Alzheimer’s & Dementia 14 (2018) 1253-1260

Featured Article

Increased risk for dementia both before and after stroke:

A population-based study in women followed over 44 years
€
Xinxin Guo*, Svante Ostling, Silke Kern, Lena Johansson, Ingmar Skoog
Neuropsychiatric Epidemiology Unit, Section for Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University
of Gothenburg, M€olndal, Sweden

Abstract Introduction: Longitudinal studies are needed to understand the long-term associations between
stroke and dementia.
Methods: A population sample of 1460 women without stroke or dementia at baseline was followed
over 44 years, from 1968 to 2012. Information on stroke and dementia was obtained from neuropsy-
chiatric examinations, key-informant interviews, hospital registry, and medical records.
Results: During 44 years follow-up, 362 women developed stroke and 325, dementia. The age-
specific incidence of the two disorders was similar. The incidence of dementia was higher in those
with stroke than among those without (33.7% vs. 18.5%; age-adjusted hazard ratio 1.44, 95% confi-
dence interval 1.15–1.81). The increased risk of dementia started already 5 years before stroke, was
highest 1 year after stroke, and continued more than 11 years after stroke.
Discussion: There is an increased risk for dementia both before and after stroke. This has implications
for understanding the relation between the two disorders and for prevention of dementia and stroke.
Ó 2018 The Authors. Published by Elsevier Inc. on behalf of the Alzheimer’s Association. This is an
open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/
4.0/).
Keywords: Stroke; Dementia; Longitudinal study; Population-based study; Women

1. Backgrounds increased shortly after stroke. However, little is known

Stroke and dementia are common disorders in the elderly.
A number of studies have reported an increased risk of de-
mentia after stroke [1–8]. The prevalence of dementia 1
year after stroke is reported to be 7%–23% [2,9,10].
Recent studies suggest that early-onset poststroke dementia
mainly results from a complex interplay between stroke
lesion features, Alzheimer’s disease pathologies, and brain
resilience, whereas delayed-onset poststroke dementia is
mainly associated with severe small vessel diseases, and
to lesser extent with Alzheimer’s disease pathologies
[11–13]. It is well known that the risk of dementia is
Competing interests: I.S. has been advisor and speaker for Takeda. Other
authors declare that they have no competing interests.
*Corresponding author. Tel.: 146 31 343 8643; Fax: 146 31 871379.
E-mail address: xinxin.guo@neuro.gu.se
about the long-term risk of dementia among stroke survi-
vors, as few studies have investigated risk of dementia
more than 5 years after stroke [1,4]. One study reported a
doubling of the risk uniformly over 10 years after stroke
[1], and the other reported an increased risk up to 5 years
after stroke [4]. A prospective study of more than 23,000
participants showed that incident stroke was associated
with an acute decline in cognitive function and also persis-
tent cognitive deficits over 6 years [14].
Dementia is also common before stroke. Based on retro-
spective information, the prevalence of dementia before
stroke is estimated to be 8%–16% [2,15,16]. Prestroke
dementia was associated with female gender, lower
education, cerebral atrophy, multiple infarcts, diabetes, and
atrial fibrillation [8,16]. A limited number of studies have
examined risk of dementia before stroke compared with
people free from stroke. One longitudinal population study
with 10 year follow-up reported that memory decline started

https://doi.org/10.1016/j.jalz.2018.05.009
1552-5260/ Ó 2018 The Authors. Published by Elsevier Inc. on behalf of the Alzheimer’s Association. This is an open access article under the CC BY-NC-ND
license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
1254 X. Guo et al. / Alzheimer’s & Dementia 14 (2018) 1253-1260
already several years before stroke and that the decline
accelerated after the index stroke [17]. Stroke survivors
had faster memory decline both before and after stroke
compared with stroke-free adults [17].
Ideally, studies on the relation between stroke and demen-
tia should be performed in large population samples fol-
lowed over a long time, allowing enough dementia cases
to occur at different time periods in relation to the index
stroke, that is, short and long time before stroke as well as
short and long time after stroke. We examined the risk of de-
mentia before and after stroke in a large population of
women followed over 44 years.
2. Methods
2.1. Study population
The study is part of the Prospective Population Study of
Women in Gothenburg [18], which was initiated in 1968.
Women born in 1908, 1914, 1918, 1922, and 1930 were sys-
tematically sampled from the Swedish Population Register.
Follow-ups were performed in 1974–1975, 1980–1981,
1992–1993, 2000–2001, 2005–2006, and 2009–2011
(Fig. 1). Seven women with stroke or transient ischemic
attack (TIA) before examination in 1968 were excluded,
leaving 1460 women for the present study (age 38,
n 5 371; age 46, n 5 433; age 50, n 5 397; age 54,
n 5 180; age 60, n 5 79). None of the women had dementia
in 1968. The examinations included neuropsychiatric and
physical examinations, psychometric testing, key informant
interviews, electrocardiography, and blood sampling.
The study was approved by the Regional Ethical Review
Board at the University of Gothenburg. All participants gave
informed consent to participate, in accordance with the pro-
visions of the Helsinki Declaration.
Neuropsychiatric examinations were performed by experi-
enced neuropsychiatrists in 1968–1969, 1974–1975, 1980–
1981, and 1992–1993 and by experienced psychiatric research
Fig. 1. The Prospective Population Study of Women in Gothenburg.
nurses in 2000–2001, 2005–2006, and 2009–2011. All exam-
inations were semi-structured, allowing for clarifying ques-
tions, and included a comprehensive psychiatric interview
and observations of mental symptoms during the interview,
as described previously [19,20]. The examinations included
ratings of common signs and symptoms of dementia, for
example, assessments of memory, orientation, general
knowledge, apraxia, visuospatial function, understanding
proverbs, following commands, naming ability, and
language. These examinations used identical instruments,
including the Comprehensive Psychopathological Rating
Scale, Gottfries-Br ane-Steen Scale, the Mini–Mental State
Examination, the Alzheimer’s Disease Assessment Scale,
and the Clinical Dementia Rating, for more than 4 decades
of follow-up. The last author (I.S.) came into the studies in
1983 and trained the examiners from 1992 to 2012. Inter-
rater agreements between psychiatrists and psychiatric
research nurses for the signs and symptoms of dementia
were between 89.4% and 100.0% (kappa values between
0.74 and 1.00).
Close informant interviews were performed by psychiat-
ric nurses since 1992. The interviews were semi-structured
and comprised questions about changes in behavior and in-
tellectual function, psychiatric symptoms, activities of daily
living, and, when relevant, age at onset for stroke and de-
mentia, and disease course.
Medical records on all women were collected from all
inpatient and outpatient departments and general practi-
tioners’ offices in Gothenburg. The Swedish Hospital
Discharge Register provided information on diagnoses of
all individuals discharged from hospitals on a nationwide ba-
sis since 1978. Diagnoses are classified according to the In-
ternational Statistical Classification of Diseases and Related
Health Problems (ICD).
2.2. Diagnoses of dementia
Dementia was diagnosed according to the Diagnostic and
Statistical Manual of Mental Disorders-III-R criteria, as
described previously [19,20]. For participants in the
neuropsychiatric examinations, dementia diagnoses were
made by neuropsychiatrists after reviewing information
from both neuropsychiatric examinations and the close
informant interview. The diagnosis was made if the
participant had dementia according to both sources of
information, or if there was clear evidence of dementia
from one source and subthreshold symptoms from the
other. For individuals lost to follow-up, dementia diagnoses
were based on information from medical records evaluated
in consensus conferences and from the Hospital Discharge
Register. In total, 325 cases of dementia were diagnosed
(95 from hospital register and/or medical records only;
119 from clinical examination and/or close informant inter-
view only; and 111 according to both sources). Among those
with dementia, 161 had Alzheimer’s disease, 46 vascular de-
mentia, 84 mixed dementia, and 34 other types of dementia.
 X. Guo et al. / Alzheimer’s & Dementia 14 (2018) 1253-1260 1255

Age of dementia onset was based on the combined informa- Poisson regressions were used to test the risk of dementia
tion sources of neuropsychiatric examination, close infor- at different time periods before and after stroke. The models
mants, and register. were adjusted first for age and later for multiple con-
founders. Selection of confounders was made by Poisson
2.3. Diagnoses of stroke regression with dementia incidence as dependent variable
and with age and each potential confounder as independent
The diagnosis of stroke was based on information from variables. The potential confounders included both variables
participants and key informants, the hospital register, and at the baseline examination (education, marital status,
medical records, as described previously [21]. Information social-economic status, alcohol consumption, smoking,
on stroke from participants was obtained using identical physical activities, hypertension, cholesterol, diabetes melli-
questionnaires at all examinations and with identical instru- tus, and myocardial infarct) and time-varying variables
ments for the close informant interviews since 1992. The in- (smoking, hypertension, cholesterol, diabetes mellitus, and
terviews included questions about sudden onset of focal myocardial infarct from 1968 to 2012). Variables were
neurological symptoms or acute aphasia, symptom duration, included in the final models if they met the criteria of
age at stroke, and admission to hospital due to stroke. All in- P  .05 in the analyses.
formation was evaluated, and diagnoses were made by two As age of stroke onset may influence relationship be-
of the authors (X.G. and I.S.). For a diagnosis of stroke, tween stroke and dementia, this relation was examined
the symptoms had to be present for more than 24 hours. In among women with first stroke before age 80 and among
those with less duration, a diagnosis of TIA was made. women with first stroke after age 80 by Cox regression.
Totally, 362 strokes were diagnosed (236 from hospital reg- Cox regressions were also used to examine the relationship
ister and/or medical records only; 14 from examinations and/ between TIA and dementia as well as between recurrent
or close informants only; 112 from both sources). stroke and dementia. SAS, version 9.4, and Stata, version
14, were used for the analyses.
2.4. Assessments of confounders
Education was dichotomized as mandatory (6–7 years)
3. Results
and more than mandatory. Social-economic status was clas-
sified as high, medium, and low based on husband’s occupa- 3.1. Incidence of stroke and dementia in the population
tion and income for married women and own occupation and
income for unmarried. Marital status was classified as mar- Characteristics of the population at baseline are presented
ried or unmarried. Smoking was classified as never smoker, in Table 1. Among 1460 women at baseline, 362 developed
ex-smoker (ceased smoking more than 1 year before the ex-
amination), or current smoker (ceased smoking within 1 year Table 1
before the examination or those smoking at the year of exam- Baseline characteristics of study population (n 5 1460)
ination). Alcohol consumption was classified as never/less Age (mean 6 SD) 46.8 6 6.2
than once a week and once or more than once a week. Levels Education, %
of physical activity in leisure time were rated as less than Mandatory 72.7
4 hours/week and more than 4 hours/week. Hypertension More than mandatory 27.3
was defined as systolic blood pressure
140 mm Hg and/ Marital status, %
Married 77.8
or diastolic blood pressure
90 mm Hg and/or taking antihy- Unmarried 22.2
pertensive medication. History of myocardial infarct was Social-economic status, %
based on self-report or hospital register. Diabetes mellitus Low 12.6
was defined as a diagnosis told by a doctor, being on antidi- Medium 45.2
abetic therapy, having two fasting venous or capillary whole High 42.2
Smoking, %
blood glucose values
7.0 mmol/L, or hospital register. Ex-smoker 6.7
Current smoker 41.6
2.5. Statistical methods Alcohol consumption, %
Never or less than once/week 24.4
Incidence rates of stroke and dementia by age intervals Once or more than once/week 75.6
are presented as cases per 1000 person-years and 95% con- Physical activity, %
fidence interval (CI). Both stroke and dementia are associ- Less than 4 hours/week 18.1
More than 4 hours/week 81.9
ated with increased mortality. Thus, mortality is a BMI (mean 6 SD) 24.1 6 3.8
competing risk for development of dementia. This may Cholesterol (mean 6 SD) 6.9 6 1.2
lead to biased comparisons between stroke and nonstroke Hypertension, % 38.5
groups due to different mortality. The association between Diabetes mellitus, % 0.8
stroke and dementia was thus tested by Cox regressions Myocardial infarct, % 0.1
both with and without competing risk of death analyses. Abbreviation: BMI, body mass index; SD, standard deviation.
1256 X. Guo et al. / Alzheimer’s & Dementia 14 (2018) 1253-1260

first-onset stroke during 49,623 person-years. Mean age of

first stroke was 77.8 years (standard deviation 8.7). Mortality
over 44 years follow-up was 81% (n 5 295) among women
with stroke and 68% (n 5 750) among women without
stroke.
Altogether, 325 women developed dementia during
49,663 person-years. Mean age of dementia onset was
79.8 years (standard deviation 7.9). Mortality was 82%
(n 5 265) among women with dementia and 69%
(n 5 780) among those without dementia.
Table 2 and Fig. 2 show the age-specific incidence of
stroke and dementia. Both incidence of stroke and dementia
increased with age. The age-specific incidence was similar
Fig. 2. Age-specific incidence rate of stroke and dementia in women.
for stroke and dementia over the life course.

The increased risk of dementia started 5 years before

3.2. Cumulative incidence of prestroke and poststroke
dementia
Among all women with stroke (N 5 362), 13.8%
(N 5 50) had prestroke dementia (0.8% developed dementia
10 years or more before stroke, 5.2% had dementia 5 years or
more before stroke), and 5.0% (n 5 18) developed dementia
at the year of the index stroke. Excluding those with pre-
stroke dementia and those with dementia at the year of
stroke, 18.4% (N 5 54) of women with stroke developed
poststroke dementia (5.1% within 1 year after stroke,
10.9% within 5 years after stroke).
3.3. Risk of dementia before and after stroke
stroke and gradually increased to stroke onset (Table 3,
Fig. 3). The risk of dementia was highest within 1 year after
stroke, declined thereafter, and remained constant from two
to more than 11 years after stroke (Table 3, Fig. 3). The as-
sociations remained after adjustment for age, birth cohort,
time-varying smoking, and baseline cholesterol.
The association was similar in women with first stroke
before age 80 (age-adjusted HR without competing risk
1.86, 95% CI 1.38–2.51; with competing risk 1.52, 95%
CI 1.12–2.06) as in women who had first stroke after age
80 (age-adjusted HR without competing risk 1.22, 95% CI
0.91–1.63; with competing risk 1.48, 95% CI 1.11–1.98).
Women with two or more recurrent strokes (N 5 107)
did not have increased risk of total dementia (age-adjusted

During 44 years of follow-up, 33.7% (N 5 122) of the

women with history of stroke and 18.5% (N 5 203) of those Table 3
without stroke developed dementia (age-adjusted HR Risk of dementia before and after stroke compared with women without
stroke
without competing risk 1.44, 95% CI 1.15–1.81; with
competing risk 1.81, 95% CI 1.44–2.27). Age of dementia Periods Dementia (N) HR (95% CI)* HR (95% CI)y
onset was similar in those with and without stroke
6 years before stroke 14 0.54 (0.31–0.94) 0.50 (0.29–0.86)
(78.9 6 6.8 vs. 77.3 6 7.8). 2–5 years before stroke 24 1.57 (1.03–2.40) 1.49 (0.97–2.28)
1 year before stroke 12 2.65 (1.48–4.75) 2.54 (1.41–4.56)
At the same year 18 3.85 (2.37–6.26) 3.51 (2.13–5.77)
1 year after stroke 15 4.17 (2.46–7.07) 4.03 (2.38–6.83)
Table 2
2–5 years after stroke 17 1.78 (1.08–2.94) 1.73 (1.05–2.85)
Incidence of dementia and stroke by age in women followed over 44 years
6–10 years after stroke 11 1.53 (0.83–2.83) 1.51 (0.82–2.78)
(N 5 1460)

11 years after stroke 11 1.81 (1.00–3.35) 1.85 (1.00–3.43)
Dementia Stroke
Abbreviation: CI, confidence interval.
Incidence Incidence NOTE. Boldface values indicate P , .05.
Age (per 1000 (per 1000 *Multivariate models for Poisson regression analyses included age.
(years) Case person-year) 95% CI Case person-year) 95% CI y
Multivariate models for Poisson regression analyses included age, birth
cohort, time-varying smoking, and cholesterol in the baseline examination.
38–44 0 0 0 2 0.85 0.10–3.07
Selection of confounders was made by Poisson regression analyses with de-
45–54 2 0.22 0.03–0.80 4 0.44 0.12–1.13
mentia incidence as dependent variable, and with age and each potential
55–64 13 0.96 0.51–1.64 15 1.11 0.62–1.83
confounder as independent variables. The potential confounders included
65–69 22 3.34 2.09–5.06 32 4.88 3.34–6.89
both variables at baseline examination (education, marital status, social-
70–74 38 6.35 4.49–8.71 69 11.63 9.05–14.72
economic status, alcohol consumption, smoking, physical activities,
75–79 58 11.23 8.52–14.5 82 16.16 12.85–20.06
hypertension, cholesterol, diabetes mellitus, and myocardial infarct), and
80–84 94 26.14 21.12–31.99 75 20.98 16.50–26.30
time-varying variables (smoking, hypertension, cholesterol, diabetes melli-
85–89 71 39.42 30.79–49.73 59 30.41 23.15–39.23
tus, and myocardial infarct from 1968 to 2012). Variables were included in
90–100 27 43.20 28.47–62.85 24 33.61 21.54–50.01
the final multivariate Poisson regression models if they met the criteria of
Abbreviation: CI, confidence interval. P  .05 in the analyses.
 X. Guo et al. / Alzheimer’s & Dementia 14 (2018) 1253-1260
Fig. 3. Hazard ratio of dementia before and after stroke compared with
women without stroke. Hazard ratio was adjusted by adjustment for age,
birth cohort, time-varying smoking, and cholesterol in the baseline exami-
nation.
HR 1.27, 95% CI 0.86–1.86) and prestroke dementia
(age-adjusted HR 0.76, 95% CI 0.40–1.45), but had
increased risk of poststroke dementia (age-adjusted HR
1.70, 95% CI 1.07–2.71). Women with only TIA (n 5 44)
did not have an increased risk of incident dementia (age-
adjusted HR 0.93, 95% CI 0.50–1.70).
4. Discussion
Based on a large representative population of women fol-
lowed over 44 years, we found an increased risk of dementia
both before and after stroke. The increased risk of dementia
started already 5 years before the index stroke and was high-
est 1 year after stroke. The increased risk continued more
than 11 years after the stroke.
Previous studies report that stroke survivors are more
likely to suffer from dementia than stroke-free individuals
[1–4]. People with stroke had lower Mini–Mental State
Examination score than controls before stroke, and the dif-
ference became more pronounced after stroke [22]. These
findings support our study. Our finding that 13% of women
with stroke had prestroke dementia is similar to hospital-
based and population-based studies [2,15,16]. The
incidence of poststroke dementia up to 1 year after stroke
was 8% in our study, which is similar to the 7%–12%
reported from other population-based samples [2,22], but
lower than reported from hospital-based series. The higher
figures for hospital-based studies may be due to the inclu-
sion of recurrent stroke and people who might have had
prestroke dementia, as the diagnosis of prestroke dementia
was only based on informant interview [9,10]. In addition,
one study excluded people who died within 1 year after
stroke [10].
Our finding that dementia risk was increased both
before and after stroke may have several explanations.
First, both stroke and dementia may be clinical manifesta-
tions of vascular burden of the brain due to large or small
vessel disease. These cerebrovascular changes may remain
clinically silent over many years. For example, ischemic
1257
white matter lesions and silent brain infarcts increase risk
of both incident stroke [23] and dementia [24,25].
Second, dementia and stroke share similar vascular risk
factors, such as hypertension, hypercholesterolemia, and
diabetes mellitus [26,27]. Third, our findings may be due
to mixed pathologies, where the cumulative effect of
cerebrovascular disease and Alzheimer encephalopathy
leads to prestroke and poststroke dementia [8,9,16,28,29].
One study showed that people with amyloid b deposition
experienced more severe and rapid cognitive decline over
3 years after stroke/TIA compared with people without
Ab deposition [30].
We found that recurrent stroke was also associated with
poststroke dementia, which was not in line with a recent
Stroke Registry Investigating Cognitive Decline study [12]
that did not found association between recurrent stroke
and late-onset dementia developed between 6 months and
3 years after stroke. Possible explanations were that the prev-
alence of recurrent stroke in our study was much higher than
that in the Stroke Registry Investigating Cognitive Decline
study due to longer follow-up time and improvement of
stroke treatment in the last decade.
The incidence of stroke and dementia increased steeply
with age and was especially high after age 80 years. The
age-specific incidence of stroke in our study is comparable
to other population studies [31–33]. The incidence of
dementia in our study is somewhat lower, especially in
the higher age range, than reported from other European
studies conducted in earlier born birth cohorts in the
1980–1990s [34–36], but comparable to studies
conducted in later born birth cohorts examined in the
2000s [37]. Several population studies showed a decrease
in the incidence of dementia across cohorts [37]. Interest-
ingly, the age-specific incidence was remarkably similar
for stroke and dementia, and there was a similar age of
onset for both disorders, as also found in the Canadian
Study of Health and Aging [38]. The similar age-specific
incidence of dementia and stroke over the life course
may also suggest common underlying etiologies of the
two disorders.
Criteria for vascular dementia such as National Institute
of Neurological Disorders and Stroke–Association Interna-
tionale pour la Recherche et l’Enseignement en Neurosci-
ences [39] and Vascular Impairment of Cognition
Classification consensus [40] stipulate that probable
vascular dementia occurs within 3 [39] or 6 [40] months after
a stroke. Other criteria, such as ICD-10 [41] and Diagnostic
and Statistical Manual of Mental Disorders-IV [42] give a
diagnosis of vascular dementia if stroke is judged to be etio-
logically related to dementia, whereas Diagnostic and Statis-
tical Manual of Mental Disorders-5 [43] and Vascular
Behavioral and Cognitive Disorders criteria [44] mention a
temporal relationship but without specification of a time
limit. Our study suggests that the time window for increased
dementia risk in relation to stroke starts 5 years before the
stroke and continues more than 11 years after. Except for
1258 X. Guo et al. / Alzheimer’s & Dementia 14 (2018) 1253-1260
the year around stroke, it could be discussed whether these
cases should be diagnosed with vascular or mixed dementia.
Strengths of this study include the large population-
based sample, the long follow-up and the use of several
information sources to diagnose stroke and dementia.
Several methodological issues need to be considered.
First, cumulative attrition is a problem in long-term
follow-up studies. While this problem was, to some
extent, alleviated by using medical records and hospital
registry in those lost to follow-up. Almost all people in
Sweden receive their hospital treatment within the public
health system, and the Hospital Discharge Register covers
the entire country. Second, the validity of stroke case
ascertainment could be questioned. A previous study re-
ported that 94% of strokes in the hospital discharge reg-
ister are correctly classified [45], and this register
misses less than 10% of stroke patients in Sweden [46].
In the present study, 88% of strokes were detected by reg-
isters. The detection of stroke was somewhat improved by
using self-reports and key informants [21]. All informa-
tion from self-reports and key informants was evaluated
by neuropsychiatrists, and the criteria were rather strict,
allowing only cases with a clear history of focal symp-
toms. These methods may thus underestimate stroke inci-
dence in the population. Actually, only 35% of total
stroke was detected by self-reports and/or key informants.
However, among those cases detected by self-reports and/
or key informants, 89% were confirmed in the hospital
register. Third, there might have been misclassification
of prestroke and poststroke dementia as dementia onset
is often gradual and insidious. It is thus difficult to judge
the exact time sequence between stroke and dementia,
especially when two events occurred close to each other.
However, there is no systematic bias in this misclassifica-
tion, as dementia onset was estimated blindly to informa-
tion on stroke onset. Furthermore, we required that stroke
and dementia should not occur at the same year for the
classification of prestroke and poststroke dementia.
Fourth, the study was conducted over 44 years during
which time large changes occurred in treatment of stroke
and its risk factors. In addition, recognition of dementia
and stroke has improved. Studies showed that the risk
of dementia in relation to stroke has also decreased dur-
ing the last decades [47,48]. Birth cohort was thus
controlled in our analyses. Fifth, our findings are
influenced by selective survival as each of dementia and
stroke is related to mortality. This may be one reason
why risk of dementia was decreased more than 6 years
before stroke, as the index stroke group comprises only
individuals who survived 6 years or more, while the
nonstroke control group comprises also individuals who
survive less than 6 years. Individuals with dementia,
especially those with risk factors for stroke, have
higher mortality and thus less chance to live more
than 6 years. Selective survival might therefore
underestimate the risk of prestroke dementia. It may
also affect the long-term risk of dementia after stroke.
Finally, only women were included in the study. World-
wide, the stroke prevalence and incidence rate were
higher in men than in women [49]. Previous studies re-
ported that women have higher risks of both prestroke
and poststroke dementia [8]. However, men with stroke
still have a higher risk for dementia than men without
stroke [1]. Future studies need to examine if the impact
of stroke on the development of dementia in men is as
strong and long-lasting as in women.
Our findings may have important implications for under-
standing the relationship between stroke and dementia, for
the prevention and treatment of dementia and stroke, and
for the classification of subtypes of dementia disorders.
Our study shows that prestroke dementia is common. It is
thus important to check patients with dementia for cardio-
vascular risk factors to prevent incidence stroke, and to eval-
uate preexisting dementia and cognitive symptoms in
patients with stroke. Our finding that dementia risk is
increased more than 11 years after stroke highlights the
importance to regularly test cognitive function among indi-
viduals with stroke, both in the short and long term, as this
may lead to early diagnosis and treatment of dementia.
Furthermore, our study underscores the importance to pre-
vent and treat stroke, as stroke lesions have significant con-
tributions on poststroke dementia. Early intervention and
treatment of vascular risk factors such as hypertension,
hyperlipidemia, diabetes, and smoking may have great im-
plications on prevention of stroke, small vessel diseases,
and cognitive impairment. Our findings need to be confirmed
by other studies. More studies are needed to investigate un-
derlying mechanisms of the association between dementia
and stroke. More research is needed to study predictors of
prestroke and poststroke dementia.
Acknowledgments
This study was supported by grants from the Swedish
Research Council for Health, Working Life and Welfare
(no 2013-2496, AGECAP 2013-2300), Swedish Council
for Working Life and Social Research (no 2001-2835,
2001-2646, 2003-0234, 2004-0150, 2004-0145, 2006-
0596, 2006-0020, 2008-1111, 2008-1229, 2010-0870), the
Alzheimer’s Association Stephanie B. Overstreet Scholars
(IIRG-00-2159), the Swedish Research Council (no.
11267, 2005-8460, 825-2007-7462, 2013-8717, 2015-
02830), Sahlgrenska University Hospital (ALF), the Swed-
ish Stroke Association, Alzheimerfonden, the Bank of
Sweden Tercentenary Foundation, Eivind och Elsa K:son
Sylvans stiftelse, Stiftelsen f€or Gamla Tj€anarinnor, and
Handlanden Hjalmar Svenssons Foundation, Swedish Brain
Power, Swedish Alzheimer Foundation, Hj€arnfonden and
 X. Guo et al. / Alzheimer’s & Dementia 14 (2018) 1253-1260
Konung Gustaf V:s och Drottning Victorias Frimurarestif-
telse.
The funders had no role in study design, data collection and
analysis, decision to publish, or preparation of the manu-
script.
RESEARCH IN CONTEXT
1. Systematic review: Few population- or hospital-
based studies have examined risk of dementia, both
short and long time before as well as short and long
time after stroke (more than 10 years after stroke). In
addition, few studies have examined how dementia
develops in relation to stroke in a population-based
sample, initially free from dementia and stroke, and
followed for more than 4 decades.
2. Interpretation: We found an increased risk of demen-
tia both before and after stroke. The increased risk of
dementia started already 5 years before stroke and
was highest 1 year after stroke. The increased risk
continued more than 11 years after the stroke.
3. Future direction: Our findings have implications for
understanding the relationship between stroke and
dementia and for prevention and treatment of demen-
tia and stroke. Studies are needed to investigate un-
derlying mechanisms of the association and to study
predictors of prestroke and poststroke dementia.
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