Author: Hans Christoph Diener, MD
Medscape
Recent studies offer potentially important insights into dementia prevention and diagnosis, migraine treatment, and nonpharmacologic headache prevention. The findings include possible protection against dementia from shingles and respiratory syncytial virus vaccination, strong diagnostic performance from a blood-based Alzheimer’s biomarker, broader ways to evaluate responses to migraine medications, and evidence that moderate aerobic exercise may reduce migraine frequency and severity.
Vaccination and dementia risk
Several studies have suggested that vaccination against herpes zoster, or shingles, may be associated with a reduced risk of dementia.
A large United States study using electronic health records from approximately 120 million individuals examined adults older than 60 who received respiratory syncytial virus vaccination, herpes zoster vaccination, or both.
The analysis included more than:
• 36,000 people who received an RSV vaccine
• 103,000 who received a herpes zoster vaccine
• 80,000 who received both vaccines
Matched individuals who received influenza vaccination served as controls.
During the following 18 months, both RSV and herpes zoster vaccination were associated with a lower incidence of dementia. The apparent protection was greatest among people who received both vaccines.
These observational findings do not prove that vaccination prevents Alzheimer’s disease. Vaccinated individuals may differ from unvaccinated individuals in health status, healthcare access, lifestyle, and other factors. The studies also cannot yet determine whether vaccination prevents dementia or merely delays its clinical appearance.
Nevertheless, the findings add to growing evidence that preventing infections or reducing infection-related inflammation may influence cognitive outcomes.
Blood-based testing for Alzheimer’s disease
The availability of monoclonal antibodies targeting beta-amyloid has increased the need for accurate biomarkers capable of identifying patients with early Alzheimer’s disease or mild cognitive impairment caused by Alzheimer’s pathology.
Amyloid positron-emission tomography and cerebrospinal-fluid testing have traditionally been used to confirm the presence of Alzheimer’s-related changes. However, these tests can be expensive, invasive, or difficult to access.
A meta-analysis involving more than 7,800 participants found that plasma phosphorylated tau 217, or p-tau217, demonstrated high diagnostic accuracy in people both with and without cognitive impairment.
The blood test may eventually reduce reliance on amyloid-PET imaging and cerebrospinal-fluid biomarkers. However, additional work is needed to determine appropriate thresholds, confirm performance across diverse populations, and establish how the test should be incorporated into routine clinical care.
Defining response to CGRP migraine therapy
Many healthcare systems require patients receiving monoclonal antibodies targeting calcitonin gene-related peptide to demonstrate at least a 50% reduction in monthly migraine days after three or six months for treatment to be continued or reimbursed.
A Spanish study followed 415 patients treated with a CGRP monoclonal antibody. After six months, 106 patients had not achieved the required 50% reduction. These individuals elected to continue treatment and pay for the medication themselves.
During the following six months, approximately 90% experienced improvement in outcomes other than the traditional 50% responder threshold.
Reported benefits included:
• Improved Migraine Disability Assessment scores in approximately 60%
• Conversion from chronic to episodic migraine in 41%
• Discontinuation of medication overuse in 46%
By 12 months, nearly 20% of the patients who had initially failed to reach the 50% threshold eventually achieved it.
These findings suggest that monthly migraine-day reduction alone may not fully capture the clinical value of treatment. Disability, attack severity, medication use, function, quality of life, and patient satisfaction should also be considered.
Fremanezumab in children and adolescents
CGRP monoclonal antibodies have historically lacked approval for pediatric migraine treatment in many regions.
A randomized study evaluated fremanezumab in children and adolescents up to 17 years old. Dosing was based on body weight:
• 120 mg for patients weighing less than 45 kilograms
• 225 mg for patients weighing at least 45 kilograms
Fremanezumab significantly reduced monthly migraine days. A 50% response was achieved by 47% of patients receiving fremanezumab compared with 27% receiving placebo.
The most common adverse effect was an injection-site reaction.
The study provides evidence that fremanezumab can be effective and generally well tolerated in pediatric patients. The findings contributed to its approval for this population in the United States, while regulatory review has also been pursued in Europe.
Aerobic exercise and migraine prevention
A meta-analysis of 15 studies evaluated aerobic exercise as a preventive treatment for migraine.
The relationship between exercise and migraine outcomes appeared to be U-shaped. Patients who exercised very little experienced more frequent and severe migraines, but excessive exercise was also associated with worse outcomes.
The apparent optimal exercise prescription was approximately 30 minutes of aerobic activity three times per week for 10 to 11 weeks.
This does not mean that every patient should follow exactly the same program. Exercise should be individualized according to cardiovascular health, physical conditioning, migraine triggers, and personal tolerance.
Clinical significance
The vaccination findings are encouraging, but they should not yet be interpreted as proof that RSV or shingles vaccines prevent Alzheimer’s disease. Vaccination decisions should continue to follow established age, health, and infection-prevention recommendations.
Plasma p-tau217 may make Alzheimer’s evaluation faster, less invasive, and more accessible, particularly as disease-modifying therapies become more widely available.
For migraine treatment, clinicians and insurers may need to consider outcomes beyond a 50% reduction in monthly migraine days. Patients may experience meaningful improvements in disability, medication overuse, attack severity, and daily functioning even when they do not meet that single numerical threshold.
Fremanezumab offers a promising preventive option for children and adolescents with migraine, while moderate aerobic exercise remains a practical and inexpensive component of migraine management.
Thank you to Medscape for allowing us to summarize this important update on dementia and migraine research.