The predictive validity of a Brain Care Score for late-life depression and a composite outcome of dementia, stroke, and late-life depression: data from the UK Biobank cohort.

Introduction: The 21-point Brain Care Score (BCS) is a novel tool designed to motivate individuals and care providers to take action to reduce the risk of stroke and dementia by encouraging lifestyle changes. Given that late-life depression is increasingly recognized to share risk factors with stroke and dementia, and is an important clinical endpoint for brain health, we tested the hypothesis that a higher BCS is associated with a reduced incidence of future depression. Additionally, we examined its association with a brain health composite outcome comprising stroke, dementia, and late-life depression. Methods: The BCS was derived from the United Kingdom Biobank baseline evaluation in participants with complete data on BCS items. Associations of BCS with the risk of subsequent incident late-life depression and the composite brain health outcome were estimated using multivariable Cox proportional hazard models. These models were adjusted for age at baseline and sex assigned at birth. Results: A total of 363,323 participants were included in this analysis, with a median BCS at baseline of 12 (IQR: 11-14). There were 6,628 incident cases of late-life depression during a median follow-up period of 13 years. Each five-point increase in baseline BCS was associated with a 33% lower risk of incident late-life depression (95% CI: 29%-36%) and a 27% lower risk of the incident composite outcome (95% CI: 24%-30%). Discussion: These data further demonstrate the shared risk factors across depression, dementia, and stroke. The findings suggest that a higher BCS, indicative of healthier lifestyle choices, is significantly associated with a lower incidence of late-life depression and a composite brain health outcome. Additional validation of the BCS is warranted to assess the weighting of its components, its motivational aspects, and its acceptability and adaptability in routine clinical care worldwide.

Brain Care Score and Neuroimaging Markers of Brain Health in Asymptomatic Middle-Age Persons.

OBJECTIVES: To investigate associations between health-related behaviors as measured using the Brain Care Score (BCS) and neuroimaging markers of white matter injury. METHODS: This prospective cohort study in the UK Biobank assessed the BCS, a novel tool designed to empower patients to address 12 dementia and stroke risk factors. The BCS ranges from 0 to 21, with higher scores suggesting better brain care. Outcomes included white matter hyperintensities (WMH) volume, fractional anisotropy (FA), and mean diffusivity (MD) obtained during 2 imaging assessments, as well as their progression between assessments, using multivariable linear regression adjusted for age and sex. RESULTS: We included 34,509 participants (average age 55 years, 53% female) with no stroke or dementia history. At first and repeat imaging assessments, every 5-point increase in baseline BCS was linked to significantly lower WMH volumes (25% 95% CI [23%-27%] first, 33% [27%-39%] repeat) and higher FA (18% [16%-20%] first, 22% [15%-28%] repeat), with a decrease in MD (9% [7%-11%] first, 10% [4%-16%] repeat). In addition, a higher baseline BCS was associated with a 10% [3%-17%] reduction in WMH progression and FA decline over time. DISCUSSION: This study extends the impact of the BCS to neuroimaging markers of clinically silent cerebrovascular disease. Our results suggest that improving one's BCS could be a valuable intervention to prevent early brain health decline.

Effects of Aerobic Exercise on Brain Age and Health in Middle-Aged and Older Adults: A Single-Arm Pilot Clinical Trial.

BACKGROUNDS: Sleep disturbances are prevalent among elderly individuals. While polysomnography (PSG) serves as the gold standard for sleep monitoring, its extensive setup and data analysis procedures impose significant costs and time constraints, thereby restricting the long-term application within the general public. Our laboratory introduced an innovative biomarker, utilizing artificial intelligence algorithms applied to PSG data to estimate brain age (BA), a metric validated in cohorts with cognitive impairments. Nevertheless, the potential of exercise, which has been a recognized means of enhancing sleep quality in middle-aged and older adults to reduce BA, remains undetermined. METHODS: We conducted an exploratory study to evaluate whether 12 weeks of moderate-intensity exercise can improve cognitive function, sleep quality, and the brain age index (BAI), a biomarker computed from overnight sleep electroencephalogram (EEG), in physically inactive middle-aged and older adults. Home wearable devices were used to monitor heart rate and overnight sleep EEG over this period. The NIH Toolbox Cognition Battery, in-lab overnight polysomnography, cardiopulmonary exercise testing, and a multiplex cytokines assay were employed to compare pre- and post-exercise brain health, exercise capacity, and plasma proteins. RESULTS: In total, 26 participants completed the initial assessment and exercise program, and 24 completed all procedures. Data are presented as mean [lower 95% CI of mean, upper 95% CI of mean]. Participants significantly increased maximal oxygen consumption (Pre: 21.11 [18.98, 23.23], Post 22.39 [20.09, 24.68], mL/kg/min; effect size: -0.33) and decreased resting heart rate (Pre: 66.66 [63.62, 67.38], Post: 65.13 [64.25, 66.93], bpm; effect size: -0.02) and sleeping heart rate (Pre: 64.55 [61.87, 667.23], Post: 62.93 [60.78, 65.09], bpm; effect size: -0.15). Total cognitive performance (Pre: 111.1 [107.6, 114.6], Post: 115.2 [111.9, 118.5]; effect size: 0.49) was significantly improved. No significant differences were seen in BAI or measures of sleep macro- and micro-architecture. Plasma IL-4 (Pre: 0.24 [0.18, 0.3], Post: 0.33 [0.24, 0.42], pg/mL; effect size: 0.49) was elevated, while IL-8 (Pre: 5.5 [4.45, 6.55], Post: 4.3 [3.66, 5], pg/mL; effect size: -0.57) was reduced. CONCLUSIONS: Cognitive function was improved by a 12-week moderate-intensity exercise program in physically inactive middle-aged and older adults, as were aerobic fitness (VO2max) and plasma cytokine profiles. However, we found no measurable effects on sleep architecture or BAI. It remains to be seen whether a study with a larger sample size and more intensive or more prolonged exercise exposure can demonstrate a beneficial effect on sleep quality and brain age.

Promoting Growth in Behavioral Neurology: A Path Forward.

Behavioral neurology & neuropsychiatry (BNNP) is a field that seeks to understand brain-behavior relationships, including fundamental brain organization principles and the many ways that brain structures and connectivity can be disrupted, leading to abnormalities of behavior, cognition, emotion, perception, and social cognition. In North America, BNNP has existed as an integrated subspecialty through the United Council for Neurologic Subspecialties since 2006. Nonetheless, the number of behavioral neurologists across academic medical centers and community settings is not keeping pace with increasing clinical and research demand. In this commentary, we provide a brief history of BNNP followed by an outline of the current challenges and opportunities for BNNP from the behavioral neurologist's perspective across clinical, research, and educational spheres. We provide a practical guide for promoting BNNP and addressing the shortage of behavioral neurologists to facilitate the continued growth and development of the subspecialty. We also urge a greater commitment to recruit trainees from diverse backgrounds so as to dismantle persistent obstacles that hinder inclusivity in BNNP-efforts that will further enhance the growth and impact of the subspecialty. With rapidly expanding diagnostic and therapeutic approaches across a range of conditions at the intersection of neurology and psychiatry, BNNP is well positioned to attract new trainees and expand its reach across clinical, research, and educational activities.

Telemedicine-Based Cognitive Examinations During COVID-19 and Beyond: Perspective of the Massachusetts General Hospital Behavioral Neurology & Neuropsychiatry Group.

Telehealth and telemedicine have encountered explosive growth since the beginning of the COVID-19 pandemic, resulting in increased access to care for patients located far from medical centers and clinics. Subspecialty clinicians in behavioral neurology & neuropsychiatry (BNNP) have implemented the use of telemedicine platforms to perform cognitive examinations that were previously office based. In this perspective article, BNNP clinicians at Massachusetts General Hospital (MGH) describe their experience performing cognitive examinations via telemedicine. The article reviews the goals, prerequisites, advantages, and potential limitations of performing a video- or telephone-based telemedicine cognitive examination. The article shares the approaches used by MGH BNNP clinicians to examine cognitive and behavioral areas, such as orientation, attention and executive functions, language, verbal learning and memory, visual learning and memory, visuospatial function, praxis, and abstract abilities, as well as to survey for neuropsychiatric symptoms and assess activities of daily living. Limitations of telemedicine-based cognitive examinations include limited access to and familiarity with telecommunication technologies on the patient side, limitations of the technology itself on the clinician side, and the limited psychometric validation of virtual assessments. Therefore, an in-person examination with a BNNP clinician or a formal in-person neuropsychological examination with a neuropsychologist may be recommended. Overall, this article emphasizes the use of standardized cognitive and behavioral assessment instruments that are either in the public domain or, if copyrighted, are nonproprietary and do not require a fee to be used by the practicing BNNP clinician.

The predictive validity of a Brain Care Score for dementia and stroke: data from the UK Biobank cohort.

Introduction: The 21-point Brain Care Score (BCS) was developed through a modified Delphi process in partnership with practitioners and patients to promote behavior changes and lifestyle choices in order to sustainably reduce the risk of dementia and stroke. We aimed to assess the associations of the BCS with risk of incident dementia and stroke. Methods: The BCS was derived from the United Kingdom Biobank (UKB) baseline evaluation for participants aged 40-69 years, recruited between 2006-2010. Associations of BCS and risk of subsequent incident dementia and stroke were estimated using Cox proportional hazard regressions, adjusted for sex assigned at birth and stratified by age groups at baseline. Results: The BCS (median: 12; IQR:11-14) was derived for 398,990 UKB participants (mean age: 57; females: 54%). There were 5,354 incident cases of dementia and 7,259 incident cases of stroke recorded during a median follow-up of 12.5 years. A five-point higher BCS at baseline was associated with a 59% (95%CI: 40-72%) lower risk of dementia among participants aged <50. Among those aged 50-59, the figure was 32% (95%CI: 20-42%) and 8% (95%CI: 2-14%) for those aged >59 years. A five-point higher BCS was associated with a 48% (95%CI: 39-56%) lower risk of stroke among participants aged <50, 52% (95%CI, 47-56%) among those aged 50-59, and 33% (95%CI, 29-37%) among those aged >59. Discussion: The BCS has clinically relevant and statistically significant associations with risk of dementia and stroke in approximately 0.4 million UK people. Future research includes investigating the feasibility, adaptability and implementation of the BCS for patients and providers worldwide.

Brain health scores to predict neurological outcomes from electronic health records.

BACKGROUND: Preserving brain health is a critical priority in primary care, yet screening for these risk factors in face-to-face primary care visits is challenging to scale to large populations. We aimed to develop automated brain health risk scores calculated from data in the electronic health record (EHR) enabling population-wide brain health screening in advance of patient care visits. METHODS: This retrospective cohort study included patients with visits to an outpatient neurology clinic at Massachusetts General Hospital, between January 2010 and March 2021. Survival analysis with an 11-year follow-up period was performed to predict the risk of intracranial hemorrhage, ischemic stroke, depression, death and composite outcome of dementia, Alzheimer's disease, and mild cognitive impairment. Variables included age, sex, vital signs, laboratory values, employment status and social covariates pertaining to marital, tobacco and alcohol status. Random sampling was performed to create a training (70%) set for hyperparameter tuning in internal 5-fold cross validation and an external hold-out testing (30%) set of patients, both stratified by age. Risk ratios for high and low risk groups were evaluated in the hold-out test set, using 1000 bootstrapping iterations to calculate 95% confidence intervals (CI). RESULTS: The cohort comprised 17,040 patients with an average age of 49 ± 15.6 years; majority were males (57 %), White (78 %) and non-Hispanic (80 %). The low and high groups average risk ratios [95 % CI] were: intracranial hemorrhage 0.46 [0.45-0.48] and 2.07 [1.95-2.20], ischemic stroke 0.57 [0.57-0.59] and 1.64 [1.52-1.69], depression 0.68 [0.39-0.74] and 1.29 [0.78-1.38], composite of dementia 0.27 [0.26-0.28] and 3.52 [3.18-3.81] and death 0.24 [0.24-0.24] and 3.96 [3.91-4.00]. CONCLUSIONS: Simple risk scores derived from routinely collected EHR accurately quantify the risk of developing common neurologic and psychiatric diseases. These scores can be computed automatically, prior to medical care visits, and may thus be useful for large-scale brain health screening.

A retrospective data analysis of psychiatric cases in Hargeisa, Somaliland between 2019 and 2020.

Background: In Somaliland, an estimated one person in every two households suffers from psychiatric disorders. Despite this, access to mental health care is limited because of shortages in facilities, human resources, funding and stigma. Aim: To present the proportion of psychiatric disorders encountered in outpatient psychiatry clinics. Setting: The University if Hargeisa (UoH), Hargesisa, Somaliland. Methods: De-identified data on patients accessing psychiatric care from doctor trainees in the dual psychiatry-neurology residency program at UoH from January 2019 to June 2020 were included in the analysis. The Institutional Review Board from UoH approved data collection and analysis. The most common psychiatric diagnoses were summarised overall and by sex and age. Results: A total of 752 patients were included in the analysis. Most were male (54.7%), with an average age of 34.9 years. The most common psychiatric diagnoses were schizophrenia (28.0%), major depressive disorder (MDD) (14.3%) and bipolar disorder type 1 (BD1) (10.5%). When stratified by sex, patients with schizophrenia and BD1 were more likely to be male (73.5% and 53.3%, respectively), and those with MDD were more likely to be female (58.8%). Trauma- and stressor-related disorders accounted for 0.4% of cases, while 0.8% of patients presented with substance use disorders (alcohol and khat), which is an underestimate of the widespread use in Somaliland. Conclusion: Additional research using structured clinical interviews is needed to determine the epidemiology of psychiatric disorders and promote policies aiming to decrease neuropsychiatric mortality and morbidity. Contribution: This work presents the first data collection related to neuropsychiatric disorders in Somaliland.

Neurocircuitry Hypothesis and Clinical Experience in Treating Neuropsychiatric Symptoms of Postacute Sequelae of Severe Acute Respiratory Syndrome Coronavirus 2.

Persistent symptoms following COVID-19 infection have been termed postacute sequelae of severe acute respiratory syndrome coronavirus 2 infection. Many of these symptoms are neuropsychiatric, such as inattention, impaired memory, and executive dysfunction; these are often colloquially termed "brain fog". These symptoms are common and often persist long after the acute phase. The pattern of these deficits combined with laboratory, neuroimaging, electroencephalographic, and neuropsychological data suggest that these symptoms may be driven by direct and indirect damage to the frontal-subcortical neural networks. Here, we review this evidence, share our clinical experience at an academic medical center, and discuss potential treatment implications. While the exact etiology remains unknown, a neurocircuit-informed understanding of postacute sequelae of severe acute respiratory syndrome coronavirus 2 infection can help guide pharmacology, neuromodulation, and physical and psychological therapeutic approaches.

Reporting on neurological burden in Hargeisa, Somaliland between 2019 and 2020: A cross-sectional study.

BACKGROUND AND OBJECTIVES: To characterize the disease burden of neurological cases in Hargeisa, Somaliland between January 2019 and June 2020 in order to shape clinical guidelines and develop policy interventions pertaining to brain health in the region. METHODS: In this retrospective, cross-sectional study, data was obtained from a case log of de-identified patients seen over an 18-month period. This case log was pulled from Hargeisa's three major city hospitals. In addition, demographic data including age and gender for each patient was obtained and gender-specific significance for each disease was determined. Patients were seen by one of three neuropsychiatry trainees at the University of Hargeisa. The Institutional Review Board from the University of Hargeisa has approved the data collection and analysis. RESULTS: Of the 1062 patients seen, 86.2% (915) presented with neurologic-specific diagnoses. 426 patients were female and 486 were male. Cerebral vascular accidents (CVAs, n = 272, 29.7%), traumatic brain injuries (TBIs, n = 113, 12.3%), infectious diseases (n = 94, 10.3%), headaches (n = 92, 10%), and epilepsy (n = 92, 10%) were the top five most prevalent diagnoses. The remaining patients (n = 147, 13.8%) presented with other non-neurologic diagnoses which may or may not capture any other co-morbidities the patients might have had. Notable sex-specific differences included headaches, which were more common (p < 0.0001) in female patients (n = 79, 18.5%) than in male patients (n = 13, 2.7%) and TBIs, which were more common (p < 0.0001) in male patients (n = 84, 17.2%) than female patients (n = 18, 4.2%). DISCUSSION: Our data contributes to neurological disease data in Hargeisa, Somaliland, with the top five prevalent diseases at three major city hospitals demonstrating a dire need for clinical guidelines and policy intervention aimed at improving brain health in the region.

Post-Acute Sequelae of SARS-CoV-2 Infection: A Descriptive Clinical Study.

OBJECTIVE: The investigators aimed to describe the clinical experience of a single center reporting on neuropsychiatric findings among patients experiencing persistent symptoms as part of post-acute sequelae of SARS-CoV-2 (PASC) infection. METHODS: Data were collected retrospectively (between February 2020 and May 2021) from a cohort (N=100) within a COVID-19 survivors study of patients with persistent symptoms enrolled after a short inpatient stay or who had been outpatients never hospitalized. Patients without confirmatory positive PCR or antibody diagnostic test results were grouped separately as presumptive cases (N=13). RESULTS: Of the 87 patients with confirmed SARS-CoV-2, 63 (72.4%) were female, and 65 (74.7%) were White. The mean age was 49.2 years (SD=14.9). The most prevalent symptoms after COVID-19 infection were fatigue, "brain fog," headache, anxiety, and sleep issues. Attention and executive function were frequently impaired. The mean Montreal Cognitive Assessment score was 26.0 (SD=2.8). Concentration and attention as well as memory issues were both significantly correlated with the complaint of brain fog. CONCLUSIONS: These preliminary findings suggest that post-acute sequelae of SARS-CoV-2 vary in frequency and duration with relation to premorbid history and that these conditions affect functional domains and patients' ability to return to work. Longitudinal research with larger cohorts is needed to characterize PASC and to optimize care, especially for vulnerable populations.

Shedding Light on the Causes and Characteristics of Stroke in Lebanon: A Systematic Review of Literature.

BACKGROUND: The prevalence and severity of stroke in Lebanon has increased over the past decade and stroke is currently the second leading cause of death in the country. METHODS: We systematically reviewed existing research on stroke prevalence, risk factors, mortality and morbidity of stroke, stroke treatment, and stroke education to assess the epidemiology of stroke in Lebanon. A literature search was conducted on the PubMed database for articles presenting data in any of these 5 categories in Lebanon, as well as articles discussing the Middle East and North Africa region generally. RESULTS: A high prevalence of modifiable risk factors (cigarette and waterpipe smoking) and risk factors that could be mitigated by lifestyle changes (obesity and hypertension) were found in Lebanon. Stroke mortality rates and risk factors of mortality were consistent with global trends, though the cost of treatment in Lebanon was significantly higher than in other developing nations. CONCLUSION: Urgent public health initiatives are needed to educate the public about the dangers of modifiable stroke risk factors and to reduce the burden of stroke in Lebanon.

Developing a Dual Residency Program in Psychiatry and Neurology in an Area of Regional Conflict: The University of Hargeisa-Massachusetts General Hospital-Boston Medical Center Experience.

Noncommunicable diseases are the leading cause of worldwide death and disability and continue to increase in both developed and developing countries. There is a need to address and treat neuropsychiatric disorders in low-income countries, especially in the Horn of Africa. Capacity building by training local doctors and health care workers is a laborious endeavor, with challenges piling up along the way. Nevertheless, the rewards are great when brain specialists who are able to address the needs in their country and treat their fellow citizens receive the training needed to do so effectively. The present article describes a coordinated administrative, educational, and clinical effort to develop and implement a dual residency program in psychiatry and neurology at the University of Hargeisa in Somaliland. The authors highlight the foundations of the program and the challenges faced during its development and implementation in an area of regional conflict. The program provides evidence that this aim is achievable and serves as a model for others seeking to replicate it in other low- and middle-income countries.