Digital speech hearing screening using a quick novel mobile hearing impairment assessment: an observational correlation study.

By 2050, 1 in 4 people worldwide will be living with hearing impairment. We propose a digital Speech Hearing Screener (dSHS) using short nonsense word recognition to measure speech-hearing ability. The importance of hearing screening is increasing due to the anticipated increase in individuals with hearing impairment globally. We compare dSHS outcomes with standardized pure-tone averages (PTA) and speech-recognition thresholds (SRT). Fifty participants (aged 55 or older underwent pure-tone and speech-recognition thresholding. One-way ANOVA was used to compare differences between hearing impaired and hearing not-impaired groups, by the dSHS, with a clinical threshold of moderately impaired hearing at 35 dB and severe hearing impairment at 50 dB. dSHS results significantly correlated with PTAs/SRTs. ANOVA results revealed the dSHS was significantly different (F(1,47) = 38.1, p < 0.001) between hearing impaired and unimpaired groups. Classification analysis using a 35 dB threshold, yielded accuracy of 85.7% for PTA-based impairment and 81.6% for SRT-based impairment. At a 50 dB threshold, dSHS classification accuracy was 79.6% for PTA-based impairment (Negative Predictive Value (NPV)-93%) and 83.7% (NPV-100%) for SRT-based impairment. The dSHS successfully differentiates between hearing-impaired and unimpaired individuals in under 3 min. This hearing screener offers a time-saving, in-clinic hearing screening to streamline the triage of those with likely hearing impairment to the appropriate follow-up assessment, thereby improving the quality of services. Future work will investigate the ability of the dSHS to help rule out hearing impairment as a cause or confounder in clinical and research applications.

Prediction of Post-Operative Delirium in Older Adults from Preoperative Cognition and Alpha Power from Resting-State EEG.

Postoperative Delirium (POD) is the most common complication following surgery among older adults, and has been consistently associated with increased mortality and morbidity, cognitive decline, and loss of independence, as well as markedly increased health-care costs. The development of new tools to identify individuals at high risk for POD could guide clinical decision-making and enable targeted interventions to potentially decrease delirium incidence and POD-related complications. In this study, we used machine learning techniques to evaluate whether baseline (pre-operative) cognitive function and resting-state electroencephalography could be used to identify patients at risk for POD. Pre-operative resting-state EEGs and the Montreal Cognitive Assessment (MoCA) were collected from 85 patients (age = 73 ± 6.4 years) undergoing elective surgery, 12 of whom subsequently developed POD. The model with the highest f1-score for predicting delirium, a linear-discriminant analysis (LDA) model incorporating MoCA scores and occipital alpha-band EEG features, was subsequently validated in an independent, prospective cohort of 51 older adults (age ≥ 60) undergoing elective surgery, 6 of whom developed POD. The LDA-based model, with a total of 7 features, was able to predict POD with area under the receiver operating characteristic curve, specificity and accuracy all >90%, and sensitivity > 80%, in the validation cohort. Notably, models incorporating both resting-state EEG and MoCA scores outperformed those including either EEG or MoCA alone. While requiring prospective validation in larger cohorts, these results suggest that prediction of POD with high accuracy may be feasible in clinical settings using simple and widely available clinical tools.

Non-invasive prehabilitation to foster widespread fMRI cortical reorganization before brain tumor surgery: lessons from a case series.

PURPOSE: The objective of this prospective, single-centre case series was to investigate feasibility, clinical outcomes, and neural correlates of non-invasive Neuromodulation-Induced Cortical Prehabilitation (NICP) before brain tumor surgery. Previous studies have shown that gross total resection is paramount to increase life expectancy but is counterbalanced by the need of preserving critical functional areas. NICP aims at expanding functional margins for extensive tumor resection without functional sequelae. Invasive NICP (intracranial neuromodulation) was effective but characterized by elevated costs and high rate of adverse events. Non-invasive NICP (transcranial neuromodulation) may represent a more feasible alternative. Nonetheless, up to this point, non-invasive NICP has been examined in only two case reports, yielding inconclusive findings. METHODS: Treatment sessions consisted of non-invasive neuromodulation, to transiently deactivate critical areas adjacent to the lesion, coupled with intensive functional training, to activate alternative nodes within the same functional network. Patients were evaluated pre-NICP, post-NICP, and at follow-up post-surgery. RESULTS: Ten patients performed the intervention. Feasibility criteria were met (retention, adherence, safety, and patient's satisfaction). Clinical outcomes showed overall stability and improvements in motor and executive function from pre- to post-NICP, and at follow-up. Relevant plasticity changes (increase in the distance between tumor and critical area) were observed when the neuromodulation target was guided by functional neuroimaging data. CONCLUSION: This is the first case series demonstrating feasibility of non-invasive NICP. Neural correlates indicate that neuroimaging-guided target selection may represent a valid strategy to leverage neuroplastic changes before neurosurgery. Further investigations are needed to confirm such preliminary findings.

Exploring the neural basis of non-invasive prehabilitation in brain tumour patients: An fMRI-based case report of language network plasticity.

Primary brain neoplasms are associated with elevated mortality and morbidity rates. Brain tumour surgery aims to achieve maximal tumour resection while minimizing damage to healthy brain tissue. Research on Neuromodulation Induced Cortical Prehabilitation (NICP) has highlighted the potential, before neurosurgery, of establishing new brain connections and transfer functional activity from one area of the brain to another. Nonetheless, the neural mechanisms underlying these processes, particularly in the context of space-occupying lesions, remain unclear. A patient with a left frontotemporoinsular tumour underwent a prehabilitation protocol providing 20 sessions of inhibitory non-invasive neuromodulation (rTMS and multichannel tDCS) over a language network coupled with intensive task training. Prehabilitation resulted in an increment of the distance between the tumour and the language network. Furthermore, enhanced functional connectivity within the language circuit was observed. The present innovative case-study exposed that inhibition of the functional network area surrounding the space-occupying lesion promotes a plastic change in the network's spatial organization, presumably through the establishment of novel functional pathways away from the lesion's site. While these outcomes are promising, prudence dictates the need for larger studies to confirm and generalize these findings.

Lifestyle trajectories in middle-aged adults and their relationship with health indicators.

Introduction: Understanding the impact of different lifestyle trajectories on health preservation and disease risk is crucial for effective interventions. Methods: This study analyzed lifestyle engagement over five years in 3,013 healthy adults aged 40-70 from the Barcelona Brain Health Initiative using K-means clustering. Nine modifiable risk factors were considered, including cognitive, physical, and social activity, vital plan, diet, obesity, smoking, alcohol consumption, and sleep. Self-reported diagnoses of new diseases at different time-points after baseline allowed to explore the association between these five profiles and health outcomes. Results: The data-driven analysis classified subjects into five lifestyle profiles, revealing associations with health behaviors and risk factors. Those exhibiting high scores in health-promoting behaviors and low-risk behaviors, demonstrate a reduced likelihood of developing diseases (p < 0.001). In contrast, profiles with risky habits showed distinct risks for psychiatric, neurological, and cardiovascular diseases. Participant's lifestyle trajectories remained relatively stable over time. Discussion: Our findings have identified risk for distinct diseases associated to specific lifestyle patterns. These results could help in the personalization of interventions based on data-driven observation of behavioral patterns and policies that promote a healthy lifestyle and can lead to better health outcomes for people in an aging society.

Successful aging after elective surgery II: Study cohort description.

BACKGROUND: The Successful Aging after Elective Surgery (SAGES) II Study was designed to examine the relationship between delirium and Alzheimer's disease and related dementias (AD/ADRD), by capturing novel fluid biomarkers, neuroimaging markers, and neurophysiological measurements. The goal of this paper is to provide the first complete description of the enrolled cohort, which details the baseline characteristics and data completion. We also describe the study modifications necessitated by the COVID-19 pandemic, and lay the foundation for future work using this cohort. METHODS: SAGES II is a prospective observational cohort study of community-dwelling adults age 65 and older undergoing major non-cardiac surgery. Participants were assessed preoperatively, throughout hospitalization, and at 1, 2, 6, 12, and 18 months following discharge to assess cognitive and physical functioning. Since participants were enrolled throughout the COVID-19 pandemic, procedural modifications were designed to reduce missing data and allow for high data quality. RESULTS: About 420 participants were enrolled with a mean (standard deviation) age of 73.4 (5.6) years, including 14% minority participants. Eighty-eight percent of participants had either total knee or hip replacements; the most common surgery was total knee replacement with 210 participants (50%). Despite the challenges posed by the COVID-19 pandemic, which required the use of novel procedures such as video assessments, there were minimal missing interviews during hospitalization and up to 1-month follow-up; nearly 90% of enrolled participants completed interviews through 6-month follow-up. CONCLUSION: While there are many longitudinal studies of older adults, this study is unique in measuring health outcomes following surgery, along with risk factors for delirium through the application of novel biomarkers-including fluid (plasma and cerebrospinal fluid), imaging, and electrophysiological markers. This paper is the first to describe the characteristics of this unique cohort and the data collected, enabling future work using this novel and important resource.

Neuromodulation-induced prehabilitation to leverage neuroplasticity before brain tumor surgery: a single-cohort feasibility trial protocol.

Introduction: Neurosurgery for brain tumors needs to find a complex balance between the effective removal of targeted tissue and the preservation of surrounding brain areas. Neuromodulation-induced cortical prehabilitation (NICP) is a promising strategy that combines temporary inhibition of critical areas (virtual lesion) with intensive behavioral training to foster the activation of alternative brain resources. By progressively reducing the functional relevance of targeted areas, the goal is to facilitate resection with reduced risks of neurological sequelae. However, it is still unclear which modality (invasive vs. non-invasive neuromodulation) and volume of therapy (behavioral training) may be optimal in terms of feasibility and efficacy. Methods and analysis: Patients undertake between 10 and 20 daily sessions consisting of neuromodulation coupled with intensive task training, individualized based on the target site and neurological functions at risk of being compromised. The primary outcome of the proposed pilot, single-cohort trial is to investigate the feasibility and potential effectiveness of a non-invasive NICP protocol on neuroplasticity and post-surgical outcomes. Secondary outcomes investigating longitudinal changes (neuroimaging, neurophysiology, and clinical) are measured pre-NICP, post-NICP, and post-surgery. Ethics and dissemination: Ethics approval was obtained from the Research Ethical Committee of Fundació Unió Catalana d'Hospitals (approval number: CEI 21/65, version 1, 13/07/2021). The results of the study will be submitted to a peer-reviewed journal and presented at scientific congresses. Clinical trial registration: ClinicalTrials.gov, identifier NCT05844605.

Successful aging after elective surgery II: Study design and methods.

BACKGROUND: The Successful Aging after Elective Surgery (SAGES) II study was designed to increase knowledge of the pathophysiology and linkages between delirium and dementia. We examine novel biomarkers potentially associated with delirium, including inflammation, Alzheimer's disease (AD) pathology and neurodegeneration, neuroimaging markers, and neurophysiologic markers. The goal of this paper is to describe the study design and methods for the SAGES II study. METHODS: The SAGES II study is a 5-year prospective observational study of 400-420 community dwelling persons, aged 65 years and older, assessed prior to scheduled surgery and followed daily throughout hospitalization to observe for development of delirium and other clinical outcomes. Delirium is measured with the Confusion Assessment Method (CAM), long form, after cognitive testing. Cognitive function is measured with a detailed neuropsychologic test battery, summarized as a weighted composite, the General Cognitive Performance (GCP) score. Other key measures include magnetic resonance imaging (MRI), transcranial magnetic stimulation (TMS)/electroencephalography (EEG), and Amyloid positron emission tomography (PET) imaging. We describe the eligibility criteria, enrollment flow, timing of assessments, and variables collected at baseline and during repeated assessments at 1, 2, 6, 12, and 18 months. RESULTS: This study describes the hospital and surgery-related variables, delirium, long-term cognitive decline, clinical outcomes, and novel biomarkers. In inter-rater reliability assessments, the CAM ratings (weighted kappa = 0.91, 95% confidence interval, CI = 0.74-1.0) in 50 paired assessments and GCP ratings (weighted kappa = 0.99, 95% CI 0.94-1.0) in 25 paired assessments. We describe procedures for data quality assurance and Covid-19 adaptations. CONCLUSIONS: This complex study presents an innovative effort to advance our understanding of the inter-relationship between delirium and dementia via novel biomarkers, collected in the context of major surgery in older adults. Strengths include the integration of MRI, TMS/EEG, PET modalities, and high-quality longitudinal data.

Neurophysiologic predictors of individual risk for post-operative delirium after elective surgery.

BACKGROUND: Post-surgical delirium is associated with increased morbidity, lasting cognitive decline, and loss of functional independence. Within a conceptual framework that delirium is triggered by stressors when vulnerabilities exist in cerebral connectivity and plasticity, we previously suggested that neurophysiologic measures might identify individuals at risk for post-surgical delirium. Here we demonstrate the feasibility of the approach and provide preliminary experimental evidence of the predictive value of such neurophysiologic measures for the risk of delirium in older persons undergoing elective surgery. METHODS: Electroencephalography (EEG) and transcranial magnetic stimulation (TMS) were collected from 23 patients prior to elective surgery. Resting-state EEG spectral power ratio (SPR) served as a measure of integrity of neural circuits. TMS-EEG metrics of plasticity (TMS-plasticity) were used as indicators of brain capacity to respond to stressors. Presence or absence of delirium was assessed using the confusion assessment method (CAM). We included individuals with no baseline clinically relevant cognitive impairment (MoCA scores ≥21) in order to focus on subclinical neurophysiological measures. RESULTS: In patients with no baseline cognitive impairment (N = 20, age = 72 ± 6), 3 developed post-surgical delirium (MoCA = 24 ± 2.6) and 17 did not (controls; MoCA = 25 ± 2.4). Patients who developed delirium had pre-surgical resting-state EEG power ratios outside the 95% confidence interval of controls, and 2/3 had TMS-plasticity measures outside the 95% CI of controls. CONCLUSIONS: Consistent with our proposed conceptual framework, this pilot study suggests that non-invasive and scalable neurophysiologic measures can identify individuals at risk of post-operative delirium. Specifically, abnormalities in resting-state EEG spectral power or TMS-plasticity may indicate sub-clinical risk for post-surgery delirium. Extension and confirmation of these findings in a larger sample is needed to assess the clinical utility of the proposed neurophysiologic markers, and to identify specific connectivity and plasticity targets for therapeutic interventions that might minimize the risk of delirium.

Exploring the interplay between mechanisms of neuroplasticity and cardiovascular health in aging adults: A multiple linear regression analysis study.

BACKGROUND: Neuroplasticity and cardiovascular health behavior are critically important factors for optimal brain health. OBJECTIVE: To assess the association between the efficacy of the mechanisms of neuroplasticity and metrics of cardiovascular heath in sedentary aging adults. METHODS: We included thirty sedentary individuals (age = 60.6 ± 3.8 y; 63 % female). All underwent assessments of neuroplasticity, measured by the change in amplitude of motor evoked potentials elicited by single-pulse Transcranial Magnetic Stimulation (TMS) at baseline and following intermittent Theta-Burst (iTBS) at regular intervals. Cardiovascular health measures were derived from the Incremental Shuttle Walking Test and included Heart Rate Recovery (HRR) at 1-min/2-min after test cessation. We also collected plasma levels of brain-derived neurotrophic factor (BDNF), vascular endothelial growth factor (VEGF), and c-reactive protein. RESULTS: We revealed moderate but significant relationships between TMS-iTBS neuroplasticity, and the predictors of cardiovascular health (|r| = 0.38 to 0.53, p < .05). HRR1 was the best predictor of neuroplasticity (ß = 0.019, p = .002). The best fit model (Likelihood ratio = 5.83, p = .016) of the association between neuroplasticity and HRR1 (ß = 0.043, p = .002) was selected when controlling for demographics and health status. VEGF and BDNF plasma levels augmented the association between neuroplasticity and HRR1. CONCLUSIONS: Our findings build on existing data demonstrating that TMS may provide insight into neuroplasticity and the role cardiovascular health have on its mechanisms. These implications serve as theoretical framework for future longitudinal and interventional studies aiming to improve cardiovascular and brain health. HRR1 is a potential prognostic measure of cardiovascular health and a surrogate marker of brain health in aging adults.

In Older Adults the Antidepressant Effect of Repetitive Transcranial Magnetic Stimulation Is Similar but Occurs Later Than in Younger Adults.

Background: Treatment resistant depression is common in older adults and treatment is often complicated by medical comorbidities and polypharmacy. Repetitive transcranial magnetic stimulation (rTMS) is a treatment option for this group due to its favorable profile. However, early influential studies suggested that rTMS is less effective in older adults. This evidence remains controversial. Methods: Here, we evaluated the rTMS treatment outcomes in a large international multicenter naturalistic cohort of >500 patients comparing older vs. younger adults. Results: We show that older adults, while having similar antidepressant response to younger adults, respond more slowly, which may help to explain differences from earlier studies when the duration of a treatment course was shorter. Conclusions: Such evidence helps to resolve a long-standing controversy in treating older depressed patients with rTMS. Moreover, these findings provide an important data point in the call to revise policy decisions from major insurance providers that have unfairly excluded older adults.

Structural integrity of the anterior mid-cingulate cortex contributes to resilience to delirium in SuperAging.

Despite its devastating clinical and societal impact, approaches to treat delirium in older adults remain elusive, making it important to identify factors that may confer resilience to this syndrome. Here, we investigated a cohort of 93 cognitively normal older patients undergoing elective surgery recruited as part of the Successful Aging after Elective Surgery study. Each participant was classified either as a SuperAger (n = 19) or typically aging older adult (n = 74) based on neuropsychological criteria, where the former was defined as those older adults whose memory function rivals that of young adults. We compared these subgroups to examine the role of preoperative memory function in the incidence and severity of postoperative delirium. We additionally investigated the association between indices of postoperative delirium symptoms and cortical thickness in functional networks implicated in SuperAging based on structural magnetic resonance imaging data that were collected preoperatively. We found that SuperAging confers the real-world benefit of resilience to delirium, as shown by lower (i.e. zero) incidence of postoperative delirium and decreased severity scores compared with typical older adults. Furthermore, greater baseline cortical thickness of the anterior mid-cingulate cortex-a key node of the brain's salience network that is also consistently implicated in SuperAging-predicted lower postoperative delirium severity scores in all patients. Taken together, these findings suggest that baseline memory function in older adults may be a useful predictor of postoperative delirium risk and severity and that superior memory function may contribute to resilience to delirium. In particular, the integrity of the anterior mid-cingulate cortex may be a potential biomarker of resilience to delirium, pointing to this region as a potential target for preventive or therapeutic interventions designed to mitigate the risk or consequences of developing this prevalent clinical syndrome.

Assessment of potential selection bias in neuroimaging studies of postoperative delirium and cognitive decline: lessons from the SAGES study.

Due to cost and participant burden, neuroimaging studies are often performed in relatively small samples of voluntary participants. This may lead to selection bias. It is important to identify factors associated with participation in neuroimaging studies and understand their effect on outcome measures. We investigated the effect of postoperative delirium on long-term (over 48 months) cognitive decline (LTCD) in 560 older surgical patients (≥ 70 years), including a nested MRI cohort (n = 146). We observed a discrepancy in the effect of delirium on cognitive decline as a function of MRI participation. Although overall difference in cognitive decline due to delirium was not greater than what might be expected due to chance (p = .21), in the non-MRI group delirium was associated with a faster pace of LTCD (-0.063, 95% CI -0.094 to -0.032, p < .001); while in the MRI group the effect of delirium was less and not significant (-0.023, 95% CI -0.076, 0.030, p = .39). Since this limits our ability to investigate the neural correlates of delirium and cognitive decline using MRI data, we attempted to mitigate the observed discrepancy using inverse probability weighting for MRI participation. The approach was not successful and the difference of the effect of delirium in slope was essentially unchanged. There was no evidence that the MRI sub-group experienced delirium that differed in severity relative to MRI non-participants. We could not attribute the observed discrepancy to selection bias based on measured factors. It may reflect a power issue due to the smaller MRI subsample or selection bias from unmeasured factors.

Individual and cumulative health afflictions are associated with greater impairment in physical and mental function in former professional American style football players.

BACKGROUND: Former American style football players (ASF players) have recognized health concerns associated with prior sport participation. It remains unknown whether categorizations of current health conditions, referred to in this report as afflictions (conceptually framed as neurocognitive, cardiovascular, cardiometabolic, sleep apnea, and chronic pain) are associated with physical and mental function. OBJECTIVE: To evaluate the association of afflictions to physical and mental function. It was hypothesized that former National Football League players with any affliction would have worse function compared to unafflicted participants. It was anticipated that multiple afflictions would result in cumulative loss of function. DESIGN: Cross-sectional retrospective design. SETTING: Academic medical multisite hospital system. PARTICIPANTS: A total of 3913 of 15,611 former ASF players who played professionally from 1960 to 2019 (response rate 25%). Assessment of Risk Factors Self-report survey. MAIN OUTCOME MEASURES: Each participant completed the Patient Reported Outcomes Measurement Information System (PROMIS) Global Health Scale and Physical Function questionnaires. Responses were used to generate two physical function and one mental function subscale scores. Raw scores were converted to T-scores categorized as impaired (T-score < 40) or unimpaired (T-score ≥ 40). Primary analyses measured the association of affliction to function (impaired or unimpaired). RESULTS: After adjusting for confounders (age, race, position, number of seasons, age of first exposure to football, alcohol use, smoking history, and current body mass index), each affliction was associated with reduced physical function on the Global physical function subscale (risk ratio [RR] = 1.23-2.45, all P < .005), physical function scale (RR = 1.24-2.75, all P < .01), and mental function scale (RR = 1.34-2.87, all P < .001), except that cardiovascular affliction was not associated with mental function (RR = 1.15, P = .15). The lowest functional measures were observed in those afflicted by chronic pain. Cumulative afflictions were associated with worse function. CONCLUSIONS: Afflictions are associated with cumulative reduction of function. Research evaluating how afflictions interact may help elucidate mechanisms for illness and develop interventions to optimize function.

Transcranial magnetic stimulation (TMS) for geriatric depression.

BACKGROUND: The prevalence of treatment-resistant geriatric depression (GD) highlights the need for treatments that preserve cognitive functions and recognize polypharmacy in elderly, yet effectively reduce symptom burden. Transcranial magnetic stimulation (TMS) is a proven intervention for treatment-resistant depression in younger adults but the efficacy of TMS to treat depressed older adults is still unclear. This review provides an updated view on the efficacy of TMS treatment for GD, discusses methodological differences between trials in TMS application, and explores avenues for optimization of TMS treatment in the context of the ageing brain. METHODS: A systematic review was conducted to identify published literature on the antidepressant efficacy of TMS for GD. Databases PubMed, Embase, and PsycINFO were searched for English language articles in peer-reviewed journals in March 2021. RESULTS: Seven randomized controlled trials (RCTs) (total n = 260, active n = 148, control n = 112) and seven uncontrolled trials (total n = 160) were included. Overall, we found substantial variability in the clinical response, ranging from 6.7% to 54.3%. CONCLUSIONS: The reviewed literature highlights large heterogeneity among studies both in terms of the employed TMS dosage and the observed clinical efficacy. This highlights the need for optimizing TMS dosage by recognizing the unique clinical features of GD. We showcase a set of novel approaches for the optimization of the TMS protocol for depression and discuss the possibility for a standardized TMS protocol tailored for the treatment of GD.

Personalised, image-guided, noninvasive brain stimulation in gliomas: Rationale, challenges and opportunities.

Malignant brain tumours are among the most aggressive human cancers, and despite intensive efforts made over the last decades, patients' survival has scarcely improved. Recently, high-grade gliomas (HGG) have been found to be electrically integrated with healthy brain tissue, a communication that facilitates tumour mitosis and invasion. This link to neuronal activity has provided new insights into HGG pathophysiology and opened prospects for therapeutic interventions based on electrical modulation of neural and synaptic activity in the proximity of tumour cells, which could potentially slow tumour growth. Noninvasive brain stimulation (NiBS), a group of techniques used in research and clinical settings to safely modulate brain activity and plasticity via electromagnetic or electrical stimulation, represents an appealing class of interventions to characterise and target the electrical properties of tumour-neuron interactions. Beyond neuronal activity, NiBS may also modulate function of a range of substrates and dynamics that locally interacts with HGG (e.g., vascular architecture, perfusion and blood-brain barrier permeability). Here we discuss emerging applications of NiBS in patients with brain tumours, covering potential mechanisms of action at both cellular, regional, network and whole-brain levels, also offering a conceptual roadmap for future research to prolong survival or promote wellbeing via personalised NiBS interventions.

Association of Plasma Neurofilament Light with Postoperative Delirium.

OBJECTIVE: To examine the association of the plasma neuroaxonal injury markers neurofilament light (NfL), total tau, glial fibrillary acid protein, and ubiquitin carboxyl-terminal hydrolase L1 with delirium, delirium severity, and cognitive performance. METHODS: Delirium case-no delirium control (n = 108) pairs were matched by age, sex, surgery type, cognition, and vascular comorbidities. Biomarkers were measured in plasma collected preoperatively (PREOP), and 2 days (POD2) and 30 days postoperatively (PO1MO) using Simoa technology (Quanterix, Lexington, MA). The Confusion Assessment Method (CAM) and CAM-S (Severity) were used to measure delirium and delirium severity, respectively. Cognitive function was measured with General Cognitive Performance (GCP) scores. RESULTS: Delirium cases had higher NfL on POD2 and PO1MO (median matched pair difference = 16.2pg/ml and 13.6pg/ml, respectively; p < 0.05). Patients with PREOP and POD2 NfL in the highest quartile (Q4) had increased risk for incident delirium (adjusted odds ratio [OR] = 3.7 [95% confidence interval (CI) = 1.1-12.6] and 4.6 [95% CI = 1.2-18.2], respectively) and experienced more severe delirium, with sum CAM-S scores 7.8 points (95% CI = 1.6-14.0) and 9.3 points higher (95% CI = 3.2-15.5). At PO1MO, delirium cases had continued high NfL (adjusted OR = 9.7, 95% CI = 2.3-41.4), and those with Q4 NfL values showed a -2.3 point decline in GCP score (-2.3 points, 95% CI = -4.7 to -0.9). INTERPRETATION: Patients with the highest PREOP or POD2 NfL levels were more likely to develop delirium. Elevated NfL at PO1MO was associated with delirium and greater cognitive decline. These findings suggest NfL may be useful as a predictive biomarker for delirium risk and long-term cognitive decline, and once confirmed would provide pathophysiological evidence for neuroaxonal injury following delirium. ANN NEUROL 2020;88:984-994.

Self-Reported Head Trauma Predicts Poor Dual Task Gait in Retired National Football League Players.

OBJECTIVE: Symptomatic head trauma associated with American-style football (ASF) has been linked to brain pathology, along with physical and mental distress in later life. However, the longer-term effects of such trauma on objective metrics of cognitive-motor function remain poorly understood. We hypothesized that ASF-related symptomatic head trauma would predict worse gait performance, particularly during dual task conditions (ie, walking while performing an additional cognitive task), in later life. METHODS: Sixty-six retired professional ASF players aged 29 to 75 years completed a health and wellness questionnaire. They also completed a validated smartphone-based assessment in their own homes, during which gait was monitored while they walked normally and while they performed a verbalized serial-subtraction cognitive task. RESULTS: Participants who reported more symptomatic head trauma, defined as the total number of impacts to the head or neck followed by concussion-related symptoms, exhibited greater dual task cost (ie, percentage increase) to stride time variability (ie, the coefficient of variation of mean stride time). Those who reported ≥1 hit followed by loss of consciousness, compared to those who did not, also exhibited greater dual task costs to this metric. Relationships between reported trauma and dual task costs were independent of age, body mass index, National Football League career duration, and history of musculoskeletal surgery. Symptomatic head trauma was not correlated with average stride times in either walking condition. INTERPRETATION: Remote, smartphone-based assessments of dual task walking may be utilized to capture meaningful data sensitive to the long-term impact of symptomatic head trauma in former professional ASF players and other contact sport athletes. ANN NEUROL 2020;87:75-83.

Technologies for Monitoring Lifestyle Habits Related to Brain Health: A Systematic Review.

Brain health refers to the preservation of brain integrity and function optimized for an individual's biological age. Several studies have demonstrated that our lifestyles habits impact our brain health and our cognitive and mental wellbeing. Monitoring such lifestyles is thus critical and mobile technologies are essential to enable such a goal. Three databases were selected to carry out the search. Then, a PRISMA and PICOTS based criteria for a more detailed review on the basis of monitoring lifestyle aspects were used to filter the publications. We identified 133 publications after removing duplicates. Fifteen were finally selected from our criteria. Many studies still use questionnaires as the only tool for monitoring and do not apply advanced analytic or AI approaches to fine-tune results. We anticipate a transformative boom in the near future developing and implementing solutions that are able to integrate, in a flexible and adaptable way, data from technologies and devices that users might already use. This will enable continuous monitoring of objective data to guide the personalized definition of lifestyle goals and data-driven coaching to offer the necessary support to ensure adherence and satisfaction.

Diabetes and the link between neuroplasticity and glutamate in the aging human motor cortex.

OBJECTIVES: In older adults, type-2 diabetes mellitus (T2DM) impacts cognition and increases dementia risk. Prior studies suggest that impaired neuroplasticity may contribute to the cognitive decline in T2DM, but the underlying mechanisms of altered neuroplasticity are unclear. We investigated the relationship of the concentration of glutamatergic metabolites with measures of cortical plasticity in older adults across the spectrum of glucose intolerance/insulin resistance. METHODS: Forty adults (50-87 years: 17-T2DM, 14-pre-diabetes, 9-controls) underwent magnetic resonance spectroscopy to quantify glutamate and other key metabolites within a 2 cm3 region around the hand knob of the left primary motor cortex. Thirty-six also underwent a separate transcranial magnetic stimulation (TMS) assessment of cortical excitability and plasticity using single-pulse TMS and intermittent theta-burst stimulation targeting the same brain region. RESULTS: Group differences were observed in relative concentrations of glutamine (p = .028), glucose (p = .008), total cholines (p = .048), and the glutamine/glutamate ratio (p = .024). Cortical plasticity was reduced in both T2DM and pre-diabetes groups relative to controls (p-values < .05). Only the T2DM group showed a significant positive association between glutamate concentration and plasticity (r = .56, p = .030). CONCLUSIONS: Neuroplastic mechanisms are already impaired in pre-diabetes. In T2DM, reduced cortico-motor plasticity is associated with lower cortical glutamate concentration. SIGNIFICANCE: Impaired plasticity in T2DM is associated with low glutamatergic metabolite levels. The glutamatergic neurotransmission system constitutes a potential therapeutic target for cognitive problems linked to plasticity-related deficiencies in T2DM.