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Objective: To identify and disseminate research priorities for the headache field that should be areas of research focus during the next 10 years. Background: Establishing research priorities helps focus and synergize the work of headache investigators, allowing them to reach the most important research goals more efficiently and completely. Methods: The Headache Research Priorities organizing and executive committees and working group chairs led a multistakeholder and international group of experts to develop headache research priorities. The research priorities were developed and reviewed by clinicians, scientists, people with headache, representatives from headache organizations, health‐care industry representatives, and the public. Priorities were revised and finalized after receiving feedback from members of the research priorities working groups and after a public comment period. Results: Twenty‐five research priorities across eight categories were identified: human models, animal models, pathophysiology, diagnosis and management, treatment, inequities and disparities, research workforce development, and quality of life. The priorities address research models and methods, development and optimization of outcome measures and endpoints, pain and non‐pain symptoms of primary and secondary headaches, investigations into mechanisms underlying headache attacks and chronification of headache disorders, treatment optimization, research workforce recruitment, development, expansion, and support, and inequities and disparities in the headache field. The priorities are focused enough that they help to guide headache research and broad enough that they are widely applicable to multiple headache types and various research methods. Conclusions: These research priorities serve as guidance for headache investigators when planning their research studies and as benchmarks by which the headache field can measure its progress over time. These priorities will need updating as research goals are met and new priorities arise. Plain Language Summary: The American Headache Society led a large, international, multistakeholder process to identify headache research topics that should be prioritized during the next 10 years. With input from headache clinicians, scientists, people with headache, representatives from headache organizations, health‐care industry representatives, and the public, 25 research priorities within 8 categories were identified. These research priorities can help guide headache researchers when planning their studies and as benchmarks by which the headache field can measure its progress over time. [ABSTRACT FROM AUTHOR]

Objective: Utilize machine learning models to identify factors associated with seeking medical care for migraine. Background: Migraine is a leading cause of disability worldwide, yet many people with migraine do not seek medical care. Methods: The web‐based survey, ObserVational survey of the Epidemiology, tReatment and Care Of MigrainE (US), annually recruited demographically representative samples of the US adult population (2018–2020). Respondents with active migraine were identified via a validated diagnostic questionnaire and/or a self‐reported medical diagnosis of migraine, and were then asked if they had consulted a healthcare professional for their headaches in the previous 12 months (i.e., "seeking care"). This included in‐person/telephone/or e‐visit at Primary Care, Specialty Care, or Emergency/Urgent Care locations. Supervised machine learning (Random Forest) and Least Absolute Shrinkage and Selection Operator (LASSO) algorithms identified 13/54 sociodemographic and clinical factors most associated with seeking medical care for migraine. Random Forest models complex relationships (including interactions) between predictor variables and a response. LASSO is also an efficient feature selection algorithm. Linear models were used to determine the multivariable association of those factors with seeking care. Results: Among 61,826 persons with migraine, the mean age was 41.7 years (±14.8) and 31,529/61,826 (51.0%) sought medical care for migraine in the previous 12 months. Of those seeking care for migraine, 23,106/31,529 (73.3%) were female, 21,320/31,529 (67.6%) were White, and 28,030/31,529 (88.9%) had health insurance. Severe interictal burden (assessed via the Migraine Interictal Burden Scale‐4, MIBS‐4) occurred in 52.8% (16,657/31,529) of those seeking care and in 23.1% (6991/30,297) of those not seeking care; similar patterns were observed for severe migraine‐related disability (assessed via the Migraine Disability Assessment Scale, MIDAS) (36.7% [11,561/31,529] vs. 14.6% [4434/30,297]) and severe ictal cutaneous allodynia (assessed via the Allodynia Symptom Checklist, ASC‐12) (21.0% [6614/31,529] vs. 7.4% [2230/30,297]). Severe interictal burden (vs. none, OR 2.64, 95% CI [2.5, 2.8]); severe migraine‐related disability (vs. little/none, OR 2.2, 95% CI [2.0, 2.3]); and severe ictal allodynia (vs. none, OR 1.7, 95% CI [1.6, 1.8]) were strongly associated with seeking care for migraine. Conclusions: Seeking medical care for migraine is associated with higher interictal burden, disability, and allodynia. These findings could support interventions to promote care‐seeking among people with migraine, encourage assessment of these factors during consultation, and prioritize these domains in selecting treatments and measuring their benefits. Plain Language Summary: In this study, we looked at factors that related to a person's decision to seek medical care for migraine in a representative sample of over 60,000 adults with migraine in the United States. We found that only about half (51.0%) of the participants reported seeking care for migraine. We also found that people were more likely to seek medical care when migraine got in the way of their lives during and between migraine attacks, and when they had allodynia (pain from stimuli that do not normally cause pain). [ABSTRACT FROM AUTHOR]

The small molecule calcitonin gene–related peptide receptor antagonists (gepants) are the only drug class with medicines indicated for both the acute and preventive treatment of migraine. Given this dual capacity to both treat and prevent, along with their favorable tolerability profiles and lack of an association with medication‐overuse headache, headache specialists have begun to use gepants in ways that transcend the traditional categories of acute and preventive treatment. One approach, called situational prevention, directs patients to treat during the interictal phase, before symptoms develop, in situations of increased risk for migraine attacks. Herein, we present three patients to illustrate scenarios of gepant use for situational prevention. In each case, a gepant was started in anticipation of a period of increased headache probability (vulnerability) and continued for a duration of 1 day to 5 consecutive days. Although this approach may expose patients to medication when headache may not have developed, the tolerability and safety profile and preventive effect of gepants may represent a feasible approach for some patients. Situational prevention is an emerging strategy for managing migraine before symptoms develop in individuals who can identify periods when the probability of headache is high. This paper is intended to increase awareness of this strategy and stimulate future randomized, placebo‐controlled trials to rigorously assess this strategy. Plain Language Summary: A new class of migraine medicines, the gepants, does not cause medication‐overuse headache; these drugs can be taken in periods of increased headache risk, even before symptoms begin, to keep headaches from coming on. This new way of treating migraine is called "situational prevention." Experience in clinical practice suggests that treating migraine patients without current symptoms during times of increased headache risk, for example in connection with the menstrual cycle, travel, stress, or relaxation after stress, may be good times for situational prevention, but studies are needed to confirm when this strategy is most likely to be beneficial. [ABSTRACT FROM AUTHOR]

The Hispanic/Latino population is one of the largest and most diverse ethnoracial groups in the United States at high risk for dementia. We examined cognitive constructs and associations with subsequent hippocampal volume (HV) and white matter hyperintensity volume (WMHV). Participants were from the Hispanic Community Health Study/Study of Latinos–Magnetic Resonance Imaging Study (n = 2029). We examined confirmatory factor analysis and longitudinal invariance using neurocognitive scores at Visits 1 (2008–2011) and 2 (2014–2018) and path analyses. We obtained a longitudinally invariant two‐factor episodic memory (EM) and working memory (WM) construct. Lower EM profile at both visits was associated with greater WMHV and smaller HV at Visit 2. Lower WM profile at both visits was associated with larger WMHV and smaller HV at Visit 2. Neurocognitive profiles were associated with subsequent neurodegeneration in a sample of Hispanics/Latinos. Identifying neurocognitive risk profiles may lead to early detection and intervention, and significantly impact the course of neurodegeneration. Highlights: Cognitive profiles predict brain integrity up to 10 years later.We observed two‐factor latent memory constructs and longitudinal invariance.These findings were observed in a Hispanic/Latino cohort. [ABSTRACT FROM AUTHOR]

Objective: To assess the prevalence and impact of neck pain during headache among respondents with migraine in the multicountry Chronic Migraine Epidemiology and Outcomes – International (CaMEO‐I) Study. Background: Neck pain among individuals with migraine is highly prevalent and contributes to disability. Methods: The CaMEO‐I was a prospective, cross‐sectional, web‐based study conducted in Canada, France, Germany, Japan, United Kingdom, and the United States. A demographically representative sample of participants from each country completed a screening survey to evaluate headache characteristics. Respondents with headache were identified as having migraine or non‐migraine headache based on modified International Classification of Headache Disorders, third edition, criteria; those with migraine completed a detailed survey with migraine‐specific assessments. Results were stratified by the presence or absence of neck pain with headache (NPWH). For these analyses, data were pooled across the six countries. Results: Of 51,969 respondents who reported headache within the past 12 months, 14,492 (27.9%) were classified as having migraine; the remaining 37,477 (72.1%) had non‐migraine headache. Overall, 9896/14,492 (68.3%) of respondents with migraine headache reported NPWH, which was significantly higher (p < 0.001) than the proportion of respondents with non‐migraine headache who reported NPWH (13,536/37,477 [36.1%]). Among respondents with migraine, moderate‐to‐severe disability was significantly more prevalent for those with NPWH versus without (47.7% [4718/9896] vs. 28.9%, p < 0.001). Respondents with NPWH versus without also had significantly greater work productivity losses, at a median (interquartile range [IQR]) of 50.0 (20.0, 71.3) vs. 30.0 (0.0, 60.0) (p < 0.001), lower quality of life (Migraine‐Specific Quality of Life questionnaire version 2.1, median [IQR] Role Function–Restrictive domain score 60.0 [42.9, 74.3] vs. 68.6 [54.3, 82.9], p < 0.001), higher prevalence of depression and anxiety symptoms (depression, 40.2% [3982/9896] vs. 28.2% [1296/4596], p < 0.001); anxiety, 41.2% [4082/9896] vs. 29.2% [1343/4596], p < 0.001), higher prevalence of cutaneous allodynia during headache (54.0% [5345/9896] vs. 36.6% [1681/4596], p < 0.001), and higher prevalence of poor acute treatment optimization (61.1% [5582/9129] vs. 53.3% [2197/4122], p < 0.001). Conclusions: Nearly 70% of respondents with migraine reported NPWH. Individuals with migraine with neck pain during their headaches had greater disability, depression, anxiety, and cutaneous allodynia (during headache) than those without neck pain during their headaches. They also had diminished quality of life and work productivity, and poorer response to acute treatment compared with those without neck pain. Plain Language Summary: We looked at data from a web‐based study of over 51,000 people across Canada, France, Germany, Japan, United Kingdom, and the United States to understand how neck pain affects people with migraine. We found that neck pain is common in people with migraine, and that those who have neck pain during their headaches have more disability, worse symptoms, more anxiety and depression, and poorer quality of life than those without neck pain. Our results show that neck pain is a serious problem for people with migraine, and it can worsen the negative impacts of migraine. [ABSTRACT FROM AUTHOR]

Objective: To characterize the long‐term (56‐week) benefits of continuous onabotulinumtoxinA treatment response in individuals with chronic migraine (CM) who achieved reduction to <15 headache days/month with treatment. Background: There are limited data exploring reductions in monthly headache days to levels consistent with episodic migraine among those experiencing CM. Understanding the impact of sustained preventive treatment response in CM can provide important information about the impact of successful therapy. Methods: The two Phase 3 REsearch Evaluating Migraine Prophylaxis Therapy trials of onabotulinumtoxinA in adults included a 24‐week, randomized, double‐blind, placebo‐controlled phase and a 32‐week open‐label phase. Data were pooled to determine proportions of individuals with <15 headache days/month while on treatment during several time periods in the double‐blind phase (Weeks 21–24; any 12 consecutive weeks; Weeks 13–24) and the entire study (Weeks 53–56; any 12 consecutive weeks; any 4‐week period). We assessed the long‐term impact on mean monthly headache days and changes from baseline on the six‐item Headache Impact Test (HIT‐6) and Migraine‐Specific Quality of Life questionnaire version 2.1 (MSQv2.1). Results: We analyzed 1384 participants with chronic migraine (double‐blind: onabotulinumtoxinA, n = 688; placebo, n = 696; open‐label: n = 688 [onabotulinumtoxinA]). The discontinuation rates prior to the completion of the full 56‐week treatment period for onabotulinumtoxinA and placebo were 25.4% (n = 175) and 29.3% (n = 204), respectively. During Weeks 13–24 of the double‐blind phase, significantly more onabotulinumtoxinA‐treated (386/688 [56.1%]) than placebo‐treated (342/696 [49.1%]) individuals had <15 headache days/month (p = 0.010), with fewer monthly headache days for onabotulinumtoxinA versus placebo responders. The proportions of participants achieving <15 monthly headache days with onabotulinumtoxinA were 60.9% (419/688) at Weeks 25–56, 81.1% (558/688) at Weeks 53–56, and 79.4% (546/688) during any consecutive 12‐week period. Mean changes from baseline on the HIT‐6 and MSQv2.1 questionnaire surpassed within‐group minimal important difference thresholds in all periods. At Week 24, onabotulinumtoxinA‐treated participants who achieved <15 monthly headache days during Weeks 21–24 had a greater mean HIT‐6 score reduction (−6.5 vs. −1.4) and greater mean MSQv2.1 Role‐Function Restrictive score improvements (21.3 vs. 6.4) than those who did not achieve <15 monthly headache days during the same period. Conclusions: Participants who achieved <15 monthly headache days with onabotulinumtoxinA treatment achieved meaningful benefits in headache‐related disability and migraine‐specific quality of life compared with those who remained at or above the 15–monthly headache days threshold. Sustained benefits observed over 56 weeks support long‐term onabotulinumtoxinA use for the prevention of CM. Plain Language Summary: It is not always clear how we should define if a preventive treatment for chronic migraine (CM) is successful. People with CM have ≥15 headache days/month, so we looked at data from two groups of patients who received long‐term treatment with onabotulinumtoxinA: the first group decreased to <15 headache days/month, and the second group continued to have ≥15 headache days/month. We found that the patients whose headaches decreased to <15 headache days/month, which we called the response threshold, said that their headaches impacted their lives much less and that they had better quality of life compared to the group who still met CM diagnostic criteria at the end of treatment. [ABSTRACT FROM AUTHOR]

INTRODUCTION: The LIfestyle for BRAin Health (LIBRA) index yields a dementia risk score based on modifiable lifestyle factors and is validated in Western samples. We investigated whether the association between LIBRA scores and incident dementia is moderated by geographical location or sociodemographic characteristics. METHODS: We combined data from 21 prospective cohorts across six continents (N = 31,680) and conducted cohort‐specific Cox proportional hazard regression analyses in a two‐step individual participant data meta‐analysis. RESULTS: A one‐standard‐deviation increase in LIBRA score was associated with a 21% higher risk for dementia. The association was stronger for Asian cohorts compared to European cohorts, and for individuals aged ≤75 years (vs older), though only within the first 5 years of follow‐up. No interactions with sex, education, or socioeconomic position were observed. DISCUSSION: Modifiable risk and protective factors appear relevant for dementia risk reduction across diverse geographical and sociodemographic groups. Highlights: A two‐step individual participant data meta‐analysis was conducted.This was done at a global scale using data from 21 ethno‐regionally diverse cohorts.The association between a modifiable dementia risk score and dementia was examined.The association was modified by geographical region and age at baseline.Yet, modifiable dementia risk and protective factors appear relevant in all investigated groups and regions. [ABSTRACT FROM AUTHOR]

Objective: To analyze data from the Chronic Migraine Epidemiology and Outcomes‐International (CaMEO‐I) Study in order to characterize preventive medication use and identify preventive usage gaps among people with migraine across multiple countries. Background: Guidelines for the preventive treatment of migraine are available from scientific organizations in various countries. Although these guidelines differ among countries, eligibility for preventive treatment is generally based on monthly headache day (MHD) frequency and associated disability. The overwhelming majority of people with migraine who are eligible for preventive treatment do not receive it. Methods: The CaMEO‐I Study was a cross‐sectional, observational, web‐based panel survey study performed in six countries: Canada, France, Germany, Japan, the United Kingdom, and the United States. People were invited to complete an online survey in their national language(s) to identify those with migraine according to modified International Classification of Headache Disorders, 3rd edition, criteria. People classified with migraine answered questions about current and ever use of both acute and preventive treatments for migraine. Available preventive medications for migraine differed by country. MHD frequency and associated disability data were collected. The American Headache Society (AHS) 2021 Consensus Statement algorithm was used to determine candidacy for preventive treatment (i.e., ≥3 monthly MHDs with severe disability, ≥4 MHDs with some disability, or ≥6 MHDs regardless of level of disability). Results: Among 90,613 valid completers of the screening survey, 14,492 met criteria for migraine and completed the full survey, with approximately 2400 respondents from each country. Based on the AHS consensus statement preventive treatment candidacy algorithm, averaging across countries, 36.2% (5246/14,492) of respondents with migraine qualified for preventive treatment. Most respondents (84.5% [4431/5246]) who met criteria for preventive treatment according to the AHS consensus statement were not using a preventive medication at the time of the survey. Moreover, 19.3% (2799/14,492) of respondents had ever used preventive medication (ever users); 58.1% (1625/2799) of respondents who reported ever using a preventive medication for migraine were still taking it. Of the respondents who were currently using a preventive medication, 50.2% (815/1625) still met the criteria for needing preventive treatment based on the AHS consensus statement. Conclusions: Most people with migraine who qualify for preventive treatment are not currently taking it. Additionally, many people currently taking preventive pharmacologic treatment still meet the algorithm criteria for needing preventive treatment, suggesting inadequate benefit from their current regimen. Plain Language Summary: People with migraine who experience frequent headaches or some level of disability may benefit from using a preventive medication for migraine. We collected data on the use of preventive medication for migraine in Canada, France, Germany, Japan, the United Kingdom, and the United States. These data demonstrated that many people who qualified for the use of a preventive treatment in the six participating countries were not currently taking a preventive medication for migraine. [ABSTRACT FROM AUTHOR]

Background: This study reviewed migraine prevalence and disability gathered through epidemiologic survey studies in the United States conducted over the past three decades. We summarized these studies and evaluated changing patterns of disease prevalence and disability. Methods: We conducted a systematic review of US studies addressing the prevalence, disability, and/or burden of migraine, including both episodic migraine (EM) and chronic migraine (CM). A Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) protocol was used in conjunction with the PubMed search engine. Eligible studies were published before February 2022, were conducted in the United States, included representative samples, and used a case definition of migraine based on the International Classification of Headache Disorders (ICHD). The primary measure of disease burden was the Migraine Disability Assessment Scale (MIDAS). The MIDAS measures days lost due to migraine over 3 months in three domains and defines groups with moderate (Grade III) or severe disability (Grade IV) using cut‐scores. Results: Of the 1609 identified records, 26 publications from 11 US population‐based studies met eligibility criteria. The prevalence of migraine in the population has remained relatively consistent for the past 30 years: ranging from 11.7% to 14.7% overall, 17.1% to 19.2% in women, and 5.6% to 7.2% in men in the studies reviewed. CM prevalence is 0.91% (1.3% among women and 0.5% of men) in adults and 0.8% in adolescents. The proportion of people with migraine and moderate‐to‐severe MIDAS disability (Grades III–IV), has trended upward across studies from 22.0% in 2005 to 39.0% in 2012, to 43.2% in 2016, and 42.4% in 2018. A consistently higher proportion of women were assigned MIDAS Grades III/IV relative to men. Conclusion: The prevalence of migraine in the United States has remained stable over the past three decades while migraine‐related disability has increased. The disability trend could reflect changes in reporting, study methodology, social and societal changes, or changes in exacerbating or remediating factors that make migraine more disabling, among other hypotheses. These issues merit further investigation. Plain Language Summary: We reviewed 11 population‐based studies that adhered to the International Classification of Headache Disorders to examine the prevalence and burden of migraine in the United States. While the prevalence of migraine has remained stable at ~12% of adults for the past 30 years (with higher rates in women), the burden of migraine, including disability and impact on work, academics, and social life, appears to be increasing. The escalating burden of migraine may result from factors like increased headache frequency or changes in study methodology, indicating a need for more population studies. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Executive functioning and processing speed are crucial elements of neuropsychological assessment. To meet the needs of the Hispanic/Latino population, we aimed to provide normative data for the Digit Symbol Substitution (DSS) test. METHODS: The target population for the Study of Latinos‐Investigation of Neurocognitive Aging included six heritage backgrounds (n = 6177). Average age was 63.4 ± 8.3 years, 54.5% were female, and mean education was 11.0 ± 4.7 years. Participants were administered the DSS as part of a larger battery. Heritage‐adjusted DSS scores, and percentile cut‐points were created using survey‐adjusted regression and quantile regression models. RESULTS: Age, education, sex, heritage, and language preference were associated with DSS scores. DISCUSSION: Significant correlates of DSS performance should be considered when evaluating cognitive performance. Representative DSS norms for Hispanics/Latinos will advance assessment and accuracy of neurocognitive disorder diagnosis in clinical practice. To facilitate interpretation, we provide norms to reduce test biases and developed an online dashboard. Highlights: Normative data for the Digit Symbol Substitution (DSS) for diverse Hispanic/Latino adults: Results from the Study of Latinos‐Investigation of Neurocognitive Aging (SOL‐INCA) This study is the first to develop norms for the DSS test across four regions of the United States.Factors such as age, education, sex, and Hispanic/Latino heritage and language preference are associated with differences in executive functioning and information processing speed.We created norms and an online dashboard (https://solincalab.shinyapps.io/dsst%5fshiny/) providing an easily accessible tool to evaluate processing speed and executive functioning in Hispanic/Latino adults. [ABSTRACT FROM AUTHOR]

Objective: To compare the safety and pharmacokinetics (PK) of dihydroergotamine (DHE) after administration of intranasal DHE powder (STS101), liquid nasal spray (LNS) DHE mesylate, and intramuscular (IM) DHE mesylate injection in healthy participants. Background: DHE is an effective acute migraine treatment; however, self‐administration difficulties have prevented its broader role in the management of migraine. Methods: This randomized, active‐controlled, five‐period crossover study was conducted over 5 weeks separated by 1‐week washout periods. Three STS101 dosage strengths (5.2, 7.0, 8.6 mg), and one dose each of LNS DHE 2.0 mg, and IM DHE 1.0 mg, were administered to 36 healthy participants. Liquid chromatography, tandem mass spectrometry was used to determine DHE (including its 8′OH‐DHE metabolite) plasma levels and to calculate PK parameters (Cmax, Tmax, AUC0‐2h, AUC0‐last, AUC0‐inf, and t1/2). Safety was evaluated by monitoring adverse events (AEs), vital signs, electrocardiograms, nasal examinations, and laboratory parameters. Results: Thirty‐six participants (mean age 36 years; 19% Hispanic Black and 81% Hispanic White) were enrolled. DHE plasma concentrations rose rapidly after STS101 5.2, 7.0, and 8.6 mg and IM DHE injection, with mean concentrations greater than 2000 pg/mL for all STS101 dose strengths at 20 min. All STS101 dose strengths showed approximately 3‐fold higher Cmax, AUC0‐2h, and AUC0‐inf, than the LNS DHE. The mean AUC0‐inf of STS101 7.0 and 8.6 mg were comparable to IM DHE (12,600 and 13,200 vs. 13,400 h × pg/mL). All STS101 dose strengths showed substantially lower variability (CV%) compared to LNS DHE for Cmax (35%–41% vs. 87%), and AUC0‐inf (37%–46% vs. 65%). STS101 was well tolerated, and all treatment‐emergent AEs were mild and transient. Conclusion: STS101 showed rapid absorption and was well tolerated with mild and transient treatment‐emergent AEs. Achieving effective DHE plasma concentrations within 10 min, STS101 displayed a favorable PK profile relative to the LNS with higher Cmax, AUC0‐2h, and AUC0inf, and with greater response consistency. The AUC0‐inf was comparable to IM DHE. Plain Language Summary: This study aimed to see whether the pharmacokinetics (i.e., how the body breaks down a medication) are different among three different formulations of dihydroergotamine (DHE), a drug used to treat migraine headaches. We found that the nasal powder version reached the blood more rapidly and at higher levels than the liquid nasal spray and was comparable to the intramuscular injection form. Participants exposed to injectable DHE and the highest strengths of the DHE nasal powder reported higher rates of side effects. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Reproductive health history may contribute to cognitive aging and risk for Alzheimer's disease, but this is understudied among Hispanic/Latina women. METHODS: Participants included 2126 Hispanic/Latina postmenopausal women (44 to 75 years) from the Study of Latinos‐Investigation of Neurocognitive Aging. Survey linear regressions separately modeled the associations between reproductive health measures (age at menarche, history of oral contraceptive use, number of pregnancies, number of live births, age at menopause, female hormone use at Visit 1, and reproductive span) with cognitive outcomes at Visit 2 (performance, 7‐year change, and mild cognitive impairment [MCI] prevalence). RESULTS: Younger age at menarche, oral contraceptive use, lower pregnancies, lower live births, and older age at menopause were associated with better cognitive performance. Older age at menarche was protective against cognitive change. Hormone use was linked to lower MCI prevalence. DISCUSSION: Several aspects of reproductive health appear to impact cognitive aging among Hispanic/Latina women. [ABSTRACT FROM AUTHOR]

INTRODUCTION: The extent to which the Big Five personality traits and subjective well‐being (SWB) are discriminatory predictors of clinical manifestation of dementia versus dementia‐related neuropathology is unclear. METHODS: Using data from eight independent studies (Ntotal= 44,531; Ndementia= 1703; baseline Mage= 49 to 81 years, 26 to 61% female; Mfollow‐up range = 3.53 to 21.00 years), Bayesian multilevel models tested whether personality traits and SWB differentially predicted neuropsychological and neuropathological characteristics of dementia. RESULTS: Synthesized and individual study results indicate that high neuroticism and negative affect and low conscientiousness, extraversion, and positive affect were associated with increased risk of long‐term dementia diagnosis. There were no consistent associations with neuropathology. DISCUSSION: This multistudy project provides robust, conceptually replicated and extended evidence that psychosocial factors are strong predictors of dementia diagnosis but not consistently associated with neuropathology at autopsy. Highlights: N(+), C(−), E(−), PA(−), and NA(+) were associated with incident diagnosis.Results were consistent despite self‐report versus clinical diagnosis of dementia.Psychological factors were not associated with neuropathology at autopsy.Individuals with higher conscientiousness and no diagnosis had less neuropathology.High C individuals may withstand neuropathology for longer before death. [ABSTRACT FROM AUTHOR]

Background and purpose: Eptinezumab reduced monthly migraine days more than placebo in the DELIVER study, a clinical trial with patients with difficult‐to‐treat migraine and prior preventive treatment failures. This post hoc analysis assesses the sustained response to eptinezumab at the population and patient level and evaluates the potential for response in initial non‐responders. Methods: Adults with chronic or episodic migraine and two to four prior preventive treatment failures were randomized to eptinezumab 100 mg, 300 mg or placebo every 12 weeks. Primary outcomes in this post hoc analysis are the proportion of patients with ≥30%, ≥50% or ≥75% reduction in monthly migraine days (i.e., migraine responder rates [MRRs]) during weeks 1–12 and weeks 13–24 and across 4‐week intervals. Secondary outcomes are maintenance and shifts in MRRs from weeks 1–12 to weeks 13–24. Results: Between weeks 1–12 and 13–24, ≥30% MRRs increased from 65.9% to 70.4% (100 mg) and from 71.0% to 74.5% (300 mg), versus 36.9% to 43.1% (placebo). The ≥50% and ≥75% MRRs were sustained or increased over the 24‐week period. The largest increase in ≥30% MRRs occurred after the second infusion with eptinezumab. The percentage of initial non‐responders (<30% MRRs during weeks 1–12) who experienced response (≥30% MRRs during weeks 13–24) to the second dose was 34.7% (100 mg) and 30.4% (300 mg) with eptinezumab versus 21.1% with placebo. Conclusion: Across MRR thresholds, most patients who responded to eptinezumab during weeks 1–12 maintained or improved response during weeks 13–24. More than one‐third of initial non‐responders became responders after their second infusion. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Few studies have examined the associations of psychosocial factors with cognitive change in Hispanics/Latinos. METHODS: Data from the Hispanic Community Health Study/Study of Latinos‐Investigation of Neurocognitive Aging (HCHS/SOL INCA) and Sociocultural studies were used (n = 2,155; ages ≥45 years). Psychosocial exposures included intrapersonal (ethnic identity, optimism, purpose in life), interpersonal (family cohesion, familism, social networks, social support), and social factors (ethnic discrimination, loneliness, subjective social status). Survey‐linear regression models examined associations between psychosocial exposures and 7‐year cognitive change (global cognition [GC], verbal learning, memory, word fluency [WF], and digit symbol substitution [DSS]). RESULTS: Familism predicted decline in GC, verbal learning, and memory; family cohesion predicted DSS decline; and loneliness predicted memory decline. Ethnic identity was protective against decline in GC and memory, optimism and social support were protective against decline in memory, and purpose in life was protective against WF decline. DISCUSSION: Psychosocial factors are differentially related to cognitive changes. Culturally relevant factors should be explored in Hispanic/Latino cognitive aging research. Highlights: Psychosocial factors are differentially related to cognitive changes in Latinos.Role of culturally relevant factors on cognition should be further explored.Familism predicted decline in global cognition, verbal learning, and memory.Ethnic identity predicted increase in global cognition and memory. [ABSTRACT FROM AUTHOR]

Objective: To describe the impact of migraine on functioning based on comprehensive data collection, analysis, and reporting of patients' experiences. Background: Qualitative research conducted to understand patients' perspectives on living with migraine has often focused on narrow topics or specific groups of patients or has been selectively reported. Methods: Qualitative interviews with 71 participants were conducted during two concept elicitation studies as part of the Migraine Clinical Outcome Assessment System (MiCOAS) project, an FDA grant‐funded program designed to develop a core set of patient‐centered outcome measures for migraine clinical trials. Participants self‐reported being diagnosed with migraine by a healthcare professional and participated in semi‐structured qualitative interviews about their experiences with the symptoms and impacts of migraine. Interview transcripts were coded to identify and define concepts, which were then grouped into broad domains based on conceptual similarities. Results: A total of 66 concepts were identified: 12 for physical functioning, 16 for cognitive functioning, 10 for social role functioning, 19 for emotional and psychological functioning, and 9 related to migraine management. Participants described a complex and varied relationship between migraine attack symptoms and impacts on functioning. Impacts from migraine were further influenced by numerous contextual factors, such as people's individual social environments and the level of day‐to‐day demand for functioning they face. Conclusion: Findings showed that migraine impacted individual functioning in multiple ways and the nature of these impacts was dependent on social‐contextual factors. The results are being used in the development of core measures designed to improve our understanding of the burden of migraine and the efficacy of migraine therapies. The results also offer new insights and raise new questions about migraine experience that can be used to guide future research. [ABSTRACT FROM AUTHOR]

Background: Greater within‐person variability in cognitive performance on mobile devices is emerging as a sensitive marker of mild cognitive impairment (MCI). It is unclear if sociodemographic differences are associated with this variability, and if so, whether these differences moderate associations between MCI status and within‐person variability. We use a digital health approach with ecological momentary assessments (EMA) to examine sociodemographic differences in within‐day variability among individuals with MCI and those who were cognitively unimpaired (CU). Method: A sample of 308 community‐dwelling older adults from the Einstein Aging Study (mean age = 77.49 years, SD = 4.86, range = 70‐90; 67% female; 45% non‐Hispanic White, 41% non‐Hispanic Black) completed neuropsychological testing and self‐reported questionnaires. Ninety‐eight individuals met Jak/Bondi criteria for MCI. All participants performed mobile tests of processing speed and memory binding on a smartphone up to six times daily over a two‐week period. We employed heterogeneous variance multilevel models to assess sociodemographic and MCI status associations with within‐day variability across assessments. We further tested whether differences in age, gender, race, and education moderated associations between MCI status and within‐day variability. Result: For processing speed, greater variability was apparent in individuals with MCI, non‐Hispanic Black participants, and individuals with less education (ps<.001). A MCI status*gender interaction occurred; the association between MCI status and variability remained significant for both genders but was smaller among women (p<.01). For memory binding, greater variability was apparent in individuals with MCI, older participants, non‐Hispanic Black participants, and individuals with less education (ps<.001). Numerous interactions occurred; in separate analyses, associations between MCI status and variability remained significant, but were smaller among women, non‐Hispanic Black participants, and individuals with less education (ps<.05). Conclusion: Individuals with MCI exhibited greater within‐day variability in mobile cognitive performance than those who were CU, but the strength of these associations varied by sociodemographic factors. These indices of variability in everyday life may serve as sensitive markers of early cognitive impairment. Future research should examine daily mechanisms and environmental perturbations (e.g., stress, sleep, air pollution) that may explain why associations between MCI status and cognitive variability appeared smaller among women, non‐Hispanic Black participants, and individuals with less education. [ABSTRACT FROM AUTHOR]

Objective: To characterize the direct impact of monthly headache days (MHDs) on health‐related quality of life (HRQoL) in people with migraine and the potential mediating effects of anxiety, depression, and allodynia. Background: Although the general relationship between increased migraine frequency (i.e., MHDs) and reduced HRQoL is well established, the degree to which reduced HRQoL is due to a direct effect of increased MHDs or attributable to mediating factors remains uncertain. Methods: Cross‐sectional baseline data from participants with migraine who completed the Core and Comorbidities/Endophenotypes modules in the 2012–2013 US Chronic Migraine Epidemiology and Outcomes (CaMEO) study, a longitudinal web‐based survey study, were analyzed. The potential contribution of depression, anxiety, and/or allodynia to the observed effects of MHDs on HRQoL as measured by the Migraine‐Specific Quality‐of‐Life Questionnaire version 2.1 (MSQ) was evaluated. Results: A total of 12,715 respondents were included in the analyses. The MSQ domain scores demonstrated progressive declines with increasing MHD categories (B = −1.23 to −0.60; p < 0.001). The observed HRQoL decrements associated with increasing MHDs were partially mediated by the presence of depression, anxiety, and allodynia. The MHD values predicted 24.0%–32.4% of the observed variation in the MSQ domains. Depression mediated 15.2%–24.3%, allodynia mediated 9.6%–16.1%, and anxiety mediated 2.3%–6.0% of the observed MHD effects on the MSQ. Conclusions: Increased MHD values were associated with lower MSQ scores; the impact of MHDs on the MSQ domain scores was partially mediated by the presence of depression, anxiety, and allodynia. MHDs remain the predominant driver of the MSQ variation; moreover, most of the variation in the MSQ remains unexplained by the variables we analyzed. Future longitudinal analyses and studies may help clarify the contribution of MHDs, comorbidities, and other factors to changes in HRQoL. [ABSTRACT FROM AUTHOR]

Objective: To evaluate an alternative method of defining acute treatment success in migraine by combining multiple indicators into a single dichotomous measure of success. Background: Migraine is characterized by a symptom complex; combining these features as a single endpoint may improve the measurement of treatment effects and better predict patient satisfaction with treatment. Methods: We used a confirmatory latent class model (LCM) with two latent classes interpreted as treatment success and treatment failure. Pooled data for placebo and ubrogepant 50 mg from the ACHIEVE I and ACHIEVE II trials and data for ubrogepant 100 mg from ACHIEVE I were used. LCM inputs included pre‐dose and 2‐h post‐dose measures of pain severity (0–3), the presence/absence of associated symptoms (nausea, photophobia, and phonophobia [0 or 1]), and functional disability (0–3). All definitions were validated against satisfaction with study medication (SWSM) at 24 h post‐dose; results were compared with 2‐hour pain freedom (2hPF). Results: This pooled analysis included 2247 participants. At 2 h post‐dose in the ubrogepant 50 and 100 mg dose groups, 53.2% (472/887) and 54.9% (246/448) of participants, respectively, were classified as achieving treatment success using the LCM‐based approach, compared to 39.0% (356/912) of participants in the placebo group. The results for treatment success using the 2hPF endpoint were 20.7% (184/887) and 21.5% (96/447) in the ubrogepant 50 and 100 mg dose groups, respectively, compared to 12.7% (116/912) for placebo. Using 24‐h SWSM as an external validator, the LCM approach sensitivity and correct classification rates were higher than for 2hPF. Conclusion: The LCM approach led to higher rates of treatment success and greater separation between ubrogepant and placebo and was a more sensitive predictor of treatment satisfaction than the regulatory endpoint of 2hPF. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study was to characterize the utility of calcitonin gene–related peptide (CGRP) and nerve growth factor (NGF) as potential biomarkers for headache and pain disorders in the post–military deployment setting. Background: The need to improve recognition, assessment, and prognoses of individuals with posttraumatic headache or other pain has increased interest in the potential of CGRP and NGF as biomarkers. Methods: The Warrior Strong Study (NCT01847040) is an observational longitudinal study of United States–based soldiers who had recently returned from deployment to Afghanistan or Iraq from 2009 to 2014. The present nested cross‐sectional analysis uses baseline data collected from soldiers returning to Fort Bragg, North Carolina. Results: In total, 264 soldiers (mean (standard deviation [SD] age 28.1 [6.4] years, 230/264 [87.1%] men, 171/263 [65.0%] White) were analyzed. Mean (SD) plasma levels of CGRP were 1.3 (1.1) pg/mL and mean levels of NGF were 1.4 (0.4) pg/mL. Age was negatively correlated with NGF (−0.01 pg/mL per year, p = 0.007) but was not associated with CGRP. Men had higher mean (SD) CGRP plasma levels than women (1.4 95% confidence interval [CI; 1.2] vs. 0.9 95% CI [0.5] pg/mL, p < 0.002, Kruskal–Wallis test). CGRP levels were lower in participants who had a headache at the time of the blood draw (1.0 [0.6] pg/mL vs. 1.4 [1.2] pg/mL, p = 0.024). NGF was lower in participants with continuous pain (all types; 1.2 [0.4] vs. 1.4 [0.4] pg/mL, p = 0.027) and was lower in participants with traumatic brain injury (TBI) + posttraumatic headache (PTH) versus TBI without PTH (1.3 [0.3] vs. 1.4 [0.4] pg/mL, p = 0.021). Otherwise, CGRP and NGF were not associated with migraine‐like headache, TBI status, or headache burden as measured by the number of medical encounters in crude or adjusted models. Conclusion: In this exploratory study, plasma levels of NGF and CGRP showed promise as biomarkers for headache and other types of pain. These findings need to be replicated in other cohorts. [ABSTRACT FROM AUTHOR]

The article reports that NPWH is more prevalent in people with migraine compared to those with non-migraine headaches, with significant impacts on disability, depression, anxiety, and work productivity. Topics include the frequency and impact of NPWH in migraine sufferers, its association with increased disease burden and reduced treatment response, and the variation in NPWH impact across different countries, notably Japan.

Background: A growing body of evidence suggests that neuroinflammation contributes actively to pathophysiology Alzheimer's disease (AD) and promotes AD progression. The predictive value of neuroinflammatory biomarkers for disease‐staging or estimating disease progression is not well understood. In this study, we investigate the diagnostic (i.e., differentiating clinical stages of disease) and prognostic (estimating probability of cognitive decline) ability of inflammatory biomarkers in combination with conventional AD biomarkers. Methods: We included 242 participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI) who had CSF biomarkers of Aβ, tau, and inflammation. Outcome of interest was clinically meaningful cognitive decline (CMCD) as defined by an increase of ≥4 on the Alzheimer's Disease Assessment Scale Cognitive Subscore 11 (ADAS‐11, scores 0‐70, higher scores indicate worse cognition). Predictor variables were categorized as demographics (D; age, sex, and education), genetic information such as APOE4 status (G), inflammatory biomarkers (I; see Table 1 for details), and cerebrospinal fluid (CSF) biomarkers of β‐amyloid (A), p‐Tau (P), and total Tau (T). Logistic regression was performed to investigate if grouped inclusion of eleven CSF inflammatory biomarkers as covariates in the models improved classification of baseline clinical diagnosis (CN, cognitively normal; MCI, mild cognitive impairment; Dementia) as well as classification of individuals with and without CMCD one year after baseline. Results: At 1‐year follow up, 25.6% experienced CMCD. Inclusion of inflammatory biomarkers improved classification of MCI vs Dementia for models base on DG (p = 0.039) and DGAPT (p = 0.016) feature‐sets. Addition of inflammatory biomarkers to model with DGAPT features, but not the DG model, improved predictive performance for CMCD in CN (p = 0.021) and MCI (p < 0.001) participants. Conclusions: Addition of CSF Inflammatory biomarkers to AD biomarkers can improve diagnostic accuracy of clinical disease stage. Furthermore, inflammatory biomarkers add incremental value to AD biomarkers for prediction of clinical course and cognitive decline. [ABSTRACT FROM AUTHOR]

Background: We aimed to developed integer‐based risk scores for predicting incident cognitive impairment up to 10 years in initially cognitively normal older adults. Methods: Participants were 479 older adults (aged 60 to 90) from longitudinal studies of aging and Alzheimer's disease from the Knight ADRC at Washington University in St. Louis. The primary outcome was incident cognitive impairment, defined as conversion from Clinical Dementia Rating (CDR®) 0 to >0. The sample was divided into training (60%) and test (40%) sets. Feature‐sets were formed from combinations of four categories of variables: demographics (D), genetics (G), cognitive measures (C), and biomarkers (B) (Details in Figure 1 legend). Utilizing a modified version of the AutoScore‐Survival algorithm, variables were ranked based on variable importance using reduction in predictive accuracy due to replacement with a random permutation value in combination with Random Survival Forests. Variables were iteratively included in constructing risk score models based on coefficients of Cox regression models. Results: Five risk score models were developed using five feature‐sets. All models retained age, APOE4 status, free recall from the Free and Cued Selective Reminding Test, hippocampal atrophy, and Tau positivity when included as potential variables in the feature‐sets. The risk score derived from the DGCB model had a Harrell's concordance index (C‐index) of 0.754 and integrated Area Under the ROC Curve (iAUC) of 0.792. The best performing model without biomarkers used the DGC feature‐set and had a C‐index of 0.694 and iAUC of 0.699 while the risk score using the DG feature‐set only had a C‐index of 0.632 and iAUC of 0.647. Participants who had risk scores in the top quartile of the DGCB model risk score had an increased rate of conversion to CDR > 0. Conclusions: We developed five risk score models for predicting incident cognitive impairment. Risk scores consisted of different sets of measures which differed in ease‐of‐access and costs. Using such simple risk scores that do not include biomakers as clinical decision support tools is practical in the clinical setting. Including biomarkers in risk scores provides slight improvement to classification accuracy, emphasizing their importance in research settings. [ABSTRACT FROM AUTHOR]

Background: β‐amyloid (Aβ), a pathologic hallmark of Alzheimer's disease (AD) is the target of recently FDA‐approved drugs. In trials and in practice, identifying individuals likely to be β‐amyloid positive (Aβ+) with accessible and affordable tests will be increasingly important. Blood‐based biomarkers (BBMs) have shown early promise in determining amyloid status. We aimed to develop machine learning‐based integer risk scores using BBMs and other accessible measures to predict Aβ positivity by PET in older, non‐demented (cognitively unimpaired or mild cognitive impairment) adults. Methods: We used data from 722 individuals (72.1 ± 7.0 years old) from the Alzheimer's Disease Neuroimaging Initiative (ADNI) to develop integer risk scores for predicting Aβ positivity. The sample was divided into training (75%) and test (25%) sets. Variables were categorized as demographics (D: age, sex, and education), genetic information (G: APOE4 status), cognitive measures (C: ADAS‐Cog‐13 and MMSE), and plasma biomarkers of p‐Tau181(T) and neurofilament light (N: NfL). Feature‐sets were formed as hierarchically constructed combinations of these categorized variables (see Figure 1). Using the AutoScore algorithm, variables were ordered according to their Random Forest Gini Index and were iteratively included in the construction of logistic regression‐derived risk score models. Variables were included based on increases in Area Under the ROC Curves (AUCs). Results: Four models were developed based on four feature‐sets. All models utilized age and APOE4 status and, when considered, all models retained ADAS‐Cog‐13, p‐Tau, and NfL. The best performing model corresponded to the DGCTN feature‐set with performance on the dedicated test set of AUC = 0.810 (C.I.: 0.745‐0.876). Using the DGCTN model on the test set, 97% of individuals with scores in the top quartile of possible risk score points were correctly identified as Aβ+. Conclusions: We developed risk score models utilizing accessible and affordable measures to predict Aβ positivity. Plasma biomarkers improve performance of risk scores indicating their value. Applications include screening in clinical settings for therapeutic care and enrichment of clinical trials. These data can be used to optimize the efficient use of PET in determining eligibility for clinical trials and amyloid targeted therapies in practice. [ABSTRACT FROM AUTHOR]

Background: The Einstein Aging Study uses smartphones in an intensive burst design to digitally assess cognition up to 6 times daily for 2 weeks once a year. These burst assessments facilitate the estimation of novel cognitive markers including learning effects and asymptotic performance within bursts and over annual assessments. Here, we examine the influence of two blood‐based biomarkers, pTau‐181 and Neurofilament Light protein (NfL), on cognitive performance measured by digital cognitive markers at baseline and across 6 annual burst assessments. Method: Participants were 293 older adults (Age = 77.4±4.9) free of dementia at baseline. Negative exponential models were used to examine two primary features of response time from the Symbol Search Test of processing speed: (1) learning rate across days within a burst and its change in rate of learning over annual follow‐up; and (2) asymptotic performance (i.e., fastest response time) at baseline and asymptotic change (the rate in which asymptotic performance changes across years). Asymptotic performance is thought to reflect best possible performance and to be relatively free of practice effects. The associations of pTau‐181 and NfL with these features at baseline and change over annual follow‐up were evaluated, adjusting for baseline age, sex, years of education and race/ethnicity. Result: Primary model results are summarized in Table 1. The expected trajectory of symbol search response time across 16 study days within each of the six annual waves, for baseline levels of pTau‐181 and NfL is shown in Figures 1 and 2. Higher levels of both Tau‐181 and of NfL were associated with slower rates of learning in the baseline burst. Higher levels of these BBB at baseline were also associated with slower learning rates from burst to burst (over years) and with greater slowing in asymptotic performance over annual follow‐ups. Conclusion: Higher levels of BBB of Tau and of neurodegeneration are associated with slower learning and with slower response times. These novel parameters derived from ambulatory cognitive testing show expected relationships with biomarkers supporting their validity. Future applications of ambulatory cognition could include the identification of subtle cognitive impairment and in measuring within person change in cognition in clinical trials or clinical practice. [ABSTRACT FROM AUTHOR]

Introduction: Sex differences in dementia risk, and risk factor (RF) associations with dementia, remain uncertain across diverse ethno‐regional groups. Methods: A total of 29,850 participants (58% women) from 21 cohorts across six continents were included in an individual participant data meta‐analysis. Sex‐specific hazard ratios (HRs), and women‐to‐men ratio of hazard ratios (RHRs) for associations between RFs and all‐cause dementia were derived from mixed‐effect Cox models. Results: Incident dementia occurred in 2089 (66% women) participants over 4.6 years (median). Women had higher dementia risk (HR, 1.12 [1.02, 1.23]) than men, particularly in low‐ and lower‐middle‐income economies. Associations between longer education and former alcohol use with dementia risk (RHR, 1.01 [1.00, 1.03] per year, and 0.55 [0.38, 0.79], respectively) were stronger for men than women; otherwise, there were no discernible sex differences in other RFs. Discussion: Dementia risk was higher in women than men, with possible variations by country‐level income settings, but most RFs appear to work similarly in women and men. [ABSTRACT FROM AUTHOR]

Background: There is renewed emphasis on including patients in determining, defining, and prioritizing outcomes for migraine treatment. Objectives: To obtain insights directly from people living with migraine on their priorities for treatment. Methods: A total of 40 qualitative interviews were conducted as part of the Migraine Clinical Outcome Assessment System project, a United States Food and Drug Administration grant‐funded program to develop a core set of patient‐centered outcome measures for migraine clinical trials. Interviews included a structured exercise in which participants rank‐ordered pre‐defined lists of potential benefits for acute and preventive migraine therapy. The 40 study participants who reported being diagnosed with migraine by a clinician ranked the benefits and explained their rationale. Results: Study participants consistently ranked either pain relief or absence of pain as their top priority for acute treatment. Relief/absence of other migraine symptoms and improved functioning were also prioritized. For preventive treatment, participants prioritized reductions in migraine frequency, symptom severity, and attack duration. Few differences were found between participants with episodic migraine and those with chronic migraine. However, participants with chronic migraine ranked "increased predictability of attacks" much higher than those with episodic migraine. Participants' rankings were influenced by prior expectations and experiences of migraine treatments, which caused many participants to deprioritize desired benefits as unrealistic. Participants also identified several additional priorities, including limited side‐effects and reliable treatment efficacy in both acute and preventive treatments. Conclusion: The results showed the participants prioritized treatment benefits aligned with existing core clinical outcomes used in migraine research, but also valued benefits that are not typically assessed, such as predictability. Participants also deprioritized important benefits when they believed treatment was unlikely to deliver those outcomes. [ABSTRACT FROM AUTHOR]

Objective: Assess the long‐term efficacy and safety of erenumab in patients with chronic migraine with acute medication overuse. Background: Overuse of acute medication in patients with chronic migraine has been linked to greater pain intensity and disability and may diminish the effectiveness of preventive therapies. Methods: This 52‐week open‐label extension study followed a 12‐week double‐blind placebo‐controlled study in which patients with chronic migraine were randomized 3:2:2 to placebo or once‐monthly erenumab 70 mg or 140 mg. Patients were stratified by region and medication overuse status. Patients received erenumab 70 mg or 140 mg throughout or switched from erenumab 70 to 140 mg (based on protocol amendment to augment safety data at higher dose). Efficacy was assessed in patients with and without medication overuse at parent study baseline. Results: Of 609 patients enrolled in the extension study, 252/609 (41.4%) met the criteria for medication overuse at parent study baseline. At Week 52, the mean change in monthly migraine days from parent study baseline was −9.3 (95% confidence interval: −10.4, −8.1 days) in the medication overuse subgroup versus −9.3 (−10.1, −8.5 days) in the non‐medication overuse subgroup (combined erenumab doses); proportion of patients achieving ≥50% reduction in monthly migraine days at Week 52 was 55.9% (90/161; 48.2%, 63.3%) versus 61.3% (136/222; 54.7%, 67.4%), respectively. Among baseline users of acute migraine‐specific medication, the mean change in monthly migraine‐specific medication days at Week 52 was −7.4 (−8.3, −6.4 days) in the medication overuse subgroup versus −5.4 (−6.1, −4.7 days) in the non–medication overuse subgroup. Most patients (197/298; 66.1%) in the medication overuse subgroup transitioned to non‐overuse status by Week 52. Erenumab 140 mg was associated with numerically greater efficacy than erenumab 70 mg across all endpoints. No new safety signals were identified. Conclusion: Long‐term erenumab treatment demonstrated sustained efficacy and safety in patients with chronic migraine with and without acute medication overuse. [ABSTRACT FROM AUTHOR]

Objective: To evaluate changes in interictal burden with galcanezumab versus placebo in patients with episodic (EM) or chronic migraine (CM). Background: The disruptive effects of migraine occur both during attacks (ictal period) and between attacks (interictal period), affecting work, school, family, and social life. Migraine clinical trials typically assess ictal burden endpoints, neglecting interictal burden. Methods: CONQUER was a 3‐month, double‐blind study that randomized adult patients with EM or CM who had experienced failure of two to four standard‐of‐care migraine preventive medication categories to receive monthly galcanezumab (n = 232) or placebo (n = 230), followed by 3 months of open‐label galcanezumab. The mean change in interictal burden, a secondary objective, was measured using the four‐item Migraine Interictal Burden Scale (MIBS‐4). The total score for MIBS‐4 can range from zero to 12, with scores ≥5 indicating severe interictal burden. Post hoc analyses evaluated shifts in MIBS‐4 severity categories and item‐level improvement. Results: The MIBS‐4 total score indicated severe interictal burden at baseline (mean [SD]: all patients, 5.5 [3.5]; EM, 5.0 [3.4]; CM, 6.2 [3.5]). Reductions in the MIBS‐4 score were significantly greater with galcanezumab versus placebo at Month 3 (mean [SE]: all patients −1.9 [0.2] vs. −0.8 [0.2], p < 0.0001; EM, −1.8 [0.3] vs. −1.1 [0.3], p = 0.033; CM, −1.8 [0.4] vs. −0.3 [0.4], p < 0.001), with further improvement at Month 6 after all patients had received galcanezumab (mean [SE]: all patients, −2.4 [0.2] vs. −2.0 [0.2]; EM, −2.3 [0.3] vs. −2.2 [0.3]; CM, −2.1 [0.4] vs. −1.5 [0.4]). The percentage of patients with severe interictal burden decreased substantially for the galcanezumab‐treated patients, from 59% (137/232) at baseline to 27% (58/217) at Month 6 (EM from 51% [70/137] to 23% [30/131]; CM from 71% [67/95] to 33% [28/86]). Conclusion: In addition to the known efficacy of galcanezumab in the ictal period, these findings suggest treatment with galcanezumab results in a significant reduction in interictal burden. [ABSTRACT FROM AUTHOR]

Introduction: Studies suggest bilingualism may delay behavioral manifestations of adverse cognitive aging including Alzheimer's dementia. Methods: Three thousand nine hundred sixty‐three participants (unweighted mean population age ≈56 years) at Hispanic Community Health Study/Study of Latinos baseline (2008–2011) self‐reported their and their parents' birth outside the United States, Spanish as their first language, and used Spanish for baseline and comparable cognitive testing 7 years later (2015–2018). Spanish/English language proficiency and patterns of use were self‐rated from 1 = only Spanish to 4 = English > Spanish. Cognitive testing included test‐specific and global composite score(s) of verbal learning, memory, word fluency, and Digit Symbol Substitution (DSS). Survey linear regression models examined associations between baseline bilingualism scores and cognition. Results: Higher second‐language (English) proficiency and use were associated with higher global cognition, fluency, and DSS at follow‐up and better than predicted change in fluency. Discussion: The bilingual experience was more consistently related to 7‐year level versus change in cognition for Hispanics/Latinos. [ABSTRACT FROM AUTHOR]

Aim: To synthesize international findings on the alcohol–dementia relationship, including representation from low‐ and middle‐income countries. Methods: Individual participant data meta‐analysis of 15 prospective epidemiological cohort studies from countries situated in six continents. Cox regression investigated the dementia risk associated with alcohol use in older adults aged over 60 years. Additional analyses assessed the alcohol–dementia relationship in the sample stratified by sex and by continent. Participants included 24 478 community dwelling individuals without a history of dementia at baseline and at least one follow‐up dementia assessment. The main outcome measure was all‐cause dementia as determined by clinical interview. Results: At baseline, the mean age across studies was 71.8 (standard deviation = 7.5, range = 60–102 years), 14 260 (58.3%) were female and 13 269 (54.2%) were current drinkers. During 151 636 person‐years of follow‐up, there were 2124 incident cases of dementia (14.0 per 1000 person‐years). When compared with abstainers, the risk for dementia was lower in occasional [hazard ratio (HR) = 0.78; 95% confidence interval (CI) = 0.68–0.89], light–moderate (HR = 0.78; 95% CI = 0.70–0.87) and moderate–heavy drinkers (HR = 0.62; 95% CI = 0.51–0.77). There was no evidence of differences between life‐time abstainers and former drinkers in terms of dementia risk (HR = 0.98; 95% CI = 0.81–1.18). In dose–response analyses, moderate drinking up to 40 g/day was associated with a lower risk of dementia when compared with lif‐time abstaining. Among current drinkers, there was no consistent evidence for differences in terms of dementia risk. Results were similar when the sample was stratified by sex. When analysed at the continent level, there was considerable heterogeneity in the alcohol–dementia relationship. Conclusions: Abstinence from alcohol appears to be associated with an increased risk for all‐cause dementia. Among current drinkers, there appears to be no consistent evidence to suggest that the amount of alcohol consumed in later life is associated with dementia risk. [ABSTRACT FROM AUTHOR]

Objectives: To capture patients' perspectives on migraine‐related cognitive symptoms during pre‐headache, headache, post‐headache, and interictal periods. Background: Migraine‐related cognitive symptoms are reported by people with migraine both during and between attacks. Associated with disability, they are increasingly viewed as a priority target for treatment. The Migraine Clinical Outcome Assessment System (MiCOAS) project is focused on developing a patient‐centered core set of outcome measures for the evaluation of migraine treatments. The project focuses on incorporating the experience of people living with migraine and the outcomes most meaningful to them. This includes an examination of the presence and functional impact of migraine‐related cognitive symptoms and their perceived impact on quality of life and disability. Methods: Forty individuals with self‐reported medically diagnosed migraine were recruited via iterative purposeful sampling for semi‐structured qualitative interviews conducted using audio‐only web conferencing. Thematic content analysis was performed to identify key concepts around migraine‐related cognitive symptoms. Recruitment continued until concept saturation was achieved. Results: Participants described symptoms consistent with migraine‐related deficits in language/speech, sustained attention, executive function, and memory that manifest during pre‐headache (36/40 [90%] reported ≥1 cognitive feature), headache (35/40 [88%] reported ≥1 cognitive feature), post‐headache (27/40 [68%] reported ≥1 cognitive feature), and interictal periods (13/40 [33%] reported ≥1 cognitive feature). Among participants reporting cognitive symptoms during pre‐headache, 32/40 (81%) endorsed 2–5 cognitive symptoms. Findings were similar during the headache phase. Participants reported language/speech problems consistent with, for example, impairments in receptive language, expressive language, and articulation. Issues with sustained attention included fogginess, confusion/disorientation, and trouble with concentration/focus. Deficits in executive function included difficulty processing information and reduced capacity for planning and decision‐making. Memory issues were reported across all phases of the migraine attack. Conclusions: This patient‐level qualitative study suggests that cognitive symptoms are common for persons with migraine, particularly in the pre‐headache and headache phases. These findings highlight the importance of assessing and ameliorating these cognitive problems. [ABSTRACT FROM AUTHOR]

Objective: To identify predictors of acute treatment optimization for migraine with "over‐the‐counter" (OTC) or prescription nonsteroidal anti‐inflammatory drugs (NSAIDs) as well as other widely used OTCs including acetaminophen, caffeine combination products (CCP), and acetylsalicylic acid (ASA, aspirin) among people with episodic migraine and to develop models that predict treatment response to each class of OTCs. Background: Efficacy of acute OTC medications for migraine varies greatly. Identifying predictors of treatment response to particular classes of medication is a step toward evidence‐based personalized therapy. Methods: For this prediction model development study, we used data from 2224 participants from the American Migraine Prevalence and Prevention (AMPP) study who were aged ≥18 years, met criteria for migraine, had <15 monthly headache days, and reported being on monotherapy for acute migraine attacks with one of the following classes medications: CCP (N = 711), acetaminophen (N = 643), ASA (N = 110), and prescription or OTC NSAIDs (N = 760). The primary outcome measures of treatment optimization were adequate 2‐h pain freedom (2hPF) and adequate 24‐h pain relief (24hPR), which were defined by responses of half the time or more to the relevant items on the Migraine Treatment Optimization Questionnaire‐6. Results: The mean (SD) age of the participants was 46.2 (13.1) years, 79.4% (1765/2224) were female, 43.7% (972/2224) reported adequate 2hPF, and 46.1% (1025/2224) reported adequate 24hPR. Those taking CCP had better 2hPF and 24PR outcomes. For those taking NSAIDs, better outcomes were associated with lower average pain intensity (2hPF: odds ratio [OR] 0.89, 95% confidence interval [CI] 0.80–0.99; 24PR: OR 0.86, 95% CI 0.77–0.96), cutaneous allodynia (2hPF: OR 0.92, 95% CI 0.89–0.96; 24PR: OR 0.91, 95% CI 0.87–0.95), depressive symptoms (2hPF: OR 0.95, 95% CI 0.92–0.98; 24PR: OR 0.95, 95% CI 0.91–0.99), and Migraine Disability Assessment Scale (MIDAS) grade (2hPF: OR 0.76, 95% CI 0.64–0.90; 24PR: OR 0.79, 95% CI 0.65–0.95). Adequate 2hPF for those taking CCP was associated with male gender (OR 1.83, 95% CI 1.21–2.77), lower average pain intensity (OR 0.80, 95% CI 0.70–0.91), lower cutaneous allodynia (OR 0.94, 95% CI 0.90–0.97), and lower Migraine Symptom Severity Scale Score (MSSS; OR 0.91, 95% CI 0.86–0.97). Adequate 24hPR for those taking CCP was associated with lower average pain intensity (OR 0.85, 95% CI 0.75–0.96), lower cutaneous allodynia (OR 0.92, 95% CI 0.89–0.96), and lower MIDAS grade (OR 0.81, 95% CI 0.68–0.96). Participants who were married (OR 1.51, 95% CI 1.05–2.19), had lower average pain intensity (OR 0.79, 95% CI 0.70–0.89), lower MSSS (OR 0.93, 95% CI 0.88–0.99), less depression (OR 0.96, 95% CI 0.93–0.99), and lower MIDAS grade (OR 0.72, 95% CI 0.59–0.87) had adequate 2hPF after taking acetaminophen. Participants who were married (OR 1.50, 95% CI 1.02–2.21), had lower pain intensity (OR 0.78, 95% CI 0.69–0.88), less depression (OR 0.95, 95% CI 0.91–0.98) and lower MIDAS grade (OR 0.53, 95% CI 0.42–0.67) had higher 24hPR following use of acetaminophen. A lower MSSS was the only factor associated with higher 2hPF and 24PR after using ASA (OR 0.78, 95% CI 0.67–0.92 and OR 0.79, 95% CI 0.67–0.93). Predictive models had modest performance in identifying responders to each class of OTC. Conclusion: A large subgroup of people with migraine had an inadequate response to their usual acute OTC migraine treatment 2‐ and 24‐h after dosing. These findings suggest a need to improve OTC treatment for some and to offer prescription acute medications for others. Predictive models identified several factors associated with better treatment‐response in each OTC class. Selecting OTC treatment based on factors predictive of treatment optimization might improve patient outcomes. [ABSTRACT FROM AUTHOR]

Objective: To evaluate potential drug–drug interactions of ubrogepant and atogepant. Background: Ubrogepant and atogepant, calcitonin gene‐related peptide (CGRP) receptor antagonists, are recently approved drugs for acute and preventive treatment of migraine, respectively. For patients with migraine who are prescribed atogepant for the preventive treatment of migraine, health care providers could prescribe ubrogepant for the acute treatment of breakthrough migraine attacks. Methods: A phase Ib, multi‐center, open‐label, fixed‐sequence study was conducted in participants diagnosed with migraine for at least 1 year. To assess the primary objective of pharmacokinetic interactions in this phase I trial, the highest United States Food and Drug Administration‐approved individual dose strengths of atogepant (60 mg once daily) and ubrogepant (100 mg) were utilized, with ubrogepant being administered on a fixed‐dose schedule every 3 days, regardless of whether a participant was experiencing a migraine attack. Secondary endpoints included safety and tolerability. Clinical safety measurements were monitored throughout the study. Results: Of the 31 participants enrolled, 26 completed the study. A single dose of ubrogepant had no statistically significant effect on atogepant pharmacokinetics. Co‐administration of ubrogepant with atogepant resulted in a 19% increase (geometric mean ratio 118.80, 90% confidence interval [CI] 108.69–129.84) in the ubrogepant area under the plasma concentration‐time curve and a 26% increase (geometric mean ratio 125.63, 90% CI 105.58–149.48) in the ubrogepant maximum plasma concentration. These statistically significant changes in ubrogepant exposure were not clinically meaningful, and no new safety concerns were identified for the combination. Conclusion: The combination use of atogepant and ubrogepant was safe and well tolerated in adult participants with a history of migraine enrolled in the study. Pharmacokinetic changes during co‐administration were not clinically meaningful. [ABSTRACT FROM AUTHOR]

Objective: To investigate the links between adolescent migraine and comorbid and co‐occurring conditions using a large, nationally representative longitudinal study. Background: Comorbidities and co‐occurring conditions play an important role in the clinical treatment of individuals with migraine. Research in this area has focused largely on the adult population using cross‐sectional data, but less is known about adolescents and how conditions may co‐occur over time from a broader developmental perspective. The goals of this manuscript were to empirically evaluate the associations between adolescent migraine and several linked conditions and explore the relative timings of onset of these conditions from adolescence to adulthood. Methods: Data came from the National Longitudinal Study of Adolescent to Adult Health (Add Health), a school‐based study of the health‐related behaviors and conditions of adolescents. The present study examined data from Wave 1 (W1, study years: 1994–1995), Wave 4 (W4, study years: 2008–2009), and Wave 5 (W5, study years: 2016–2018). Analyses and visual plots were used to evaluate potential links between parent‐reported adolescent migraine status (PR‐AdMig) at W1 and 15 medical conditions identified based on self‐reported medical diagnoses (SR‐MDs) at W4 and W5. Based on prior literature in adults, we identified 11 conditions predicted to be associated with PR‐AdMig and four conditions predicted not to be associated with PR‐AdMig. The analyses were exploratory and post hoc. Results: The total sample size pooling over all analyses was n = 13,786, but the wave‐specific sample sizes differed due to missing data (W4 analyses, n = 12,692; W5 analyses, n = 10,340); 7243/13,786 (unweighted: 52.5%; weighted: 50.5%) of participants were female, 7640/13,786 (unweighted: 55.4%; weighted: 68.6%) were White, and 1580/13,786 (unweighted: 11.5%; weighted: 12.0%) had PR‐AdMig. The average ages were 15.8 years at W1, 28.7 years at W4, and 37.8 years at W5. Findings showed that PR‐AdMig was associated with anxiety/panic disorder (W4: PR‐AdMig vs. Control weighted %: 17.1% vs. 12.6%, unadjusted odds ratio [OR] = 1.43, 95% confidence interval [CI] 1.18–1.74, p = 0.0003; W5: 31.6% vs. 22.4%, OR = 1.60, 95% CI 1.28–2.02, p < 0.0001), asthma/chronic bronchitis/emphysema (W4: 20.0% vs. 14.7%, OR = 1.45, 95% CI 1.20–1.76, p < 0.001; W5: 21.0% vs. 14.6%, OR = 1.55, 95% CI 1.25–1.94, p < 0.001), attention deficit hyperactivity disorder (W4: 8.3% vs. 5.4%, OR = 1.58, 95% CI 1.18–2.10, p = 0.002), depression (W4: 23.7% vs. 15.4%, OR = 1.71, 95% CI 1.43–2.04, p < 0.0001; W5: 33.8% vs. 25.1%, OR = 1.53, 95% CI 1.22–1.90, p < 0.001), epilepsy/seizure disorder (W4: 2.2% vs. 1.2%, OR = 1.84, 95% CI 1.23–2.76, p = 0.004), migraine (W4: 38.8% vs. 11.9%, OR = 4.7, 95% CI 4.1–5.5, p < 0.001), post‐traumatic stress disorder (W4: 4.1% vs. 2.8%, OR = 1.45, 95% CI 1.01–2.08, p = 0.042; W5: 11.3% vs. 7.1%, OR = 1.67, 95% CI 1.27–2.20, p < 0.001), and sleep apnea (W5: 11.0% vs. 7.6%, OR = 1.51, 95% CI 1.15–1.98, p = 0.003). Among theoretically unlinked conditions, only hepatitis C at W4 was shown to have a relationship with adolescent onset migraine (0.7% vs. 0.2%, OR = 3.63, 95% CI 1.32–10.0, p = 0.013). Visual plots suggested that the retrospective, self‐report timing of onset of specific subsets of co‐occurring conditions tended to group together over time. Conclusions: Consistent with the existing headache literature, results showed that adolescent migraine was associated with other medical and psychological conditions and visual plots suggested that there may be developmental patterns in the occurrence of migraine with other related conditions. [ABSTRACT FROM AUTHOR]

Introduction: We investigated the utility of the Telephone‐Montreal Cognitive Assessment (T‐MoCA) to track cognition in a diverse sample from the Einstein Aging Study. Methods: Telephone and in‐person MoCA data, collected annually, were used to evaluate longitudinal cognitive performance. Joint models of T‐MoCA and in‐person MoCA compared changes, variance, and test‐retest reliability measured by intraclass correlation coefficient by racial/ethnic group. Results: There were no significant differences in baseline performance or longitudinal changes across three study waves for both MoCA formats. T‐MoCA performance improved over waves 1–3 but declined afterward. Test‐retest reliability was lower for the T‐MoCA than for the in‐person MoCA. In comparison with non‐Hispanic Whites, non‐Hispanic Blacks and Hispanics performed worse at baseline on both MoCA formats and showed lower correlations between T‐MoCA and in‐person versions. Conclusions: The T‐MoCA provides valuable information on cognitive change, despite racial/ethnic disparities and practice effects. We discuss implications for health disparity populations. Highlights: We assessed the comparability of Telephone‐Montreal Cognitive Assessment (T‐MoCA) and in‐person MoCA for tracking cognition.Changes within 3 years in T‐MoCA were similar to that for the in‐person MoCA.T‐MoCA is subject to practice effects and shows difference in performance by race/ethnicity.Test‐retest reliability of T‐MoCA is lower than that for in‐person MoCA. [ABSTRACT FROM AUTHOR]

Background: Excessive alcohol intake and no alcohol intake are associated with an increased risk of dementia relative to low to moderate alcohol consumption. We aimed to investigate the cross‐sectional association between different levels of alcohol consumption and cognition in the Anti‐Amyloid Treatment in Asymptomatic Alzheimer's Disease (A4 Study). We examined whether this association would differ between sexes or based on individuals' β‐amyloid (Aβ) status (Aβ+ vs Aβ‐; Aβ+: PET Composite SUVR > 1.15, Aβ‐: Others). Method: A total of 4387 cognitively unimpaired older adults who had both objective and subjective cognitive assessments and amyloid Positron Emission Tomography (PET) imaging. Participants were classified into 4 categories based on their average daily alcohol use: none, one, two, and three or more drinks/day. Multivariable linear regression was used to test the main effects as well as interactions with sex and Aβ levels. Result: Participants were on average 71.28 (SD = 4.67) years old and 59% female. In the whole population, individuals who reported no alcohol consumption had lower scores on the Preclinical Alzheimer Cognitive Composite (PACC) compared to those who reported consuming one (β[SE] = 0.19[0.08], p = 0.017) or two (β[SE] = 0.22[0.11], p = 0.05) drinks/day (Table 1, Figure 1). In sex‐stratified analysis, the association between alcohol consumption and cognition was more prominent in females. Female participants who consumed two drinks/day had better performance on PACC (β[SE] = 0.32[0.16], p = 0.043) and Cognitive Function Index (CFI; β[SE] = ‐0.27[0.12], p = 0.026) compared to those who reported no alcohol consumption (Figure 2). In an Aβ status‐stratified sample, the association between alcohol consumption and cognition was present only in the Aβ‐ subgroup. Among Aβ‐ individuals, those who consumed one drink/day had better performance on PACC (β[SE] = 0.28[0.09], p = 0.003) and CFI (β[SE] = ‐0.18[0.07], p = 0.009) compared to those who reported no alcohol consumption (Figure 3). The interaction between Aβ status and alcohol consumption on cognition was not significant. Conclusion: Low or moderate consumption of alcohol is associated with better cognitive performance in cognitively unimpaired individuals. The association is more prominent in Aβ‐ individuals, which might indicate that the pathophysiologic mechanism underlying the effect of alcohol on cognition is independent of AD‐pathology. The interaction with Aβ status requires further investigation with larger samples consuming 3 or more drinks/day. [ABSTRACT FROM AUTHOR]

Background: Alzheimer's disease (AD) is a phenotypically and pathologically heterogenous disorder. We used MRI in amyloid positive patients enrolled in the placebo arm of the Phase 3 Trial of solanezumab for mild dementia due to AD (EXPEDITION3) to identify more homogeneous subgroups based on variation in volumetrics. Methods: We implemented the self‐organizing map algorithm on baseline volumetric MRI measures from nine brain regions of interest (ROIs) to cluster 1041 individuals enrolled in the placebo arm of the EXPEDITION3 trial. Volumetric MRI differences were compared among clusters. Demographics as well as baseline and longitudinal cognitive performance metrics were used to evaluate cluster characteristics. Results: Three distinct clusters, with an overall silhouette coefficient of 0.383, were identified based on MRI volumetrics. Cluster 1 (N=400) had the largest baseline volumetric measures across all ROIs and the best cognitive performance at baseline (Table 1). Cluster 2 (N=269) had larger hippocampal and medial temporal lobe volumes, but smaller parietal lobe volumes in comparison with the third cluster (N=372) (Figure 1). Spider plots show the normalized test performance at baseline and follow‐up with larger values corresponding to worse test performance; Cluster 1 shows relatively little cognitive change (Figure 2). Spider plots of regional MRI volumes show smaller volumes for Clusters 2 and 3 relative to Cluster 1 and asymmetries that reflect regional differences in atrophy (Figure 2). The mean change from baseline to week 80 in the ADAS‐cog14 score for Clusters 1, 2, and 3 were 4.28 (SE=0.35), 10.14 (SE=0.51), and 7.90 (SE=0.43), respectively. Significant between‐group mean differences were observed between Clusters 1 and 2 (difference, 2.38; 95% CI, 1.85 to 2.91; P<0.001), Clusters 1 and 3 (difference, 1.93; 95% CI, 1.41 to 2.44; P<0.001), but not between Clusters 2 and 3 (difference, 0.45; 95% CI, ‐0.11 to 1.02; P=0.146) in ADAS‐cog14 (Figure 3). Conclusions: Volumetric MRI can be used to identify homogenous clusters of amyloid positive individuals with mild dementia. The groups identified differ in baseline and longitudinal characteristics. Cluster 1 shows little ADAS‐cog14 change over the first 40 weeks of study on placebo treatment and may be unsuitable for identifying early benefits of treatment. [ABSTRACT FROM AUTHOR]

The article discusses the validation of a migraine diagnostic screening tool, ID-migraine-Mx, in Latin-American Spanish. The study compares its operating characteristics in English and Spanish and explores the potential for a policy recommendation for migraine screening. Accurate screening is crucial to improve outcomes for people with migraine.

Background: The Telephone‐Montreal Cognitive Assessment (T‐MoCA) is a widely‐used, remotely administered cognitive screen. The T‐MoCA demonstrates adequate psychometric properties and may be used when standard, in‐person administration of the MoCA is not feasible (Katz et al., 2020). There is a critical need to investigate the agreement of the T‐MoCA across administration modalities (in‐person versus telehealth) among ethnically and racially diverse populations. Methods: The Einstein Aging Study (EAS) includes a community‐based of racially/ethnically diverse community‐dwelling individuals, ≥ age 70 from the Bronx, NY. Participants (N = 424) were free of dementia at enrollment and completed the T‐MoCA along with in‐person neuropsychological tests including the MoCA‐22, which excludes items unsuitable for telephone administration paralleling the T‐MoCA (Table 1). Intraclass correlation coefficients (ICCs) between T‐MoCA and MoCA‐22 were used to measure agreement. Linear mixed effects models were applied to compare mean scores and ICCs among ethnic/racial groups, with and without adjusting for age, gender, education and depressive symptoms. Results: Participants were on average 78.2 years, 65.8% female, 47.6% non‐Hispanic White, 38.0% non‐Hispanic Black, and 14.4% Hispanic. There was no significant difference between mean T‐MoCA and MoCA‐22 scores and no differential associations with age, gender, education, and depressive symptoms. For both modalities, NH Black (difference ‐1.54, p<.0001) and Hispanic (difference ‐2.04, p<.0001) groups demonstrated significantly lower scores compared to non‐Hispanic Whites (Table 2). As shown in Table 2, ICCs among non‐Hispanic White, non‐Hispanic Black, and Hispanic groups were 0.64, 0.50 and 0.42, respectively, and comparisons of ICCs to non‐Hispanic White were significantly lower in non‐Hispanic Black (p = 0.0495) and borderline significant in Hispanic participants (p = 0.0552). Findings were similar after adjusting for covariates. Conclusion: The agreement between telephone and in‐person modalities of the MoCA was weaker in non‐Hispanic Black and Hispanic participants (compared to non‐Hispanic White). Further investigation of factors and/or items that contribute to these lower correlations is warranted. Although the T‐MoCA and other remotely administered cognitive screens have the potential to broaden accessibility to marginalized groups, researchers must use caution when developing or selecting appropriate demographically adjusted norms and interpreting scores of diverse older adults. [ABSTRACT FROM AUTHOR]

The article offers insights into the social impact of migraine and discusses the choices society has in responding to this problem. It highlights the interconnectedness of individuals with migraine and the potential benefits of accommodating their needs, such as increased productivity and improved well-being for everyone.

Background: Stigma is increasingly recognized as an important social feature of living with migraine. Methods: Adults with migraine recruited from neurology offices completed the validated Stigma Scale for Chronic Illnesses 8‐item version (SSCI‐8); two outcome measures (the Migraine Disability Assessment [MIDAS] and the Migraine‐Specific Quality of Life Questionnaire v 2.1 [MSQ]); and measures of allodynia (Allodynia Symptom Checklist [ASC‐12]), pain cognition (Pain Catastrophizing Scale [PCS]), and psychiatric symptoms (Patient Reported Measurement Information System Anxiety [PROMIS‐A] and Depression [PROMIS‐D]). Pearson and Spearman correlations evaluated bivariate relationships, and linear (MSQ) and logistic (MIDAS Severe Disability, scores ≥21) regressions evaluated the unique variance associated with SSCI‐8 beyond other study variables. Conditional process analysis evaluated mediation hypotheses between study variables. Results: Participants (n = 121) reported levels of stigma on par with other chronic illnesses (SSCI‐8 M = 53.0, standard deviation [SD] = 7.8), with 25/127 (19.6%) reporting clinically significant levels of stigma (SSCI‐8 T‐score ≥ 60). Higher SSCI‐8 scores were associated with higher monthly headache day frequency (r = 0.35), MIDAS (ρ = 0.41), ASC‐12 (r = 0.24, p < 0.01), PCS (r = 0.46), both PROMIS‐A (r = 0.43) and D (r = 0.42), and lower MSQ subscale scores (Role Restriction r = −0.50; Role Prevention r = −0.48; Emotion Function r = −0.50), all ps <0.001 unless otherwise noted. The SSCI‐8 contributed significantly beyond migraine symptoms and other psychological factors for MSQ Emotion Function (5% unique variance) and MIDAS Severe Disability (6% of unique variance). The SSCI‐8 mediated relationships between headache frequency and the MSQ subscales and MIDAS Severe Disability. The PCS mediated relationships between the SSCI‐8 and MSQ subscales. The PROMIS‐D mediated relationships between the SSCI‐8 and MSQ Role Restriction and MSQ Role Prevention. Conclusions: Migraine stigma has medium to large associations with migraine outcomes and psychiatric symptoms and is independently associated with migraine disability and emotion‐related quality of life. Migraine stigma is an important contributor to the relationship between headache frequency and migraine outcomes. [ABSTRACT FROM AUTHOR]

Objective: Evaluate the efficacy, safety, and tolerability of zavegepant nasal spray in the acute treatment of migraine. Background: Calcitonin gene‐related peptide‐targeting agents are a novel class of therapeutics for migraine, but none are currently available as a nonoral option for acute treatment. Zavegepant, a high‐affinity, selective, and structurally unique calcitonin gene‐related peptide‐receptor antagonist in late‐stage development, is formulated as a nasal spray for the acute treatment of migraine. Methods: This randomized, dose‐ranging, placebo‐controlled, Phase 2/3 trial in adults aged ≥18 years with migraine (NCT03872453) was conducted at US study sites. Participants were randomized by an interactive web response system and treated a single attack of moderate to severe pain intensity with zavegepant nasal spray 5, 10, 20 mg, or placebo. Coprimary efficacy endpoints were pain freedom and freedom from the most bothersome symptom at 2 h postdose. Results: Of the 1673 participants aged 18 to 79 years who were randomized, 1588 were treated with study medication, and 1581 (mean age 40.8 years, 85.5% female) were analyzed for efficacy: zavegepant 5 mg (n = 387), 10 mg (n = 391), 20 mg (n = 402), and placebo (n = 401). Zavegepant 10 and 20 mg were more effective than placebo on the coprimary endpoints of pain freedom at 2 h postdose (placebo: 15.5% [98.3% confidence interval (CI), 11.1, 19.8]; 10 mg: 22.5% [98.3% CI, 17.5, 27.6; p = 0.0113]; 20 mg: 23.1% [98.3% CI, 18.1, 28.2; p = 0.0055]) and freedom from the most bothersome symptom at 2 h postdose (placebo: 33.7% [98.3% CI, 28.0, 39.3]; 10 mg: 41.9% [98.3% CI, 36.0, 47.9; p = 0.0155]; 20 mg: 42.5% [98.3% CI, 36.6, 48.4; p = 0.0094]). Findings for the 5 mg dose were not significant. The most common treatment‐emergent adverse events with zavegepant 10 and 20 mg and placebo were dysgeusia (13.5% to 16.1% vs. 3.5%), nausea (2.7% to 4.1% vs. 0.5%), and nasal discomfort (1.3% to 5.2% vs. 0.2%). Most adverse events were mild or moderate and resolved without treatment. There was no signal of hepatotoxicity. Conclusion: Zavegepant nasal spray, in single doses of 10 or 20 mg, was effective for the acute treatment of migraine, with a favorable safety profile. Additional research is needed to confirm its potential as a nonoral medication for the acute treatment of migraine. [ABSTRACT FROM AUTHOR]

Objective: To evaluate whether patients discharged to home after an emergency department (ED) visit for headache face a heightened short‐term risk of stroke. Background: Stroke hospitalizations that occur soon after ED visits for headache complaints may reflect diagnostic error. Methods: We conducted a retrospective cohort study using statewide administrative claims data for all ED visits and admissions at nonfederal hospitals in Florida 2005–2018 and New York 2005–2016. Using standard International Classification of Diseases (ICD) codes, we identified adult patients discharged to home from the ED (treat‐and‐release visit) with a benign headache diagnosis (cohort of interest) as well as those with a diagnosis of renal colic or back pain (negative controls). The primary study outcome was hospitalization within 30 days for stroke (ischemic or hemorrhagic) defined using validated ICD codes. We assess the relationship between index ED visit discharge diagnosis and stroke hospitalization adjusting for patient demographics and vascular comorbidities. Results: We identified 1,502,831 patients with an ED treat‐and‐release headache visit; mean age was 41 (standard deviation: 17) years and 1,044,520 (70%) were female. A total of 2150 (0.14%) patients with headache were hospitalized for stroke within 30 days. In adjusted analysis, stroke risk was higher after headache compared to renal colic (hazard ratio [HR]: 2.69; 95% confidence interval [CI]: 2.29–3.16) or back pain (HR: 4.0; 95% CI: 3.74–4.3). In the subgroup of 26,714 (1.78%) patients with headache who received brain magnetic resonance imaging at index ED visit, stroke risk was only slightly elevated compared to renal colic (HR: 1.47; 95% CI: 1.22–1.78) or back pain (HR: 1.49; 95% CI: 1.24–1.80). Conclusion: Approximately 1 in 700 patients discharged to home from the ED with a headache diagnosis had a stroke in the following month. Stroke risk was three to four times higher after an ED visit for headache compared to renal colic or back pain. [ABSTRACT FROM AUTHOR]

Objective: To assess the utility of the novel patient‐identified (PI) most bothersome symptom (MBS) measure from PROMISE‐2, a phase 3 trial of eptinezumab for the preventive treatment of chronic migraine. Background: Relief of bothersome migraine symptoms can influence satisfaction with treatment and therapeutic persistence. Understanding the impact of preventive treatment on a PI‐MBS could improve clinical decision‐making. Methods: In PROMISE‐2, patients with chronic migraine received eptinezumab 100, 300 mg, or placebo administered intravenously every 12 weeks for up to 2 doses (n = 1072). PI‐MBS was an exploratory outcome requiring each patient to self‐report their MBS in response to an open‐ended question. At baseline and week 12, patients rated overall improvement in PI‐MBS. The relationships among PI‐MBS at week 12 and change in monthly migraine days (MMDs) from baseline to month 3 (weeks 9–12), Patient Global Impression of Change at week 12, and changes from baseline to week 12 in the 6‐item Headache Impact Test total, EuroQol 5‐dimensions 5‐levels visual analog scale, and 36‐item Short‐Form Health Survey component scores were assessed. Results: Treatment groups had similar baseline characteristics and reported a total of 23 unique PI‐MBS, most commonly light sensitivity (200/1072, 18.7%), nausea/vomiting (162/1072, 15.1%), and pain with activity (147/1072, 13.7%). Improvements in PI‐MBS at week 12 correlated with changes in MMDs (ρ = −0.49; p < 0.0001) and other patient‐reported outcomes. Controlling for changes in MMDs, PI‐MBS improvement predicted other patient‐reported outcomes in expected directions. The magnitude of the standardized mean differences between placebo and active treatment for PI‐MBS were 0.31 (p < 0.0001 vs. placebo) and 0.54 (p < 0.0001 vs. placebo) for eptinezumab 100 and 300 mg, respectively. Conclusions: Improvement in PI‐MBS at week 12 was associated with improvement in other patient‐reported outcome measures, and PI‐MBS may be an important patient‐centered measure of treatment benefits in patients with chronic migraine. [ABSTRACT FROM AUTHOR]

Objective: To identify predictors of acute treatment response for nonprescription (over‐the‐counter [OTC]) medications among people with migraine and develop improved models for predicting treatment response. Background: Pain freedom and sustained pain relief are important priorities in the acute treatment of migraine. OTC medications are widely used for migraine; however, it is not clear which treatment works best for each patient without going through the trial and error process. Methods: A prediction model development study was completed using the 2006 American Migraine Prevalence and Prevention Study survey, from participants who were aged ≥18, met criteria and headache day frequency for episodic migraine, did not take prescription medication for migraine, and used ≥1 of the following acute migraine medication classes: acetaminophen, aspirin, NSAIDs, or caffeine containing combination products (CCP). Two items from the Migraine Treatment Optimization Questionnaire were used to evaluate treatment response, adequate 2‐h pain freedom (2hPF) and 24‐h pain relief (24hPR), which were defined by a response to treatment ≥half the time at 2 h and 24 h post treatment, respectively. We identified predictors of adequate treatment response and developed models to predict probability of treatment response to each medication class. Results: The sample included 3852 participants (3038 [79.0%] females) with an average age of 45.0 years (SD = 12.8). Only 1602/3852 (41.6%) and 1718/3852 (44.6%) of the participants reported adequate 2hPF and 24hPR, respectively. Adequate treatment‐response was significantly predicted by lower average headache pain intensity, less cutaneous allodynia, and lower depressive symptom scores. Lower migraine symptom severity was predictive of adequate 2hPF and fewer monthly headache days was predictive of adequate 24hPR. Among participants reporting OTC monotherapy (n = 2168, 56.3%) individuals taking CCP were more likely to have adequate 2hPF (OR = 1.55, 95% CI 1.23–1.95) and 24hPR (OR = 1.79, 95% CI 1.18–1.88) in comparison with those taking acetaminophen. Predictive models were modestly predictive of responders to OTC medications (c‐statistics = 0.65; 95% CI 0.62–0.68). Conclusion: These results show that response to acute migraine treatments is not optimized in the majority of people with migraine treating with OTC medications. Predictive models can improve our ability to choose the best therapeutic option for individuals with episodic migraine and increase the proportion of patients with optimized response to treatments. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study was to determine the associations among migraine disability assessment scores, healthcare resource utilization (HCRU; medical visits and pharmacy use) and direct medical costs among people with episodic migraine in a real‐world setting. Background: Migraine is a public health concern associated with a substantial economic burden in the United States. However, the association between migraine disability and direct medical costs among people with migraine is unknown. Method: This retrospective, cohort study used claims and electronic health record data from the Decision Resources Group database. Adults with migraine with or without aura, defined by International Classification of Disease Revision 9 (ICD‐9) or ICD Revision 10 (ICD‐10) codes, and a completed Migraine Disability Assessment Scale (MIDAS) questionnaire from January 2016 to December 2018 were included (chronic migraine codes not included). The associations of MIDAS score with the cost of HCRU for the 6 months after MIDAS assessment were explored. Results were stratified by treatment setting. Results: Among 7662 included patients, MIDAS scores were distributed as: 3348 (43.7%; I, little/none), 1107 (14.4%; II, mild), 1225 (16.0%; III, moderate), 893 (11.7%; IVa, severe), and 1089 (14.2%; IVb, very severe). Worsening disability was associated with higher medical costs (adjusted from a multivariable model). In the primary care setting, healthcare visit costs were $206 (95% confidence interval: $144–294) for grade I and $631 ($384–1036) for grade IVb patients; corresponding pharmacy costs were $203 (grade I; $136–301) and $719 (grade IVb; $410–1259). For specialty care (e.g., neurologist), healthcare visits cost $509 ($411–629) for grade I and $885 ($634–1236) for grade IVb patients; corresponding pharmacy costs were $494 (grade I; $378–645) and $1020 (grade IVb; $643–1620). Conclusion: Higher levels of migraine‐related disability (MIDAS assessed) are associated with increased HCRU costs among Americans with episodic migraine. Migraine disability assessment could be useful in the development, testing, and prescription of cost‐effective treatments for people with high migraine‐related disability. [ABSTRACT FROM AUTHOR]

Background: The coronavirus disease 2019 (COVID‐19) pandemic is an ongoing global health crisis that has had a range of impacts on people living with migraine. Methods: Qualitative interviews performed as part of the Migraine Clinical Outcome Assessment System project, a multi‐stage Food and Drug Administration–grant funded program to develop a patient‐centered core set of outcome measures for use in migraine clinical trials, offered an opportunity to explore the experience of living with migraine during the pandemic as well as to examine whether migraine treatment priorities, symptoms, and associated disability changed due to the pandemic. Semi‐structured interviews were conducted in the United States between the summer and fall of 2020 with 40 individuals with self‐reported, medically diagnosed migraine who self‐reported that they had not tested positive for or been diagnosed with COVID‐19. Results: Seventy percent (n = 28) of the sample reported ≥1 pandemic‐related impact on their life with migraine. Fourteen participants reported both positive and negative impacts, twelve reported negative impacts only, and two reported positive impacts only. Among those reporting ≥1 pandemic‐related impact, nine participants (32%) reported more frequent and five (17%) reported less frequent migraine attacks. Other negative impacts included interrupted medical care (n = 9; 32%), and greater stress (n = 13; 46%). The most frequent positive impact reported was greater access to health care (n = 8; 29%). Ictal and interictal symptoms were not noted to change due to the pandemic, but some respondents reported less disability due to increased flexibility of schedules and reduced expectations. Treatment priorities did not change due to the pandemic. Conclusion: The global COVID‐19 pandemic has resulted in both negative and positive impacts for people living with migraine. Lessons to be considered when moving into a post‐pandemic world include benefits of and satisfaction with telehealth and the benefits and importance of healthy lifestyle habits and flexibility such as improved sleep, reduced stress, and fewer social expectations. [ABSTRACT FROM AUTHOR]

Background: The asymptomatic period for persons with preclinical Alzheimer's disease (AD) lasts for several years despite the presence of AD biomarkers. These biomarkers are critical for disease detection and monitoring, but collection is burdensome and costly. Sensitive cognitive measures such as Stages of Objective Memory Impairment (SOMI) may be a low‐cost alternative or adjunctive marker of disease‐progression risk. Here, we used longitudinal data from the Knight Alzheimer's Disease Research Center to investigate the odds of disease progression associated with baseline SOMI stage and cerebrospinal fluid (CSF) biomarkers of Aβ42/Aβ40 ratio, p‐tau181, and t‐tau. Methods: We used data from 617 cognitively unimpaired participants with baseline Clinical Dementia Rating (CDR) of 0, CSF measures, and longitudinal Free and Cued Selective Reminding Test (FCSRT) scores used to classify participants into different SOMI stages (Table 1). We examined the association between SOMI stage, CSF biomarkers, and incident cognitive impairment based on time to conversion from CDR of 0 to CDR>0 (incident cognitive impairment) using Cox Models. Results: Participants, at enrollment (Table 2), were on average 67.2 (SD = 9.4) years old, 56.6% were female, and had average 7.5 years of follow‐up (range 1‐18). At baseline, 325 (52.7%) were SOMI‐0, 206 (33.4%) were SOMI‐1, 64 (10.4%) were SOMI‐2, and 22 (3.6%) were SOMI‐3 or ‐4 (merged groups). A total of 127 (20.6%) individuals converted to CDR>0. The Cox proportional hazards regression models indicated that in comparison with individuals in SOMI‐0 stage, those in SOMI‐3/4 stage were more than twice as likely to show disease progression (HR=2.43 (95% CI, 1.21‐4.89, p=0.013)) (Table 3). Adding individual CSF biomarkers to the models did not affect the association of SOMI‐3/4 with incident cognitive impairment (p<0.05 for all). In models that included SOMI stages and all CSF biomarkers, SOMI‐3/4 (HR=2.13, 95% CI 1.07‐4.12, p=0.033) Aβ42/Aβ40 (HR=9.76e‐6, 95% CI=2.70e‐10 ‐ 0.35, p=0.031) and t‐tau (HR=1.001, 95% CI=1.000‐1.002, p=0.018), but not p‐tau (p=0.645), showed significant association with incident cognitive impairment. Conclusions: SOMI‐3/4 predicts incident cognitive impairment (change in CDR) independently from CSF AD biomarkers. These results support the utility of SOMI stage as an early marker of incident cognitive impairment. [ABSTRACT FROM AUTHOR]