Download Silent and Symptomatic Infarcts on Cranial Computerized

Silent and Symptomatic Infarcts on Cranial Computerized
Tomography in Relation to Dementia and Mortality
A Population-Based Study in 85-Year-Old Subjects
Martin Liebetrau, MD; Bertil Steen, MD, PhD; Gerhard F. Hamann, MD; Ingmar Skoog, MD, PhD
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Background and Purpose—Incidental findings of infarcts on brain imaging are common, but their clinical significance is
not clear. We examined the prevalence of symptomatic and silent infarcts on cranial computerized tomography (cCT)
and their relation to dementia and mortality in a representative sample of 239 85-year-olds living in Gothenburg Sweden.
Methods—Information on stroke was obtained from an inpatient hospital linkage system, self-reports, and key informants.
Dementia was defined according to the Diagnostic and Statistical Manual of Mental Disorders, 3rd revision. Cortical
and lacunar infarcts were diagnosed on cCT.
Results—The prevalence of cerebral infarcts was 17.1%, and half of those were clinically silent (8.6%). The frequency of
dementia was increased in those with symptomatic (OR, 5.5; 95% CI, 2.1 to 14.1) and silent infarcts (OR, 2.7; 95% CI,
1.1 to 6.7). Infarcts increased the risk for dementia and its severity in women but not in men. The 3-year mortality rate
was increased in those with symptomatic (OR, 4.0; 95% CI, 1.6 to 9.6) and silent infarcts (OR, 3.4; 95% CI, 1.4 to 8.5).
Conclusions—Almost one fifth of 85-year-olds have infarcts on cCT, and half of those are clinically silent. These infarcts
are related to an increased rate of dementia and 3-year mortality. Cerebrovascular disease as a cause of dementia may
be underrated because of silent infarcts. It has to be elucidated whether treatment of risk factors for stroke may reduce
the consequences of silent infarcts. (Stroke. 2004;35:000-000.)
Key Words: infarcts, silent 䡲 dementia 䡲 elderly 䡲 epidemiology 䡲 mortality
T
decades. Findings regarding cCT therefore still have clinical
implications.
The aim of this study was to estimate the prevalence of
symptomatic and silent infarcts on cCT and its relation to
dementia and mortality in a population-based study of
85-year-olds.
he frequency of dementia and stroke increases with age.1
These disorders have become major health problems in
Western societies because of the increasing number of elderly
people.
Many strokes are clinically silent, and their frequency is
reported to increase with age.2 Silent brain infarcts were
previously regarded to be of little clinical significance but
have recently been reported to be related to an increased
incidence of future stroke3,4 and dementia.5
The frequency of clinically silent infarcts might be overestimated in elderly populations, because elderly individuals
may not remember a stroke because of cognitive impairment
or they may not be admitted to hospital for their stroke. We
have recently reported on the importance to use several
different sources of information to obtain a stroke history in
the elderly.6
Most studies on silent infarcts have been performed on
magnetic resonance imaging (MRI), which has several advantages over cranial computerized tomography (cCT) scan,
such as a higher sensitivity to detect small infarcts. However,
cCT is still widely used in Western countries and will be the
main imaging tool in the developing world for the next
Subjects and Methods
All 85-year-olds born between July 1, 1901, and June 30, 1902, and
registered for census purposes in Gothenburg, Sweden were invited
to take part in a health survey. The sample has been described in
detail previously and included 494 individuals (response rate 64%;
347 nondemented and 147 demented),7 and it was found to be
representative for all 85-year-olds in Gothenburg.
All demented (n⫽147) and a systematic subsample of 269
nondemented individuals were invited to cCT; 104 demented (response rate 70.1%; 28 men, 76 women) and 135 nondemented
(response rate 50.2%; 46 men, 89 women) individuals accepted
(n⫽239). There were no significant differences between participants
and nonparticipants within the demented and nondemented groups
regarding gender, marital status, registration as a psychiatric outpatient or inpatient, mental disorders, institutionalization, 3-year mortality rate, history of focal neurological symptoms, cardiovascular
disorders, hypertension, or mean systolic and diastolic blood
pressure.
Received April 7, 2004; accepted April 22, 2004.
From the Department of Neurology (M.L., G.F.H.), Klinikum Grosshadern, Ludwig-Maximilians-University, Munich, Germany; the Department of
Geriatric Medicine (B.S.) and the Institute of Clinical Neuroscience (M.L., I.S.), Neuroepidemiology Unit, Sahlgrenska Academy, Göteborg University,
Göteborg, Sweden.
Correspondence to Dr Ingmar Skoog, Institute of Clinical Neuroscience, Department of Psychiatry, Sahlgrenska University Hospital, SE-41345
Göteborg, Sweden. E-mail [email protected]
© 2004 American Heart Association, Inc.
Stroke is available at http://www.strokeaha.org
DOI: 10.1161/01.STR.0000131928.47478.44
1
2
Stroke
August 2004
Thirty-nine men and 115 women had ⱕ6 years of education, and
24 men and 32 women had more education than that (missing
information in 25 demented and 4 nondemented individuals).
Informed consent was obtained from all participants or their
relatives. The study was approved by the Ethics Committee for
Medical Research at Göteborg University in Gothenburg.
The study included nurse home visits, physical examinations by
geriatricians, neuropsychiatric examinations, key informant interviews and laboratory tests as described previously.6
CT Scan Examinations
All cCT scans were performed without contrast enhancement and
with 10-mm continuous slices on a Philips Tomoscan 310 (n⫽133)
and a General Electric 8800 (n⫽106). The median interval between
the psychiatric examination and CT scan was 13 days, the mean time
was 27.0 (SD⫾42.6) days. The cCT scans were examined for
ischemic infarcts (large cortical infarcts and lacunar infarcts) and
white matter lesions (WML) by 2 experienced radiologists, blinded
to the results of the other examinations.
Diagnostic Procedures: Stroke
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Information on stroke/transient ischemic attack (TIA) was derived
from 3 different sources of information: a hospital linkage system,
self-reports, and key informants.6 All individuals (n⫽239) and 198
close informants were interviewed by a neuropsychiatrist regarding
the occurrence of stroke. The participants were also interviewed by
a geriatrician who examined the participants regarding focal signs
indicating previous stroke/TIA. All side notes and answers to these
questions were examined by a neuropsychiatrist and a stroke
neurologist. Only patients with a definite history of acute focal
symptoms (eg, hemiparesis or acute aphasia) were included. The
computerized inpatient register system includes all individuals who
were admitted to hospital with a main or secondary diagnosis of
stroke/TIA since 1978 according to the International Classification
of Diseases, 9th edition (ICD-9) (ICD-9 codes 430 to 438 for
stroke/TIA). According to previous studies, 94% of registered
strokes are correctly classified.8
We used a conservative approach for the definition of silent
infarcts, which were defined as individuals with infarcts on cCT
without any history of stroke/TIA irrespective of whether the stroke
symptoms corresponded to the lesion. Symptomatic infarcts were
defined as individuals with infarcts on cCT and a history of
stroke/TIA.
Dementia
The diagnosis of dementia was made according to the Diagnostic
and Statistical Manual of Mental Disorders, 3rd revision (DSM-IIIR)9 as previously described.7 Severity of dementia was also diagnosed according to the DSM-III-R criteria, in which the degree of
severity is related to the need for assistance in daily living.
Statistical Methods
The association between infarcts on cCT, history of stroke, dementia
at age 85, and 3-year mortality were tested for significance with
Fisher exact test, odds ratios were calculated with logistic regression
analyses. Confidence intervals (at the 95% level) were calculated
with exact tests using binomial distribution. Correction for oversampling of dementia was performed by first calculating the prevalence
of infarcts in nondemented and demented individuals separately and
then calculating the total prevalence of infarcts in the population by
using the known prevalence of dementia in the population as
reported previously.7 We also included education in logistic regression analyses, but this did not change the odds ratios considerably.
Because of the large group of demented subjects with no information
on education, we chose not to show these analyses.
Results
Table 1 shows the baseline characteristics in demented and
nondemented individuals. The demented subjects had less
hypertension and a higher 3-year mortality rate.
TABLE 1.
Demographic Factors in 85-Year-Olds
Dementia
No (%)
Yes (%)
OR (95% CI)
Female (n⫽165/239)
65.9
73.1
1.40 (0.80–2.46)
High education (n⫽56/210)
30.5
20.3
0.58 (0.30–1.12)
Hypertension (n⫽92/233)
45.9
31.0
0.53 (0.31–0.91)
Hypercholesterolemia (n⫽35/200)
19.5
14.3
0.69 (0.32–1.50)
Diabetes mellitus (n⫽18/234)
7.4
8.1
1.10 (0.42–2.89)
Smoker (n⫽14/226)
4.4
8.8
2.07 (0.69–6.19)
Overweight (n⫽74/159)
48.8
38.2
0.65 (0.30–1.41)
Atrial fibrillation (n⫽27/201)
11.4
17.4
1.64 (0.72–3.74)
Myocardial infarct (n⫽22/224)
9.6
10.1
1.06 (0.43–2.59)
Use of antithrombotics
3.0
1.9
0.64 (0.12–3.58)
3-Year mortality (n⫽89/239)
23.0
55.8
4.23 (2.42–7.39)
Total (n⫽239)
56.5
43.5
Prevalence of Cerebral Infarcts on cCT
The prevalence of cerebral infarcts was 19.2% (46/239), with
no gender difference. After correction for oversampling of
demented individuals in the general population, the prevalence of infarcts was 17.1%. Among the 46 individuals with
infarcts on cCT, 16 (34.8%) had only large infarcts, 29
(63.0%) had only lacunar infarcts, and 1 (2.2%) had both.
Infarcts on cCT in Relation to History of Stroke
Among those with infarcts on cCT, 47.8% had no history of
stroke/TIA from any of the 3 different sources of information.
The prevalence of silent infarcts was thus 9.2% (men 8.1%,
women 9.6%). After correction for oversampling of dementia, the prevalence of silent infarcts was 8.6%.
If only 1 source of information was used to exclude history
of stroke/TIA, the prevalence of silent infarcts was higher
than using all 3 sources (Table 2). The proportion of lacunar
infarcts was higher among those with silent infarcts than in
those with symptomatic infarcts (77.3% versus 52.2%; OR,
3.1; 95% CI, 0.9 to 11.3).
Among those with a of stroke history (n⫽64), infarcts on
CT were found in only 24 cases (38%). For the different
sources of information, an infarct was found in 30% (14/46)
of self-reported strokes, in 47% (18/38) of those reported by
key informants, and in 39% (18/46) of those found in the
hospital linkage system. In the latter source, 10.9% were
recorded as TIA. No major differences were observed when
demented and nondemented individuals were analyzed sepaTABLE 2. Prevalence and Proportion of Silent Infarcts
Depending on Different Sources of Information
Source of Information to
Detect Stroke History (Infarcts on
cCT/Individuals With This Source of
Information)
Proportion of
Silent Infarcts/Total
Infarcts, n
(%, 95% CI)
Silent Infarcts
in the Total
Population %,
(Corrected)
Self-reports (n⫽46/239)
32 (69.6, 54.1–81.8)
13.4 (12.7)
Relatives (n⫽38/198)
20 (52.6, 36.1–68.7)
10.1 (8.8)
Self-reports and relatives (n⫽46/239)
25 (54.3, 39.1–68.8)
10.5 (10.0)
Hospital linkage system (n⫽46/239)
28 (60.9, 45.4–74.6)
11.7 (10.8)
All information (n⫽46/239)
22 (47.8, 33.1–62.9)
9.2 (8.6)
Liebetrau et al
Silent and Symptomatic Infarcts in 85-Year-Olds
3
TABLE 3. Prevalence of Dementia in Relation to Stroke History and Infarcts on
cCT in 85-Year-Olds
Dementia
No
Yes
Prevalence, % (95% CI)
106
47
30.7 (23.7–38.8)
1
Silent infarct (n⫽22)
10
12
54.5 (32.7–74.9)
2.7
(1.1–6.7)
History, no infarct
(not confirmed infarct, n⫽40)
12
28
70.0 (53.3–82.9)
5.3
(2.5–11.2)
No infarct, no history (n⫽153)
Symptomatic infarct (n⫽24)
Infarct or history (n⫽86)
Total (n⫽239)
OR
95% CI
7
17
70.8 (48.8–86.6)
5.5
(2.1–14.1)
29
57
66.3 (55.2–75.9)
4.4
(2.5–7.8)
135
104
43.5 (37.2–50.1)
dementia were higher in women than in men among those
with lacunar infarcts (OR, 4.9; 95% CI, 1.0 to 24.2), whereas
no such difference was found among those without infarcts
(OR, 1.2; 95% CI, 0.7 to 2.2). The dementia was more severe
in women than in men with infarcts on cCT (OR for severe
dementia in women compared with men, 11.2; 95% CI, 1.2 to
105.1), whereas no such sex difference was found among
those without infarcts on cCT (OR, 0.8; 95% CI, 0.3 to 1.9).
rately. Either a history of stroke or an infarct on cCT was
found in 86 (36.0%) of the 85-year-olds (31.4% after correction for oversampling of dementia).
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Cerebral Infarcts in Relation to Dementia
The prevalence of dementia was higher in individuals with
infarcts on cCT than in those without (63.0% versus 38.9%;
OR, 2.7; 95% CI, 1.4 to 5.2). Individuals with silent infarcts
on cCT had almost 3-fold increased odds of dementia than
85-year-olds without history of stroke or infarcts on cCT
(Table 3). The odds of dementia were even more increased in
those with history of stroke without infarcts on cCT, and in
those with infarcts on cCT and history of stroke. Silent
infarcts were related to dementia irrespective of source of
information used to exclude stroke.
The frequency of WMLs was higher in subjects with
infarcts on cCT (69.6%, n⫽32/46) than in those without
(43.2%, n⫽83/192; OR, 3.00; 95% CI, 1.5 to 6.0). Compared
with those without WMLs, stroke history, or infarcts, the
odds ratio for dementia in those with WMLs without stroke or
infarcts was 4.3 (95% CI, 2.1 to 9.0), in WMLs with silent
infarcts 9.3 (95% CI, 2.8 to 30.8), in WMLs with history
without infarct 19.7 (95% CI, 5.8 to 66.3), and in WMLs with
symptomatic infarcts 15.0 (95% CI, 4.3 to 52.2).
The dementia was more severe in those with infarcts on
cCT (mild dementia 10.3%, moderate dementia: 31.7%,
severe dementia 58.6%) than in those without infarcts on cCT
(mild 32.0%, moderate 37.3%, severe 30.7%; test of linearby-linear trend P⫽0.004).
Women showed a trend for a higher prevalence of dementia than men among individuals with infarcts on cCT (82.8%
versus 58.8%; OR, 3.4; 95% CI, 0.9 to 13.1). The odds for
Three-Year Mortality Rate in Those With
Cerebral Infarcts
Overall, the 3-year mortality rate was higher in those with
than in those without infarcts on cCT (OR, 2.7; 95% CI, 1.4
to 5.2). Mortality rate was increased in those with silent
infarcts, symptomatic infarcts, and stroke history without
infarcts compared with those without infarcts or stroke
history (Table 4).
Discussion
Almost one fifth of 85-year-olds had infarcts on cCT. Half of
those were silent despite using 3 sources of information
(self-reports, key-informants, and hospital linkage system) to
exclude history of stroke. Silent infarcts had clinical relevance, because they were associated with increased odds of
dementia and 3-year mortality. This adds to recent studies
showing that silent infarcts are related to an increased
incidence of future stroke3,4 and dementia.5 Furthermore,
cerebral infarcts on cCT or stroke history (elucidated by 3
sources of information) were found in more than one third of
this population of 85-year-olds, further underlining the importance of cerebrovascular disease in the very elderly.
TABLE 4. Three-Year Mortality Rate in Relation to Stroke History and Infarcts on cCT in
85-Year-Olds
Survivors
No infarct, no history (n⫽153)
Yes
No
3-Year Mortality
Rate % (95% CI)
OR
1
95% CI
113
40
26.1 (19.5–34.0)
Infarct, no history (silent infarct, n⫽22)
10
12
54.5 (32.7–74.9)
3.4
(1.4–8.5)
History, no infarct (not confirmed infarct, n⫽40)
17
23
57.5 (41.0–72.6)
3.8
(1.9–7.9)
Symptomatic infarct (n⫽24)
10
14
58.3 (36.9–77.2)
4.0
(1.6–9.6)
37
49
57.0 (45.9–67.5)
3.7
(2.1–6.5)
150
89
37.2 (31.1–43.7)
Infarct or history (n⫽86)
Total (n⫽239)
4
Stroke
August 2004
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Almost one tenth of 85-year-olds had silent infarcts on
cCT. Two other population studies examined the frequency of
silent infarcts on MRI and reported even higher frequencies10,11 of 35% in individuals ⬇85 years old.10 However,
none of those studies combined self-reports, relatives, and a
hospital linkage system to detect stroke history. In our study,
the proportion of silent infarcts among all infarcts (48%)
decreased the more sources of information that were used.
Using only self-reports, 70% of all infarcts detected by cCT
were silent, which decreased to 54% when information from
key informants was added. A second reason for the low
frequency was that we used a conservative approach for the
definition of silent infarcts, which were defined as individuals
with infarcts on cCT without any history of stroke or TIA,
irrespective of whether the symptoms corresponded to the
lesion. Thus, in some cases of symptomatic stroke, the infarct
might have been at a different location than indicated by the
clinical symptoms. However, individuals often have difficulties remembering having a stroke and thus even more
difficulties remembering details of the symptomatology.
Therefore, classification of silent infarcts in individuals with
a history of stroke is uncertain. Finally, probably even more
important, the other studies used MRI whereas we used cCT,
which has a lower sensitivity than MRI to detect small
cerebral infarcts.2,12,13 This is supported by the Rotterdam
study, in which the proportion of large infarcts (10%) among
the silent infarcts was lower than in our study.2 However,
lesions detected by cCT may have more clinical
consequences.12
A large proportion of those with a stroke history had no
infarcts on cCT. One reason for this might be the use of cCT,
which may not detect small infarcts in the brain stem or
cortex. Another reason might be that it was difficult to
separate TIA and stroke by self-report and key informants.
However, the frequency of TIA in those admitted to hospital
for stroke reasons was only 11%. It is noteworthy that strokes
reported by key informants was most often confirmed by cCT
(in 47%), and that only 39% of patients with strokes diagnosed by the hospital stroke register had infarcts on cCT.
Nevertheless, stroke history without infarcts on cCT was
related to dementia and an increased mortality rate.
We found that silent and symptomatic infarcts, as well as
stroke history without infarcts, were all related to dementia.
This is in accordance with other studies reporting associations
between infarcts on cCT scan14 or MRI15 and dementia. The
relation between silent infarcts and dementia has been debated.16 However, empirical evidence is scarce. Only one population study has previously reported on the association
between silent infarcts and dementia, which found that silent
infarcts at baseline increased the risk of dementia during
follow-up.5 However, it was not clear whether people with
symptomatic stroke during follow-up were excluded. Two
studies reported that silent infarcts did not increase dementia
risk in stroke patients.17,18 These results may be confounded
by the effect of symptomatic infarcts. We excluded all cases
of TIA or stroke from the silent infarct group, even if the
symptoms could not be explained by the location of the
infarct. Thus, the association with dementia reported in our
study could not be explained by a history of stroke at other
locations than the infarct. WMLs were more common in
85-year-olds with infarcts than in those without, and there
was an interaction effect between WMLs and silent infarcts to
increase the odds for dementia.
The association between infarcts on cCT and dementia was
stronger in women than in men, especially regarding lacunar
infarcts. Women with infarcts also had more severe dementia.
There are several possible explanations for this gender
difference. One is that fewer men survive to older ages.
Survival effects are thus probably more pronounced in men.
Thus, men in this age group may be more resistant to factors
causing dementia, or women may have vulnerability factors
that increase their risk for dementia when cerebral insults
occur. The findings are concordant with other studies reporting that the incidence of dementia is higher in women than in
men after age 85.19,20
Silent infarcts were related to an increased 3-year mortality
rate, in accordance with 1 previous study in which silent
infarcts increased mortality rate in individuals with clinical
stroke.21 Our study is the first population-based study examining the mortality rate in stroke-free individuals with silent
infarcts. The 3-year mortality rate in those with silent infarcts
was in the same range as in individuals with symptomatic
infarcts.
Some further methodological issues have to be discussed.
Among the strengths of the study are the extensive datagathering, that the sample was representative of the general
population in this age group, and that it included individuals
living in the community as well as those living in institutions.7 There are also some limitations. First, although there
were no differences between participants and nonparticipants
in the cCT-examined sample, the high refusal rate in the
nondemented group necessitates that the question of representativeness be considered cautiously, because we cannot
exclude the possibility that those who did not participate
differed from participants in other factors. Second, we used
cCT to detect infarcts. MRI obviously has several advantages
over cCT in detecting infarcts, including a higher sensitivity
to detect small infarcts. However, cCT is still widely used in
clinical settings in Western countries and will likely be the
main imaging tool in developing countries for the next
decades. Our findings of an association between silent infarcts on cCT and dementia therefore have clinical implications. Third, the study was cross-sectional, which may limit
the possibility to evaluate directions of associations. However, the cross-sectional design highlights the occurrence of
silent infarcts in individuals with manifest dementia.
In summary, silent infarcts on cCT are common among the
very elderly. Cerebrovascular causes of dementia may thus be
underrated in epidemiological studies not using brain imaging. These silent infarcts have clinical consequences, such as
increased risk for dementia, future stroke, and 3-year mortality rate. Thus, when silent infarcts are detected on brain
imaging, a search for treatable risk factors should be executed. It has to be elucidated whether treatment of risk factors
for stroke may reduce the consequences of silent infarcts.
Acknowledgments
We thank Valter Sundh for his technical assistance. This project was
supported by grants from the European Neurologic Society, the
Liebetrau et al
Swedish Research Council (no. 11267), Swedish Council for Working Life and Social Research (no. 1154), Stiftelsen SöderströmKönigska Sjukhemmet, Stiftelsen för Gamla Tjänarinnor, Handlanden Hjalmar Svenssons Forskningsfond, The Swedish Society of
Medicine, and The Göteborg Medical Society.
Silent and Symptomatic Infarcts in 85-Year-Olds
12.
References
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1. Aevarsson O, Skoog I. A population-based study on the incidence of
dementia disorders between 85 and 88 years of age. J Am Geriatr
Soc. 1996;44:1455–1460.
2. Vermeer SE, Den Heijer T, Koudstaal PJ, Oudkerk M, Hofman A,
Breteler MM. Incidence and risk factors of silent brain infarcts in the
population-based Rotterdam scan study. Stroke. 2003;34:392–396.
3. Bernick C, Kuller L, Dulberg C, Longstreth WT Jr, Manolio T,
Beauchamp N, Price T. Silent MRI infarcts and the risk of future stroke:
the cardiovascular health study. Neurology. 2001;57:1222–1229.
4. Vermeer SE, Hollander M, van Dijk EJ, Hofman A, Koudstaal PJ,
Breteler MM. Silent brain infarcts and white matter lesions increase
stroke risk in the general population: the Rotterdam Scan Study. Stroke.
2003;34:1126 –1129.
5. Vermeer SE, Prins ND, Den Heijer T, Hofman A, Koudstaal PJ, Breteler
MM. Silent brain infarcts and the risk of dementia and cognitive decline.
N Engl J Med. 2003;348:1215–1222.
6. Liebetrau M, Steen B, Skoog I. Stroke in 85-year-olds. Prevalence,
incidence, risk factors and relation to mortality and dementia. Stroke.
2003;34:2617–2622.
7. Skoog I, Nilsson L, Palmertz B, Andreasson LA, Svanborg A. A
population-based study of dementia in 85-year-olds. N Engl J Med.
1993;328:153–158.
8. Lindblad U, Rastam L, Ranstam J, Peterson M. Validity of register data
on acute myocardial infarction and acute stroke: the Skaraborg Hypertension Project. Scand J Soc Med. 1993;21:3–9.
9. Diagnostic and Statistical Manual of Mental Disorders. 3rd ed., Rev.
Washington, DC: American Psychiatric Association; 1987.
10. Vermeer SE, Koudstaal PJ, Oudkerk M, Hofman A, Breteler MM. Prevalence and risk factors of silent brain infarcts in the population-based
Rotterdam Scan Study. Stroke. 2002;33:21–25.
11. Price TR, Manolio TA, Kronmal RA, Kittner SJ, Yue NC, Robbins J,
Anton-Culver H, O’Leary DH. Silent brain infarction on magnetic res-
13.
14.
15.
16.
17.
18.
19.
20.
21.
5
onance imaging and neurological abnormalities in community-dwelling
older adults. The Cardiovascular Health Study. CHS Collaborative
Research Group. Stroke. 1997;28:1158 –1164.
Lopez OL, Becker JT, Jungreis CA, Rezek D, Estol C, Boller F, DeKosky
ST. Computed tomography— but not magnetic resonance imaging—
identified periventricular white-matter lesions predict symptomatic cerebrovascular disease in probable Alzheimer’s disease. Arch Neurol. 1995;
52:659 – 664.
Feinberg WM, Seeger JF, Carmody RF, Anderson DC, Hart RG, Pearce
LA. Epidemiologic features of asymptomatic cerebral infarction in
patients with nonvalvular atrial fibrillation. Arch Intern Med. 1990;150:
2340 –2344.
Tatemichi TK, Foulkes MA, Mohr JP, Hewitt JR, Hier DB, Price TR,
Wolf PA. Dementia in stroke survivors in the Stroke Data Bank cohort.
Prevalence, incidence, risk factors, and computed tomographic findings.
Stroke. 1990;21:858 – 866.
Kuller LH, Lopez OL, Newman A, Beauchamp NJ, Burke G, Dulberg C,
Fitzpatrick A, Fried L, Haan MN. Risk factors for dementia in the
cardiovascular health cognition study. Neuroepidemiology. 2003;22:
13–22.
Corea F, Henon H, Milia P, Amici S, Leys D. Silent infarcts and outcome.
Cerebrovasc Dis. 2000;10:42– 44.
Ricci S, Celani MG, La Rosa F, Righetti E, Duca E, Caputo N. Silent
brain infarctions in patients with first-ever stroke. A community-based
study in Umbria, Italy. Stroke. 1993;24:647– 651.
Bornstein NM, Gur AY, Treves TA, Reider-Groswasser I, Aronovich BD,
Klimovitzky SS, Varssano D, Korczyn AD. Do silent brain infarctions
predict the development of dementia after first ischemic stroke? Stroke.
1996;27:904 –905.
Ott A, Breteler MM, van Harskamp F, Stijnen T, Hofman A. Incidence
and risk of dementia. The Rotterdam Study. Am J Epidemiol. 1998;147:
574 –580.
Fratiglioni L, Viitanen M, von Strauss E, Tontodonati V, Herlitz A,
Winblad B. Very old women at highest risk of dementia and Alzheimer’s
disease: incidence data from the Kungsholmen Project, Stockholm. Neurology. 1997;48:132–138.
Corea F, Tambasco N, Luccioli R, Ciorba E, Parnetti L, Gallai V. Brain
CT-scan in acute stroke patients: silent infarcts and relation to outcome.
Clin Exp Hypertens. 2002;24:669 – 676.
Silent and Symptomatic Infarcts on Cranial Computerized Tomography in Relation to
Dementia and Mortality. A Population-Based Study in 85-Year-Old Subjects
Martin Liebetrau, Bertil Steen, Gerhard F. Hamann and Ingmar Skoog
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