Is headache a risk factor for dementia? A systematic review and meta-analysis

Abstract

Objective In this systematic review and meta-analysis, we critically evaluate available evidence regarding the association between primary headaches and subsequent decline of cognitive function and dementia. Background Recent studies suggested that headache disorders may increase the risk for dementia. However, available studies are conflicting. Methods To identify qualifying studies, we searched scientific databases, including Pubmed, Scopus, Web of Science, Science Direct and BMC, screening for relevant papers. In order to reduce the heterogeneity between different studies, the analyses were further subdivided according to the clinical diagnoses and the study methodologies. Results We identified 23 studies investigating the association between primary headaches and the risk of dementia. Of these, 18 met our inclusion criteria for meta-analysis (covering 924.140 individuals). Overall effect-size shows that primary headaches were associated with a small increase in dementia risk (OR = 1,15; CI 95%: 1,03–1,28; p = 0,02). Analyzing subgroups, we found that migraine was associated with both a moderate increased risk of all-cause dementia (OR = 1,26; p = 0,00; 95% CI: 1,13–1,40) as well as a moderate increased risk of Alzheimer’s disease (OR = 2,00; p = 0,00; 95% CI: 1,46–2,75). This association was significant in both case–control and retrospective cohort studies but not in prospective studies. Conclusions Our study supports the presence of a link between primary headaches and dementia. However, in the subgroup analysis, only patients with migraine showed a moderate increase risk for all-cause dementia and for Alzheimer’s disease. Additional rigorous studies are needed to elucidate the possible role of primary headaches on the risk of developing cognitive impairment and dementia.

Independent causal effect of migraines on Alzheimer’s disease risk: a multivariate Mendelian randomization study

“…Recent studies have explored potential links between migraines and AD. However, these investigations have yielded conflicting conclusions ( 13–18 ), possibly attributed to differences in research methods, sample sizes, and study designs ( 19 , 20 ).…”

“…This proactive approach aids in the early identification of individuals at risk for AD, enabling the implementation of appropriate prevention and intervention measures. This bears significance in the endeavor to mitigate the development of AD and alleviate its socio-economic burden ( 19 , 20 ).…”

“…Nevertheless, it is important to highlight that existing investigations concerning the link between migraines and AD predominantly comprise retrospective studies ( 13–18 ), thereby introducing complexities in ascertaining causality. Rigorous randomized controlled trials (RCTs) grapple with practical challenges within this realm, encompassing concerns related to population bias, disparities in measuring and reporting outcomes, intricacies associated with prolonged follow-up durations, and the presence of diverse confounding elements ( 13–16 , 19 , 20 ). Moreover, addressing the potential for reverse causation in study design proves to be notably intricate t ( 13 ).…”