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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]

Objective: To assess rates of traversing barriers to care to access optimal clinical outcomes in people with migraine internationally. Background: People in need of medical care for migraine should consult a health care professional knowledgeable in migraine management, obtain an accurate diagnosis, and receive an individualized treatment plan, which includes scientific society guideline-recommended treatments where appropriate. Methods: The Chronic Migraine Epidemiology and Outcomes-International (CaMEO-I) Study was a cross-sectional, web-based survey conducted from July 2021 through March 2022 in Canada, France, Germany, Japan, the United Kingdom, and the United States (US). Respondents who met modified International Classification of Headache Disorders, 3rd edition, criteria for migraine and had Migraine Disability Assessment Scale (MIDAS) scores of ≥ 6 (i.e., mild, moderate, or severe disability) were deemed to need medical care and were included in this analysis. Minimally effective treatment required that participants were currently consulting a health care professional for headache (barrier 1), reported an accurate diagnosis (barrier 2), and reported use of minimally appropriate pharmacologic treatment (barrier 3; based on American Headache Society 2021 Consensus Statement recommendations). Proportions of respondents who successfully traversed each barrier were calculated, and chi-square tests were used to assess overall difference among countries. Results: Among 14,492 respondents with migraine, 8,330 had MIDAS scores of ≥ 6, were deemed in need of medical care, and were included in this analysis. Current headache consultation was reported by 35.1% (2926/8330) of respondents. Compared with the US, consultation rates and diagnosis rates were statistically significantly lower in all other countries except France where they were statistically significantly higher. Total appropriate treatment rates were also statistically significantly lower in all other countries compared with the US except France, which did not differ from the US. All 3 barriers were traversed by only 11.5% (955/8330) of respondents, with differences among countries (P < 0.001). Conclusions: Of people with migraine in need of medical care for migraine, less than 15% traverse all 3 barriers to care. Although rates of consultation, diagnosis, and treatment differed among countries, improvements are needed in all countries studied to reduce the global burden of migraine. Trial registration: NA. [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]

Background: Cardiovascular disease (CVD) risk factors are highly prevalent among Hispanic/Latino adults, while the prevalence of MRI infarcts is not well-documented. We, therefore, sought to examine the relationships between CVD risk factors and infarcts with brain structure among Hispanic/Latino individuals. Methods: Participants included 1,886 Hispanic/Latino adults (50-85 years) who underwent magnetic resonance imaging (MRI) as part of the Study of Latinos--Investigation of Neurocognitive Aging-MRI (SOL-INCA-MRI) study. CVD risk was measured approximately 10.5 years before MRI using the Framingham cardiovascular risk score, a measure of 10-year CVD risk (low (<10%), medium (10 - < 20%), and high (≥20%)). MR infarcts were determined as present or absent. Outcomes included total brain, cerebral and lobar cortical gray matter, hippocampal, lateral ventricle, and total white matter hyperintensity (WMH) volumes. Linear regression models tested associations between CVD risk and infarct with MRI outcomes and for modifications by age and sex. Results: Sixty percent of participants were at medium or high CVD risk. Medium and high CVD risk were associated with lower total brain and frontal gray matter and higher WMH volumes compared to those with low CVD risk. High CVD risk was additionally associated with lower total cortical gray matter and parietal volumes and larger lateral ventricle volumes. Men tended to have greater CVDRF-related differences in total brain volumes than women. The association of CVD risk factors on total brain volumes increased with age, equal to an approximate 7-year increase in total brain aging among the high-CVD-risk group compared to the low-risk group. The presence of infarct(s) was associated with lower total brain volumes, which was equal to an approximate 5-year increase in brain aging compared to individuals without infarcts. Infarcts were also associated with smaller total cortical gray matter, frontal and parietal volumes, and larger lateral ventricle and WMH volumes. Conclusion: The high prevalence of CVD risk among Hispanic/Latino adults may be associated with accelerated brain aging. [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]

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]

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]

Objective: The role of subjective cognitive concerns (SCC) as a diagnostic criterion for MCI remains uncertain and limits the development of a universally (or widely)-accepted MCI definition. The optimal MCI definition should define an at-risk state and accurately predict the development of incident dementia. Questions remain about operationalization of definitions of self- and informantreported SCCs and their individual and joint associations with incident dementia. Methods: The present study included Einstein Aging Study participants who were non-Hispanic White or Black, free of dementia at enrollment, had follow-up, and completed neuropsychological tests and self-reported SCC at enrollment to determine MCI status. Informant-reported SCC at baseline were assessed via the CERAD clinical history questionnaire. Self-reported SCC were measured using the CERAD, items from the EAS Health Self-Assessment, and the single memory item from the Geriatric Depression Scale. Cox proportional hazards models examined the association of different operationalizations of SCC with Petersen and Jak/Bondi MCI definitions on the risk of dementia, further controlling for age, sex, education, and race/ethnicity. Time-dependent sensitivity and specificity at specific time points for each definition, and Youden’s index were calculated as an accuracy measure. Cox proportional hazards models were also used to evaluate the associations of combinations of self- and informant-reported SCC with the risk of incident dementia. Results: 91% of the sample endorsed at least one SCC. Youden’s index showed that not including SCC in either Jak/Bondi or Petersen classifications had the best balance between sensitivity and specificity across follow-up. A subset of individuals with informants, on average, had a lower proportion of non-Hispanic Blacks and 94% endorsed at least one self-reported SCC. Both informant-reported and self-reported SCC were significantly associated with incident dementia. Conclusion: Our findings suggest that the SCC criterion may not improve the predictive validity for dementia when included in widely-employed definitions of MCI. Consistent with some prior research, informant-reported SCC was more related to risk of incident dementia than self-reported SCC. Given that requiring informant report as a diagnostic criterion may unintentionally exclude health disparate groups, additional consideration is needed to determine how best to utilize informant-report in MCI diagnosis. [ABSTRACT FROM AUTHOR]

The Hispanic/Latino population experiences socioeconomic adversities across the lifespan and is at greater risk of cognitive impairment, yet little is known about the role of life-course socioeconomic position (SEP) in cognitive function in this population. Using baseline data (2008–2011) from adults (aged 45–74 years) of the Hispanic Community Health Study/Study of Latinos, we assessed the association between childhood SEP and socioeconomic mobility with cognitive function, and whether this association was mediated by midlife SEP. Childhood SEP was assessed using parental education. An index combining participants' education and household income represented midlife SEP. Socioeconomic mobility was categorized as stable low, downward or upward mobility, and stable high-SEP. Cognitive function measures were modeled using survey linear regression with inverse-probability weighting, accounting for covariates. We used mediation analysis to estimate the indirect effect of childhood SEP on cognition through midlife SEP. High childhood SEP was associated with global cognition in adulthood (coefficient for parental education beyond high school vs. less than high school = 0.26, 95% confidence interval: 0.15, 0.37). This association was partially mediated through midlife SEP (indirect effect coefficient = 0.16, 95% confidence interval: 0.15, 0.18). Low SEP through the life course was associated with the lowest cognitive function. This study provides evidence that life-course SEP influences cognitive performance in adulthood. [ABSTRACT FROM AUTHOR]

Background: Individuals with migraine frequently experience pre- and post-headache symptoms. This analysis aimed to characterize the relative frequency and burden of pre- and post-headache symptoms in people with migraine using data collected through the Chronic Migraine Epidemiology and Outcomes – International Study. Methods: This cross-sectional, observational, web-based survey was conducted in 2021–2022 in Canada, France, Germany, Japan, the United Kingdom, and the United States. Respondents who met modified International Classification of Headache Disorders, 3rd edition, criteria were offered the opportunity to participate. Information collected included migraine-related disability, depression/anxiety symptoms, cutaneous allodynia, activity limitations, and acute treatment optimization. Respondents indicated how often they had pre- or post-headache symptoms using a 5-point scale, ranging from 0 to 4, with a rating of 2 or higher classified as a pre- or post-headache symptom case. Modeling was used to examine relationships with monthly headache days (MHDs) and activity limitations during pre-headache and post-headache phases. Results: Among a total of 14,492 respondents, pre-headache symptoms were reported by 66.9%, while post-headache symptoms were reported by 60.2%. Both pre-headache and post-headache symptoms were reported by 49.5% of respondents, only pre-headache by 17.4%, only post-headache by 10.7%, and neither pre- nor post-headache symptoms by 22.4%. Compared with respondents who experienced only pre- or post-headache symptoms, respondents who experienced both pre- and post-headache symptoms had the highest rates of 4–7, 8–14, and ≥ 15 monthly headache days (23.1%, 14.1%, and 10.9%, respectively). Of respondents with both pre- and post-headache symptoms, 58.5% reported moderate-to-severe disability, 47.7% reported clinically significant symptoms of depression, 49.0% reported clinically significant symptoms of anxiety, and 63.8% reported cutaneous allodynia with headache (ASC-12). Moderate-to-severe activity limitations were reported during the pre-headache (29.5%) and post-headache phases (27.2%). For all outcomes modeled, after controlling for covariates, having pre-headache symptoms, post-headache symptoms, or both were associated with worse outcomes than having neither. Conclusions: Pre- and post-headache phases of migraine are common, carry unrecognized burden, and may be a target for treatment. [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]

Background: Individuals using onabotulinumtoxinA as a preventive migraine treatment often use acute treatments for breakthrough attacks. Data on real-world effectiveness of the small-molecule calcitonin gene–related peptide (CGRP) receptor antagonist ubrogepant in combination with onabotulinumtoxinA are limited. Methods: COURAGE, a prospective, multiple attack, observational study, evaluated the real-world effectiveness of ubrogepant (50 or 100 mg) for acute treatment of migraine in people receiving onabotulinumtoxinA, an anti-CGRP monoclonal antibody (mAb), or both. This analysis focused only on onabotulinumtoxinA users. The Migraine Buddy app was used to identify eligible participants and track response to treated attacks. For each ubrogepant-treated attack, meaningful pain relief (MPR) and return to normal function (RNF) at 2 and 4 h post-dose over 30 days was assessed. MPR was defined as a level of relief that is meaningful to the participant, usually occurring before the pain is all gone. After 30 days, satisfaction was reported on a 7-point scale and overall acute treatment optimization was evaluated using the migraine Treatment Optimization Questionnaire-4 (mTOQ-4). Results: This analysis included 122 participants who received ubrogepant and onabotulinumtoxinA and reported on 599 ubrogepant-treated attacks. Following the first ubrogepant-treated attack, MPR was achieved in 53.3% of participants 2 h post-dose and in 76.2% of participants 4 h post-dose. RNF was achieved in 25.4% of participants 2 h post-dose and in 45.9% of participants 4 h post-dose. MPR and RNF results were similar across up to 10 ubrogepant-treated attacks. After 30 days, satisfaction with ubrogepant in combination with onabotulinumtoxinA was reported by 69.8% of participants and acute treatment optimization (defined as mTOQ-4 score ≥ 4) was achieved in 77.6%. Conclusions: In this prospective real-world effectiveness study, ubrogepant treatment in onabotulinumtoxinA users with self-identified migraine was associated with high rates of MPR and RNF at 2 and 4 h as well as satisfaction and acute treatment optimization. Although the lack of a contemporaneous control group limits causal inference, these findings demonstrate the feasibility of using a novel, app-based design to evaluate the real-world effectiveness and satisfaction of treatments. [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]

Background: No available studies demonstrate validity and meaningful change thresholds of Work Productivity and Activity Impairment (WPAI) questionnaire in patients with migraine. In this post-hoc analysis, we assessed reliability, validity, responsiveness, and meaningful within-patient change from baseline to Month 3 for Work Productivity and Activity Impairment (WPAI) domain scores in patients with episodic migraine (EM) or chronic migraine (CM). Method: The Phase 3, multicenter, randomized, double-blind, placebo-controlled CONQUER study (NCT03559257, N = 462) enrolled patients with EM or CM who failed two to four categories of prior preventive medication in past ten years. The analyses were performed for WPAI domain scores (absenteeism, presenteeism, overall work productivity, and non-work-related activity impairment). Migraine Specific Quality of Life Questionnaire version 2.1 (MSQv2.1) domain scores (Role Function-Restrictive [RFR] and Role Function-Preventive [RFP]), and monthly migraine headache days were used as anchors. Responder criteria were changes from baseline to Month 3 for each of these anchors and were defined as: increase in MSQ-RFR by ≥ 25.71 points and MSQ-RFP by ≥ 20.00 points and a 50% reduction in monthly migraine headache days. Assessments were performed for overall population, and patients with EM or CM. The meaningful change threshold was determined based on Youden index, Phi coefficient and sensitivity. Results: Of 462 randomized patients, 444 who completed WPAI questionnaire were included in post-hoc analysis. Test–retest reliability over 3 months in a stable subgroup revealed moderate correlations for non-work-related Activity Impairment (ICC = 0.446) presenteeism (ICC = 0.438) and a fair correlation for overall work productivity loss (ICC = 0.360). At baseline, all correlations between WPAI domain scores and continuous anchor variables exceeded recommended threshold of ≥ 0.30, except for WPAI domain scores with number of monthly migraine headache days. Patients achieving pre-specified responsiveness thresholds for monthly migraine headache days, and MSQ-RFP, MSQ-RFR from baseline to Month 3 (responders) showed significant improvements in WPAI domain scores compared with non-responders (P < 0.001). The meaningful change thresholds of -20 (% unit) were identified for WPAI domain scores. Conclusion: In conclusion, WPAI has sufficient validity, reliability, responsiveness, and appropriate interpretation standards to assess the impact of EM or CM on presenteeism and overall work productivity loss and non-work-related activity impairment. Trial registration: NCT number of CONQUER study, NCT03559257. [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 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 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 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]

Background: Electronic health records (EHR) data can be used to understand population level quality of care especially when supplemented with patient reported data. However, survey non-response can result in biased population estimates. As a case study, we demonstrate that EHR and survey data can be combined to estimate primary care population prescription treatment status for migraine stratified by migraine disability, without and with adjustment for survey non-response bias. We selected disability as it is associated with survey participation and patterns of prescribing for migraine. Methods: A stratified random sample of Sutter Health adult primary care (PC) patients completed a digital survey about headache, migraine, and migraine related disability. The survey data from respondents with migraine were combined with their EHR data to estimate the proportion who had prescription orders for acute or preventive migraine treatments. Separate proportions were also estimated for those with mild disability (denoted "mild migraine") versus moderate to severe disability (denoted mod-severe migraine) without and with correction, using the inverse propensity weighting method, for non-response bias. We hypothesized that correction for non-response bias would result in smaller differences in proportions who had a treatment order by migraine disability status. Results: The response rate among 28,268 patients was 8.2%. Among survey respondents, 37.2% had an acute treatment order and 16.8% had a preventive treatment order. The response bias corrected proportions were 26.2% and 11.6%, respectively, and these estimates did not differ from the total source population estimates (i.e., 26.4% for acute treatments, 12.0% for preventive treatments), validating the correction method. Acute treatment orders proportions were 32.3% for mild migraine versus 37.3% for mod-severe migraine and preventive treatment order proportions were 12.0% for mild migraine and 17.7% for mod-severe migraine. The response bias corrected proportions for acute treatments were 24.8% for mild migraine and 26.6% for mod-severe migraine and the proportions for preventive treatment were 8.1% for mild migraine and 12.0% for mod-severe migraine. Conclusions: In this study, we combined survey data with EHR data to better understand treatment needs among patients diagnosed with migraine. Migraine-related disability is directly related to preventive treatment orders but less so for acute treatments. Estimates of treatment status by self-reported disability status were substantially over-estimated among those with moderate to severe migraine-related disability without correction for non-response bias. [ABSTRACT FROM AUTHOR]

Background: The ultimate validation of a clinical marker for Alzheimer's disease (AD) is its association with AD neuropathology.Objective: To examine how well the Stages of Objective Memory Impairment (SOMI) system predicts intermediate/high AD neuropathologic change and extent of neurofibrillary tangle (NFT) pathology defined by Braak stage, in comparison to the Clinical Dementia Rating (CDR) Scale sum of boxes (CDR-SB).Methods: 251 well-characterized participants from the Knight ADRC clinicopathologic series were classified into SOMI stage at their last assessment prior to death using the free recall and total recall scores from the picture version of the Free and Cued Selective Reminding Test with Immediate Recall (pFCSRT + IR). Logistic regression models assessed the predictive validity of SOMI and CDR-SB for intermediate/high AD neuropathologic change. Receiver operating characteristics (ROC) analysis evaluated the discriminative validity of SOMI and CDR-SB for AD pathology. Ordinal logistic regression was used to predict Braak stage using SOMI and CDR-SB in separate and joint models.Results: The diagnostic accuracy of SOMI for AD diagnosis was similar to that of the CDR-SB (AUC: 85%versus 83%). In separate models, both SOMI and CDR-SB predicted Braak stage. In a joint model SOMI remained a significant predictor of Braak stage but CDR-SB did not.Conclusion: SOMI provides a neuropathologically validated staging system for episodic memory impairment in the AD continuum and should be useful in predicting tau positivity based on its association with Braak stage. [ABSTRACT FROM AUTHOR]

Aims: To investigate the effectiveness of single and concomitant treatment of migraine and temporomandibular disorders (TMD) in women with the comorbidity. Methods: Eligible female patients met International Classification of Headache Disorders, second edition (ICHD-2) criteria for migraine with or without aura and the Research Diagnostic Criteria for myofascial TMD (Grade ll or lll). After a run-in period (30 days), women with both migraine and TMD were enrolled into a four-arm, double-blind, placebocontrolled, factorial study testing the separate and joint effects of a migraine treatment (propranolol 90 mg) and a TMD treatment (stabilization splint [SS]) in four groups of patients. The four treatment groups were propranolol and SS (n = 22); propranolol placebo and SS (n = 23); propranolol and non-occlusal splint (NOS) (n = 23); and propranolol placebo and NOS (n = 21). The primary endpoint for migraine was change in headache days from baseline to the third month, and the secondary endpoint was change in days with at least moderate headache in the same period. The TMD endpoints included pain threshold and mandibular vertical range of motion. Data were analyzed using analysis of variance (ANOVA, Dunn's post-hoc test) or Kruskal-Wallis test. Results: For the primary endpoint, in intention-to-treat (ITT) analyses (n = 94), propranolol and SS were associated with a nonsignificant reduction in the number of headache days, relative to all other groups. For per-protocol (PP) Completer analyses (n = 89), differences in the number of headache days reached significance (P < .05). The propranolol and SS group was significantly superior to the other groups on all other headache endpoints and in disability, in both ITT and PP analyses. No significant differences among groups were seen for the TMD parameters. Conclusion: In women with TMD and migraine, migraine significantly improved only when both conditions were treated. The best treatment choice for TMD pain in women with migraine is yet to be defined. [ABSTRACT FROM AUTHOR]

Background: Among older adults, poorer cognitive functioning has been associated with impairments in instrumental activities of daily living (IADLs). However, IADL impairments among older Hispanics/Latinos is poorly understood.Objective: To characterize the relationships between cognition and risk for IADL impairment among diverse Hispanics/Latinos.Methods: Participants included 6,292 community-dwelling adults from the Study of Latinos - Investigation of Neurocognitive Aging, an ancillary study of 45+ year-olds in the Hispanic Community Health Study/Study of Latinos. Cognitive data (learning, memory, executive functioning, processing speed, and a Global cognitive composite) were collected at Visit 1. IADL functioning was self-reported 7 years later, and treated as a categorical (i.e., risk) and continuous (i.e., degree) measures of impairment. Survey two-part models (mixture of logit and generalized linear model with Gaussian distribution) and ordered logistic regression tested the associations of cognitive performance (individual tests and composite z-score) with IADL impairment. Additionally, we investigated the moderating role of age, sex, and Hispanic/Latino background on the association between cognition and IADL impairment.Results: Across all cognitive measures, poorer performance was associated with higher odds of IADL impairment 7 years later. Associations were generally stronger for the oldest group (70+ years) relative to the youngest group (50-59 years). Sex and Hispanic/Latino background did not modify the associations. Across the full sample, lower scores on learning, memory, and the Global cognitive composite were also associated with higher degree of IADL impairment.Conclusion: Across diverse Hispanics/Latinos, cognitive health is an important predictor of everyday functioning 7 years later, especially in older adulthood. [ABSTRACT FROM AUTHOR]

Background: Amyloid-β positivity (Aβ+) based on PET imaging is part of the enrollment criteria for many of the clinical trials of Alzheimer's disease (AD), particularly in trials for amyloid-targeted therapy. Predicting Aβ positivity prior to PET imaging can decrease unnecessary patient burden and costs of running these trials.Objective: The aim of this study was to evaluate the performance of a machine learning model in estimating the individual risk of Aβ+ based on gold-standard of PET imaging.Methods: We used data from an amnestic mild cognitive impairment (aMCI) subset of the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort to develop and validate the models. The predictors of Aβ status included demographic and ApoE4 status in all models plus a combination of neuropsychological tests (NP), MRI volumetrics, and cerebrospinal fluid (CSF) biomarkers.Results: The models that included NP and MRI measures separately showed an area under the receiver operating characteristics (AUC) of 0.74 and 0.72, respectively. However, using NP and MRI measures jointly in the model did not improve prediction. The models including CSF biomarkers significantly outperformed other models with AUCs between 0.89 to 0.92.Conclusions: Predictive models can be effectively used to identify persons with aMCI likely to be amyloid positive on a subsequent PET scan. [ABSTRACT FROM AUTHOR]

Background: Conceptualizing cognitive aging as a step-sequential process is useful in identifying particular stages of cognitive function and impairment.Objective: We applied latent transition analysis (LTA) to determine 1) whether the underlying structure of cognitive profiles found at every measurement occasion are uniform across three waves of assessment, 2) whether class-instability is predictive of distal outcomes, and 3) whether class-reversions from impaired to non-impaired using latent modelling is lower than when using clinical criteria of mild cognitive impairment (MCI).Methods: A mover-stayer LTA model with dementia as a distal outcome was specified to model transitions of ten neuropsychological measures over three annual waves in the Rush Memory and Aging Project (n = 1,661). The predictive validity of the mover-stayer status for incident Alzheimer's disease (AD) was then assessed.Results: We identified a five-class model across the three time-points: Mixed-Domain Impairment, Memory-Specific Impairment, Frontal Impairment, Average, and Superior Cognition. None of the individuals in the Impairment classes reverted to the Average or Superior classes. Conventional MCI classification identified 26.4% and 14.1% at Times 1 and 2 as false-positive cases. "Movers" had 87% increased risk of developing dementia compared to those classified as "Stayers".Conclusion: Our findings support the use of latent variable modelling that incorporates comprehensive neuropsychological assessment to identify and classify cognitive impairment. [ABSTRACT FROM AUTHOR]

Background: Predicting clinical course of cognitive decline can boost clinical trials' power and improve our clinical decision-making. Machine learning (ML) algorithms are specifically designed for the purpose of prediction; however. identifying optimal features or algorithms is still a challenge.Objective: To investigate the accuracy of different ML methods and different features to classify cognitively normal (CN) individuals from Alzheimer's disease (AD) and to predict longitudinal outcome in participants with mild cognitive impairment (MCI).Methods: A total of 1,329 participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI) were included: 424 CN, 656 MCI, and 249 AD individuals. Four feature-sets at baseline (hippocampal volume and volume of 47 cortical and subcortical regions with and without demographics and APOE4) and six machine learning methods (decision trees, support vector machines, K-nearest neighbor, ensemble linear discriminant, boosted trees, and random forests) were used to classify participants with normal cognition from participants with AD. Subsequently the model with best classification performance was used for predicting clinical outcome of MCI participants.Results: Ensemble linear discriminant models using demographics and all volumetric magnetic resonance imaging measures as feature-set showed the best performance in classification of CN versus AD participants (accuracy = 92.8%, sensitivity = 95.8%, and specificity = 88.3%). Prediction accuracy of future conversion from MCI to AD for this ensemble linear discriminant at 6, 12, 24, 36, and 48 months was 63.8% (sensitivity = 74.4, specificity = 63.1), 68.9% (sensitivity = 75.9, specificity = 67.8), 74.9% (sensitivity = 71.5, specificity = 76.3), 75.3%, (sensitivity = 65.2, specificity = 79.7), and 77.0% (sensitivity = 59.6, specificity = 86.1), respectively.Conclusions: Machine learning models trained for classification of CN versus AD can improve our prediction ability of MCI conversion to AD. [ABSTRACT FROM AUTHOR]

Background: The transition from normal cognition to Alzheimer's disease is considered a continuum, with amnestic mild cognitive impairment (aMCI) an intermediate clinical cognitive state. Although prior work suggests that dementia incidence rates may be declining, there is little information regarding temporal trends in aMCI incidence.Objective: To determine whether age specific rates of aMCI have changed over sequential birth cohorts among individuals included in the population-based Einstein Aging Study (EAS) cohort. A secondary objective was to examine trends in aMCI rates among Blacks and Whites and by sex.Methods: Age specific incidence of aMCI was examined by birth year among 1,233 individuals age 70 years and above enrolled in the population-based EAS cohort between November 1, 1993 and February 22, 2016 and who had at least one annual follow-up assessment (5,321 person years of follow-up). Poisson regression was used to determine whether there has been a change in age specific aMCI rates over sequential years of birth.Results: No significant change in aMCI rates was identified in the overall cohort, among Blacks or Whites, or among males or females born between 1899 and 1946.Conclusions: Despite a trend for decreased dementia incidence in the EAS cohort, rates of incident aMCI have not changed. These apparently conflicting results may indicate a delay or decrease in the rates of transition from aMCI to dementia within the cohort. However, further studies are needed to confirm whether rates of aMCI have changed in other populations, and how aMCI rates are related to secular trends in dementia risk factors. [ABSTRACT FROM AUTHOR]

The effects of soccer-related head impacts, beyond overt concussions, on Patient Reported Outcomes (PROs) have not been explored to date. Generalized estimating equations were employed to determine the association between soccer-related head impacts (headers in the prior 2 weeks, unintentional head impacts in the prior 2 weeks, headers in the prior 12 months and lifetime concussions) on PROs including depression, anxiety, sleep disturbance and sleep impairment. Compared to players with no unintentional head impacts in the prior 2 weeks, players with one unintentional exposure reported more symptoms of anxiety (p = 0.002) and players with 2+ exposures reported more symptoms of depression (p = 0.006) and anxiety (p < 0.001). In contrast, players in the 3rd Quartile of 12 mo. headers reported less anxiety (p = 0.001), sleep disturbance (p = 0.002) and sleep impairment (p < 0.001) compared to those in the 1st quartile. Unintentional head impacts are associated with worse PROs while more headers are paradoxically associated with better PROs. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study was to test whether behavioral weight loss (BWL) intervention decreases headaches in women with comorbid migraine and overweight or obesity.Methods: This randomized, single-blind trial allocated women 18 to 50 years old with 4 to 20 migraine days per month and a BMI = 25.0-49.9 kg/m2 to 16 weeks of BWL (n = 54), which targeted exercise and eating behaviors for weight loss, or to migraine education control (ME, n = 56), which delivered didactic instruction on migraine and treatments. Participants completed a 4-week smartphone headache diary at baseline, posttreatment (16-20 wk), and follow-up (32-36 wk). The primary outcome was posttreatment change in migraine days per month, analyzed via linear mixed effects models.Results: Of 110 participants randomly assigned, 85 (78%) and 80 (73%) completed posttreatment and follow-up. Although the BWL group achieved greater weight loss (mean [95% CI] in kilograms) than the ME group at posttreatment (-3.8 [-2.5 to -5.0] vs. + 0.9 [-0.4 to 2.2], P < 0.001) and follow-up (-3.2 [-2.0 to -4.5] vs. + 1.1 [-0.2 to 2.4], P < 0.001), there were no significant group (BWL vs. ME) differences (mean [95% CI]) in migraine days per month at posttreatment (-3.0 [-2.0 to -4.0] vs. -4.0 [-2.9 to -5.0], P = 0.185) or follow-up (-3.8 [-2.7 to -4.8] vs. -4.4 [-3.4 to -5.5], P = 0.378).Conclusions: Contrary to hypotheses, BWL and ME yielded similar, sustained reductions in migraine headaches. Future research should evaluate whether adding BWL to standard pharmacological and/or nonpharmacological migraine treatment approaches yields greater benefits. [ABSTRACT FROM AUTHOR]

Background: The role of cervical muscle (neck) strength in traumatic brain and spine injury and chronic neck pain disorders is an area of active research. Characterization of the normal ranges of neck strength in healthy young adults is essential to designing future investigations of how strength may act as a modifier for risk and progression in head and neck disorders.Objective: To develop a normative reference database of neck strength in a healthy young adult population, and to evaluate the relationship of neck strength to anthropometric measurements.Design: Cross-sectional.Setting: An academic medical center research institution.Participants: A total of 157 healthy young adults (18-35 years of age) had their neck strength measured with fixed frame dynamometry (FFD) during 1 visit to establish a normative neck strength database.Interventions: Not applicable.Main Outcome Measurements: Peak and average strength of the neck muscles were measured in extension, forward flexion, and right and left lateral flexion using FFD. The ranges of peak and average neck strength were characterized and correlated with anthropometric characteristics.Results: In all, 157 subjects (84 male, 73 female; average age 27 years) were included in the normative sample. Neck strength ranged from 38 to 383 Newtons in men and from 15 to 223 Newtons in women. Normative data are provided for each gender in all 4 directions. Weight, body mass index, neck circumference, and estimated neck muscle volume were modestly correlated with neck strength in multiple directions (correlation coefficients < .4). In a multivariate regression model, weight in women and neck volume in men were significant predictors of neck strength.Conclusions: Neck strength in healthy young adults exhibits a broad range, is significantly different in men from that in women, and correlates only modestly with anthropometric characteristics.Level Of Evidence: Not applicable. [ABSTRACT FROM AUTHOR]

Background: The Perceived Stress Scale (PSS) is made up of two subscales but is typically used as a single summary measure. However, research has shown that the two subscales may have differential properties in older adults.Objective: To evaluate the internal consistency, test-retest reliability, and the concurrent and predictive validity for development of amnestic mild cognitive impairment (aMCI) of the positively-worded (PSS-PW) and negatively-worded (PSS-NW) subscale scores of the PSS in older adults.Methods: We recruited community residing older adults free of dementia from the Einstein Aging Study. Reliability of the PSS-PW and PSS-NW was assessed using Cronbach's alpha for internal consistency and intraclass correlation for one year test-retest reliability. Concurrent validity was evaluated by examining the relationship between the PSS subscales and depression, anxiety, neuroticism, and positive and negative affect. Predictive validity was assessed using multivariate Cox regression analyses to examine the relationship between baseline PSS-PW and PSS-NW score and subsequent onset of aMCI.Results: Both PSS-PW and PSS-NW showed adequate internal consistency and retest reliabilities. Both the PSS-PW and PSS-NW were associated with depression, neuroticism, and negative affect. The PSS-NW was uniquely associated with anxiety while the PSS-PW was uniquely associated with positive affect. Only the PSS-PW was associated with a statistically significant increased risk of incident aMCI (HR = 1.27; 95% CI: 1.06-1.51 for every 5-point increase in PSS-PW).Conclusions: Evaluating the separate effects of the two PSS subscales may reveal more information than simply using a single summation score. Future research should investigate the PSS-PW and PSS-NW as separate subscales. [ABSTRACT FROM AUTHOR]

There is a growing recognition of sex differences in Alzheimer's disease (AD). Females show an advantage over males on tests of verbal memory, which are used to diagnose AD and its precursor, amnestic mild cognitive impairment (aMCI). Women retain this advantage in aMCI despite reduced hippocampal volume and temporal lobe glucose metabolism. Here we examined whether this female advantage endures despite evidence of AD-specific pathology, cortical amyloid-β (Aβ) deposition measured with [18F]AV45 (florbetapir) positron emission tomography. Participants with normal cognition (N = 304), aMCI (N = 515), and AD dementia (N = 175) were drawn from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Across and within diagnostic groups, we conducted linear regressions to examine the interaction of sex with cortical Aβ burden on immediate and delayed recall on the Rey Auditory Verbal Learning Test (RAVLT) adjusting for age, education, and APOE4. In the overall group, sex by cortical Aβ interaction was significant for delayed recall only. Overall, delayed recall performance was significantly better in women versus men among those with low to moderate Aβ burden, but women and men performed similarly among those with high Aβ burden. In diagnosis-stratified analyses, a significant sex by cortical Aβ interaction was observed for delayed recall in the aMCI group, but not in the normal or AD dementia groups. Thus, women maintain a verbal memory advantage over men in aMCI despite similar levels of AD pathology. Although this advantage may benefit women by delaying verbal memory impairment until more advanced pathology, it may also delay diagnosis of aMCI and treatment intervention. [ABSTRACT FROM AUTHOR]

Background Though migraine, particularly migraine with aura, is a cardiovascular (CV) risk factor, the scope and distribution of cardiovascular disease in representative samples of people with migraine are not known. This is important because many widely used acute migraine treatments, including triptans, ergot alkaloids, and nonsteroidal anti-inflammatory drugs, carry precautions, warnings, or contraindications for use in persons with CV disease. Objectives To assess the scope and distribution of cardiovascular events, conditions, and procedures in persons with episodic migraine in a representative sample of the US population, using data from the American Migraine Prevalence and Prevention (AMPP) Study. Methods Eligible subjects completed the 2009 AMPP survey, met ICHD-3beta criteria for migraine, and had a headache frequency of less than 15 days per month (episodic migraine). A survey on cardiovascular events (ie, myocardial infarction), conditions (ie, angina), and procedures (ie, carotid endarterectomy) was adopted from the Women's Health Study and the Physician's Health Studies. Cardiovascular events and conditions were defined by participant reports of having both experienced and received a physician diagnosis for a particular event or condition. The distribution of CV events, conditions, and procedures was summarized for the entire migraine sample and in groups defined by gender and age (22-39, 40-59, and ≥60). To assess the numbers of persons with episodic migraine in the US, we applied age and gender stratified estimates of migraine prevalence to the 2015 Census data. To estimate the number of cardiovascular events, conditions, and procedures in the US migraine population, we applied age and gender stratified event rates to the number of persons with episodic migraine in each stratum. Results The 2009 AMPP Study survey was returned by 11,792 study participants out of 16,983 (64.9% response rate), including 6723 individuals who met study criteria for episodic migraine (5227 women and 1496 men). Among 22-39 year olds with episodic migraine, 3.4% reported having received a physician diagnosis of CV events or conditions and 1.1% reported undergoing CV related procedures. Among 40-59 year olds, 10.2% reported having received a physician diagnosis of CV events or conditions and 3.5% reported CV related procedures. For those age 60 or older, 22.3% reported CV events or conditions and 8.8% reported CV procedures. Prevalence of events, conditions, and procedures was higher in men than women and also in older age groups. However, the absolute number of CV events, procedures, and conditions was greater for women than men due to the higher population prevalence of episodic migraine in women. We projected that 2.0 million women and 665,000 men in the US had episodic migraine and a history of one or more CV event, condition, or procedure. By age group, it is estimated that 579,000 among those aged 22-39, 1.37 million of those aged 40-59, and 696,000 of those 60 and older with episodic migraine have ever had at least one CV event, procedure, or condition. Conclusion Based on these analyses, we estimate that there are roughly 2.6 million people with episodic migraine aged 22 and older in the US with one or more prior CV event, condition, or procedure. For this group, cardiovascular contraindications to many migraine-specific acute migraine therapies may make treatment challenging. [ABSTRACT FROM AUTHOR]

Background: Among older adults, pain intensity and pain interference are more common in women than men and associated with obesity and inflammatory markers.Objective: We examined whether the obesity and pain relationship is mediated by the high-sensitivity C-reactive protein (hsCRP), a nonspecific marker of systemic inflammation, and whether this relationship differs by sex.Methods: Items from Medical Outcomes Study Short Form-36 were used to measure pain intensity and pain interference in daily life. Ordinal logistic regression was used to assess the cross-sectional association among body mass index (BMI), hsCRP levels, pain intensity and pain interference using gender-stratified models adjusted for demographic variables.Results: Participants included 667 community-residing adults over the age of 70 years, free of dementia, enrolled in the Einstein Aging Study (EAS). In women (n = 410), pain intensity was associated with obesity [BMI ≥30 vs. normal, odds ratio (OR) = 2.29, 95% confidence interval (CI) 1.43-3.68] and higher hsCRP (OR = 1.28, 95% CI 1.08-1.51). In a model with obesity and hsCRP, both remained significant, but the association between hsCRP and pain intensity was somewhat attenuated. Obesity (OR = 3.04, 95% CI 1.81-5.11) and higher hsCRP levels (OR = 1.30, 95% CI 1.08-1.56) were also independently associated with greater pain interference in women. After adjustment for pain intensity and BMI, hsCRP was no longer associated with pain interference in women. Greater pain intensity and being overweight or obese continued to be significantly associated with pain interference in women. In men (n = 257), obesity and hsCRP were not associated with pain intensity or pain interference.Conclusions: In women, the relationship between obesity and higher levels of pain intensity or interference may be accounted for by factors related to hsCRP. [ABSTRACT FROM AUTHOR]

Background Pain freedom at 2 hours and sustained pain response at 24 hours are important outcomes of acute migraine therapy. Some studies have examined rates and predictors of successful treatment outcomes for single attacks in clinical trials. However, little is known about predictors of typical response to acute treatment over multiple attacks in the population. Objectives To identify sociodemographic features, headache characteristics, comorbidities and treatment-related factors that predict acute treatment success or failure at 2 hours and 24 hours post dose in a US population sample of persons with episodic migraine. Methods Eligible respondents completed the 2006 American Migraine Prevalence and Prevention Study survey, met criteria for episodic migraine, reported the use of acute treatment for migraine and answered questions on acute treatment outcomes from the Migraine Treatment Optimization Questionnaire (mTOQ). One question focused on 2 hour pain free (2hPF) response and the other focused on pain relief at 2 hours and 24 hours (24hPR). For each question, responses were considered adequate if they were achieved 'half the time or more' and inadequate if they were achieved 'never,' 'rarely,' or 'less than half the time.' Models were run to identify predictors of outcomes in relation to usual acute treatment: (1) Inadequate 2hPF response; (2) Inadequate 24hPR response; and (3) Inadequate 24 hour Sustained Pain Freedom (24hSPF), which was a conditional analysis of pain freedom at 24 hours among those who initially had an adequate pain freedom response at 2 hours. Binary logistic regression models were used to separately predict each of the 3 outcomes adjusting for covariates. Potential predictor variables were analyzed independently and variables that did not contribute significantly to outcome prediction were trimmed. The retained variables were entered into a final multivariable binary logistic regression that included age, sex, and the covariates that survived the trimming process. Odds ratio (OR) and 95% confidence interval (CI) statistics were generated for each variable. A value of P ≤ .05 was used to identify statistically significant variables. Results Among 8233 eligible respondents with episodic migraine, 56.0% of respondents reported Inadequate 2hPF response to usual acute treatment and 53.7% reported Inadequate 24hPR. Among the 44.0% of individuals who achieved Adequate 2hPF (N = 3621), 25.7% reported Inadequate 24hSPR or recurrence. Significant predictors of Inadequate 2hPF response included demographic variables (male sex and higher body mass index [BMI]), headache features (higher headache pain intensity, cutaneous allodynia, more headache days per month), comorbidity (depression), and migraine pharmacologic treatment factors (not using preventive migraine medications). Significant predictors of Inadequate 24hPR included headache features (more headache days per month, higher migraine symptom severity composite score, cutaneous allodynia), comorbidity (depression), and migraine pharmacologic treatment factors (medication overuse). Significant predictors of Inadequate 24hSPR were greater monthly headache day frequency, cutaneous allodynia, depression, medication overuse, and higher migraine symptom severity composite score. Conclusions These results provide a snapshot of the effectiveness of usual acute treatment as well as predictors of inadequate acute treatment response in a large population sample of people with episodic migraine. These results highlight the high rates of unmet treatment needs in people with migraine. Similarities and differences in predictors vary with outcome for reasons that are discussed. [ABSTRACT FROM AUTHOR]

Objectives To examine the association between diet and executive function, episodic memory and global verbal cognition in the Einstein Aging Study ( EAS) cohort and determine whether race modifies this relationship. Design Cross-sectional. Setting Community. Participants EAS participants without dementia who completed the Rapid Eating and Activity Assessment for Patients ( REAP) (N = 492). Measurements The previously validated REAP is based on the 2000 U.S. dietary guidelines. REAP scores were dichotomized as less-healthy (

The objective of this study was to investigate the relationship of medial temporal lobe and posterior cingulate cortex (PCC) volumetrics as well as fractional anisotropy of the cingulum angular bundle (CAB) and the cingulum cingulate gyrus (CCG) bundle to performance on measures of verbal memory in non-demented older adults. The participants were 100 non-demented adults over the age of 70 years from the Einstein Aging Study. Volumetric data were estimated from T1-weighted images. The entire cingulum was reconstructed using diffusion tensor MRI and probabilistic tractography. Association between verbal episodic memory and MRI measures including volume of hippocampus (HIP), entorhinal cortex (ERC), PCC and fractional anisotropy of CAB and CCG bundle were modeled using linear regression. Relationships between atrophy of these structures and regional cingulum fractional anisotropy were also explored. Decreased HIP volume on the left and decreased fractional anisotropy of left CAB were associated with lower memory performance. Volume changes in ERC, PCC and CCG disruption were not associated with memory performance. In regression models, left HIP volume and left CAB-FA were each independently associated with episodic memory. The results suggest that microstructural changes in the left CAB and decreased left HIP volume independently influence episodic memory performance in older adults without dementia. The importance of these findings in age and illness-related memory decline require additional exploration. [ABSTRACT FROM AUTHOR]

Objective To assess the rates and predictors of traversing steps essential to good medical care for chronic migraine, including: (1) medical consultation, (2) accurate diagnosis, and (3) minimal pharmacologic treatment. Candidate predictors included socioeconomic, demographic, and headache-specific variables. Background Previous research has established that barriers to effective management for episodic migraine include the absence of health insurance, lack of appropriate medical consultation, failure to receive an accurate diagnosis, and not being offered a regimen with acute and preventive treatments. Methods/Design The Chronic Migraine Epidemiology and Outcomes (CaMEO) Study, a longitudinal web-based panel study of migraine, included a cross-sectional module focused on patterns of and barriers to medical care. Participants eligible for this analysis met the study criteria for chronic migraine, had evidence of headache-related disability, and provided data on health insurance status. The main outcomes in the current analysis included the proportion of respondents who sought consultation for headache with a designated healthcare professional, self-reported receiving a diagnosis of chronic or transformed migraine, and received minimal pharmacologic treatment for headache with a focus on prescribed acute and preventive treatments. Results In the CaMEO Study, 80,783 respondents provided study data, 16,789 (20.8% of respondents) met criteria for migraine, and 1476 (8.8% of those with migraine) met chronic migraine criteria. In total, 1254 participants (85.0% of those with chronic migraine) met inclusion criteria for this analysis. Of those, 512 respondents (40.8%) reported currently consulting with a healthcare professional for headache. Odds of consulting increased with increasing age (OR 1.02; 95% CI 1.01-1.03), body mass index (BMI) (OR 1.01; 95% CI 1.00-1.03), migraine-related disability (OR 1.02; 95% CI 1.00-1.04), and migraine severity (OR 1.16; 95% CI 1.11-1.22) and presence of health insurance (OR 4.61; 95% CI 3.05-6.96). Among those consulting a healthcare professional, 126 (24.6%) received an accurate diagnosis and 56 of those with a correct diagnosis (44.4%) received both acute and preventive pharmacologic treatments; odds of a CM diagnosis were higher for women (OR 1.93; 95% CI 1.03-3.61), those with greater migraine severity (OR 1.25; 95% CI 1.14-1.37), and those currently consulting a specialist (OR 2.38; 95% CI 1.54-3.69). No predictors of receiving appropriate treatment were identified among those currently consulting. Among our sample of people with chronic migraine, only 56 (4.5%) individuals successfully traversed the series of 3 barriers to successful chronic migraine care (ie, consulted a healthcare professional for migraine, received an accurate diagnosis, and were prescribed minimal acute and preventive pharmacologic treatments). Conclusion Our findings suggest that <5% of persons with chronic migraine traversed 3 barriers to receiving care for headache (consultation, diagnosis, and treatment), representing a large unmet need for improving care in this population. Predictors of consulting a healthcare professional included age, having health insurance, greater migraine-related disability, and greater migraine symptom severity. Among those consulting, predictors of an appropriate diagnosis included consulting a specialist, female sex, and greater migraine severity. Public health efforts are needed to improve outcomes for patients with chronic migraine by a range of interventions and educational efforts aimed at improving consultation rates, diagnostic accuracy, and adherence to minimal pharmacologic treatment. [ABSTRACT FROM AUTHOR]

Objective: The aim of this paper was to assess the relationship between pain and sleep in older adults taking depression, stress, and medical comorbidities into account.Methods: A cross-sectional analysis was performed using Einstein Aging Study, a community-based cohort study of adults aged 70 years and older. Ratings of pain intensity and interference from the Medical Outcomes Study (MOS) Short-Form 36 were used to assign individuals to low-pain versus high-pain severity. Sleep disturbance was assessed using the nine-item sleep problems index from the Medical Outcomes Study Sleep Scale. Other measures included the Geriatric Depression Scale and Perceived Stress Scale (PSS). Linear regression models were used to assess the association between pain grade and sleep disturbance adjusted for demographics, PSS, Geriatric Depression Scale, and other comorbidities.Results: Five hundred sixty-two eligible participants with a mean age of 78.22 years (standard deviation = 5.43) were included; 64% were women. Pain grade [β = 5.40, 95% confidence interval (CI) 2.56-8.21, p < 0.001] was associated with sleep disturbance after adjusting for demographic variables. In models including pain grade (β = 3.08, 95% CI 0.32-5.85, p = 0.03) and PSS (β = 0.57, 95% CI 0.39-0.75, p < 0.001), both were associated with sleep disturbance, although the PSS attenuated the relationship between pain and sleep by 34%. Depression, when added to previous model, was also associated with sleep (β = 2.17, 95% CI 1.48-2.85, p < 0.001) and attenuated the relationship between pain (β = 2.41, 95% CI -0.25 to 5.08, p = 0.07) and sleep by 22%. Stratified for depression, we found that pain, stress, and other medical comorbidities were significantly associated with sleep disturbance in non-depressed individuals but not individuals with depression.Conclusions: Pain, stress, and medical comorbidities are associated with sleep disturbance, especially in non-depressed older adults. [ABSTRACT FROM AUTHOR]

Background: Episodic memory testing is fundamental for the diagnosis of Alzheimer's disease (AD). Although the Free and Cued Selective Reminding Test (FCSRT) is widely used for this purpose, it may not be sensitive enough for early detection of subtle decline in preclinical AD. The Memory Binding Test (MBT) intends to overcome this limitation.Objectives: To analyze the test-retest reliability of the MBT and its convergent validity with the FCRST.Methods: 36 cognitively healthy participants of the ALFA Study, aged 45 to 65, were included for the test-retest study and 69 for the convergent analysis. They were visited twice in a period of 6 ± 2 weeks. Test-retest reliability was determined by the calculation of the intra-class correlation coefficient (ICC). Score differences were studied by computing the mean percentage of score variation between visits and visualized by Bland-Altman plots. Convergent validity was determined by Pearson's correlations.Results: ICC values in the test-retest reliability analysis of the MBT direct scores ranged from 0.64 to 0.76. Subjects showed consistent practice effects, with mean amounts of score increasing between 10% and 26%. Pearson correlation between MBT and FCSRT direct scores showed r values between 0.40 and 0.53. The FCSRT displayed ceiling effects not observed in the MBT.Conclusions: The MBT shows adequate test-retest reliability and overall moderate convergent validity with the FCSRT. Unlike the FCSRT, the MBT does not have ceiling effects and it may therefore be especially useful in longitudinal studies, facilitating the measurement of subtle memory performance decline and the detection of very early AD. [ABSTRACT FROM AUTHOR]

Objective The objective of this study was to compare the societal direct and indirect costs of chronic and episodic migraine in the United States. Background Episodic and chronic migraine are distinguished by the frequency of headache-days. Chronic migraine has a greater overall impact on quality of life than does episodic migraine. Individuals with chronic migraine also use more healthcare resources (resulting in higher direct costs) and experience greater decreases in productivity (resulting in higher indirect costs) than those with episodic migraine as shown in the American Migraine Prevalence and Prevention (AMPP) Study. Methods The International Burden of Migraine Study utilized a web-based questionnaire to elicit data on several topics related to the burden of migraine illness, including health resource utilization and productivity losses. Potential survey participants were identified by Synovate Healthcare (Chicago, IL, USA) from a pool of registered panelists from various countries. The panelists were screened online to determine eligibility and to identify individuals with migraine (episodic or chronic), based on reported symptoms. Participants from the United States were divided into episodic and chronic migraine groups, based on reported headache-day per month frequency. Direct and indirect costs were estimated by applying estimated unit costs to reported headache-related productivity losses and resource use. Costs were compared between participants with episodic and chronic migraine. Results Mean [standard deviation] total annual cost of headache among people with chronic migraine ($8243 [$10,646]) was over three times that of episodic migraine ($2649 [$4634], P < .001). Participants with chronic migraine had significantly greater direct medical costs ($4943 [$6382]) and indirect (lost productivity) costs ($3300 [$6907]) than did participants with episodic migraine (direct, $1705 [$3591]; indirect, $943 [$2084]) ( P < .001 for each). Unlike previous findings, direct medical costs constituted the majority of total headache-related costs for both chronic migraine (60.0%, $4943 of $8243) and episodic migraine (64.3%, $1705 of $2649) participants. A large portion of direct medical costs are attributable to pharmaceutical utilization among both chronic migraine (80%, $3925 of 4943) and episodic migraine (70%, $1196 of $1705) participants. Conclusion The results of this study build on previous results of the AMPP Study, demonstrating that headache-related direct, indirect, and total costs are significantly greater among individuals with chronic migraine than with episodic migraine in the United States. [ABSTRACT FROM AUTHOR]

Objectives To examine the relationship of headache frequency to the stages of the menopausal transition in mid-life women with migraine. Background Past studies suggest that the perimenopause is associated with an increased prevalence of migraine, particularly in those with a history of premenstrual syndrome. The effect of the menopausal transition on the frequency of headache attacks in women with migraine has not been explored. Methods This was a cross-sectional observational study. Using data from the 2006 American Migraine, Prevalence and Prevention study survey, women meeting modified ICHD-3 beta criteria for migraine between the ages of 35-65 years were included in analyses. Women who had never menstruated or were pregnant, breastfeeding, or using exogenous sex hormones were excluded. The 2006 survey was selected because it included detailed questions on the menstrual cycle. The stages of the menopausal transition were defined based upon the self-reported cycle length and/or duration of amenorrhea. The primary outcome, high vs low headache frequency, was defined using a cut score of ≥10 headache days per month. Binary logistic regression models were used to assess the influence of menopausal stage on headache frequency category using premenopause as the reference group. Adjustments for stage of menopausal transition and sociodemographics (eg, age and income) were included in the first model, while the second model included sociodemographics, depression, body mass index, preventative medications, and medication overuse. Results The study sample included 3664 women at a mean age of 46 years. Among women who were premenopausal, 8.0% (99/1242) were in the high frequency headache group in comparison with 12.2% (154/1266) of perimenopausal and 12.0% (131/1095) of postmenopausal women. Compared with premenopausal women, the adjusted odds of being in the high frequency headache group was 1.62 (95% CI = 1.23, 2.12) for perimenopausal and 1.76 (95% CI = 1.23, 2.52) for postmenopausal women (Model 1). In model 2, high frequency headache was only increased in perimenopausal women with an OR of 1.42 (95% CI = 1.03, 1.94). Conclusions The risk of high frequency headache is increased in women during the perimenopause compared to premenopause in the fully adjusted model. The fact that the increased risk of high frequency headache was not statistically significant for menopause in the fully adjusted models suggests that different mechanisms might account for the increased risk for this stage of the menopausal transition. Recognition of the increased risk of high frequency headache during the menopausal transition suggests a need for optimized preventive treatment of migraine during this time of women's life. [ABSTRACT FROM AUTHOR]

Objectives To test the hypothesis that in persons with episodic migraine (EM), asthma is a risk factor for the onset of chronic migraine (CM). Background Migraine and asthma are comorbid chronic disorders with episodic attacks thought to involve inflammatory and neurological mechanisms. Herein, we assess the influence of asthma on the clinical course of EM. Methods To be eligible for this observational cohort study, AMPP Study participants had to meet criteria for EM in 2008, complete the validated six-item asthma questionnaire from the European Community Respiratory Health Survey (ECRHS) in 2008, and provide follow-up data in 2009. Using the ECRHS, we defined asthma as a binary variable (present or absent) based on an empirical cut score and developed a Respiratory Symptom Severity Score (RSSS) based on the number of positive responses (no severity = 0 positive responses, low severity = 1-2 positive responses, moderate severity = 3-4 positive responses, high severity = 5-6 positive responses). Chronic migraine was the primary outcome measure and was defined as those with ≥15 headache days per month on the 2009 AMPP Study survey. We used logistic regression in separate models to assess the influence of asthma as a binary variable (Model 1) and RSSS score categories (Model 2 using no respiratory symptoms as the reference) on CM onset after adjusting for sociodemographic factors, headache day frequency, migraine preventive medication use, and medication overuse. Results The eligible sample for this study included 4446 individuals with EM in 2008 of whom 17% had asthma. This group had a mean age of 50.4 and was 80.8% female. In 2009, new onset CM developed in 2.9% (131/4446) of the 2008 EM cohort, including 5.4% (40/746) of the asthma subgroup and 2.5% (91/3700) of the non-asthma subgroup. In comparison to those without asthma, the adjusted odds for individuals with asthma and EM in 2008 to develop CM in 2009 were greater than two (adjusted odds ratio [aOR] 2.1; 95% CI: 1.4-3.1). Using the RSSS, the aOR for CM onset increased with the number of asthma symptoms, but only those in the high RSSS category showed a statistically significant increase in the odds of chronic migraine onset in comparison with the no RSSS reference group (aOR 3.3; 95% CI 1.7-6.2). Conclusions Asthma is associated with an increased risk of new onset CM 1 year later among individuals with EM, with the highest risk being among those with the greatest number of respiratory symptoms. The exact mechanisms underlying this association are unknown, but could suggest mast cell degranulation, autonomic dysfunction, or shared genetic or environmental factors. [ABSTRACT FROM AUTHOR]

Background: The Memory Binding Test (MBT) is a novel test based on the learning of two lists of words, developed to detect early memory impairment suggestive of Alzheimer's disease (AD).Objective: To present and provide reference data of the Spanish MBT in a midlife population of mainly first-degree descendants of AD patients.Methods: 472 cognitively unimpaired subjects, aged 45 to 65 and participants of the ALFA STUDY, were included. Raw scores were transformed to scaled scores on which multivariate regression analysis was applied adjusting by age, gender, and education level. A standard linear regression was employed to derive the scaled score adjusted. Sociodemographic corrections were applied and an adjustment table was constructed.Results: Performance was heterogeneously influenced by sociodemographic factors. Age negatively influenced free recall. Education tends to have an influence in the results showing lower performance with lower education level. Women tend to outperform men in the learning of the first list and total recall. Only a few variables were unaffected by sociodemographic factors such as those related to semantic proactive interference (SPI) and to the retention of learned material. Our results point out that some vulnerability to SPI is expectable in cognitively healthy subjects. Close to 100% of the learned material was maintained across the delay interval.Conclusion: This study contributes with reference data for the MBT providing the necessary adjustments for sociodemographic characteristics. Our data may prove to be useful for detecting asymptomatic at-risk candidates for secondary prevention studies of AD. [ABSTRACT FROM AUTHOR]

Research increasingly suggests that subjective cognitive decline (SCD) in older adults, in the absence of objective cognitive dysfunction or depression, may be a harbinger of non-normative cognitive decline and eventual progression to dementia. Little is known, however, about the key features of self-report measures currently used to assess SCD. The Subjective Cognitive Decline Initiative (SCD-I) Working Group is an international consortium established to develop a conceptual framework and research criteria for SCD (Jessen et al., 2014, Alzheimers Dement 10, 844-852). In the current study we systematically compared cognitive self-report items used by 19 SCD-I Working Group studies, representing 8 countries and 5 languages. We identified 34 self-report measures comprising 640 cognitive self-report items. There was little overlap among measures- approximately 75% of measures were used by only one study. Wide variation existed in response options and item content. Items pertaining to the memory domain predominated, accounting for about 60% of items surveyed, followed by executive function and attention, with 16% and 11% of the items, respectively. Items relating to memory for the names of people and the placement of common objects were represented on the greatest percentage of measures (56% each). Working group members reported that instrument selection decisions were often based on practical considerations beyond the study of SCD specifically, such as availability and brevity of measures. Results document the heterogeneity of approaches across studies to the emerging construct of SCD. We offer preliminary recommendations for instrument selection and future research directions including identifying items and measure formats associated with important clinical outcomes. [ABSTRACT FROM AUTHOR]