Association between migraine and risk of dementia: a systematic review and meta-analysis

Abstract

Migraines, a prevalent neurological disorder, are increasingly linked to an elevated risk of dementia, including Alzheimer’s disease (AD) and vascular dementia (VaD). This systematic review and meta-analysis examined 12 cohort studies with 465,358 participants to assess this association. The results showed a significant relationship between migraines and dementia risk (OR = 1.35, 95% CI: 1.21–1.50), particularly chronic migraines (OR = 1.48, 95% CI: 1.44–1.52). Women, younger individuals, and those with a family history of dementia were at higher risk. Shared vascular risk factors, neurovascular dysfunction, and hormonal influences are potential mechanisms underlying this link. Chronic migraine may act as an early marker for cognitive decline, highlighting the need for targeted interventions and vascular risk management in at-risk individuals. Further research is essential to explore causal pathways and prevention strategies to reduce dementia risk in migraine patients.

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Nigora S. Kadyrkhodjayeva, Anna V. Prokhorova, & Nozimakhon A. Gulomova. (2025). Association between migraine and risk of dementia: a systematic review and meta-analysis. The American Journal of Medical Sciences and Pharmaceutical Research, 7(01), 89–95. https://doi.org/10.37547/tajmspr/Volume07Issue01-13
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Abstract

Migraines, a prevalent neurological disorder, are increasingly linked to an elevated risk of dementia, including Alzheimer’s disease (AD) and vascular dementia (VaD). This systematic review and meta-analysis examined 12 cohort studies with 465,358 participants to assess this association. The results showed a significant relationship between migraines and dementia risk (OR = 1.35, 95% CI: 1.21–1.50), particularly chronic migraines (OR = 1.48, 95% CI: 1.44–1.52). Women, younger individuals, and those with a family history of dementia were at higher risk. Shared vascular risk factors, neurovascular dysfunction, and hormonal influences are potential mechanisms underlying this link. Chronic migraine may act as an early marker for cognitive decline, highlighting the need for targeted interventions and vascular risk management in at-risk individuals. Further research is essential to explore causal pathways and prevention strategies to reduce dementia risk in migraine patients.


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TYPE

Original Research

PAGE NO.

89-95

DOI

10.37547/tajmspr/Volume07Issue01-13



OPEN ACCESS

SUBMITED

23 October 2024

ACCEPTED

25 December 2024

PUBLISHED

30 January 2025

VOLUME

Vol.07 Issue01 2025

CITATION

Nigora S. Kadyrkhodjayeva, Anna V. Prokhorova, & Nozimakhon A.
Gulomova. (2025). Association between migraine and risk of dementia: a
systematic review and meta-analysis. The American Journal of Medical
Sciences and Pharmaceutical Research, 7(01), 89

95.

https://doi.org/10.37547/tajmspr/Volume07Issue01-13

COPYRIGHT

© 2025 Original content from this work may be used under the terms
of the creative commons attributes 4.0 License.

Association between
migraine and risk of
dementia: a systematic
review and meta-analysis

Nigora S. Kadyrkhodjayeva

MD. PhD, Department of Neurology, AKFA Medline University Hospital, 5A
Kichik Khalka Yuli St., Almazar District, Tashkent 100211, Uzbekistan

Anna V. Prokhorova

MD, Doctor of Medical Science, Medical Director, Center for Sensory
Integration and Speech Development, Tashkent, Uzbekistan

Nozimakhon A. Gulomova

Central Asian University, 264 Milliy Bog St., Barkamol MFY, Mirzo Ulugbek
District, Tashkent 111221, Uzbekistan

Abstract:

Migraines, a prevalent neurological disorder,

are increasingly linked to an elevated risk of dementia,

including Alzheimer’s disease (AD) and vascular dementia

(VaD). This systematic review and meta-analysis
examined 12 cohort studies with 465,358 participants to
assess this association. The results showed a significant
relationship between migraines and dementia risk (OR =
1.35, 95% CI: 1.21

1.50), particularly chronic migraines

(OR = 1.48, 95% CI: 1.44

1.52). Women, younger

individuals, and those with a family history of dementia
were at higher risk. Shared vascular risk factors,
neurovascular dysfunction, and hormonal influences are
potential mechanisms underlying this link. Chronic
migraine may act as an early marker for cognitive decline,
highlighting the need for targeted interventions and
vascular risk management in at-risk individuals. Further
research is essential to explore causal pathways and
prevention strategies to reduce dementia risk in migraine
patients.

Keywords:

Chronic migraines, neurological disorder.

Introduction:

Headache disorders, including migraines,

are among the most prevalent neurological conditions
globally, affecting a significant portion of the
population. Headache and dementia are both prevalent
neurological conditions that significantly contribute to


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daily dysfunction and reduced quality of life [1].
Headache disorders are even more widespread,
affecting up to 46% of the adult population, making it
the fifth leading cause of disability worldwide. While
headache prevalence decreases significantly in adults
over the age of 50, it remains a common complaint
among the elderly. Tension-type headache (TTH), the
most frequent type of primary headache, is typically
characterized by bilateral, non-throbbing mild to
moderate pain. With a lifetime prevalence as high as
78%, it represents a significant health burden despite
its relatively lower intensity compared to migraines.
Migraines, on the other hand, are more complex,
presenting as recurrent attacks of moderate to severe,
pulsating, unilateral head pain, often accompanied by
nausea, photophobia, and phonophobia. The
prevalence of migraines is approximately 16% in
individuals aged 45

64 years, with a noticeable decline

as people age. Migraines are chronic, debilitating
conditions typically characterized by episodic or
chronic headaches, which can severely impact an
individual's quality of life [2-4]. Traditionally, migraines
have been associated with various vascular risk factors,
such as hypertension, stroke, and cardiovascular
diseases [5]. However, emerging evidence suggests
that migraines may also play a significant role in the
development

of

cognitive

decline

and

neurodegenerative diseases, including Alzheimer’s

disease (AD) and vascular dementia (VaD) [6-8].

Recent studies have shown that migraines, particularly
chronic and severe forms, are associated with a range
of neurological abnormalities that may contribute to
cognitive impairment [9]. These include reduced
cerebral blood flow, alterations in white matter
integrity, and increased levels of neuroinflammation
[10]. These findings highlight the complex interplay
between migraine pathophysiology and long-term
brain health, raising important questions about the
potential role of migraines as a risk factor for
dementia. Headache phase of migraines are has an
indirect effect on cognitive abilities, although
psychiatric conditions are not noted. It is also known
that chronic migraine sufferers are more prone to
severe cognitive challenges compared to those with
infrequent episodes [11,12]. These challenges may
include issues with attention, memory, and processing
speed, along with task performance that require
executive functions [13].

The meta-analysis revealed that individuals with
migraines have reduced general cognitive and
language function compared to those without
migraines [14]. The prevalence of dementia is rising
steadily worldwide, particularly as the global
population ages. Dementia, the most common

neurological disorder among the elderly, has been
shown to have a prevalence of 6.0%, with 3.9% of cases

being Alzheimer’s disease (AD), 1.6% vascular dementia

(VD), and 0.5% other forms of dementia. Due to its
progressive nature, dementia is typically characterized
by memory impairment, executive dysfunction, and
behavioral disinhibition. The public health burden of
dementia is expected to rise dramatically, with the
number of patients projected to double every 20 years,
reaching 65.7 million by 2030 as the population ages
According to the Centers for Disease Control and
Prevention (CDC), in 2014, it was estimated that five
million adults aged 65 and older were living with
dementia in the United States. This number is projected
to nearly triple to almost 14 million by 2060, presenting
a significant public health challenge as the population
ages [15]. As dementia, especially AD and VaD, becomes
more prevalent, understanding the potential risk factors
associated with these conditions is becoming
increasingly important [16]. In patients with migraines,
structural brain changes such as reduced grey matter,
white matter hyperintensities on MRI, and brain
parenchymal defects have been observed, highlighting
potential long-term impacts on brain health. These
findings raise the possibility that migraine disorders,
especially chronic or severe forms, may be associated
with increased risks of cognitive decline and dementia
in later life.

METHODS

The study aimed to investigate the association between
migraine and dementia, including Alzheimer's disease
(AD) and vascular dementia (VaD), in human subjects.
Two reviewers independently conducted a manual
search of PubMed, Cochrane Library, Embase, and Web
of Science from 2001 to 2020, focusing on cohort, case-
control, and longitudinal studies. A total of 12 cohort
studies comprising 465,3528 participants were
analyzed. Eligible studies reported risk measures such as
hazard ratios (HRs), odds ratios (ORs), or relative risks
(RRs) with corresponding 95% confidence intervals (CIs).
Studies were excluded if they were not peer-reviewed,
lacked relevant outcomes or necessary data, or involved
participants diagnosed with dementia before the
study's baseline to prevent reverse causality.
Conference abstracts and studies with incomplete data
were also excluded.

The inclusion criteria ensured that studies were focused
on human subjects with migraine and dementia,
reporting detailed and measurable outcomes. The
quality of the included cohort studies was assessed
using the Newcastle-Ottawa Scale (NOS), which
evaluated selection, comparability, and exposure or
outcome assessment. A random-effects model was used
to estimate pooled ORs for the association between


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migraine and dementia. Subgroup analyses were
conducted based on sex, migraine type (episodic vs.
chronic), and study design. Heterogeneity was
assessed using the I² statistic, while publication bias
was evaluated with funnel plots and Egger's test. The
rigorous methodology and comprehensive analysis
provided robust insights into the relationship between
migraine and dementia risk.

RESULTS

Out of 45,872 records identified in the initial search, 32
studies met the eligibility criteria. The final analysis

included 12 cohort studies, with a total of 465,358
participants. These studies involved patients with a
variety of migraine types and included participants from
different countries, with a mean follow-up of 10 years.

The pooled ORs indicated a statistically significant
association between a history of migraine and an
increased risk of dementia (OR = 1.35, 95% CI: 1.21

1.50), AD (OR = 1.49, 95% CI: 1.08

2.05), and VaD (OR =

1.72, 95% CI: 1.32

2.25). These associations remained

significant even after adjustment for confounders such
as age, sex, hypertension, and diabetes (Table 1).

Condition

Odds Ratio (OR)

95% Confidence Interval

(CI)

Dementia

1.35

1.21–1.50

Alzheimer's Disease (AD)

1.49

1.08–2.05

Vascular Dementia (VaD)

1.72

1.32–2.25

Table 1. Combined ORs for Migraine and Risk of Dementia, AD, and VaD

Subgroup analysis revealed distinct patterns of
dementia risk associated with migraines. Women with
a history of migraine had a significantly higher risk of
developing dementia compared to men (OR = 1.32,
95% CI: 1.16

1.51). Chronic migraine posed a greater

risk for dementia than episodic migraine (OR = 1.48,

95% CI: 1.44

1.52). Additionally, participants under the

age of 65 with a history of migraine demonstrated a
significantly elevated risk of developing Alzheimer's
disease compared to those without migraines (HR =
1.58, 95% CI: 1.52

1.64). These findings underscore the

influence of sex, migraine type, and age on the
association between migraine and dementia (Table 2).

Subgroup

Condition

Odds Ratio (OR)

95% Confidence

Interval (CI)

Sex

Dementia (Women vs.

Men)

1.32

1.16–1.51

Migraine Type

Chronic Migraine vs.

Episodic Migraine

1.48

1.44–1.52

Age

Participants under 65

(Migraine vs. No Migraine)

1.58

1.52–1.64

Table 2.

Subgroup Analysis of Dementia Risk Factors in Migraine Patients

In the cohort study using data from the National Health
Insurance Service (NHIS), chronic migraine was found
to be an independent risk factor for AD, with an HR of
1.72 (95% CI: 1.39

2.13). This study involved 10.6

million individuals and adjusted for age, sex, and
comorbidities. Additionally, this cohort study
demonstrated that individuals with a family history of
dementia who also had migraine were at an even
higher risk for developing AD and VaD.

DISCUSSION

Our findings provide robust evidence of an association
between migraine and an increased risk of dementia,

particularly Alzheimer's disease (AD) and vascular

dementia (VaD). The pooled odds ratios (ORs) from the
meta-analysis indicate a significant risk of developing
dementia in individuals with a history of migraine (OR =
1.35, 95% CI: 1.21

1.50), AD (OR = 1.49, 95% CI: 1.08

2.05), and VaD (OR = 1.72, 95% CI: 1.32

2.25). These

findings are consistent with earlier studies suggesting
that migraine, especially chronic migraine, may be
linked to neurovascular changes that predispose
individuals to cognitive decline [17]. The observed
association aligns with findings from the National Health
Insurance Service (NHIS) cohort study, which found that
chronic migraine was an independent risk factor for AD
(HR = 1.72, 95% CI: 1.39

2.13) [18-20].

Several potential mechanisms could explain the


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relationship between migraine and dementia. One of
the most prominent factors is the shared vascular risk
factors between migraine and dementia, such as
hypertension, diabetes, and obesity [21-24]. These
comorbidities are known to damage the vasculature,
which may accelerate the development of both
cognitive decline and migraine [25,26]. For example,
hypertension and diabetes increase the risk of stroke,
which in turn contributes to the development of VaD.
Additionally, migraine attacks are thought to be
associated with alterations in blood-brain barrier
integrity and neuroinflammatory processes, which are
also implicated in dementia pathogenesis [27-30].

Moreover, neurovascular dysfunction, which has been
observed in individuals with chronic migraines, could
further explain the increased risk of dementia. Cortical
and subcortical changes, including grey matter
atrophy, are common in chronic migraineurs and could
predispose individuals to neurodegenerative diseases
like AD [31-33]. Migraines may also act as a precursor
to vascular changes that disrupt cognitive function in
the long term [34-38].

Our analysis found that the risk of dementia is
significantly higher in women with a history of
migraine (OR = 1.32, 95% CI: 1.16

1.51) [39,40]. This

finding is consistent with previous literature, which
suggests that gender plays a significant role in the
severity of dementia risk. Female migraineurs,
especially those with chronic migraine, may be at a
heightened risk due to hormonal influences, as
estrogen is thought to impact both vascular health and
neurodegenerative processes.

In terms of migraine type, chronic migraine was
associated with a significantly higher risk of dementia
compared to episodic migraine (OR = 1.48, 95% CI:
1.44

1.52). This supports the hypothesis that the more

frequent and prolonged nature of chronic migraine
increases the likelihood of neurovascular damage and
cognitive decline [41].

The compounded risk of dementia in individuals with
both migraine and vascular comorbidities, such as
hypertension and diabetes, is a noteworthy finding.
Studies have suggested that these comorbid
conditions may exacerbate the risk of dementia in
migraine sufferers by contributing to vascular
dysfunction, which is a known pathway to cognitive
decline. The presence of both conditions may act
synergistically, leading to a greater overall burden on
cognitive function [42,43].

A cohort study using data from the National Health
Insurance Service (NHIS) demonstrated that chronic
migraine was an independent risk factor for AD, with
an HR of 1.72 (95% CI: 1.39

2.13). Furthermore, this

study indicated that individuals with a family history of
dementia who also had migraine were at an even higher
risk for developing AD and VaD. These findings
underscore the importance of identifying individuals
with migraine who also have vascular risk factors, as
they may be at a significantly elevated risk of dementia
[44-48].

Hypertension, diabetes, and obesity are significant
modifiable factors contributing to dementia risk in
migraineurs, emphasizing the importance of managing
these conditions to reduce long-term neurological
complications [49]. Additionally, a family history of
dementia presents a non-modifiable risk factor, further
underscoring the potential genetic predisposition in
these cases. Addressing modifiable risk factors through
early intervention and preventive measures may play a
crucial role in mitigating the heightened risk of
dementia in this population [50-54].

While the evidence strongly suggests an association
between migraine and dementia, it is essential to note
that the relationship does not imply causality. Further
research is needed to elucidate the underlying
mechanisms and to determine whether treating
migraine could reduce the risk of developing dementia.
Longitudinal studies with larger sample sizes and more
comprehensive data on vascular and genetic risk factors
will be crucial in understanding how migraine
contributes to dementia development [55,56].

Additionally, future research should focus on exploring
potential interventions that could mitigate the risk of
dementia in individuals with chronic migraine. These
could include optimizing the management of vascular
risk factors (e.g., hypertension, diabetes), enhancing
migraine treatment strategies, and investigating
whether medications targeting neuroinflammation or
cerebrovascular health could offer protective benefits
for those at higher risk of dementia

CONCLUSIONS

This review highlights a significant association between
migraines and increased dementia risk, particularly with
chronic

migraines.

However,

the

underlying

pathophysiological mechanisms remain unclear. Further
studies

focusing

on

neurovascular

changes,

inflammation, and advanced diagnostic methods are
needed to better understand and mitigate this risk.

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Clinical Psychiatry, vol. 81, no. 6, pp. 75

82, 2020, DOI:

10.4088/JCP.20m13553.

Lee, Y., Cho, J., Han, M., et al. "The role of migraine in

neurodegenerative disorders: A prospective cohort
study." Neuroepidemiology, vol. 53, no. 4, pp. 227

234,

2019, DOI: 10.1159/000502791.

Surov, A., Meyer, H., Degenhard, B., et al. "Cerebral
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6.

Lee, S.Y., Lim, J.S., Oh, D.J., et al. "Increased risk of
neurodegenerative dementia in women with migraines:
A nested case-control study using a national sample
cohort." Medicine (Baltimore), vol. 98, no. 7, pp.
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Lee, H.J., Yu, H., Gil, M.S., et al. "Mid- and late-life
migraine is associated with an increased risk of all-cause

dementia and Alzheimer’s disease, but not vascular

dementia: A nationwide retrospective cohort study."
Journal of Personalized Medicine, vol. 11, no. 10, 2021,
DOI: 10.3390/jpm11101089.

Favier, L., Dutheil, F., Perrier, P., et al. "Migraine and

Alzheimer’s disease: A longitudinal cohort study."
Alzheimer’s Research & Therapy, vol. 11, no

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Islamoska, S., Hansen, A.M., Wang, H.X., et al. "Mid- to
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national register-based follow-up study." The Journal of
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10.1186/s10194-020-01166-7.

Latysheva, N., Filatova, E., Osipova, D., et al. "Cognitive
impairment in chronic migraine: A cross-sectional study
in a clinic-based sample." Arquivos de Neuro-
Psiquiatria, vol. 78, pp. e1

e7, 2020, DOI:

10.1590/0004-282X20190159.

Chuang, C.S., Lin, C.L., Lin, M.C., et al. "Migraine and risk
of dementia: A nationwide retrospective cohort study."
Neuroepidemiology, vol. 41, no. 3

4, pp. 139

145,

2013, DOI: 10.1159/000353559.

Byers, A.L., Yaffe, K. "Depression and risk of developing
dementia." Nature Reviews Neurology, vol. 7, pp. 323

331, 2011, DOI: 10.1038/nrneurol.2011.60.

Rapp, M.A., Schnaider-Beeri, M., Grossman, H.T., et al.
"Increased hippocampal plaques and tangles in patients
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167, 2006, DOI: 10.1001/archpsyc.63.2.161.

Wint, D. "Depression: A shared risk factor for
cardiovascular and Alzheimer disease." Cleveland Clinic
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S46, 2011, DOI:

10.3949/ccjm.78.s1.07.

Yin, J.H., Tsai, C.L., Lee, P.J., et al. "Age-specific and
gender-dependent impact of primary headache


background image

The American Journal of Medical Sciences and Pharmaceutical Research

95

https://www.theamericanjournals.com/index.php/tajmspr

The American Journal of Medical Sciences and Pharmaceutical Research

disorders on dementia risk." Medicine (Baltimore), vol.
97,

pp.

e13789,

2018,

DOI:

10.1097/MD.0000000000013789.

Karner, E., Delazer, M., Benke, T., et al. "Cognitive
functions, emotional behavior, and quality of life in
familial

hemiplegic

migraine."

Cognitive

and

Behavioral Neurology, vol. 23, no. 2, pp. 106

111,

2010, DOI: 10.1097/WNN.0b013e3181e4b7b2.

Hou, J., Zhang, Y., Chen, J., et al. "Cognitive impairment
in migraineurs: A population-based study." Neurology,
vol. 92, no. 8, pp. e845

e852, 2019, DOI:

10.1212/WNL.0000000000007041.

Tzeng, N.S., Chung, C.H., Lin, F.H., et al. "Headaches
and risk of dementia." American Journal of the Medical
Sciences, vol. 353, no. 3, pp. 197

206, 2017, DOI:

10.1016/j.amjms.2016.12.014.

Yang, F.C., Lin, T.Y., Chen, H.J., et al. "Increased risk of
dementia in patients with tension-type headache: A
nationwide retrospective population-based cohort
study." PLOS ONE, vol. 11, no. 6, pp. e0156097, 2016,
DOI: 10.1371/journal.pone.0156097.

Kostev, K., Bohlken, J., Jacob, L. "Association between
migraine headaches and dementia in more than 7,400
patients followed in general practices in the United

Kingdom." Journal of Alzheimer’s Disease, vol. 71, no.

2, pp. 353

360, 2019, DOI: 10.3233/JAD-190581.

Lee, S.Y., Lim, J.S., Oh, D.J., et al. "Increased risk of
neurodegenerative dementia in women with
migraines: A nested case

control study using a

national sample cohort." Medicine (Baltimore), vol. 98,
no.

7,

pp.

e14467,

2019,

DOI:

10.1097/MD.0000000000014467.

George, K.M., Folsom, A.R., Sharrett, A.R., et al.
"Migraine headache and risk of dementia in the
atherosclerosis risk in communities neurocognitive
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953, 2020,

DOI: 10.1111/head.13794.

Morton, R.E., St John, P.D., Tyas, S.L. "Migraine and the
risk of all-

cause dementia, Alzheimer’s disease, and

vascular dementia: A prospective cohort study in
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1667

1676, 2019, DOI: 10.1002/gps.5180.

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