HRS). PARTICIPANTS: Participants (N = 13,952) aged 55+ had complete lifetime trauma and cognitive testing data at the 2006/08, 2010/12, and/or 2014/16 waves. MEASURES: Trauma indices comprised childhood and adulthood event counts. Outcomes included baseline performance and trajectories on the Telephone Interview for Cognitive Status. DESIGN: Main and nonlinear trauma effects were modeled via linear regression, and overall contributions assessed with omnibus likelihood ratio tests. RESULTS: Black participants (N = 2,345) reported marginally lower adulthood trauma exposure than White participants (N = 11,607) with no other exposure differentials observed. In White participants only, greater childhood trauma exposure predicted worse baseline cognition but slower change over time. Across race, adulthood trauma robustly associated with baseline cognition. Relationships were frequently nonlinear: low but nonzero trauma predicted highest cognitive scores, with much poorer cognition observed as trauma exposure increased. Relationships between adulthood trauma and trajectory were limited to the White sample. CONCLUSION: Traumatic experiences, particularly in adulthood, may impact late-life cognitive health if not addressed. Findings highlight foci for clinical researchers and providers: adverse life events as a source of cognitive risk, and identification of community-specific resources that buffer behavioral, physical, and mental health sequelae of previous and incident trauma.

Effects of mTBI with loss of consciousness on neurobehavioral symptoms, depression, and insomnia in former collegiate and NFL football athletes.

OBJECTIVE: Considering that diagnostic decisions about mTBI are often predicated on clinical symptom criteria, it is imperative to determine which initial presentation features of mTBI have prognostic significance for identifying those at high risk for long-term functional impairment. SETTING: Zoom interview Participants: Male, former NCAA Division I, and professional-level National Football League (NFL) athletes (n = 177) between the ages of 27 and 85 (M = 54.1, SD = 14.7). DESIGN: Cross-sectional case-control. Main Measures: History of mild TBI, history of loss of consciousness (LOC), depression symptoms, insomnia, neurobehavioral symptoms. RESULTS: Number of mTBI exposures did not predict neurobehavioral symptoms (B = 0.21, SE = 0.18, p = 0.23), but number of mTBI + LOC events did (B = 2.27, SE = 0.64, p = <.001). Further analysis revealed that the number of mTBI + LOC events predicted neurobehavioral symptoms indirectly through both depression (B = 0.85, 95% CI = [0.27, 1.52) and insomnia (B = 0.81, 95% CI = [0.3, 1.4]). Further, the direct effect of mTBI + LOC events on neurobehavioral symptoms became non-significant when depression and insomnia were added to the model (B = 0.78, SE = 0.45, p = 0.08). CONCLUSIONS: Findings support LOC at time of injury as an important predictor of long-term outcomes. Additionally, results suggest depression and insomnia as potential mediators in the association between mTBI + LOC and neurobehavioral symptoms. These findings provide justification for early depression and insomnia symptom monitoring following mTBI + LOC.

Flortaucipir tau PET findings from former professional and college American football players in the DIAGNOSE CTE research project.

INTRODUCTION: Tau is a key pathology in chronic traumatic encephalopathy (CTE). Here, we report our findings in tau positron emission tomography (PET) measurements from the DIAGNOSE CTE Research Project. METHOD: We compare flortaucipir PET measures from 104 former professional players (PRO), 58 former college football players (COL), and 56 same-age men without exposure to repetitive head impacts (RHI) or traumatic brain injury (unexposed [UE]); characterize their associations with RHI exposure; and compare players who did or did not meet diagnostic criteria for traumatic encephalopathy syndrome (TES). RESULTS: Significantly elevated flortaucipir uptake was observed in former football players (PRO+COL) in prespecified regions (p < 0.05). Association between regional flortaucipir uptake and estimated cumulative head impact exposure was only observed in the superior frontal region in former players over 60 years old. Flortaucipir PET was not able to differentiate TES groups. DISCUSSION: Additional studies are needed to further understand tau pathology in CTE and other individuals with a history of RHI.

Detecting rhythmic spiking through the power spectra of point process model residuals.

Objective: Oscillations figure prominently as neurological disease hallmarks and neuromodulation targets. To detect oscillations in a neuron's spiking, one might attempt to seek peaks in the spike train's power spectral density (PSD) which exceed a flat baseline. Yet for a non-oscillating neuron, the PSD is not flat: The recovery period ("RP", the post-spike drop in spike probability, starting with the refractory period) introduces global spectral distortion. An established "shuffling" procedure corrects for RP distortion by removing the spectral component explained by the inter-spike interval (ISI) distribution. However, this procedure sacrifices oscillation-related information present in the ISIs, and therefore in the PSD. We asked whether point process models (PPMs) might achieve more selective RP distortion removal, thereby enabling improved oscillation detection. Approach: In a novel "residuals" method, we first estimate the RP duration (nr) from the ISI distribution. We then fit the spike train with a PPM that predicts spike likelihood based on the time elapsed since the most recent of any spikes falling within the preceding nr milliseconds. Finally, we compute the PSD of the model's residuals. Main results: We compared the residuals and shuffling methods' ability to enable accurate oscillation detection with flat baseline-assuming tests. Over synthetic data, the residuals method generally outperformed the shuffling method in classification of true- versus false-positive oscillatory power, principally due to enhanced sensitivity in sparse spike trains. In single-unit data from the internal globus pallidus (GPi) and ventrolateral anterior thalamus (VLa) of a parkinsonian monkey -- in which alpha-beta oscillations (8-30 Hz) were anticipated -- the residuals method reported the greatest incidence of significant alpha-beta power, with low firing rates predicting residuals-selective oscillation detection. Significance: These results encourage continued development of the residuals approach, to support more accurate oscillation detection. Improved identification of oscillations could promote improved disease models and therapeutic technologies.

Detecting rhythmic spiking through the power spectra of point process model residuals.

Objective. Oscillations figure prominently as neurological disease hallmarks and neuromodulation targets. To detect oscillations in a neuron's spiking, one might attempt to seek peaks in the spike train's power spectral density (PSD) which exceed a flat baseline. Yet for a non-oscillating neuron, the PSD is not flat: The recovery period ('RP', the post-spike drop in spike probability, starting with the refractory period) introduces global spectral distortion. An established 'shuffling' procedure corrects for RP distortion by removing the spectral component explained by the inter-spike interval (ISI) distribution. However, this procedure sacrifices oscillation-related information present in the ISIs, and therefore in the PSD. We asked whether point process models (PPMs) might achieve more selective RP distortion removal, thereby enabling improved oscillation detection.Approach. In a novel 'residuals' method, we first estimate the RP duration (nr) from the ISI distribution. We then fit the spike train with a PPM that predicts spike likelihood based on the time elapsed since the most recent of any spikes falling within the precedingnrmilliseconds. Finally, we compute the PSD of the model's residuals.Main results. We compared the residuals and shuffling methods' ability to enable accurate oscillation detection with flat baseline-assuming tests. Over synthetic data, the residuals method generally outperformed the shuffling method in classification of true- versus false-positive oscillatory power, principally due to enhanced sensitivity in sparse spike trains. In single-unit data from the internal globus pallidus (GPi) and ventrolateral anterior thalamus (VLa) of a parkinsonian monkey-in which alpha-beta oscillations (8-30 Hz) were anticipated-the residuals method reported the greatest incidence of significant alpha-beta power, with low firing rates predicting residuals-selective oscillation detection.Significance. These results encourage continued development of the residuals approach, to support more accurate oscillation detection. Improved identification of oscillations could promote improved disease models and therapeutic technologies.

A neurocomputational view of the effects of Parkinson's disease on speech production.

The purpose of this article is to review the scientific literature concerning speech in Parkinson's disease (PD) with reference to the DIVA/GODIVA neurocomputational modeling framework. Within this theoretical view, the basal ganglia (BG) contribute to several different aspects of speech motor learning and execution. First, the BG are posited to play a role in the initiation and scaling of speech movements. Within the DIVA/GODIVA framework, initiation and scaling are carried out by initiation map nodes in the supplementary motor area acting in concert with the BG. Reduced support of the initiation map from the BG in PD would result in reduced movement intensity as well as susceptibility to early termination of movement. A second proposed role concerns the learning of common speech sequences, such as phoneme sequences comprising words; this view receives support from the animal literature as well as studies identifying speech sequence learning deficits in PD. Third, the BG may play a role in the temporary buffering and sequencing of longer speech utterances such as phrases during conversational speech. Although the literature does not support a critical role for the BG in representing sequence order (since incorrectly ordered speech is not characteristic of PD), the BG are posited to contribute to the scaling of individual movements in the sequence, including increasing movement intensity for emphatic stress on key words. Therapeutic interventions for PD have inconsistent effects on speech. In contrast to dopaminergic treatments, which typically either leave speech unchanged or lead to minor improvements, deep brain stimulation (DBS) can degrade speech in some cases and improve it in others. However, cases of degradation may be due to unintended stimulation of efferent motor projections to the speech articulators. Findings of spared speech after bilateral pallidotomy appear to indicate that any role played by the BG in adult speech must be supplementary rather than mandatory, with the sequential order of well-learned sequences apparently represented elsewhere (e.g., in cortico-cortical projections).

Evidentiary Significance of Routine EEG in Refractory Cases: A Paradigm Shift in Psychiatry.

Over the past decade, the Diagnostic and Statistical Manual's method of prescribing medications based on presenting symptoms has been challenged. The shift toward precision medicine began with the National Institute of Mental Health and culminated with the World Psychiatric Association's posit that a paradigm shift is needed. This study supports that shift by providing evidence explaining the high rate of psychiatric medication failure and suggests a possible first step toward precision medicine. A large psychiatric practice began collecting electroencephalograms (EEGs) for this study in 2012. The EEGs were analyzed by the same neurophysiologist (board certified in electroencephalography) on 1,233 patients. This study identified 4 EEG biomarkers accounting for medication failure in refractory patients: focal slowing, spindling excessive beta, encephalopathy, and isolated epileptiform discharges. Each EEG biomarker suggests underlying brain dysregulation, which may explain why prior medication attempts have failed. The EEG biomarkers cannot be identified based on current psychiatric assessment methods, and depending upon the localization, intensity, and duration, can all present as complex behavioral or psychiatric issues. The study highlights that the EEG biomarker identification approach can be a positive step toward personalized medicine in psychiatry, furthering the clinical thinking of "testing the organ we are trying to treat."

Safety of non-cuffed tunneled central venous catheters in adults with cystic fibrosis.

BACKGROUND: Peripherally inserted central catheters (PICCs) are the most common route of intravenous (I.V.) access for treatment of cystic fibrosis (CF) pulmonary exacerbations, but repeated PICC placement can result in upper extremity peripheral venous stenosis. Once peripheral stenosis develops, a non-cuffed tunneled central venous catheter (NcTCVC) is an alternative route for IV access. While these are regularly used at some CF centers, the safety and complication rate compared to PICCs in adults with CF has not been reported. This study aims to describe the safety of NcTCVCs in adults with CF. METHODS: A retrospective cohort study was performed at a CF Foundation accredited institution including adults with CF who received NcTCVCs in interventional radiology from 7/19/2007 to 3/09/2020. Complications analyzed included catheter related deep venous thrombosis (DVT), central line associated blood stream infection (CLABSI), and catheter related central venous stenosis. Complications were considered attributable if they occurred while the catheter was in place or within 30 days of catheter removal. RESULTS: During the study duration, 386 NcTCVCs were placed in 60 unique patients (55 % female) with a mean of 6.4 catheters per patient. Majority of NcTCVCs placed were 4 French (61.4 %). Average duration of indwelling NcTCVC was 16.2 days. No patients demonstrated catheter attributable symptomatic DVT. The incidence of DVT, CLABSI, and central venous stenosis was 0 (0 %), 4 (1 %), and 1 (0.3 %), respectively. CONCLUSIONS: Many adults with CF have required insertion of numerous PICCs for the treatment of recurrent pulmonary exacerbations. In those adults that develop PICC-associated peripheral vein stenosis precluding PICC placement, these results indicate NcTCVCs are a safe alternative.

Clinical Outcomes and Tau Pathology in Retired Football Players: Associations With Diagnosed and Witnessed Sleep Apnea.

Background and Objectives: Obstructive sleep apnea (SA) is common in older men and a contributor to negative cognitive, psychiatric, and brain health outcomes. Little is known about SA in those who played contact sports and are at increased risk of neurodegenerative disease(s) and other neuropathologies associated with repetitive head impacts (RHI). In this study, we investigated the frequency of diagnosed and witnessed SA and its contribution to clinical symptoms and tau pathology using PET imaging among male former college and former professional American football players. Methods: The sample included 120 former National Football League (NFL) players, 60 former college players, and 60 asymptomatic men without exposure to RHI (i.e., controls). Diagnosed SA was self-reported, and all participants completed the Mayo Sleep Questionnaire (MSQ, informant version), the Epworth Sleepiness Scale (ESS), neuropsychological testing, and tau (flortaucipir) PET imaging. Associations between sleep indices (diagnosed SA, MSQ items, and the ESS) and derived neuropsychological factor scores, self-reported depression (Beck Depression Inventory-II [BDI-II]), informant-reported neurobehavioral dysregulation (Behavior Rating Inventory of Executive Function-Adult Version [BRIEF-A] Behavioral Regulation Index [BRI]), and tau PET uptake, were tested. Results: Approximately 36.7% of NFL players had diagnosed SA compared with 30% of the former college football players and 16.7% of the controls. Former NFL players and college football players also had higher ESS scores compared with the controls. Years of football play was not associated with any of the sleep metrics. Among the former NFL players, diagnosed SA was associated with worse Executive Function and Psychomotor Speed factor scores, greater BDI-II scores, and higher flortaucipir PET standard uptake value ratios, independent of age, race, body mass index, and APOE ε4 gene carrier status. Higher ESS scores correlated with higher BDI-II and BRIEF-A BRI scores. Continuous positive airway pressure use mitigated all of the abovementioned associations. Among the former college football players, witnessed apnea and higher ESS scores were associated with higher BRIEF-A BRI and BDI-II scores, respectively. No other associations were observed in this subgroup. Discussion: Former elite American football players are at risk of SA. Our findings suggest that SA might contribute to cognitive, neuropsychiatric, and tau outcomes in this population. Like all neurodegenerative diseases, this study emphasizes the multifactorial contributions to negative brain health outcomes and the importance of sleep for optimal brain health.

Significado clinico del patron mixto de anticuerpos (antinucleares y anticitoplasmaticos) / Clinical significance of mixed anti-nuclear and anti-cytoplasmic antibody pattern

Aunque se ha investigado extensamente el significado clinico de los anticuerpos antinuecleares (ANA) y se han reconocido algunas correlaciones, no esta establecido el valor diagnostico del patron mixto de ANA y anticitoplasmaticos (ANA + ACA). Nosotros observamos dicho patron mixto en el suero de 43 pacientes de un total de 7.121 examinados (0.6%). La combinacion mas comun fue con el patron homogeneo de ANA. Las entidades asociadas al patron mixto son basicamente las mismas que se asocian con los diferentes ANA; el Lupus Eritematoso Sistemico (LES) es la mas frecuente. Concluimos que la informacion obtenida del hallazgo de un patron combinado ANA + ACA es la misma que se obtiene con los ANA positivos y que su presencia en pacientes con LES no caracteriza a ningun subgrupo de la enfermedad en particular

To date, the clinical significance of combined antinuclear (ANA) and anti-cytoplasmic (ACA) indirect immunofluorescent staining has not been comprehensively studied. ANA + ACA staining was observed in 43 (0.6%) out of 7.121 consecutive sera during ANA screening for immunologic disorders in a referral hospital; both inpatient and outpatient population were included. Homogeneous ANA + cytoplasmic was by far the most common staining pattern among 6 different fluorescent combinations detected. Disease distribution was similar in groups of patients with ANA + ACA and in those with only ANA +. We conclude that information provided by mixed antibody pattern is similar to the one obtained with the sole presence of ANA; also that the presence of the mixed pattern does not characterize any particular subgroup of LES patiens.

Metabolismo del acido araquidonico y actividad de fosfolipasa A2 en pacientes con artritis reumatoidea / Arachinodic acid metabolism and activity of phospholipase A2 in patients with rheumatoid arthritis

El metabolismo del acido araquinodico (AA) y la actividad de la fosfolipasa A2 (FLA2), fueron estudiados en neutrofilos segmentados (NS) pertenecientes a diez pacientes con artritis reumatoidea (AR), que recibian distintos antinflamatorios no esteroides (AINE), diez pacientes con AR sin tratamiento con AINE y diez voluntarios sanos. El porcentaje de AA que se metabolizo a leuctorieno B4 (LTB4) fue significativamente mayor en los pacientes sin tratamiento que en el grupo control; en los pacientes en tratamiento con AINE se observo una disminucion en LTB4, que no fue estadisticamente diferente del grupo de control. La actividad de la enfermedad, medida por parametros clinicos, mostro correlacion con la generacion del LTB4, y la actividad de la FLA2. Estos resultados preliminares sugieren que un aumento en la actividad de la FLA2, es al menos en parte, responsable del aumento en la generacion de LTB4 y que el tratamiento con AINE puede, eventualmente, modificar esta anormalidad