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IntroductionPolygenic Risk Scores (PRSs) are summaries of genetic risk alleles for an outcome.MethodsWe used summary statistics from five GWASs of AD to construct PRSs in 4,189 diverse Hispanics/Latinos (mean age 63 years) from the Study of Latinos-Investigation of Neurocognitive Aging (SOL-INCA). We assessed the PRS associations with MCI in the combined set of people and in diverse subgroups, and when including and excluding the APOE gene region. We also assessed PRS associations with MCI in an independent dataset from the Mass General Brigham Biobank.ResultsA simple sum of 5 PRSs ("PRSsum"), each constructed based on a different AD GWAS, was associated with MCI (OR = 1.28, 95% CI [1.14, 1.41]) in a model adjusted for counts of the APOE-[Formula: see text] and APOE-[Formula: see text] alleles. Associations of single-GWAS PRSs were weaker. When removing SNPs from the APOE region from the PRSs, the association of PRSsum with MCI was weaker (OR = 1.17, 95% CI [1.04,1.31] with adjustment for APOE alleles). In all association analyses, APOE-[Formula: see text] and APOE-[Formula: see text] alleles were not associated with MCI.DiscussionA sum of AD PRSs is associated with MCI in Hispanic/Latino older adults. Despite no association of APOE-[Formula: see text] and APOE-[Formula: see text] alleles with MCI, the association of the AD PRS with MCI is stronger when including the APOE region. Thus, APOE variants different than the classic APOE alleles may be important predictors of MCI in Hispanic/Latino adults.

We aimed to examine the relationship between Apolipoprotein E ε4 (APOE*4) carriage on cognitive decline, and whether these associations were moderated by sex, baseline age, ethnicity, and vascular risk factors. Participants were 19,225 individuals aged 54-103 years from 15 longitudinal cohort studies with a mean follow-up duration ranging between 1.2 and 10.7 years. Two-step individual participant data meta-analysis was used to pool results of study-wise analyses predicting memory and general cognitive decline from carriage of one or two APOE*4 alleles, and moderation of these associations by age, sex, vascular risk factors, and ethnicity. Separate pooled estimates were calculated in both men and women who were younger (ie, 62 years) and older (ie, 80 years) at baseline. Results showed that APOE*4 carriage was related to faster general cognitive decline in women, and faster memory decline in men. A stronger dose-dependent effect was observed in older men, with faster general cognitive and memory decline in those carrying two versus one APOE*4 allele. Vascular risk factors were related to an increased effect of APOE*4 on memory decline in younger women, but a weaker effect of APOE*4 on general cognitive decline in older men. The relationship between APOE*4 carriage and memory decline was larger in older-aged Asians than Whites. In sum, APOE*4 is related to cognitive decline in men and women, although these effects are enhanced by age and carriage of two APOE*4 alleles in men, a higher numbers of vascular risk factors during the early stages of late adulthood in women, and Asian ethnicity.

ObjectiveHispanics/Latinos are the largest ethnic/racial group in the U.S., have the highest prevalence of diabetes, and are at increased risk for neurodegenerative disorders. Currently, little is known about the relationship between diabetes and cognitive decline and disorders among diverse Hispanics/Latinos. The purpose of this study is to clarify these relationships in diverse middle-aged and older Hispanics/Latinos.Research design and methodsThe Study of Latinos-Investigation of Neurocognitive Aging (SOL-INCA) is an ancillary study of the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). HCHS/SOL is a multisite (Bronx, NY; Chicago, IL; Miami, FL; and San Diego, CA), probability-sampled (i.e., representative of targeted populations), and prospective cohort study. Between 2016 and 2018, SOL-INCA enrolled diverse Hispanics/Latinos aged ≥50 years (n = 6,377). Global cognitive decline and mild cognitive impairment (MCI) were the primary outcomes.ResultsPrevalent diabetes at visit 1, but not incident diabetes at visit 2, was associated with significantly steeper global cognitive decline (βGC = -0.16 [95% CI -0.25; -0.07]; P < 0.001), domain-specific cognitive decline, and higher odds of MCI (odds ratio 1.74 [95% CI 1.34; 2.26]; P < 0.001) compared with no diabetes in age- and sex-adjusted models.ConclusionsDiabetes was associated with cognitive decline and increased MCI prevalence among diverse Hispanics/Latinos, primarily among those with prevalent diabetes at visit 1. Our findings suggest that significant cognitive decline and MCI may be considered additional disease complications of diabetes among diverse middle-aged and older Hispanics/Latinos.

IntroductionWe estimated the prevalence and correlates of mild cognitive impairment (MCI) among middle-aged and older diverse Hispanics/Latinos.MethodsMiddle-aged and older diverse Hispanics/Latinos enrolled (n = 6377; 50-86 years) in this multisite prospective cohort study were evaluated for MCI using the National Institute on Aging-Alzheimer's Association diagnostic criteria.ResultsThe overall MCI prevalence was 9.8%, which varied between Hispanic/Latino groups. Older age, high cardiovascular disease (CVD) risk, and elevated depressive symptoms were significant correlates of MCI prevalence. Apolipoprotein E4 (APOE) and APOE2 were not significantly associated with MCI.DiscussionMCI prevalence varied among Hispanic/Latino backgrounds, but not as widely as reported in the previous studies. CVD risk and depressive symptoms were associated with increased MCI, whereas APOE4 was not, suggesting alternative etiologies for MCI among diverse Hispanics/Latinos. Our findings suggest that mitigating CVD risk factors may offer important pathways to understanding and reducing MCI and possibly dementia among diverse Hispanics/Latinos.

BackgroundWith no effective treatments for cognitive decline or dementia, improving the evidence base for modifiable risk factors is a research priority. This study investigated associations between risk factors and late-life cognitive decline on a global scale, including comparisons between ethno-regional groups.Methods and findingsWe harmonized longitudinal data from 20 population-based cohorts from 15 countries over 5 continents, including 48,522 individuals (58.4% women) aged 54-105 (mean = 72.7) years and without dementia at baseline. Studies had 2-15 years of follow-up. The risk factors investigated were age, sex, education, alcohol consumption, anxiety, apolipoprotein E ε4 allele (APOE*4) status, atrial fibrillation, blood pressure and pulse pressure, body mass index, cardiovascular disease, depression, diabetes, self-rated health, high cholesterol, hypertension, peripheral vascular disease, physical activity, smoking, and history of stroke. Associations with risk factors were determined for a global cognitive composite outcome (memory, language, processing speed, and executive functioning tests) and Mini-Mental State Examination score. Individual participant data meta-analyses of multivariable linear mixed model results pooled across cohorts revealed that for at least 1 cognitive outcome, age (B = -0.1, SE = 0.01), APOE*4 carriage (B = -0.31, SE = 0.11), depression (B = -0.11, SE = 0.06), diabetes (B = -0.23, SE = 0.10), current smoking (B = -0.20, SE = 0.08), and history of stroke (B = -0.22, SE = 0.09) were independently associated with poorer cognitive performance (p < 0.05 for all), and higher levels of education (B = 0.12, SE = 0.02) and vigorous physical activity (B = 0.17, SE = 0.06) were associated with better performance (p < 0.01 for both). Age (B = -0.07, SE = 0.01), APOE*4 carriage (B = -0.41, SE = 0.18), and diabetes (B = -0.18, SE = 0.10) were independently associated with faster cognitive decline (p < 0.05 for all). Different effects between Asian people and white people included stronger associations for Asian people between ever smoking and poorer cognition (group by risk factor interaction: B = -0.24, SE = 0.12), and between diabetes and cognitive decline (B = -0.66, SE = 0.27; p < 0.05 for both). Limitations of our study include a loss or distortion of risk factor data with harmonization, and not investigating factors at midlife.ConclusionsThese results suggest that education, smoking, physical activity, diabetes, and stroke are all modifiable factors associated with cognitive decline. If these factors are determined to be causal, controlling them could minimize worldwide levels of cognitive decline. However, any global prevention strategy may need to consider ethno-regional differences.

Allostatic load (AL), an index of biological "wear and tear" on the body from cumulative exposure to stress, has been little studied in US Hispanics/Latinos. We investigated AL accumulation patterns by age, sex, and nativity in the Hispanic Community Health Study/Study of Latinos. We studied 15,830 Hispanic/Latinos of Mexican, Cuban, Dominican, Puerto Rican, Central and South American descent aged 18-74 years, 77% of whom were foreign-born. Consistent with the conceptualization of AL, we developed an index based upon 16 physiological markers that spanned the cardiometabolic, parasympathetic, and inflammatory systems. We computed mean adjusted AL scores using log-linear models across age-groups (18-44, 45-54, 55-74 years), by sex and nativity status. Among foreign-born individuals, differences in AL by duration of residence in the US (

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

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

Neck pain and headache are 2 of the most common complications of whiplash injury. Therefore, we performed a systematic literature search on PubMed and Embase for publications reporting on the prevalence of neck pain and headache after whiplash injury. The literature search identified 2709 citations of which 44 contained relevant original data. Of these, 27 studies provided data for the quantitative analysis. For non-population-based studies, the present metaanalysis showed that a pooled relative frequency of neck pain was 84% confidence interval (68–95%) and a pooled relative frequency of headache was 60% (46–73%), within 7 days after whiplash injury. At 12 months after injury, 38% (32–45%) of patients with whiplash still experienced neck pain, while 38% (18–60%) of whiplash patients reported headache at the same time interval after injury. However, we also found considerable heterogeneity among studies with I2-values ranging from 89% to 98% for the aforementioned meta-analyses. We believe that the considerable heterogeneity among studies underscores the need for clear-cut definitions of whiplash injury and standardized reporting guidelines for postwhiplash sequelae such as neck pain and headache. Future studies should seek to optimize these aspects paving the way for a better understanding of the clinical characteristics and natural course of whiplash-associated sequelae. [ABSTRACT FROM AUTHOR]

Objectives: To describe patterns of perceived stress across stages of the migraine cycle, within and between individuals and migraine episodes as defined for this study. Methods: Individuals with migraine aged ≥18 years, who were registered to use the digital health platform N1‐HeadacheTM, and completed 90 days of daily data entry regarding migraine, headache symptoms, and lifestyle factors were eligible for inclusion. Perceived stress was rated once a day at the participant's chosen time with a single question, "How stressed have you felt today?" with response options graded on a 0‐10 scale. Days were categorized into phases of the migraine cycle: Ppre = pre‐migraine headache (the 2 days prior to the first day with migraine headache), P0 = migraine headache days, Ppost = post‐migraine headache (the 2 days following the last migraine day with migraine headache), and Pi = interictal days (all other days). Episodes, defined as discrete occurrences of migraine with days in all 4 phases, were eligible if there was at least 1 reported daily perceived stress value in each phase. Individuals with ≥5 valid episodes, and ≥75% compliance (tracking 90 days in 120 calendar days or less) were eligible for inclusion in the analysis. Results: Data from 351 participants and 2115 episodes were included in this analysis. Eighty‐six percent of the sample (302/351) were female. The mean number of migraine days per month was 6.1 (range 2‐13, standard deviation = 2.3) and the mean number of episodes was 6.0 (range 5‐10, standard deviation = 1.0) over the 90‐day period. Only 8 (8/351, 2.3%) participants had chronic migraine (defined as 15 or more headache days per month with at least 8 days meeting criteria for migraine). Cluster analysis revealed 3 common patterns of perceived stress variation across the migraine cycle. For cluster 1, the "let down" pattern, perceived stress in the interictal phase (Pi) falls in the pre‐headache phase (Ppre) and then decreases more in the migraine phase (P0) relative to Pi. For cluster 2, the "flat" pattern, perceived stress is relatively unchanging throughout the migraine cycle. For cluster 3, the "stress as a trigger/symptom" pattern, perceived stress in Ppre increases relative to Pi, and increases further in P0 relative to Pi. Episodes were distributed across clusters as follows: cluster 1: 354/2115, 16.7%; cluster 2: 1253/2115, 59.2%, and cluster 3: 508/2115, 24.0%. Twelve participants (12/351, 3.4%) had more than 50% of their episodes fall into cluster 1, 216 participants (216/351, 61.5%) had more than 50% of their episodes fall into cluster 2, and 25 participants (25/351, 7.1%) had more than 50% of their episodes fall into cluster 3. There were 40 participants with ≥90% of their episodes in cluster 2, with no participants having ≥90% of their episodes in cluster 1 or 3. Conclusions: On an aggregate level, perceived stress peaks during the pain phase of the migraine cycle. However, on an individual and episode basis, there are 3 dominant patterns of perceived stress variation across the migraine cycle. Elucidating how patterns of perceived stress vary across the migraine cycle may contribute insights into disease biology, triggers and protective factors, and provide a framework for targeting individualized treatment plans. [ABSTRACT FROM AUTHOR]

Background: Subjective cognitive decline (SCD) is recognized as a risk stage for Alzheimer's disease (AD) and other dementias, but its prevalence is not well known. We aimed to use uniform criteria to better estimate SCD prevalence across international cohorts. Methods: We combined individual participant data for 16 cohorts from 15 countries (members of the COSMIC consortium) and used qualitative and quantitative (Item Response Theory/IRT) harmonization techniques to estimate SCD prevalence. Results: The sample comprised 39,387 cognitively unimpaired individuals above age 60. The prevalence of SCD across studies was around one quarter with both qualitative harmonization/QH (23.8%, 95%CI = 23.3–24.4%) and IRT (25.6%, 95%CI = 25.1–26.1%); however, prevalence estimates varied largely between studies (QH 6.1%, 95%CI = 5.1–7.0%, to 52.7%, 95%CI = 47.4–58.0%; IRT: 7.8%, 95%CI = 6.8–8.9%, to 52.7%, 95%CI = 47.4–58.0%). Across studies, SCD prevalence was higher in men than women, in lower levels of education, in Asian and Black African people compared to White people, in lower- and middle-income countries compared to high-income countries, and in studies conducted in later decades. Conclusions: SCD is frequent in old age. Having a quarter of older individuals with SCD warrants further investigation of its significance, as a risk stage for AD and other dementias, and of ways to help individuals with SCD who seek medical advice. Moreover, a standardized instrument to measure SCD is needed to overcome the measurement variability currently dominant in the field. [ABSTRACT FROM AUTHOR]

Objectives: The objectives of this study were to determine the rates of nausea, phonophobia, and photophobia reported overall and as the most bothersome symptom (MBS) in individuals with migraine and to identify individual characteristics associated with each of the 3 candidate MBSs. Background: The MBS has emerged as an important coprimary efficacy endpoint in clinical trials of acute treatments for migraine, as recommended by the Food and Drug Administration. The current understanding of how persons with migraine designate an associated symptom as the most bothersome has been assessed primarily in the context of randomized trials. Methods: Respondents (n = 95,821) in the cross‐sectional, observational Migraine in America Symptoms and Treatment (MAST) study were adults (aged ≥18 years) recruited from a US nationwide online research panel. A validated diagnostic screener identified 15,133 individuals who met modified International Classification of Headache Disorders (ICHD)‐3 beta criteria for migraine and reported at least 1 monthly headache day (MHD) over the previous 3 months. The survey ascertained sociodemographic variables, headache‐related disability, MHDs, cutaneous allodynia, medication overuse, a migraine symptom severity score, pain interference, noncephalic pain, anxiety and depression symptoms, visual aura over the previous year, and acute treatment optimization. The current analysis is based on respondents who also completed a 6‐month follow‐up assessment that included questions about their most bothersome headache symptom. Results: A total of 7518 respondents completed the 6‐month follow‐up, and 6045 met inclusion criteria and were included in the analysis. The mean age of respondents was 47 (SD 13.4) years, 76.0% (4596/6045) were women, and 84.8% (5103/6017) were white. Among all respondents, 64.9% reported all 3 migraine symptoms. The MBS was photophobia in 49.1% (2967/6045), nausea in 28.1% (1697/6045), and phonophobia in 22.8% (1381/6045). Respondents reporting photophobia as the MBS were more likely to be men, to be obese, and to report visual aura. Those reporting nausea as the MBS were more likely to be women, to have lower incomes, and to report lower levels of treatment optimization. Respondents reporting phonophobia as the MBS were more likely to have cutaneous allodynia and less likely to have visual aura. Conclusion: Most people with migraine in the MAST observational study reported all 3 cardinal symptoms of nausea, photophobia, and phonophobia. As in clinical trials, the most common MBS was photophobia. Patient profiles differed among the groups defined by their MBS. [ABSTRACT FROM AUTHOR]

Introduction: We estimated the prevalence and correlates of mild cognitive impairment (MCI) among middle‐aged and older diverse Hispanics/Latinos. Methods: Middle‐aged and older diverse Hispanics/Latinos enrolled (n = 6377; 50–86 years) in this multisite prospective cohort study were evaluated for MCI using the National Institute on Aging–Alzheimer's Association diagnostic criteria. Results: The overall MCI prevalence was 9.8%, which varied between Hispanic/Latino groups. Older age, high cardiovascular disease (CVD) risk, and elevated depressive symptoms were significant correlates of MCI prevalence. Apolipoprotein E4 (APOE) and APOE2 were not significantly associated with MCI. Discussion: MCI prevalence varied among Hispanic/Latino backgrounds, but not as widely as reported in the previous studies. CVD risk and depressive symptoms were associated with increased MCI, whereas APOE4 was not, suggesting alternative etiologies for MCI among diverse Hispanics/Latinos. Our findings suggest that mitigating CVD risk factors may offer important pathways to understanding and reducing MCI and possibly dementia among diverse Hispanics/Latinos. [ABSTRACT FROM AUTHOR]

Objectives: To characterize unmet treatment needs in a sample of Migraine in America Symptoms and Treatment (MAST) Study participants using oral, acute prescription migraine medications. Background: The MAST Study is a 2017 study of US adults with migraine that profiles current treatment patterns and identifies and quantifies unmet treatment needs. Methods: Cross‐sectional data from an online survey of US adults meeting ICHD‐3 beta criteria for migraine. For inclusion in this paper, respondents self‐reported a history of 3 or more monthly headache days (MHDs) in the past 3 months and at least 1 MHD in the past 30 days, and current use of orally administered acute prescription medication for headache. Three domains of unmet need were identified: inadequate treatment response (ie, inadequate 2‐hour pain freedom, recurrence within 24 hours of initial relief), demanding attack characteristics (rapid onset of attack, headache associated with sleep), and unique patient characteristics (opioid or barbiturate overuse, cardiovascular comorbidity). Sociodemographics, oral medication use, and coexisting conditions and symptoms (ie, level of treatment optimization, psychological symptoms, attack‐related cutaneous allodynia, and migraine symptom severity) were assessed for each domain and by the number of unmet need domains. Results: Overall, 15,133 respondents met inclusion criteria, 26.0% (3930/15,133) reported current use of oral acute prescription medication to treat headache. Eligible participants had a mean age of 45.0 years, 73.6% [2892/3930] were women and 81.1% [3186/3930]) were White. A total of 95.8% (3765/3930) of respondents had at least 1 unmet acute treatment need; 89.5% (3516/3930) reported demanding attack characteristics, 74.1% (2912/3930) reported inadequate treatment response, and 16.1% (634/3930) presented with unique patient characteristics. Common areas of unmet need were rapid headache onset (65.3% [2567/3930]), moderate to severe disability (55.6% [2187/3930]), inadequate 2‐hours pain freedom (49.0% [1892/3930]), and headache recurrence within 24 hours (38.0% [1493/3930]). An increasing number of unmet treatment need domains was associated with worsening psychological symptoms, attack‐related cutaneous allodynia and migraine symptom severity. Conclusion: Nearly all MAST Study respondents using acute oral prescription medications for migraine reported at least 1 unmet treatment need. As unmet needs increased, so did coexisting conditions and symptom severity. [ABSTRACT FROM AUTHOR]

Objectives: To summarize the baseline methods for the Migraine in America Symptoms and Treatment (MAST) Study and evaluate gender differences in sociodemographics and headache features; consultation and diagnosis patterns; and patterns of acute and preventive treatment use for migraine among study participants. Background: The MAST Study is a longitudinal, internet‐based panel study of symptoms, approaches to management, and unmet treatment needs among US adults with migraine. This analysis focuses on the initial cross‐sectional survey, conducted beginning in 2016, and is intended to update results from earlier national epidemiologic surveys of people with migraine in the United States. Methods: Respondents to the MAST Study were recruited from a US nationwide online research panel. Stratified random sampling identified a representative cohort of adults (aged ≥18 years). We administered a validated diagnostic screener based on modified ICHD‐3 beta criteria to identify individuals with migraine averaging at least 1 monthly headache day (MHD) over the previous 3 months. A baseline assessment evaluated sociodemographic and headache features, patterns of consultation and diagnosis, and use of acute and preventive medications for migraine. Frequency data and chi‐square contrasts (P < .05) were used to compare respondents based on gender. Results: Baseline survey data (N = 95,821) identified 18,353 respondents who met criteria for migraine, including 15,133 (women n = 11,049, men n = 4084) reporting at least 1 MHD for the preceding 3 months. The mean age of the sample was 43.1 (13.6) years; 73.0% of respondents were women, and 81.0% were Caucasian. Compared with men, women were younger (46.1 vs 42.0 years; P < .001); had more MHDs (5.6 vs 5.3; P < .001); and were more likely to report moderate or severe headache‐related disability (45.9% vs 35.8%; P < .001) and cutaneous allodynia (43.7% vs 29.5%; P < .001). The lifetime rate of medical consultation for headache was 79.8% overall and slightly higher in women than in men. Women were more likely than men to have been diagnosed with migraine (48.3% vs 38.8%, P < .001). While 95.1% of people with migraine currently used acute treatment, the majority (58.9%) used over‐the‐counter (OTC) drugs to the exclusion of prescription drugs, while 11.3% used exclusively prescription drugs, and 20.5% used both. Among acute prescription medication users, women were more likely than men to take triptans (17.7% vs 14.3%, P < .001), while men were more likely than women to take opioids (14.5% vs 9.2%, P < .001). Oral formulations were used predominately (92.7% of the medication users), but men were more likely to use nasal sprays (13.6% vs 9.4%, P < .001) and injectables (7.9% vs 3.4%, P < .001). Men (14.5%) were also significantly more likely than women (10.4%) to be taking daily oral preventive medication (P < .001). Conclusions: The MAST Study identified a large sample of women and men with migraine from a sampling frame that broadly resembles the US population. Low participation rate increases the risk of response bias, however, comparisons with Census data and prior population studies for the demographic and headache characteristics of the current sample suggest that findings are generalizable to the population of people with migraine. Women had more MHDs than men, and they were more likely to report migraine‐related disability and cutaneous allodynia. The lifetime consultation rate for headache was relatively high, but many with migraine symptoms reported never having received a diagnosis of migraine from a healthcare professional. Acute prescription and preventive migraine treatments are underused. Migraine persists as an underdiagnosed and undertreated public health problem in 2018, and there are many opportunities to improve the diagnosis and treatment of people with this painful, disabling condition. [ABSTRACT FROM AUTHOR]

Objective To compare the methods and baseline characteristics of the American Migraine Prevalence and Prevention (AMPP) and Chronic Migraine Epidemiology and Outcomes (CaMEO) studies. Background The AMPP and CaMEO studies are the largest longitudinal efforts designed to improve our understanding of episodic and chronic migraine in the United States. The studies have complementary strengths and weaknesses. Methods This analysis compares and contrasts the study methods and participation rates of the AMPP and CaMEO studies. We then compare and contrast baseline results in terms of demographic characteristics, headache features, and disability as measured by the Migraine Disability Assessment Scale (MIDAS) among people with episodic and chronic migraine. Results AMPP and CaMEO sampled from panels constructed to be representative of the US population. The AMPP Study collected data using a mailed questionnaire while CaMEO relied on a web survey methodology. Response rates were higher in AMPP (64.8%) than in CaMEO (16.5%). Both studies assessed headache features using the American Migraine Study/AMPP diagnostic module. Both identified persons with episodic (<15 headache days/month) and chronic migraine (≥15 headache days/month) based on the International Classification of Headache Disorders. AMPP collected data annually over 5 years, while CaMEO collected data quarterly over 15 months. Baseline demographic distribution was generally similar, indicating that each study was broadly representative of the US population. The proportion of persons with migraine who had chronic migraine was similar (AMPP, 6.6%; CaMEO, 8.8%). Respondents had similar median headache frequency (days/month) by sex for chronic migraine (AMPP: men = 21.7, women = 20.0; CaMEO: men = 20.0, women = 20.0) and episodic migraine (AMPP: men = 1.7, women = 2.0; CaMEO: men = 2.0, women = 3.0). Median MIDAS scores were substantially higher in both studies for chronic migraine (severe disability [Grade IV]; AMPP: men = 33.0, women = 45.0; CaMEO: men = 32.0, women = 38.0) than episodic migraine (little/mild disability [Grade I/II]; AMPP: men = 3.0, women = 6.0; CaMEO: men = 4.0, women = 7.0). Rates of moderate/severe disability (Grade III/IV) were substantially higher in both studies for chronic migraine (AMPP: men = 66.9%, women = 78.9%; CaMEO: men = 71.0%, women = 82.6%) than episodic migraine (AMPP: men = 23.0%, women = 31.8%; CaMEO: men = 26.7%, women = 37.9%). More women than men respondents in both studies experienced moderate/severe disability. Conclusions AMPP and CaMEO are longitudinal cohort studies that used different methods, but yielded similar results for demographic features, headache frequency, and headache-related disability. Both studies found more severe headache-related disability in those with chronic versus episodic migraine. [ABSTRACT FROM AUTHOR]

We sought to examine and describe neurocognitive function among middle-aged and older Hispanic/Latino Hispanic Community Health Study/Study of Latinos (HCHS/SOL) participants. We analyzed baseline cross-sectional data from the middle-aged and older (ages 45–74 years old) participants (n = 9,063) to calculate neurocognitive function scores and their correlates. Older age and higher depressive symptoms scores were associated with lower average neurocognitive performance, whereas greater educational attainment and household income were associated with higher neurocognitive performance. Hispanic/Latino heritage groups significantly varied in neurocognitive performances. Some neurocognitive differences between Hispanics/Latinos were maintained after controlling for language preference, education, household income, and depressive symptoms.We found notable differences in neurocognitive scores between Hispanic/Latino heritage groups that were not fully explained by the cultural and socioeconomic correlates examined in this study. Further investigations into plausible biological and environmental factors contributing to the Hispanic/Latino heritage group differences in neurocognitive found in the HCHS/SOL arewarranted. [ABSTRACT FROM AUTHOR]

Objective: To assess symptoms of attention-deficit/hyperactivity disorder (ADHD) and their impact among adults with epilepsy from a large community-based survey. Methods: Adults who self-reported epilepsy were sent a postal survey including the Adult ADHD Self-Report Scale version 6 (ASRS-6), Physicians Health Questionnaire (PHQ-9), Generalized Anxiety Disorder Assessment 7 (GAD-7), and questions about seizure frequency and number of antiepileptic drugs (AEDs) during the preceding 3 months. Individuals with ASRS-6 scores >14 were classified as ASRS+, and those with lower scores as ASRS. Outcome measures included the Quality of Life in Epilepsy Inventory 10 (QOLIE-10), Quality of Life and Enjoyment and Satisfaction Questionnaire (Q-LES-Q), and the Sheehan Disability Scale (SDS). The relationship of ADHD symptoms to quality of life outcomes was modeled hierarchically, with linear regression controlling for sociodemographic covariates, comorbid depression and anxiety, seizure frequency, and number of AEDs. Results: Among 1,361 of respondents with active epilepsy, 18.4% (n = 251) were classified as ASRS+ and at risk for ADHD. Compared to ASRS- cases, ASRS+ individuals were more likely to have elevated depression and anxiety scores as well as greater seizure frequency and more AED use (p < 0.05 for all). Modeling results comparing ASRS+ and ASRS- cases, controlling for all covariates, indicated that ASRS+ cases had lower quality of life (Beta [β] = -3.07, 95% confidence interval [CI] -4.19 to -1.96) and worse physical (β = -0.048 95% CI -0.076 to -0.020) and social functioning (β = -0.058, 95% CI -0.081 to -0.035) on the Q-LES-Q, and increases in family (β = 1.57, 95% CI 1.09-2.05), social (β = 1.68, 95% CI 1.20-2.16), and work-related disability (b-1.86, 95% CI 1.27-2.46). Significance: ADHD symptoms occur in nearly one of five adults with epilepsy, and are associated with increased psychosocial morbidity and lowered QOL. Future studies should clarify the nature and causes ofADHD symptoms in adults with epilepsy. [ABSTRACT FROM AUTHOR]

Objectives Refine the classification of migraine subtypes by applying factor mixture models ( FMM) to a large population sample of people with headache. Background Current classification of primary headache disorders is symptom-based and uses somewhat arbitrary boundaries developed by expert consensus. Symptom profiles and headache frequency are used to distinguish among probable migraine (PM), episodic migraine ( EM), high-frequency episodic migraine ( HFEM), and chronic migraine ( CM). Herein, we used statistical approaches to parse the heterogeneity in the broad group of persons with migraine and test the hypothesis that the groups that emerge differ in prognosis. Methods The American Migraine Prevalence and Prevention study mailed surveys to a sample of 120,000 US households selected to represent the US population in 2004. Follow-up surveys were sent to a random sample of 24,000 respondents with 'severe headache' on an annual basis from 2005 to 2009. People meeting International Classification of Headache Disorders, Second Edition, criteria for migraine were classified as EM (<15 headache days/month) and CM (≥15 headache days/month) based on modified Silberstein- Lipton criteria. The EM group was subdivided into HFEM (10 to 14 headache days/month) and low-frequency episodic migraine ( LFEM; <10 headache days/month). Factor mixture models ( FMM) identified 5 subgroups of migraine (taxa) using data from the 2005 survey on the severity of migraine symptoms, average migraine pain intensity, headache-related disability, cutaneous allodynia and depression, as well as monthly headache and migraine frequency as determinants of class membership. We assessed the validity of these taxa by examining the distribution of clinical diagnoses at cross-section and the rate of CM onset within these groups. Results Data from the 2005 American Migraine Prevalence and Prevention survey were used for the FMM and data from the 2006-2009 surveys were used to assess prognosis of groups defined based on FMM. In total, 12,860 participants were eligible for classification analysis, including 10,162 with LFEM and 601 with HFEM, 1302 with probable migraine, and 795 with CM. Of these, 3152 (24.5%), 1076 (8.4%), 3896 (30.3%), 2251 (17.5%), and 2485 (19.3%) were assigned to Taxons 1, 2, 3, 4, and 5, respectively. Overall, there was a strong association between taxon assignment and clinical diagnosis. As the most prevalent disorder in the sample, EM was the largest contributor to each of the 5 taxa, constituting more than 80% of each group other than Taxon 2. Taxon 2 was enriched with the most severe spectrum of migraine including the highest concentrations of CM (28.4%) and HFEM (22.6%), whereas Taxon 5 represented the least severe end of the migraine spectrum including the lowest concentrations of CM (0%) and HFEM (0.08%). Validity of taxon assignment was tested by the ability of taxon membership to predict clinical course. For Taxon 2, 22% of those free of CM at baseline developed it. For Taxon 5, less than 2% of CM-free Taxon 5 members developed it. Conclusion Statistically based classification using FMM extends traditional clinical syndrome-based diagnosis. FMM can serve as an important tool to parse phenotypic heterogeneity and identify natural migraine subgroups. This approach may improve our ability to diagnosis migraine, to select initial therapy, to predict prognosis, and to discover biomarkers and genes. [ABSTRACT FROM AUTHOR]

Objectives To assess the influence of triptan or nonsteroidal anti-inflammatory drug ( NSAID) use on the likelihood of developing chronic migraine ( CM) among persons with episodic migraine ( EM). Background CM is common in tertiary headache care, and relative to EM, CM is associated with a number of deleterious outcomes, including higher headache-related disability, reduced health-related quality of life, and increased direct and indirect costs. Symptomatic medication use has emerged as an important risk factor for the development of CM. Limited evidence based on a single year of follow up suggests that the association between NSAID and triptan use with the onset of CM varies in a dose-dependent manner that interacts with headache frequency. However, this interaction has never been explicitly studied. Herein, we evaluate results from a large-scale, 5-year, population-based observational study to characterize these relationships and test the hypothesis that NSAID use may modify the effect of triptan use on CM onset. Methods In the American Migraine Prevalence and Prevention ( AMPP) study, 11,249 participants had EM in 2005 and provided up to 5 years of annual follow-up data. We analyzed the characteristics of persons with EM 1 year that predicted new onset CM in the subsequent year, focusing on treatment with NSAIDs and triptans as exposures. These adjacent years of data provide the basis for analysis and are termed 'couplets.' Repeated measures logistic regression with a subject-specific random intercept was used to model the likelihood of transition from EM to CM as a function of NSAID or triptan dose while controlling for a number of covariates including headache features, use of other medications, and the number of couplets per individual. Results The analysis included 9031 individuals with EM contributing up to 5 years of data and up to 4 couplets each. Results indicated that on average, 55% of the participants used NSAIDs in any given year and 2% transitioned to CM over subsequent years. Among the 20% using triptans, 3% per year transitioned to CM. Among persons with less than 10 headache days per month, frequency of NSAID use was associated with dose-dependent reductions in risk of CM onset. Among those with 10-14 headache days per month, increasing days per month of NSAID use was associated with increasing risk of CM onset. Increasing days per month of triptan use was associated with increased risk of transitioning to CM. Combination use of NSAIDs and triptans was not protective against transition to CM, but was also not statistically significantly associated with increased risk of CM onset. Conclusion Triptan use in EM is associated with an increased risk of CM onset that increases with days of medication use. For NSAIDs, effects depend on headache days per month. NSAIDs are protective in individuals with less than 10 headache days per month but associated with increased risk with 10 or more headache days per month. Combining a triptan and NSAID was not associated with a statistically significant increased risk of CM onset, whereas increased risk of CM onset was significantly associated with triptan monotherapy. [ABSTRACT FROM AUTHOR]

Objectives. Although apolipoprotein E (APOE) genetic variation may influence risk of gait decline and disability in aging through multiple mechanisms, a systematic examination of this relationship has been lacking. Our objective was to quantify the risk of gait decline and disability associated with the APOE ε4 allele in aging. Methods. We evaluated 627 community-dwelling adults aged 70 and older (white 67.8%) with APOE genotype and quantitative gait measurements participating in the Einstein Aging Study over a median follow-up of 3.0 years. Main outcomes were gait speed decline (cm/s/year) and incident disability. Results. APOE ε4 allele frequency was 24.1%. Presence of APOE ε4 was not significantly associated with gait speed decline overall (p = .37) but was associated with faster gait speed decline in older men (estimate: −1.16, 95% CI: −2.31 to −0.01, p = .04). The interaction between the ε4 allele and male sex predicted gait speed decline (estimate: −1.70, 95% CI: −3.33 to −0.07, p = .04). Presence of the APOE ε4 allele was associated with increased risk of disability in older men (HR 3.72, 95% CI: 1.44–9.59, p = .007). Associations of the ε4 allele with study outcomes remained significant even after accounting for several potential confounders including vascular and cognitive status. The strength of the associations was stronger in the white subgroup. Conclusion. This preliminary report suggests that the APOE ε4 allele is associated with increased risk of gait speed decline and disability in older men. [ABSTRACT FROM PUBLISHER]

Background Despite the expanding therapeutic armamentarium, many people with episodic migraine ( EM) have unmet acute treatment needs. Objective To determine the relative frequency of prespecified types of 'unmet treatment needs' in persons with EM in a US population-based sample. Methods Eligible participants completed the 2009 American Migraine Prevalence and Prevention Study survey and met International Classification of Headache Disorders-2nd edition (ICHD-2) criteria for migraine with an average headache day frequency of <15 days per month ( EM). We identified 5 domains of unmet treatment needs: (1) dissatisfaction with current acute treatment using 3 summary items from the Patient Perception of Migraine Questionnaire-revised edition ( PPMQ-R); (2) moderate or severe headache-related disability defined by a Migraine Disability Assessment Scale score of ≥11; (3) excessive use of opioids or barbiturates defined as use on ≥4 days/month or by meeting Diagnostic and Statistical Manual for Mental Disorders-4th edition criteria for dependence; (4) recurrent use of the emergency department or urgent care clinic for headache defined by ≥2 visits in the preceding year for headache; and (5) history of cardiovascular events indicating a possible contraindication to triptan use. For each respondent, we identified their unmet treatment needs in each category and classified them as having no unmet needs or 1 or more unmet needs. Results Of 5591 respondents with EM, 2274 (40.7%) had 1 or more unmet needs; 1467 (26.2%) had exactly 1 unmet need, and 807 (14.4%) had 2 or more unmet needs. Among those with at least 1 unmet need, 1069 (47.0%) had moderate or severe headache-related disability, 851 (37.4%) were dissatisfied with their acute treatment regimen, 728 (32.0%) had excessive opioid or barbiturate use and/or probable dependence, 595 (26.2%) had a history of cardiovascular events, and 129 (5.7%) reported ≥2 visits in the preceding year to the emergency department/urgent care clinic for headache. Persons with more headache days, depression, or generalized anxiety were more likely to have unmet treatment needs. Conclusion In a population sample of individuals with EM, more than 40% have at least 1 unmet need in the area of acute treatment. The leading reasons for unmet needs, which include headache-related disability and dissatisfaction with current acute treatment, suggest opportunities for improving outcomes for persons with EM. [ABSTRACT FROM AUTHOR]

Background The strikingly higher prevalence of migraine in females compared with males is one of the hallmarks of migraine. A large global body of evidence exists on the sex differences in the prevalence of migraine with female to male ratios ranging from 2 : 1 to 3 : 1 and peaking in midlife. Some data are available on sex differences in associated symptoms, headache-related disability and impairment, and healthcare resource utilization in migraine. Few data are available on corresponding sex differences in probable migraine ( PM) and other severe headache (ie, nonmigraine-spectrum severe headache). Gaining a clear understanding of sex differences in a range of severe headache disorders may help differentiate the range of headache types. Herein, we compare sexes on prevalence and a range of clinical variables for migraine, PM, and other severe headache in a large sample from the US population. Methods This study analyzed data from the 2004 American Migraine Prevalence and Prevention Study. Total and demographic-stratified sex-specific, prevalence estimates of headache subtypes (migraine, PM, and other severe headache) are reported. Log-binomial models are used to calculate sex-specific adjusted prevalence ratios and 95% confidence intervals for each across demographic strata. A smoothed sex prevalence ratio (female to male) figure is presented for migraine and PM. Results One hundred sixty-two thousand seven hundred fifty-six individuals aged 12 and older responded to the 2004 American Migraine Prevalence and Prevention Study survey (64.9% response rate). Twenty-eight thousand two hundred sixty-one (17.4%) reported 'severe headache' in the preceding year (23.5% of females and 10.6% of males), 11.8% met International Classification of Headache Disorders-2 criteria for migraine (17.3% of females and 5.7% of males), 4.6% met criteria for PM (5.3% of females and 3.9% of males), and 1.0% were categorized with other severe headache (0.9% of females and 1.0% of males). Sex differences were observed in the prevalence of migraine and PM, but not for other severe headache. Adjusted female to male prevalence ratios ranged from 1.48 to 3.25 across the lifetime for migraine and from 1.22 to 1.53 for PM. Sex differences were also observed in associated symptomology, aura, headache-related disability, healthcare resource utilization, and diagnosis for migraine and PM. Despite higher rates of migraine diagnosis by a healthcare professional, females with migraine were less likely than males to be using preventive pharmacologic treatment for headache. Conclusions In this large, US population sample, both migraine and PM were more common among females, but a sex difference was not observed in the prevalence of other severe headache. The sex difference in migraine and PM held true across age and for most other sociodemographic variables with the exception of race for PM. Females with migraine and PM had higher rates of most migraine symptoms, aura, greater associated impairment, and higher healthcare resource utilization than males. Corresponding sex differences were not observed among individuals with other severe headache on the majority of these comparisons. Results suggest that PM is part of the migraine spectrum whereas other severe headache types are not. Results also substantiate existing literature on sex differences in primary headaches and extend results to additional headache types and related factors. [ABSTRACT FROM AUTHOR]

Objectives To characterize the extent of measurement error arising from rounding in headache frequency reporting (days per month) in a population sample of headache sufferers. Background When reporting numerical health information, individuals tend to round their estimates. The tendency to round to the nearest 5 days when reporting headache frequency can distort distributions and engender unreliability in frequency estimates in both clinical and research contexts. Methods This secondary analysis of the 2005 American Migraine Prevalence and Prevention study survey characterized the population distribution of 30-day headache frequency among community headache sufferers and determined the extent of numerical rounding ('heaping') in self-reported data. Headache frequency distributions (days per month) were examined using a simplified version of Wang and Heitjan's approach to heaping to estimate the probability that headache sufferers round to a multiple of 5 when providing frequency reports. Multiple imputation was used to estimate a theoretical 'true' headache frequency. Results Of the 24,000 surveys, headache frequency data were available for 15,976 respondents diagnosed with migraine (68.6%), probable migraine (8.3%), or episodic tension-type headache (10.0%); the remainder had other headache types. The mean number of headaches days/month was 3.7 (standard deviation = 5.6). Examination of the distribution of headache frequency reports revealed a disproportionate number of responses centered on multiples of 5 days. The odds that headache frequency was rounded to 5 increased by 24% with each 1-day increase in headache frequency (odds ratio: 1.24, 95% confidence interval: 1.23 to 1.25), indicating that heaping occurs most commonly at higher headache frequencies. Women were more likely to round than men, and rounding decreased with increasing age and increased with symptoms of depression. Conclusions Because of the coarsening induced by rounding, caution should be used when distinguishing between episodic and chronic headache sufferers using self-reported estimates of headache frequency. Unreliability in frequency estimates is of particular concern among individuals with high-frequency (chronic) headache. Employing shorter recall intervals when assessing headache frequency, preferably using daily diaries, may improve accuracy and allow more precise estimation of chronic migraine onset and remission. [ABSTRACT FROM AUTHOR]

Objective Our objective was to characterize patterns of preventive medication use in persons with episodic migraine ( EM) and chronic migraine ( CM). Background Several classes of medications are used both on- and off-label for the prevention of migraine, including β-blockers (eg, propranolol, timolol), tricyclic antidepressants (eg, amitriptyline), anti-epileptic drugs (eg, topiramate, valproic acid), and neurotoxins (eg, onabotulinumtoxin A). Methods Preventive medication use and reasons for discontinuation were collected in an international, Web-based, cross-sectional survey of adults with migraine during 2010. Descriptive analyses were conducted on demographics and headache-related disability as measured by the Migraine Disability Assessment Scale, stratified by use of preventive medication, and EM or CM. Univariate and multivariate logistic regression models were constructed to assess predictors of preventive medication use. Results One thousand one hundred and sixty-five respondents completed the survey. Only 28.3% of EM and 44.8% of CM respondents were currently using preventive medication; any use of prophylaxis (prior or current) was reported by 43.4% of those with EM and 65.9% with CM. The mean number of prophylactic medications ever used was 2.92 for EM and 3.94 for CM. Antidepressants were used most frequently ( EM 60.9%; CM 54.7%), followed by β-blockers ( EM 35.4%; CM 36.8%) and anti-epileptics ( EM 28.6%; CM 36.3%). Odds of preventive medication use were higher among CM than EM, adjusting for age, gender, race, years of daily headache, and country (odds ratio 2.72; 95% confidence interval 2.15 to 3.57). Greater headache-related disability and older age were also associated with greater odds of ever having used prophylaxis, regardless of headache frequency. Conclusions Less than half the persons with EM and CM were currently using preventive medication for migraine, with treatment rates being higher for CM, as expected. Those with CM tried more medications than those with EM, possibly reflecting higher levels of treatment need. [ABSTRACT FROM AUTHOR]

Background While nausea is a defining feature of migraine, the association of nausea with other headache features and its influence on the burden of migraine have not been quantified. Population-based data were used to elucidate the relative frequency and burden of migraine-associated nausea in persons with migraine. Methods Participants with episodic migraine who completed the 2009 American Migraine Prevalence and Prevention survey rated their headache-related nausea as occurring none of the time, rarely,

Background.- US Headache Consortium Guidelines state that persons with migraine with headache-related disability should receive certain acute treatments including migraine-specific and other medications. However, many eligible individuals do not receive these therapies. Individuals with migraine may experience barriers to receiving minimal appropriate care. We aimed to identify barriers to care in a population sample of individuals with episodic migraine. We assessed barriers at 3 levels: medical consultation, diagnosis, and acute pharmacologic therapy use and assessed the contribution of socioeconomic, demographic, and headache-specific variables to these barriers. Methods.- We identified 3 steps that were minimally necessary to achieve guideline-defined appropriate acute pharmacologic therapy as: (1) consulting a prescribing health care professional; (2) receiving a migraine diagnosis; and (3) using migraine-specific or other appropriate acute treatments. We used data from the 2009 American Migraine Prevalence and Prevention study sample to identify persons with episodic migraine with unmet treatment needs, defined by a Migraine Disability Assessment Scale (MIDAS) score corresponding to Grade II (mild), III (moderate), or IV (severe) headache-related disability. We determined whether these individuals had consulted a health care professional for headache over the previous year, if they ever received a medical diagnosis of migraine from a health care professional, and whether they were currently using appropriate acute treatment for migraine (ie, a triptan, prescription non-steroidal anti-inflammatory drug, or an isometheptene-containing agent). We analyzed several socioeconomic, demographic, and headache-specific variables to determine if they were related to barriers in any of the 3 defined steps. Results.- Of 775 eligible participants with episodic migraine and headache-related disability, 45.5% (n = 353/775) had consulted health care professional for headache in the preceding year. Among those individuals, 86.7% (n = 306/353) reported receiving a medical diagnosis of migraine. Among the diagnosed consulters, 66.7% (204/306) currently used acute migraine-specific treatments. Only 204 (26.3%) individuals successfully completed all 3 steps. Multivariate logistic regression models revealed that the strongest predictors of current consulting for headache were having health insurance {odds ratio (OR) = 1.73 (95% confidence interval [CI], 1.07-2.79)}, high headache-related disability (OR = 1.06 [95% CI, 1.0-1.14] for a 10-point change in MIDAS score), and a high composite migraine symptom severity score (OR = 1.19 [95% CI, 1.05-1.36]). Among consulters, diagnosis was much more likely in women than men (OR = 4.25 [95% CI, 1.61-11.2]) and became increasingly likely with increasing average headache pain severity (OR = 1.44 [95% CI, 1.12-1.87]) and migraine symptom severity score. Among those who were diagnosed, annual household income was the strongest predictor of currently using guideline-defined appropriate acute treatment (OR = 1.44 [95% CI, 1.07-1.93]) followed by a 10-point change in MIDAS score (OR 1.16 [95% CI, 1.02-1.35]). Conclusions.- Among persons with migraine in need of medical care (MIDAS Grade II or greater), only one quarter traversed the 3 steps we proposed to be necessary to achieving minimally appropriate care (consulting, diagnosis, and treatment/medication use). Health insurance status was an important predictor of consulting. Among consulters, women were far more likely to be diagnosed than men, suggesting that gender bias in diagnosis may be an important barrier for men. There were economic barriers related to use of appropriate prescription medications. Public health efforts should focus on improving consultation rates, particularly in the uninsured and diagnostic rates particularly in males with migraine. [ABSTRACT FROM AUTHOR]

Objectives.- To estimate the prevalence and distribution of chronic migraine (CM) in the US population and compare the age- and sex-specific profiles of headache-related disability in persons with CM and episodic migraine. Background.- Global estimates of CM prevalence using various definitions typically range from 1.4% to 2.2%, but the influence of sociodemographic factors has not been completely characterized. Methods.- The American Migraine Prevalence and Prevention Study mailed surveys to a sample of 120,000 US households selected to represent the US population. Data on headache frequency, symptoms, sociodemographics, and headache-related disability (using the Migraine Disability Assessment Scale) were obtained. Modified Silberstein-Lipton criteria were used to classify CM (meeting International Classification of Headache Disorders, second edition, criteria for migraine with a headache frequency of ≥15 days over the preceding 3 months). Results.- Surveys were returned by 162,756 individuals aged ≥12 years; 19,189 individuals (11.79%) met International Classification of Headache Disorders, second edition, criteria for migraine (17.27% of females; 5.72% of males), and 0.91% met criteria for CM (1.29% of females; 0.48% of males). Relative to 12 to 17 year olds, the age- and sex-specific prevalence for CM peaked in the 40s at 1.89% (prevalence ratio 4.57; 95% confidence interval 3.13-6.67) for females and 0.79% (prevalence ratio 3.35; 95% confidence interval 1.99-5.63) for males. In univariate and adjusted models, CM prevalence was inversely related to annual household income. Lower income groups had higher rates of CM. Individuals with CM had greater headache-related disability than those with episodic migraine and were more likely to be in the highest Migraine Disability Assessment Scale grade (37.96% vs 9.50%, respectively). Headache-related disability was highest among females with CM compared with males. CM represented 7.68% of migraine cases overall, and the proportion generally increased with age. Conclusions.- In the US population, the prevalence of CM was nearly 1%. In adjusted models, CM prevalence was highest among females, in mid-life, and in households with the lowest annual income. Severe headache-related disability was more common among persons with CM and most common among females with CM. [ABSTRACT FROM AUTHOR]

Objective: to determine the association of high sensitivity C-reactive protein (HsCRP) levels with a risk of mobility disability and decline in older adults with and without vascular disease.Design: prospective cohort.Setting: community-residing population.Subjects: six hundred and twenty-four adults age 70 and older (62% women) with gait and HsCRP assessments.Main outcome measures: incident mobility disability (velocity <70 cm/s) and annual rates of decline on gait velocity.Results: elevated HsCRP levels (≥3 mg/l) at baseline present in 224 of the 624 eligible subjects was associated with a faster annual decline in gait velocity of 0.91 cm/s (P = 0.02). Subjects with elevated HsCRP levels had increased risk of mobility disability (hazard ratio: 1.85, 95% CI: 1.09–3.14). Each one-unit increase in log HsCRP levels in the 406 subjects without prevalent mobility disability was associated with increased risk of mobility disability (hazard ratio: 1.33, 95% CI: 1.05–1.68). The association of baseline HsCRP levels with mobility disability and decline was stronger in the 224 individuals without vascular disease. The associations were not significant in the 400 subjects with vascular disease.Conclusions: HsCRP levels predict mobility disability and accelerated decline in walking speed in older adults. These associations were stronger in those without vascular disease. [ABSTRACT FROM PUBLISHER]

Background.- Though triptans are considered the standard of acute therapy for migraine attacks with headache-related disability, they are used by the minority of potentially eligible persons. Understanding the socio-demographic and headache features that predict triptan use may help to clarify barriers to optimal treatment. Objective.- To assess the sociodemographic and headache features associated with triptan use in a US population sample of persons with episodic migraine. Methods.- The American Migraine Prevalence and Prevention Study (AMPP) is a longitudinal study conducted in a representative sample of US headache sufferers. Episodic migraineurs (n = 11,388) who provided treatment data in 2005 were included in the current analyses. We assessed factors associated with triptan use through univariate and multivariate analyses. Multivariate analyses were adjusted for sociodemographic factors, headache-related disability, cutaneous allodynia, depression, and preventive headache medication use. Results.- Among persons with episodic migraine, 18.31% reported current use of triptans for acute headache treatment. In univariate analyses, triptan use was most common in midlife (ages 30-59), among females, and was more common in Caucasians than in African Americans. Triptan use increased with headache frequency, headache-related disability and allodynia, but decreased among persons with depression. In multivariate analyses, female gender, Caucasian race, age 40-49, higher levels of education (college or higher), annual household income of ≥$40,000, having health insurance, the presence of cutaneous allodynia, greater headache-related disability, and preventive medication use for migraine were significantly associated with triptan use. Conclusions.- Less than 1 in 5 persons with migraine in the United States who were respondents to this survey used triptans for acute headache treatment over the course of a year. Several markers of severe headache, including disability and allodynia, were associated with increased triptan use. Groups less likely to get triptans included males, African Americans, older adults, and the uninsured. Predictors of use provide insight into groups with unmet treatment needs. [ABSTRACT FROM AUTHOR]

( Headache 2011;51:693-706) To estimate the prevalence of chronic migraine (CM) among adolescents and to describe the epidemiologic profile, headache characteristics, disability, and healthcare utilization of adolescents with CM in the USA. Chronic daily headache (CDH) and CM occur in children and adolescents, but are poorly understood in these populations because their presentation is different from that in adults. It may be difficult to assign a definitive diagnosis to young people suffering from CDH because symptoms may fail to meet the criteria for one of the CDH subtypes. A large sample of households with at least one resident aged 12 to 19 years was selected in balance with the US Census. Data were collected in 3 phases: (1) mailed questionnaire; (2) telephone interview; and (3) 30-day interactive voice response system diary. CM prevalence was estimated by adapting the second edition of the International Classification of Headache Disorders criteria for CM to include pediatric migraine diagnostic criteria. The population was stratified for medication overuse. Medication overuse was defined as 15 or more days per month of acute medication use. Included in the study were measures of headache characteristics, headache impact (Headache Impact Test), disability (Pediatric Migraine Disability Assessment), and healthcare and medication use. Data are reported on subjects 12 to 17 years of age only. The US adolescent (12-17 years) prevalence rate for CM was 0.79% (0.00-1.70) excluding those with medication overuse and 1.75% (0.62-2.89) when adolescents with medication overuse were included. The majority of adolescents with CM had Headache Impact Test scores greater than or equal to 60, indicating severe headache impact, and mean Pediatric Migraine Disability Assessment scores greater than 17, indicating severe headache and disability. The majority of adolescents with CM (approximately 60%) had not visited a healthcare provider in the previous year and less than one in 5 reported taking medications to prevent headaches during the last month. Results suggest that CM occurs less frequently in adolescents than adults, but like adults, adolescents are severely burdened by the disorder. Data support an unmet medical need; however, the development of optimal criteria for diagnosing adolescents with CM is critical to fully understanding how medical needs can be met within this complex population. [ABSTRACT FROM AUTHOR]

( Headache 2011;51:533-543) To evaluate the efficacy and tolerability of telcagepant when co-administered with ibuprofen or acetaminophen for the acute treatment of migraine. Telcagepant is an oral calcitonin gene-related peptide receptor antagonist which is being evaluated for the acute treatment of migraine. Combining telcagepant with analgesics that have a different mechanism of action could produce greater efficacy. Randomized, double-blind, placebo-controlled study. Patients were randomized to treat a moderate or severe migraine headache with either telcagepant 280 mg + ibuprofen 400 mg (N = 171), telcagepant 280 mg + acetaminophen 1000 mg (N = 171), telcagepant 280 mg (N = 170), or placebo (N = 171). The primary efficacy endpoint was 2-hour pain freedom. The study had approximately 88% power to detect an additive effect of at least 15 percentage points (telcagepant combination vs telcagepant monotherapy) and 48% power to detect an additive effect of at least 10 percentage points. Safety and tolerability were assessed by adverse events and laboratory tests. The percentages of patients with 2-hour pain freedom were greater in each active treatment group compared to placebo ( P < .001): telcagepant + ibuprofen = 35.2%, telcagepant + acetaminophen = 38.3%, telcagepant = 31.2%, placebo = 10.9%. No significant differences were seen for either of the combination groups vs telcagepant monotherapy, but both were numerically larger than telcagepant monotherapy. All the active treatments were generally well tolerated. The percentage of patients reporting any adverse event within 48 hours was higher in the active treatment groups than placebo: telcagepant + ibuprofen = 30.3%, telcagepant + acetaminophen = 31.6%, telcagepant = 24.8%, placebo = 18.2%. The most common adverse events reported by ≥4 patients in one or more of the treatment groups that included telcagepant were fatigue, nausea, dizziness, somnolence, dry mouth, and tremor. The combination of telcagepant 280 mg with either ibuprofen 400 mg or acetaminophen 1000 mg did not show a statistically significant difference from telcagepant alone. Numerically greater treatment effects in the combination treatment groups over the telcagepant 280 mg monotherapy suggest that telcagepant combination treatments may merit further evaluation in studies powered to detect smaller additive benefits. (Clinicaltrials.gov; NCT00758836). [ABSTRACT FROM AUTHOR]

To estimate the prevalence of neuropsychiatric and pain disorders in adults with epilepsy in the United States. In 2008, an 11-item survey including validated questions to screen for a lifetime history of epilepsy was mailed to 340,000 households from two national panels selected to be generally representative of the noninstitutionalized U.S. population. Information on epilepsy and other disorders was collected from 172,959 respondents aged 18 or older. Propensity scoring was used to match respondents with and without epilepsy on baseline characteristics and risk factors for epilepsy. Prevalence ratios (PRs) of comorbidities in respondents with epilepsy were calculated using log-binomial generalized linear models. Comorbidities were categorized as neuropsychiatric (anxiety, depression, bipolar disorder, attention-deficit/hyperactivity disorder, sleep disorder/apnea, and movement disorder/tremor), pain (migraine headache, chronic pain, fibromyalgia, neuropathic pain), and other (asthma, diabetes, and high blood pressure). Two percent (3,488) of respondents reported ever having been told they had epilepsy or a seizure disorder. Respondents with self-reported epilepsy were more likely (p < 0.001) than those without epilepsy to report all six neuropsychiatric disorders (PR from 1.27-2.39), all four pain disorders (PR 1.36-1.96), and asthma (PR 1.25). Neuropsychiatric conditions and pain disorder comorbidities were reported more often in individuals with self-reported epilepsy than in those without epilepsy. Identification of these conditions is an important consideration in the clinical management of epilepsy. [ABSTRACT FROM AUTHOR]

( Headache 2010;50:1144-1152) Post-dural puncture headache (PDPH) is a frequent complication of dural puncture whether performed for diagnostic purposes or accidentally, as a complication of anesthesia. Because both procedures are common, clinicians interested in headache should be familiar with this entity. The differential diagnosis of PDPH is broad and includes other complications of dural puncture as well as headaches attributable to the condition which lead to the procedure. The patterns of development of PDPH depend on a number of procedure- and nonprocedure-related risk factors. Knowledge of procedure-related factors supports interventions designed to reduce the incidence of PDPH. Finally, despite best preventive efforts, PDPH may still occur and be associated with significant morbidity. Therefore, it is important to know the management and prognosis of this disorder. In this review, we will highlight diagnosis and clinical characteristics of PDPH, differential diagnosis, frequency, and risk factors as well as pathophysiology of PDPH. [ABSTRACT FROM AUTHOR]

The triptan era has been a time of remarkable progress for migraine diagnosis and treatment. In this paper, we review some of the advances achieved in migraine science during this era focusing on 3 themes: lessons from clinical practice, lessons from epidemiology and lessons from pathophysiology. Science has shown that migraine is a disorder of the brain, and that the key events happen in the the trigeminal neuronal pathways, not on blood vessels. Clinical science has led to the observation that migraine sometimes progresses or remits. This in turn led to longitudinal epidemiologic studies focusing on factors that determine migraine prognosis. In addition, these studies raised questions about the mechanisms of migraine progression, including the role of allodynia, obesity, inflammation, and medications as determinants of progression. This in turn opens a new set of scientific questions about the neurobiologic determinants of migraine, as well as of its clinical course, and exciting opportunities to develop new therapies for this highly disabling brain disorder. [ABSTRACT FROM AUTHOR]

Migraine is frequently associated with menstruation in female migraineurs, and consequently it is commonly referred to as menstrually associated migraine. The trigger thought to be partially responsible for menstrually associated migraine is a significant drop in circulating estrogen that is noted during 2-3 days prior to onset of menses. It is estimated that approximately 50% of women have an increased risk of experiencing migraine during the premenstrual phase of decreasing estrogen levels. Understanding the biological basis of migraine associated with menses will facilitate an accurate diagnosis and help patients recognize time susceptible to migraine exacerbations. This paper will review the biological bases for the hormonal changes that occur during the menstrual cycle and review the prevalence and burden of menstrual migraine among female headache sufferers. [ABSTRACT FROM AUTHOR]

The proposed definitions for refractory migraine (RM) and refractory chronic migraine (R-CM) comprise 5 key components that must be operationalized for epidemiologic research. Persons with RM or R-CM must meet the second edition of the International Classification of Headache Disorders criteria for migraine or chronic migraine. They must experience significant interference with function or quality of life due to headaches. This interference must be present despite adequate treatment in 3 domains: modification of triggers and lifestyle factors, acute medication, and preventive medicines. The epidemiologic data which address these 5 components will be reviewed herein though specifically designed studies will be required to fully explore RM and R-CM. In addition, 2 “modifiers” of RM and R-CM have been proposed; one addresses medication overuse and the other considers disability based on a Migraine Disability Assessment score of 11 or greater. The epidemiology of these modifiers is discussed. [ABSTRACT FROM AUTHOR]

About 4% of the adult population and about 1% to 2% of children experience chronic attacks on a daily or near daily basis. While there is uncertainty about the biological mechanisms that lead to headache “chronification,” the epidemiologic literature has provided some insight into modifiable and nonmodifiable factors that appear to influence risk of headache progression. This review summarizes the evidence from population-based studies related to the chronic daily headache phenotype, natural history, and risk factors that may influence incidence, prevalence, or prognosis. [ABSTRACT FROM AUTHOR]