Articles

Long-term effects of migraine on

cognitive function
A population-based study of Danish twins
D. Gaist, MD, PhD; L. Pedersen, MSc; C. Madsen, MD; I. Tsiropoulos, MD; S. Bak, MD, PhD;
S. Sindrup, MD, PhD; M. McGue, PhD; B. Krogh Rasmussen, MD, PhD; and K. Christensen, MD, PhD

Abstract—Objective: To investigate the cognitive functioning of migraineurs vs nonmigraineurs in a large population-

based sample of middle-aged twins where headache diagnoses were established by neurologists. Methods: Twins identified
through the population-based Danish Twin Registry participated in face-to-face structured interviews, which included
cognitive tests and two previously validated questions screening for migraine. Twins who screened positive for migraine
and their co-twins were invited to participate in a telephone-based interview conducted by neurologists, who established
headache diagnoses according to the International Headache Society criteria. Cognitive scores on fluency, digit span,
delayed word recall, and symbol digit substitution test were compared between migraineurs and nonmigraineurs. Com-
parisons within monozygotic and dizygotic same sex twin pairs discordant for migraine were also performed. Results: Of
the 1,789 twins who were eligible for inclusion in the present study, 1,393 (77.8%) were interviewed. A diagnosis of
migraine was established in 536 twins (migraine without aura n ⫽ 347; migraine with aura n ⫽ 157). Average scores on
cognitive tests in twins with migraine or one of the migraine subtypes did not differ from those of nonmigraineurs in any
of the tests. Comparisons within twin pairs discordant for migraine produced highly comparable results. Adjustment for
possible confounders and stratification by cumulated number of lifetime attacks did not influence the results. Conclusions:
A lifetime diagnosis of migraine was not associated with cognitive deficits in middle-aged subjects.
NEUROLOGY 2005;64:600 –607

A recent cross-sectional study found that subjects
with migraine, in particular migraine with aura
(MA), were more prone to subclinical strokes in the
area supplied by the posterial cerebral artery as
evaluated by brain MR images.1 The study also re-
ported an increased occurrence of deep white matter
lesions in female migraineurs.1 Since such lesions
accrue with age and are associated with cognitive
decline and dementia this finding has led to renewed
speculation on whether migraine is a progressive
brain disease.2,3
A number of studies have concluded that migraine
has a deleterious effect on cognitive skills, a finding
reported for both migraine without aura (MO) and
MA.4-7 Other studies addressing the same issue
found no differences in cognitive skills between mi-
graineurs and controls.8-12 Potential problems of sam-
ple size, subject selection, the method used to
establish headache diagnoses, and other method-
ologic issues may, at least in part, explain the con-
flicting results reached by these studies. We sought
to overcome several methodologic shortcomings by
conducting a large population-based study among
middle-aged Danish twins in which headache diag-
noses were established by neurologists according to
the International Headache Society (IHS) criteria.13

Methods. The subjects were identified and included through a

Additional material related to this article can be found on the Neurology
two-step procedure. First, a large cohort of twins was traced
Web site. Go to www.neurology.org and scroll down the Table of Con-
through a population-based register and invited to participate in a
tents for the February 22 issue to find the title link for this article.
structured interview (baseline interview), which included cogni-

See also page 590

From the Danish Twin Register & Epidemiology (Drs. Gaist, Bak, and Christensen), Institute of Public Health, University of Southern Denmark;
Department of Neurology (Drs. Gaist, Madsen, Tsiropoulos, Bak, and Sindrup), Odense University Hospital; Department of Clinical Epidemiology (Dr.
Pedersen), Aarhus & Aalborg University Hospital, Denmark; Department of Psychology (Dr. McGue), University of Minnesota, Minneapolis; and Department
of Neurology (Dr. Krogh Rasmussen), Hillerød Hospital, Denmark.
Supported by the Danish Medical Research Council (grant 22– 00 – 0451) and the Danish Headache Society.
Received May 27, 2004. Accepted in final form October 25, 2004.
Address correspondence and reprint requests to Dr. David Gaist, Epidemiology, IST, University of Southern Denmark, Sdr. Boulevard 23A, 5000 Odense C,
Denmark; e-mail: dg@dadlnet.dk

600 Copyright © 2005 by AAN Enterprises, Inc.

tive tests and questions screening for migraine. In the second
step, all twins who screened positive on the migraine questions
and their co-twins were invited to be telephone interviewed by
neurologists regarding their headaches (neurologist interview).
Baseline interview. The Study of Middle Aged Danish Twins
Survey (MADT) has previously been described.14 In brief, 40 pairs
of each zygosity (monozygotic [MZ], dizygotic same sex [DZss], and
dizygotic opposite sex [DZos]) were selected at random from the
population-based Danish Twin Registry15 within each of the 22
birth cohorts 1931 through 1952. Owing to insufficient numbers of
MZ pairs in the birth cohorts of 1933, 1934, and 1936, we re-
trieved an additional 11 MZ pairs from the birth cohorts of 1931
and 1935. Of the 2,640 pairs identified, 5,189 twins were eligible
for participation in the study (91 twins were deceased or had
moved). The subjects had all previously answered a questionnaire
that included items on similarity of the twins, based on which we
assigned zygosity, a method found to result in misclassification
rates of less than 5%.16
Face-to-face interviews in the twins’ homes were conducted by
a total of 100 interviewers from the Danish National Institute of
Social Research.17 The survey, which lasted an average of 11/2
hours, comprised an extensive structured questionnaire, tests of
cognitive and physical functioning, and sampling of DNA. All in-
terviewers received a detailed training program by a physician
(D.G.) and were closely monitored in the 6-month period (October
1998 through March 1999) during which the interviews were com-
pleted. To avoid interviewer bias, which would inflate twin simi-
larity, twins from a pair were never interviewed by the same
interviewer. In all, 4,314 (83.1%) twins participated in the base-
line interview. Participation of intact pairs was highest for MZ
males (77.7%) and lowest for DZos (72.9%). Nonparticipation was
not highly selected, but showed patterns recognized from other
studies: a tendency for lower participation of fraternal twins, per-
sons not married, and urban area dwellers. However, men were
more likely to participate than women.14
Cognitive function measures. A series of cognitive tests18,19
was integrated in the baseline interview and included a test of
fluency, forward and backward digit span, a modified 12-word
learning test with immediate and delayed word recall, and a
symbol-digit substitution test. We assessed the subjects’ cognitive
function through their performance on the fluency test, the digit
span (combined sum of scores on forward and backward digit
span), the delayed word recall test, and the digit-symbol substitu-
tion test. The fluency test requires the examinee to name as many
animals as he or she can in 1 minute. The test is useful for
detecting frontal lobe damage and early mental decline.20,21 The
digit span test and the delayed word recall test are widely used
tests of working memory and long-term memory. The digit-symbol
substitution test is a timed test that involves the pairing of num-
bers with corresponding symbols according to a code that is visible
to the participant. This test has frequently been employed in
neuropsychologic and epidemiologic contexts to assess sustained
attention and psychomotor speed.22 Furthermore, similar versions
of the digit span, delayed word recall, and the symbol substitution
test have been used in previous studies of migraine and cognitive
function.5,6,9,11
Neurologist interview. The following two questions were used
to screen for migraine in the questionnaire part of the baseline
interview: “Have you ever had migraine?” and “Have you ever had
visual disturbances lasting from 5 to 60 minutes, which were
followed by a headache?” Twins answering positively to either of
these questions were considered screening positive for migraine.
These questions were previously employed in a study on Danish
twins.23 To assess the validity of our screening instrument we
identified all pairs where both twins had screened negative for
migraine and randomly selected 100 subjects from 100 different
twin pairs.
Twins identified for participation in the telephone interview
were sent a letter of invitation and a brief questionnaire. Nonre-
sponders were approached up to three times by mail. Responders
were telephone-interviewed by a neurologist, who used a struc-
tured interview and established the participants’ headaches ac-
cording to the IHS classification, 1st version.13 Four neurologists
carried out the interviews and twins from a pair were never inter-
viewed by the same neurologist.
Potential confounders. Several lifestyle (smoking, alcohol,
and medication consumption) and demographic factors (childhood
socioeconomic status, educational attainment) as well as disor-
ders, diseases, and life events (depression, stroke, chronic tension
type headache, head trauma) have been reported to be linked with
cognitive skills, and could, if distributed unevenly between mi-
graineurs and nonmigraineurs, confound the association between
migraine and cognitive functioning. We used information gathered
during the baseline interview and the neurologist interview to
control for these potential confounders.
We used information collected at the time of the baseline inter-
view to classify the subjects’ smoking (current, past, never) and
alcohol habits (abstainer, 0 to 9, 10 to 19, 20⫹ drinks per week),
number of years of schooling (⬍9, 9 to 10, 11⫹ years), and voca-
tional training (0, 1 to 2, 3 to 4, 5⫹ years), and self-reported
physician lifetime diagnoses of depression, medication treated hy-
pertension, or other diseases with potential influence on cognitive
skills (stroke, PD, epilepsy, or hypothyroidism). Depressive symp-
toms at the time of the baseline interview were furthermore as-
sessed by an adapted form of the Camdex Depression Scale24 and
subjects were classified into three groups based on the quartile
values of the baseline cohort (lower quartile [⬍22], 2nd and 3rd
quartile [22 to 24], upper quartile [25⫹]). Subjects were asked
whether they had ever received a blow to the head resulting in
loss of consciousness, and twins answering affirmatively were
identified. At the time of the baseline interview subjects were
asked to report any use of medication within the prior 14 days. All
reported drugs were subsequently classified by a chemist accord-
ing to the Anatomic Therapeutic Chemical (ATC) system.25 Sub-
jects reporting use of drugs belonging to ATC codes N05
(anxiolytics and antipsychotic drugs), N02A (strong analgesics), or
N06 (antidepressants) were identified. We also identified all sub-
jects with a diagnosis of chronic tension-type headache (IHS 2.2)
as established through the neurologist interview.
Finally, we identified monozygotic and same sex dizygotic
pairs where both twins in a pair participated in the present study
but only one of the twins was classified as having migraine accord-
ing to the neurologist interviews, i.e., pairs discordant for mi-
graine. The comparisons for education and cognitive test scores we
carried out within these pairs not only adjust for the effects of
genes (100% in MZ twins and 50% in DZ twins), age, and sex, but
also adjust for socioeconomic status in childhood.
Since migraine is more prevalent in women and several poten-
tial confounders vary in their distribution across sexes we chose to
present all main results stratified by sex.
Statistical analysis. Individual-based analyses. We com-
pared cognitive scores across strata of sex, age, and educational
attainment in participants of the baseline interview. To assess the
influence of nonparticipation in the present study, we compared
means and distributions of cognitive measures and potential con-
founders in neurology interview participants and nonparticipants.
These comparisons were also performed between participants
with migraine including the major subtypes (MO and MA) and
nonmigraineurs. The differences in cognitive test scores between
migraineurs and nonmigraineurs were furthermore adjusted for
the effect of potential confounders in an analysis of variance
(ANOVA) model. We had a priori selected age, sex, educational
attainment, and depressive symptom score as variables to be in-
cluded in the model. Since we cannot overrule that educational
attainment and depression lie on the causal pathway of a poten-
tial association between migraine and cognitive performance, we
also fitted models where these variables were not included. Other
variables were only included in the model if bivariate analyses
showed that their distribution varied significantly (p ⱕ 0.05) be-
tween migraineurs and nonmigraineurs. However, the effect of
certain variables that only involved few subjects, e.g., chronic
tension-type headache, was gauged by comparing the main analy-
ses run with and without the involved subjects.
We repeated the analyses after stratifying the subjects into
three age groups (⬍50, 50 to 59, 60⫹). Furthermore, to assess the
effect of the cumulative number of attacks of migraine on cogni-
tive function we compared the mean cognitive scores of subjects
with MO and MA across three strata of reported lifetime number
of attacks: ⬍50, 50 to 99, and 100⫹. We also performed these
analyses for strata of duration of migraine attacks (⬍20, 20 to 29,
and 30⫹ years), and age at migraine debut (⬍20, 20 to 29, 30⫹
years old).
Our choice of controls could be questioned due to the inclusion
of co-twins to the migraineurs and subjects with self-reported
February (2 of 2) 2005 NEUROLOGY 64 601
Table 1 Mean cognitive scores (SD) of 4,311 Danish twins participating in the baseline interview

Female* Male*

Symbol digit Symbol digit

Fluency, Digit span,† Delayed recall, substitution, Fluency, Digit span,† Delayed recall, substitution,
n ⫽ 2,113 n ⫽ 2,114 n ⫽ 2,108 n ⫽ 2,040 n ⫽ 2,191 n ⫽ 2,195 n ⫽ 2,187 n ⫽ 2,119

All 24.0 (7.3) 10.9 (3.3) 5.5 (2.4) 47.4 (13.2) 24.5 (7.4) 11.1 (3.6) 4.7 (2.2) 46.2 (12.2)
Age, y
⬍50 25.4 (7.1) 11.5 (3.4) 6.4 (2.4) 53.4 (11.7) 25.2 (7.6) 11.4 (3.8) 5.5 (2.3) 50.8 (10.1)
50–54 24.3 (7.3) 10.9 (3.3) 5.8 (2.5) 49.2 (11.2) 25.0 (7.6) 11.5 (3.6) 4.9 (2.2) 48.8 (11.9)
55–59 24.0 (7.4) 10.8 (3.6) 5.3 (2.3) 47.2 (13.5) 24.8 (7.1) 11.1 (3.3) 4.5 (2.2) 45.9 (11.8)
60⫹ 23.1 (7.1) 10.8 (3.2) 4.9 (2.3) 43.1 (13.5) 23.6 (7.2) 10.6 (3.5) 4.4 (2.0) 42.3 (12.4)
Schooling, y
⬍9 22.4 (6.7) 10.1 (2.9) 4.9 (2.3) 42.9 (13.2) 22.9 (7.2) 10.0 (3.8) 4.2 (2.0) 42.1 (12.1)
9–10 25.4 (7.3) 11.6 (3.6) 6.0 (2.3) 51.7 (11.5) 25.8 (6.6) 12.1 (3.6) 5.2 (2.1) 50.8 (9.9)
11⫹ 28.2 (7.4) 12.9 (3.5) 7.1 (2.3) 55.3 (9.4) 29.1 (7.9) 13.7 (3.7) 5.9 (2.4) 54.3 (9.3)
Vocational training, y
0 21.7 (6.7) 9.8 (3.0) 4.7 (2.3) 41.6 (13.1) 21.6 (7.5) 9.4 (3.2) 3.9 (2.2) 39.0 (12.6)
1–2 24.3 (7.1) 11.2 (3.3) 5.7 (2.3) 49.1 (12.3) 24.3 (6.8) 10.9 (3.3) 4.7 (2.1) 46.1 (11.2)
3–4 27.1 (7.3) 12.0 (3.4) 6.4 (2.6) 52.2 (12.8) 26.8 (7.9) 12.7 (3.6) 5.3 (2.3) 52.3 (12.0)
5⫹ 28.2 (7.0) 13.5 (3.1) 7.1 (2.2) 54.4 (7.8) 29.0 (7.0) 13.6 (3.7) 5.8 (2.4) 53.2 (9.4)

* No cognitive tests completed by one woman and six men.

† Sum of scores on digit forward span and digit backward span.

migraine that was not verified at the neurologist interview. We
therefore repeated the analyses using another control group com-
prising twins from pairs where both twins had screened negative
for migraine.
Within-pair analyses. We also performed within-pair compar-
isons of the cognitive scores of twins with migraine, MO or MA,
with that of their nonmigraineur co-twins. Within-pair differences
in mean cognitive scores were adjusted for potential confounders
through an ANOVA model that a priori included educational at-
tainment and depressive symptom score. Other variables were
chosen for inclusion as described above. Within-pair comparisons
for cognitive scores were also performed stratified by age (⬍55,
55⫹ years), cumulative number of attacks (⬍50, 50⫹), and zygos-
ity (monozygotic vs same sex dizygotic).
To account for the non-independence of the observations on
twins, subjects from pairs where both twins participated (intact
pairs) were analyzed as clusters of two in all multivariate models.
Our primary goal was to study whether migraine through its
attacks had a detrimental effect on cognitive skills. We viewed
educational attainment as a potential confounder and adjusted for
its effect in the multivariate analyses. However, some mi-
graineurs have attacks at an age where they might interfere with
their schooling or vocational training. Furthermore, according to
some researchers migraine may be a neurodevelopmental disor-
der26,27 in which case poor educational attainment may be linked
with migraine. We therefore also present data on educational
attainment for both the entire dataset and the intrapair
comparisons.
In the within-pair comparisons we also estimated ORs for edu-
cational attainment using conditional logistic regression. In order
to provide more robust estimates we collapsed the data into two
groups for this analysis (schooling: ⬍9, 10⫹ years; vocational
training: 0 to 2, 3⫹ years).
Results. The cognitive scores of participants in the base-
line interview varied across strata of sex, age, and educa-
tional attainment in a predictable manner (table 1). Of the
4,314 twins participating in the baseline survey, 1,789
were eligible for inclusion in the neurologist interview, and
1,393 (77.9%) subjects aged 45 to 67 years participated
602 NEUROLOGY 64 February (2 of 2) 2005
(figure). Participation rate did not vary by sex (78.0% in
women vs 77.7% in men). We stratified eligible subjects by
sex and migraine screening status and found that in these
strata participants were generally younger (mean differ-
ence 0.6 to 1.1 years) than nonparticipants, with the excep-
tion of screening positive men (mean difference ⫺0.3
years) (table 2). Participants had completed more years of
schooling and vocational training, and achieved higher
scores on all cognitive tests vs nonparticipants (see table
2). However, with the exception of schooling, the magni-
tude of these differences did not vary substantially by screen-
ing status (see table 2). In a separate analysis comparing the
combined group of migraineurs and screening-positive non-
participants vs the combined group of non-migraineurs and
screening-negative nonparticipants (worse case scenario
analysis), the two groups achieved highly comparable cogni-
tive scores (data not presented).
A lifetime diagnosis of migraine (IHS 1) was established
in 536 subjects henceforth referred to as migraineurs. Mi-
graineurs comprised 347 subjects with MO (IHS 1.1), 157
subjects with MA (IHS 1.2), and 85 twins with migrainous
disorder (IHS 1.7). Twins with migrainous disorder ful-
filled all but one of the criteria for a diagnosis of MO (83
twins) or MA (2 twins). A diagnosis of chronic tension-type
headache (IHS 2.2) was established in 68 subjects, and a
further 5 subjects had episodic cluster headache (IHS 3.1).
In all, 64 subjects were diagnosed with secondary head-
aches. Although 17 of these subjects also had migraine, the
debut of the primary and secondary headaches was sepa-
rated by more than a year in all cases. Finally, 51 mi-
graineurs and 5 nonmigraineurs had had a headache that
they could not recall in sufficient detail to permit a diagno-
sis to be established and were therefore classified under
IHS 13, ”Headache not classifiable.”

Figure. Flow chart of study participation. *Baseline in-
terview comprised 4,314 twins. However, in all, 22 twins
emigrated (3), died (16), or were lost to follow-up due to
secret address (3) after completion of baseline interview,
but before selection for present study. A further three twins
did not respond to migraine screening questions and were
also excluded. One twin died after random selection but
before contact was established.
A total of 75 twins participated from the random sample
of 100 pairs where both twins were screening negative. A
diagnosis of MO was made in one twin, MA in none, and
migrainous disorder in two twins. The negative predictive
value of the screening questions for migraine including
migrainous disorder (IHS 1) was 96.0% (95% CI [88.8% to
99.2%]), for MO it was 98.7% (95% CI [92.8% to 99.9%]),
and for MA 100% (one sided 97.5% CI: 95.2%).
Compared with nonmigraineurs of the same sex, mi-
graineurs were of similar age, but less frequently single,
current smokers, or heavy alcohol drinkers, and these dif-
ferences were more marked in men (table 3). Male mi-
graineurs also had a higher current depressive symptom
score compared with nonmigraineurs (p ⫽ 0.08). A neurol-
ogist diagnosis of chronic tension-type headache was 1.7
times more common in women (p ⫽ 0.05) and 4.5 times
more common in male migraineurs (p ⫽ 0.001) vs nonmi-
graineurs of the same sex. Female migraineurs were more
frequently current users of medications with a potential
negative influence on cognition than nonmigraineurs
(13.6% vs 9.4%; p ⫽ 0.07) (see table 3). Less marked differ-
ences were found for a number of other potential confound-
ers of the association between cognitive skills and
migraine (see table 3). Comparison of schooling and voca-
tional training between twins with migraine or one of the
migraine subtypes and nonmigraineurs did not reveal any
consistent patterns for migraine and MO (table 4). How-
ever, subjects with MA of both sexes had higher schooling
than nonmigraineurs, and female twins with MA had re-
ceived more vocational training than female nonmi-
graineurs, although none of these differences were
significant. Sex-stratified cognitive scores of migraineurs
and nonmigraineurs were highly comparable, although
subjects with migraine, MO or MA, consistently scored
marginally better than nonmigraineurs (see table 4).
Stratifying by age produced similar results (data not pre-
sented) as did adjusting for potential confounders (see ta-
ble E-1 on the Neurology Web site at www.neurology.org).
Consecutive inclusion of variables in the multivariate mod-
els as described in Methods had little impact on the results
(data not presented). Repeating the analyses with the
2,599 screening-negative twins as a control group produced
highly comparable results (data not presented).
Cognitive scores showed little variation when stratified
by the cumulative number of attacks of MO a subject had
had. Although not significantly so, subjects who reported
having had more than 100 attacks of MA had lower scores
on the digit span (mean 11.1 [SD: 3.4]), delayed word recall
(5.4 [2.4]), and symbol digit substitution test (47.7 [11.6])
than both subjects with 50 to 100 lifetime attacks (12.7
[4.9]; 6.0 [1.9]]; 48.2 [9.7]) and less than 50 lifetime attacks
(11.8 [3.9]; 5.9 [2.0]; 49.3 [12.1]) of MA. These differences
were less marked in women and were attenuated after
adjustment for potential confounders (data not presented).
No association was found between the age at migraine
debut or the number of years with migraine and cognitive
skills (data not presented).
Within–pair comparisons. We identified a total of 139
twin pairs (61 monozygotic and 78 same sex dizygotic) that
were discordant for migraine, MO or MA. Comparisons of
mean cognitive scores revealed only minor differences of
similar magnitude and direction as the individual-based
analyses described above, in spite of the fact that the twins
with migraine had fewer years of schooling and vocational
training than their co-twins (table 5). Adjusted within-pair
comparisons and analyses stratified by age and sex, and
cumulative number of lifetime attacks produced similar
results (data not presented).
Twins with migraine had completed fewer years of
schooling (10⫹ years OR: 0.31 [0.14 to 0.74]), and this
difference was also apparent in twin pairs discordant for
MO and MA (see table 5). Twins with migraine, MO, or
MA were not significantly different with regard to voca-
tional training compared with their co-twins (see table 5).
Discussion. We found that 536 middle-aged Danes
with a lifetime diagnosis of migraine or one of its
main subtypes achieved cognitive scores that were
highly comparable with those of 857 nonmigraineurs
in the same age group. Our results were not influ-
enced by several potential confounders. Stratifica-
tion by number of lifetime attacks of MO or MA had
no major impact on our results. Our study suggests
that a lifetime history of migraine or one of its prin-
cipal subtypes has little impact on cognitive function.
A number of studies provide evidence of cognitive
February (2 of 2) 2005 NEUROLOGY 64 603
Table 2 Eligible subjects stratified by sex, migraine screening status, and participation in present study (n ⫽ 1,789)

Female Male

Screening positive Screening negative Screening positive Screening negative

Participants, Nonparticipants, Participants, Nonparticipants, Participants, Nonparticipants, Participants, Nonparticipants,

n ⫽ 570 n ⫽ 148 n ⫽ 240 n ⫽ 81 n ⫽ 302 n ⫽ 82 n ⫽ 281 n ⫽ 85

Age, y, mean (SD) 56.2 (6.1) 58.3 (5.9) 56.2 (6.2) 58.2 (6.0) 56.5 (6.3) 56.2 (6.5) 56.9 (6.3) 57.5 (6.9)
Schooling, y, n (%)
⬍9 288 (50.5) 101 (68.2) 130 (54.2) 57 (70.4) 156 (51.7) 51 (62.2) 156 (55.5) 57 (67.1)
9–10 219 (38.4) 42 (28.4) 91 (37.9) 18 (22.2) 109 (36.1) 26 (31.7) 90 (32.0) 17 (20.0)
11⫹ 63 (11.1) 4 (2.7) 19 (7.9) 6 (7.4) 37 (12.3) 5 (6.1) 35 (12.5) 11 (12.9)
Vocational training, y,
n (%)
0 148 (26.0) 73 (49.3) 76 (31.7) 42 (51.9) 51 (16.9) 26 (31.7) 44 (15.7) 28 (32.9)
1–2 314 (55.1) 59 (39.9) 124 (51.7) 26 (32.1) 177 (58.6) 47 (57.3) 167 (59.4) 46 (54.1)
3–4 89 (15.6) 14 (9.5) 33 (13.8) 13 (16.0) 41 (13.6) 5 (6.1) 43 (15.3) 7 (8.2)
5⫹ 18 (3.2) 2 (1.4) 7 (2.9) 0 (0.0) 33 (10.9) 4 (4.9) 27 (9.6) 4 (4.7)
Cognitive test scores,
mean (SD)
Fluency* 24.4 (7.0) 21.6 (8.0) 24.4 (6.4) 21.9 (7.5) 24.9 (7.1) 22.0 (8.0) 25.3 (7.1) 23.2 (6.6)
Digit span† 11.0 (3.5) 9.8 (3.5) 11.2 (3.2) 10.0 (3.3) 11.3 (3.6) 10.5 (3.7) 11.4 (3.4) 10.4 (3.2)
Delayed word 5.8 (2.4) 4.8 (2.6) 5.7 (2.2) 5.0 (2.5) 4.8 (2.3) 4.5 (2.2) 4.8 (2.2) 3.8 (2.0)
recall‡
Symbol digit 48.9 (12.5) 43.6 (13.9) 48.2 (13.7) 42.7 (13.1) 46.9 (12.9) 44.3 (13.7) 45.7 (11.0) 42.9 (13.9)
substitution§

* One missing value.

† Sum of score for digit forward and digit backward span.
‡ Three missing values.
§ Fifty-nine missing values (female screening positive: 21 participants, 7 nonparticipants; female screening negative: 3 participants, 4 nonparticipants,
male screening positive: 12 participants, 3 nonparticipants; male screening negative: 4 participants, 5 nonparticipants).

deficits in migraineurs, in particular in subjects with
MA,5-7,28 involving psychomotor skills,4,6,7 memory,4,5,7
and dysfunctions in the early stages of visual pro-
cessing.29 However, in other studies of this issue no
evidence of interictal cortical dysfunction was found in
subjects with migraine or MA.8-12 Several authors have
suggested that these inconsistencies in the literature
may be due to methodologic issues such as sample size,
highly unrepresentative samples, and lack of adequate
comparison groups.6,9,27 Interestingly, our results are in
line with the only other study of the subject that was
carried out in a large population-based setting. This
study identified 99 middle-aged subjects with self-
reported current migraine within the cohort of the
Maastricht Aging Study and found that they fared
equally well on the letter-digit substitution test and
delayed recall tests compared with 1,753 nonmi-
graineurs from the same cohort.11
Some researchers believe that migraine may be a
neurodevelopmental disorder, in which case cogni-
tive function would be expected to be affected even
before the onset of migraine attacks.26,27 A cohort of
980 3-year-old children from New Zealand were fol-
lowed up for 23 years, serially subjected to neuropsy-
chological tests, and had migraine diagnoses
established according to the IHS criteria at age 26.
Compared with headache-free individuals, subjects
who later developed migraine were more frequently
604 NEUROLOGY 64 February (2 of 2) 2005
left-handed and had lower performances at age 3 to
13 on tests of verbal ability, but not on other tests of
IQ.27 Migraineurs in that study had also performed
less well on school examinations at the age of 15 to
17 and had not achieved bachelor degrees as fre-
quently as headache-free subjects.27 Also, a number
of cross-sectional studies, in particular from the
United States, have reported an inverse relationship
between migraine prevalence and socioeconomic sta-
tus as measured by education or income,30-33 al-
though this association was less pronounced in a
more recent study.34 In our study, we found no evi-
dence of a link between educational attainment and
migraine in the overall analyses. However, in the
within-pair comparisons, which are particularly in-
teresting since these analyses control the large num-
ber of factors the twins share including childhood
socioeconomic status, a tendency toward lower num-
ber of years of schooling in subjects with migraine,
and in particular MA, was found. However, as the
confidence limits indicate, our results concerning ed-
ucational attainment in the within-pair analysis
should be interpreted with caution.
Our study has a number of strengths. The sample
is large and population-based, and the participation
rate was high. The cognitive tests we used are sensi-
tive to even mild cognitive impairment as demon-
strated by the analyses of the entire baseline sample
Table 3 Characteristics of study participants stratified by sex and migraine diagnosis (n ⫽ 1,393)

Female Male

Migraineurs, Nonmigraineurs, p Migraineurs, Nonmigraineurs, p

n ⫽ 376 n ⫽ 434 Value* n ⫽ 160 n ⫽ 423 Value*

Age, y, mean (SD) 56.4 (6.2) 56.1 (6.1) 0.48 56.3 (6.1) 56.8 (6.4) 0.31
Married or cohabiting 301 (80.1) 338 (77.9) 0.45 147 (91.9) 347 (82.0) 0.003
Alcohol,† drinks per week
Abstainers 46 (12.2) 48 (11.1) 0.57 4 (2.5) 21 (5.0) 0.09
0–9 274 (72.9) 312 (71.9) 94 (58.8) 211 (50.0)
10–19 42 (11.2) 57 (13.1) 42 (26.3) 114 (27.0)
20⫹ 10 (2.7) 13 (3.0) 20 (12.5) 76 (18.0)
Smoker
Current 140 (37.2) 178 (41.0) 0.32 52 (32.5) 183 (43.3) 0.05
Past 87 (23.1) 83 (19.1) 61 (38.1) 146 (34.5)
Never 149 (39.6) 173 (39.9) 47 (29.4) 94 (22.2)
Current depressive symptom score†‡
⬍22 103 (27.4) 98 (22.6) 0.30 53 (33.1) 179 (42.3) 0.08
22–24 131 (34.8) 161 (37.2) 54 (33.8) 137 (32.4)
25⫹ 142 (37.8) 174 (40.1) 53 (33.1) 107 (25.3)
Ever self-reported physician diagnosed
Depression 80 (21.3) 74 (17.1) 0.13 17 (10.6) 45 (10.6) 0.99
Hypertension (drug treated) 75 (19.9) 74 (17.1) 0.29 24 (15.0) 62 (14.7) 0.92
Other disease with potential influence 26 (6.9) 41 (9.4) 0.19 8 (5.0) 17 (4.0) 0.60
on cognition§
Ever head-blow with loss of 76 (20.2) 83 (19.1) 0.71 53 (33.1) 126 (29.8) 0.45
consciousness†
Current drug use with potential cognitive 51 (13.6) 41 (9.4) 0.07 9 (5.6) 32 (7.6) 0.41
influence
Chronic tension-type headache§ 31 (8.2) 21 (4.8) 0.05 10 (6.3) 6 (1.4) 0.001

Numbers (%) unless otherwise stated.

* Comparison between migraineurs and nonmigraineurs, ␹2 test for proportions and t-test for means.
† Information was missing for nine twins on alcohol, one on depressive symptom score, two on head-blow with LOC.
‡ Assessed by an adapted form of the Camdex Depression Scale (see ref. Johnson 2003).
§ According to International Headache Society criteria (2.2) and established through neurologist interview.

of 4,311 twins where poorer cognitive scores were
achieved with increasing age, even within the rela-
tively narrow age-bands employed. Headache diag-
noses were established by experienced neurologists
according to the IHS criteria. The cognitive tests and
the questions screening for migraine were adminis-
tered as part of the baseline interview, at which time
both the trained interviewers and the subjects were
unaware of our research hypothesis. The extensive
baseline interview information allowed us to gauge
the effect of, and if necessary control for a multitude
of confounders. Finally, the twin design enabled us
to perform within-pair comparisons where we were
also able to adjust for any potential confounding ef-
fects of childhood socioeconomic environment.
Our study also has potential limitations. We used
a screening instrument to identify potential mi-
graineurs. This approach could have resulted in false
negative cases, i.e., subjects who had migraine but
were screening negative. Our validation study indi-
cated that this is not a major concern, since the
negative predictive value of the screening instru-
ment was very high. Nonparticipants clearly had
lower cognitive scores and educational attainment
than participants, which could have biased our re-
sults. However, the participation rate was high and
most of the observed differences were equally pro-
nounced among screening positive and screening
negative eligible subjects. Furthermore, cognitive
scores of migraineurs and nonmigraineurs remained
highly comparable even after we included nonpartic-
ipants according to screening status (worse case
scenario analysis). We therefore believe that nonpar-
ticipation had no major impact on our results. Our
choice of control group could be questioned, mostly
owing to the high proportion of unconfirmed self-
reported migraine. However, repeating the analyses
with the use of a large control group unrelated to the
February (2 of 2) 2005 NEUROLOGY 64 605
Table 4 Education and cognitive test scores of 1,393 middle-aged Danish twins by sex and migraine diagnosis

Migraine Migraine without aura Migraine with aura Nonmigraineurs

Female, Male, Female, Male, Female, Male, Female, Male,

n ⫽ 376 n ⫽ 160 n ⫽ 255 n ⫽ 92 n ⫽ 100 n ⫽ 57 n ⫽ 434 n ⫽ 423

Cognitive tests,* mean (SD)

Fluency 24.5 (6.3) 25.2 (7.0) 24.3 (6.9) 25.6 (6.9) 24.9 (5.5) 25.9 (7.1) 24.2 (7.2) 25.0 (7.0)
Digit span 11.2 (3.6) 11.4 (3.9) 11.1 (3.5) 11.5 (3.9) 11.6 (3.9) 12.1 (4.2) 11.0 (3.2) 11.3 (3.4)
Delayed word recall† 5.9 (2.2) 5.0 (2.2) 5.8 (2.3) 4.8 (2.4) 5.9 (2.3) 5.4 (1.8) 5.7 (2.4) 4.7 (2.3)
Symbol digit substitution‡ 49.0 (12.6) 47.1 (11.7) 48.9 (12.4) 47.2 (11.6) 49.3 (11.9) 47.1 (10.5) 48.4 (13.1) 46.0 (12.2)
Schooling,* y, n (%)
⬍9 197 (52.4) 87 (54.4) 146 (57.3) 48 (52.2) 43 (43.0) 25 (43.9) 221 (50.9) 225 (53.2)
9–10 137 (36.4) 53 (33.1) 83 (32.5) 35 (38.0) 41 (41.0) 22 (38.6) 173 (39.9) 146 (34.5)
11⫹ 42 (11.2) 20 (12.5) 26 (10.2) 9 (9.8) 16 (16.0) 10 (17.5) 40 (9.2) 52 (12.3)
Vocational training,* y, n (%)
0 102 (27.1) 29 (18.1) 74 (29.0) 15 (16.3) 20 (20.0) 10 (17.5) 122 (28.1) 66 (15.6)
1–2 200 (53.2) 93 (58.1) 135 (52.9) 54 (58.7) 57 (57.0) 31 (54.4) 238 (54.8) 251 (59.3)
3–4 63 (16.8) 21 (13.1) 39 (15.3) 11 (12.0) 21 (21.0) 10 (17.5) 59 (13.6) 63 (14.9)
5⫹ 10 (2.7) 17 (10.6) 6 (2.4) 12 (13.0) 2 (2.0) 6 (10.5) 15 (3.5) 43 (10.2)

* Migraineurs (migraine, MO, or MA) compared with nonmigraineurs of same sex; t-test for means and ␹2 test for proportions. Men
with MA had better score on delayed recall (p ⫽ 0.03) compared with nonmigraineurs. All other tests produced p values greater than 0.10.
† Test not performed by one female and one male nonmigraineur.
‡ Test not performed by 11 female and 3 male migraineurs and 13 female and 13 male nonmigraineurs.

migraineurs and consisting entirely of subjects from some subjects who had problems recalling lifetime
pairs where both twins screened negative for mi- headache characteristics. We cannot overrule that
graine did not influence our results. It could be ar- this is the case for some migraineurs, in particular
gued that the age group studied may have included those with milder or less frequent headache attacks.

Table 5 Cognitive scores and educational attainment of 139 middle-aged Danish twin pairs discordant for a lifetime diagnosis of
migraine

Migraine, n ⫽ 139 pairs Migraine without aura, n ⫽ 94 pairs Migraine with aura, n ⫽ 30 pairs

Adjusted Adjusted Adjusted

difference in difference in difference in
cognitive score cognitive score cognitive score
Case Co-twin (95% CI)* Case Co-twin (95% CI)* Case Co-twin (95% CI)*

Cognitive tests,
mean (SD)
Fluency 24.4 (6.8) 24.5 (7.0) 0.3 (⫺1.2 to 1.8) 24.7 (6.9) 24.3 (7.3) 0.9 (⫺1.1 to 2.9) 24.1 (8.1) 24.9 (7.0) ⫺0.4 (⫺5.7 to 4.9)
Digit span 11.2 (3.5) 10.6 (3.0) 0.9 (0.2 to 1.6) 11.0 (3.5) 10.4 (2.9) 0.9 (⫺0.1 to 1.8) 11.7 (3.5) 11.5 (3.0) 0.4 (⫺1.2 to 2.0)
Delayed word 5.6 (2.4) 5.5 (2.3) 0.3 (⫺0.2 to 0.7) 5.7 (2.4) 5.4 (2.3) 0.5 (⫺0.1 to 1.1) 5.6 (2.4) 5.5 (2.2) 0.4 (⫺0.9 to 1.7)
recall
Symbol digit 48.2 (11.2) 46.3 (13.0) 3.0 (0.6 to 5.4) 47.7 (10.1) 45.0 (13.0) 3.5 (0.5 to 6.5) 48.4 (11.3) 47.8 (13.8) 2.9 (⫺3.9 to 9.6)
substitution†
Schooling, y, n (%) OR OR OR
(95% CI)‡ (95% CI)‡ (95% CI)‡

⬍9 78 (56.1) 63 (45.3) 1 (reference) 55 (58.5) 43 (45.7) 1 (reference) 15 (50.0) 10 (33.3) 1 (reference)

10⫹ 61 (43.9) 76 (54.7) 0.31 (0.14–0.74) 39 (41.5) 51 (54.3) 0.25 (0.08–0.74) 15 (50.0) 20 (66.7) 0.17 (0.02–1.38)
Vocational training,§
y, n (%)
0–2 110 (79.7) 102 (73.9) 1 (reference) 75 (80.7) 70 (75.3) 1 (reference) 21 (70.0) 20 (66.7) 1 (reference)
3⫹ 28 (20.3) 36 (26.1) 0.53 (0.24–1.19) 18 (19.4) 23 (24.7) 0.55 (0.20–1.47) 9 (30.0) 10 (33.3) 0.67 (0.11–3.98)

* Difference in cognitive score (95% CI) adjusted for schooling, vocational education, depressive symptom score, and smoking.
† Missing information on four migraineurs and three nonmigraineurs (seven migraine pairs and three migraine without aura pairs).
‡ OR (95% CI) estimated through conditional logistic regression.
§ One pair not included due to missing information on one subject with migraine.

606 NEUROLOGY 64 February (2 of 2) 2005

Several lines of evidence in our data suggest that
this is not a major problem. Our finding of highly
comparable cognitive scores between migraineurs
and nonmigraineurs was not affected by age stratifi-
cation. The youngest age stratum included subjects
who were 46 to 49 years old, an age group where we
would not expect major problems in recollecting mi-
graine attacks. Furthermore, the neurologists re-
ported that they could not classify a headache due to
lack of detail on characteristics in only five nonmi-
graineurs. Finally, using the method described in a
previous Danish twin study,35 we estimated the ad-
justed lifetime prevalence of migraine, MO, and MA
in the entire baseline cohort to be 20.0% (95% CI:
18.9% to 21.2%), 12.4% (11.5% to 13.5%), and 5.6%
(5.0% to 6.4%). These estimates are highly compara-
ble with previous epidemiologic studies of the preva-
lence of migraine in Denmark.36,37
In older studies twins achieved lower mean cogni-
tive test scores compared with singletons.38,39 How-
ever, more recent research that overcame the
methodologic problems of previous studies found no
difference in cognitive skills between twins and sin-
gletons.40 We therefore believe that the use of twins
does not influence the generalizability of our results.
A recent population-based neuroimaging study re-
ported that migraineurs were at increased risk of
subclinical strokes in the area supplied by the poste-
rial cerebral artery compared with age- and sex-
matched controls.1 Our study was not able to address
this issue. However, in the same neuroimaging study
it was reported that female subjects with MO or MA
had a higher deep white matter lesion load, a link
that was more pronounced in subjects with frequent
attacks. This finding raised concern as to whether
such brain lesions, if truly associated with migraine,
may lead to cognitive impairment.3 Lack of imaging
data in our study and other design issues do not
permit straightforward comparisons with the results
of the neuroimaging study.1 In spite of these limita-
tions we believe that migraineurs should find it reas-
suring that the present study found no evidence of a
link between migraine and cognitive skills.
References
1. Kruit MC, van Buchem MA, Hofman PAM, et al. Migraine as a risk
factor for subclinical brain lesions. JAMA 2004;291:427– 434.
2. Lipton RB, Pan J. Is migraine a progressive brain disease? JAMA
2004;291:493– 494.
3. Tietjen GE. Stroke and migraine linked by silent strokes. Lancet Neu-
rol 2004;3:267.
4. Zeitlin C, Oddy M. Cognitive impairment in patients with severe mi-
graine. Br J Clin Psychol 1984;23:27–35.
5. HookerWD, Raskin NH. Neuropsychologic alterations in classic and
common migraine. Arch Neurol 1986;43:709 –712.
6. Mulder EJCM, Linssen WHJP, Passchier J, Orlebeke JF, de Geus EJC.
Interictal and postictal cognitive changes in migraine. Cephalalgia
1999;19:557–565.
7. Calandre EP, Bembibre J, Arnedo ML, Becerra D. Cognitive distur-
bances and regional cerebral blood flow abnormalities in migraine pa-
tients: their relationship with the clinical manifestations of the illness.
Cephalalgia 2002;22:291–302.
8. Sinforiani E, Farina S, Mancuso A, Manzoni GC, Bono G, Mazzucchi A.
Analysis of higher nervous functions in migraine and cluster headache.
Funct Neurol 1987;2:69 –77.
9. Leijdekkers ML, Passchier J, Goudswaard P, Menges LJ, Orlebeke JF.
Migraine patients cognitively impaired? Headache 1990;30:352–358.
10. Palmer JE, Chronicle EP. Cognitive processing in migraine: a failure to
find facilitation in patients with aura. Cephalalgia 1998;18:125–132.
11. Jelicic M, van Boxtel MPJ, Houx PJ, Jolles J. Does migraine headache
affect cognitive function in the elderly? Report from the Maastricht
Aging Study (MAAS). Headache 2000;40:715–719.
12. Haverkamp F, Hönscheid A, Müller-Sinik K. Cognitive development in
children with migraine and their healthy unaffected siblings. Headache
2002;42:776 –779.
13. Headache Classification Committee of the International Headache Soci-
ety. Classification and diagnostic criteria for headache disorders, cra-
nial neuralgias, and facial pain. Cephalalgia 1988;8(suppl 7):1–96.
14. Gaist D, Bathum L, Skytthe A, et al. Strength and anthropometric
measures in identical and fraternal twins: no evidence of masculiniza-
tion of females with male co-twins. Epidemiology 2000;11:340 –343.
15. Skytthe A, Kyvik K, Holm NV, Vaupel JW, Christensen K. The Danish
Twin Registry: 127 birth cohorts of twins. Twin Res 2002;5:352–357.
16. Hauge M. The Danish Twin Register. In: Mednick SA, Baert AE, Back-
man BP, eds. Prospective longitudinal research: an empirical basis for
the primary prevention of psychosocial disorders. London: Oxford Uni-
versity Press, 1981;218 –221.
17. Christensen K, Holm NV, McGue M, Corder L, Vaupel JW. A Danish
population-based twin study on general health in the elderly. J Aging
Health 1999;11:49 – 64.
18. McGue M, Christensen K. The heritability of cognitive functioning in
the very old: evidence from Danish twins aged 75 years and older.
Psychol Aging 2001;16:272–280.
19. Andersen K, Nybo H, Gaist D, et al. Cognitive impairment and mortal-
ity among nonagenarians: The Danish 1905 cohort survey. Dement
Geriatr Cogn Disord 2002;13:156 –163.
20. Benton AL, Eslinger PJ, Damasio AR. Normative observations on neu-
ropsychological test performances in old age. J Clin Neuropsychol 1981;
3:33– 42.
21. Duff Canning SJ, Leach L, Stuss D, Ngo L, Black SE. Diagnostic utility
of abbreviated fluency measures in Alzheimer disease and vascular
dementia. Neurology 2004;62:556 –562.
22. Pavlik VN, de Moraes SA, Szklo M, Knopman DS, Mosley TH, Hyman
DJ. Relation between cognitive function and mortality in middle-aged
adults. The atherosclerosis risk in communities study. Am J Epidemiol
2003;157:327–334.
23. Gervil M, Ulrich V, Olesen J, Russell MB. Screening for migraine in the
general population: validation of a simple questionnaire. Cephalalgia
1998;18:342–348.
24. Johnson W, McGue M, Gaist D, Vaupel JW, Christensen K. Frequency
and heritability of depression symptomatology in the second half of life:
evidence from Danish twins over 45. Psychol Med 2002;32:1175–1185.
25. WHO Collaborating Centre for Drug Statistics Methodology. Anatomi-
cal therapeutic chemical (ATC) classification index including defined
daily doses (DDD) for plain substances. Oslo: WHO, 1995.
26. Geschwind N, Behan P. Left-handedness: associations with immune
disease, migraine and developmental learning disorders. Proc Natl
Acad Sci USA 1982;79:5097–5100.
27. Waldie KE, Hausmann M, Milne BJ, Poulton R. Migraine and cognitive
function: a life-course study. Neurology 2002;59:904 –908.
28. Chronicle EP, Wilkins AJ, Coleston DM. Thresholds for detection of a
target against background grating suggest visual dysfunction in migraine
with aura but not migraine without aura. Cephalalgia 1995;15:117–122.
29. Wray SH, Mijovic-Prelec D, Kosslyn SM. Visual processing in mi-
graineurs. Brain 1995;118:25–35.
30. Breslau N, Davis GC, Andreski P. Migraine, psychiatric disorders, and
suicide attempts: an epidemiologic study of young adults. Psychiatry
Res 1991;37:11–23.
31. Stewart WF, Lipton R, Celentano DD, Reed JL. Prevalence of migraine
headache in the United States. Relation to age, income, race, and other
sociodemographic factors. JAMA 1992;267:64 – 69.
32. Stang PE, Osterhaus JT. Impact of migraine in the United States: data
from the National Health Interview Survey. Headache 1993;33:29 –35.
33. Lipton RB, Stewart WF, Diamond S, Diamond ML, Reed M. Prevalence
and burden of migraine in the United States: data from the American
Migraine Study II. Headache 2001;41:646 – 657.
34. Lipton RB, Scher AI, Kolodner K, Liberman J, Steiner TJ, Stewart WF.
Migraine in the United States: epidemiology and patterns of health
care use. Neurology 2002;58:885– 894.
35. Gervil M, Ulrich V, Kaprio J, Olesen J, Russell MB. The relative role of
genetic and environmental factors in migraine without aura. Neurology
1999;53:995–999.
36. Rasmussen BK, Jensen R, Schroll M, Olesen J. Epidemiology of head-
ache in a general population—a prevalence study. J Clin Epidemiol
1991;44:1147–1157.
37. Russell MB, Rasmussen BK, Thorvaldsen P, Olesen J. Prevalence and
sex-ratio of the subtypes of migraine. Int J Epidemiol 1995;24:612– 618.
38. Byrns R, Healy J. The intelligence of twins. J Genet Psychol 1936;49:
474 – 478.
39. Record RG, McKeown T, Edwards JH. An investigation of the difference
in measured intelligence between twins and single births. Ann Hum
Genet 1970;34:11–20.
40. Posthuma D, de Geus EJC, Bleichrodt N, Boomsma DI. Twin-singleton
differences in intelligence? Twin Res 2000;3:83– 87.
February (2 of 2) 2005 NEUROLOGY 64 607
 Long-term effects of migraine on cognitive function: A population-based study of
Danish twins
D. Gaist, L. Pedersen, C. Madsen, et al.
Neurology 2005;64;600-607
DOI 10.1212/01.WNL.0000151858.15482.66

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