Lipton, Richard B.

Background: High adherence to the Mediterranean Diet (MeDi) was associated with better cognitive performance and decreased memory decline among Hispanic or Latino adults. Objective: Investigate if higher adherence to the MeDi improves white matter (WM) integrity among Hispanic/Latino adults and if this effect is mediated by cardiovascular health (CVH). Methods: We included 2,774 participants from the Study of Latinos-Investigation of Neurocognitive Aging-MRI Ancillary Study. Participants completed 24-hour dietary recalls at baseline (2008-2011) which were used to calculate a MeDi score (MeDiS, range 0-9). Brain MRI and diffusion tensor images were collected between 2018 and 2022 on a 3T MRI scanner using a standardized protocol. WM integrity was ascertained using WM hyperintensity (WMH) volume and fractional anisotropy (FA). WMH volumes were residualized for total cranial volume and Ln-transformed prior to analysis. The association of MRI outcomes with MeDiS and its components was investigated using weighted linear regression analysis with complex survey design adjusting for age, sex, sociodemographic characteristics. Cardiovascular health was assessed using the Life’s Simple 7 (LS7, range 0-14) score. The mediating effect of LS7 on the primary outcome was reported as Average Causal Mediation Effects (ACME) and Average Direct Effects (ADE). Statistical significance was set at p<0.05. Results: Mean age (95% CI) at MRI scan was 64.0 (63.4 to 65.2) and 44% were males. Mean MeDiS was 5.01 (4.89 to 5.12) and LS7 was 7.1 (7.0 to 7.3). In our fully adjusted model, increasing MeDi adherence was associated with decreased LnWMH volume (β=-0.07, 95% CI -0.10 to -0.03) and increased FA (β=0.002, 95% CI 0.001 to 0.003). Increasing LS7 scores partially mediated the relationship between MeDiS and WMHs (ACME=-0.01, ADE=-0.08, p<0.05, percent mediation=9%) and between MeDiS and FA (ACME=0.0001, ADE=0.002, p<0.01, percent mediated=8%). Among the different MeDi components, consumption of whole grains and fish above sex-specific energy adjusted energy median intake predicted lower WMH volume and increase FA (p<0.05 for both). Conclusions: Among diverse Hispanic/Latino adults, high MeDi adherence was associated with preserved WM integrity. This association was partially mediated by CVH. This suggests that the beneficial effect of MeDi on brain health is not fully explained by vascular risk factors. A culturally tailored MeDi may preserve brain health among Hispanic/Latino adults.

Abstract 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.

Abstract The small molecule calcitonin gene–related peptide receptor antagonists (gepants) are the only drug class with medicines indicated for both the acute and preventive treatment of migraine. Given this dual capacity to both treat and prevent, along with their favorable tolerability profiles and lack of an association with medication‐overuse headache, headache specialists have begun to use gepants in ways that transcend the traditional categories of acute and preventive treatment. One approach, called situational prevention , directs patients to treat during the interictal phase, before symptoms develop, in situations of increased risk for migraine attacks. Herein, we present three patients to illustrate scenarios of gepant use for situational prevention. In each case, a gepant was started in anticipation of a period of increased headache probability (vulnerability) and continued for a duration of 1 day to 5 consecutive days. Although this approach may expose patients to medication when headache may not have developed, the tolerability and safety profile and preventive effect of gepants may represent a feasible approach for some patients. Situational prevention is an emerging strategy for managing migraine before symptoms develop in individuals who can identify periods when the probability of headache is high. This paper is intended to increase awareness of this strategy and stimulate future randomized, placebo‐controlled trials to rigorously assess this strategy.

Abstract 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.