798

Original Contributions

Prevalence and Etiology of Dementia

in a Japanese Community
Kazuo Ueda, MD; Hideo Kawano, MD; Yutaka Hasuo, MD; and Masatoshi Fujishima, MD

Background and Purpose: We sought to determine the type-specific prevalence of dementia and its risk
factors in elderly persons from the Japanese community of Hisayama.
Methods: We studied the prevalence of dementia in 887 Hisayama residents (353 men and 534 women)
aged 65 years or older (screening rate, 94.6%) using various items of clinical information, neurological
examination, and dementia scales. We also studied brain morphology in 50 of 59 determined to have
dementia by computed tomography or autopsy during the subsequent 54 -month period. Factors relevant
to dementia were compared between 27 patients with vascular dementia and 789 control subjects without
dementia in a retrospective fashion.
Results: The prevalence rate of dementia among Hisayama residents aged 65 or older was estimated at
6.7%, with a females to males ratio of 1:2. Among 50 cases of dementia in which brain morphology was
examined, the frequency of vascular dementia was 56%; this rate was 2.2 times higher than that for senile
dementia of the Alzheimer type. Aging, hypertension, electrocardiographic abnormalities, and high
hematocrit were significantly (p<0.05) and independently associated with the occurrence of vascular
dementia.
Conclusions: Prevalence of dementia among the Hisayama residents was relatively identical to that
previously reported, but vascular dementia was more predominant Risk factors for vascular dementia
were similar to those for lacunar infarcts. Control of hypertension may be a key to reducing dementia
among the Japanese population. (Stroke 1992;23:798-803)
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KEY WORDS • dementia • epidemiology • Japan • risk factors

T he reported prevalence of severe dementia has

varied from 1.3% to 6.2% in persons aged 65
years or older, with mild impairment in 4.3-
15.4%.'-13 Variation in the estimated prevalence may
partially be due to methodological differences, such as
the differing diagnostic criteria and varying thorough-
ness of case findings. An additional important issue is
the relative variation of diseases causing dementia in
the elderly, particularly senile dementia of the Alzhei-
mer type and vascular dementia. Many of the preva-
lence studies that attempted a clinical differentiation
between these two have also demonstrated a discrep-
ancy in the incidence of these two entities. This discrep-
ancy may simply reflect the difficulty of accurate
diagnosis.
At present, there are only a few reports14-17 that
provide prevalence rates of dementia in Japan. It is
expected that vascular dementia is more prevalent
among the Japanese population than senile dementia of
From the Second Department of Internal Medicine, Faculty of
Medicine, Kyushu University, Fukuoka, Japan.
Presented at the 1st International Stroke Congress, October 18,
1989, Kyoto, Japan.
Supported in part by Scientific Research Grant No. 01440039
from the Ministry of Education, Japan, and research grants from
the Research Foundation for Clinical Medicine and Takeda
Medical Research Foundation.
Address for correspondence: Kazuo Ueda, MD, 2nd Depart-
ment of Internal Medicine, Faculty of Medicine, Kyushu Univer-
sity, 3-1-1, Maidashi, Higashi-ku, Fukuoka City 812, Japan.
Received June 7, 1991; accepted February 28, 1992.
the Alzheimer type because, until the 1970s, cere-
brovascular disease was the leading cause of death in
Japan.
An epidemiological study of cerebral stroke has been
carried out prospectively in a Japanese rural commu-
nity, Hisayama, since 196118'19; its chief characteristic is
that almost all study subjects have been autopsied at
death. In addition, new cases of stroke have been
examined by computed tomographic (CT) scan for the
past 10 years.20 The design of this study provides a good
opportunity to inquire into the prevalence of dementia
by etiology in a Japanese community and, possibly, to
analyze risk factors of dementia. Our survey differs from
previous Japanese investigations in the following as-
pects: 1) the brain pathology of the identified cases of
dementia was studied by CT scan or postmortem exam-
ination during the subsequent period of follow-up,
which has enhanced diagnostic certainty, and 2) it was
possible to analyze the risk factors of vascular dementia
in the general population because previous medical or
health data were available for many participants.
Subjects and Methods
Screening and Follow-up
Hisayama is a Japanese rural community adjacent to
the city of Fukuoka, the metropolis of Kyushu Island; it
has a population of approximately 7,000. In this town, a
prospective population study was initiated in 1961 to
explore the epidemiology of cerebrovascular disease in
a general population sample aged 40 years or older. The

age, occupational, educational, economic, and social
composition of the population had been almost identi-
cal to that of the whole of Japan according to a 1960
census. The details in characteristics of the town18 and
the study design1920 are given elsewhere. At the time of
the national census in 1985, there were 938 Hisayama
residents aged 65 years and older (378 men and 560
women). During the 8 months from May to December
1985, we examined a total of 887 subjects from this
population (353 men and 534 women) to identify cases
of dementia, with a screening rate of 94.6% (men,
93.3%; women, 95.4%). We screened 805 subjects at the
regular examination for health checkup of the Hisayama
study and examined the remaining 77 by a door-to-door,
structured interview. A study physician with 3 years'
experience working in a psychological ward and two
trained nurses worked as a team for screening under the
direction or surveillance of a psychiatrist. Because five
subjects had been admitted to hospitals or institutes, the
study physician visited patients and conducted inter-
views and neurological examinations. Of 51 unexamined
subjects, 26 died and 10 moved out of town during the
screening period; only 15 refused the examination.
According to the 1985 census, the age composition of
the study population was almost identical to that of the
whole of Japan.
The screening examination included an interview at
which inquiries were made about chronic conditions
diagnosed by physicians, drugs that had been pre-
scribed, current fitness for work, and the history of
limitations due to illness and invalidity. In addition, we
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obtained information about the subject's normal daily
life activity by asking 13 questions on a checklist. When
neurological deficits were seen, we investigated a more
detailed history of cerebral stroke and scrutinized var-
ious items of medical information, including hospital
records, roentgenograms, and laboratory examinations.
From Diagnostic and Statistical Manual of Mental Disor-
ders, third edition (DSM-III),21 we adopted the primary
scale to determine dementia; we used Karasawa's crite-
ria for clinical evaluation of elderly dementia22 as
supplementation. The latter has been widely used
throughout Japan and divides cases with dementia into
four grades of severity according to loss of intellectual
abilities, severity of interference with social and occu-
pational functioning, and inability to care for oneself.
Psychological symptoms were estimated by checking 12
items such as memory impairment and delirium, and by
checking 13 abnormal behaviors such as aggressiveness
and dirtiness. Hasegawa's dementia rating scale,23 com-
prising 11 questions to test memory, cognitive, and
calculation capacities, was also used to define demented
cases. Each question has an independent score, the sum
of which ranges from 0 to 32.5. This procedure is similar
to that in the Mini-Mental State test.24 We suspected
that subjects had mild dementia if the sum of the scores
was less than 20.0 and severe dementia if the sum was
less than 10.0. An ischemic score by the method of
Hachinski et al25 was applied to all cases with dementia
to discriminate vascular dementia from senile dementia
of the Alzheimer type. We suspected that patients had
senile dementia of the Alzheimer type if Hachinski's
ischemic score was less than 4.0 and vascular dementia
if it was greater than 8.0. The cases in which the
ischemic score fell between 5.0 and 7.0 were classified as
Ueda et al Dementia: Prevalence and Risk Factors 799
"mixed type" or "other." The final diagnosis of demen-
tia was made by the panel of study physicians, including
a psychiatrist referring to collected data.
During the 8-month period from May to December
1985, we detected 59 cases of dementia out of 887
subjects aged 65 years or older among the Hisayama
residents. All patients with dementia were followed up
by the usual surveillance methods of the Hisayama
study,26 and when patients died, autopsies were per-
formed at the Department of Pathology of Kyushu
University. Brain was cut at 1-cm intervals, and speci-
mens were taken from 14 areas of the bilateral frontal,
temporal, parietal, and occipital lobes; hippocampus;
basal ganglia; and thalami. Paraffin-embedded speci-
mens were stained for neuropathology with hematoxy-
lin and eosin, periodic acid-Schiff, Mallory-Weise, Bo-
dian, and Congo red; the immunological method using
amyloid antibodies was used to determine the presence
of amyloid core. Neuropathologists determined the final
diagnosis for the type of dementia, and we have dis-
cussed the accuracy of diagnosis in the clinical patho-
logical conference. If new cerebral strokes occurred or
patients were institutionalized during the follow-up, we
gathered medical information concerning illness and
referred to hospital records. A CT study was made at
least once after the screening in almost all patients,
mainly using CT (Toshiba) with 5-cm slices. Dementia
was classified by its etiology into the following three
types: vascular dementia, senile dementia of the Alz-
heimer type, and other (including mixed type). Moder-
ate-to-severe brain atrophy with neither vascular lesions
nor asymmetrical ventricular dilation and with or with-
out periventricular lucency on CT scan was considered
to indicate senile dementia of the Alzheimer type. A
CT finding of diffuse periventricular lucency or leuko-
araiosis27 only was not regarded as sufficient proof of
vascular dementia. In pathology, senile dementia of the
Alzheimer type was diagnosed by findings of both senile
plaques and neurofibrillary tangles (paired helical fila-
ment) (at least found in each three microscopic areas in
the half of specimens). This report presents the results
obtained during the period of 4 years and 6 months from
January 1986 to July 1990. A significant level for statis-
tical difference was set at p< 0.05 based on the Mantel-
Haenszel x2 with two-tailed test after controlling for
age.28
Analysis of Risk Factors
To elucidate the risk factors of vascular dementia or
senile dementia of the Alzheimer type, we collected the
following data on the screened population from the
previous health checkup retrospectively: systolic and
diastolic blood pressures, body mass index [weight/
height2], serum total cholesterol, hematocrit, electrocar-
diographic abnormalities (Minnesota code III, and/or
IVw), glucose intolerance,29 drinking habits (consumed
34 g or more of ethanol a day), smoking habits (smoked
10 cigarettes or more a day), and history of hyperten-
sion. Because the date of the onset of clinical dementia
could not necessarily be determined in all cases, we
obtained such data from the records of the regular
examinations in 1973-1974, or if data were lacking, in
1978, which were at a 12- or 7-year interval from the
present screening, respectively. We made a comparison
 800 Stroke Vol 23, No 6 June 1992

TABLE 1. Prevalence of Dementia in Residents of Hisayama, Japan, Aged 65 Years and Older, 1985
Men Women Total
Age Subjects Cases Subjects Cases Subjects Cases
(years) («) (") Rate/1,000 95% CI (») («) Rate/1,000 95% CI (n) («) Rate/1,000 95% CI
65-69 118 2 16.9 161 3 18.6 279 5 17.9
70-74 108 4 37.0 145 2 13.8 253 6 23.7
75-79 68 1 14.7 114 8 70.2 182 9 49.5
80-84 47 7 148.9 72 11 152.8 119 18 1513
85+ 12 5 416.7 42 16 381.0 54 21 388.9

Total 353 19 53.8 534 40 74.9 887 59 663

Age-adjusted* 57.4 36.2-77.4 70.0 52,6-97.2 64.9 50.1-819
*Age composition was adjusted to that of the whole of Japan in 1985. CI, confidence interval.

of risk factors between nondemented cases (controls)
and cases with vascular dementia or senile dementia of
the Alzheimer type by analysis of covariance (Bonfer-
roni),30 but because of the small number of cases with
senile dementia of the Alzheimer type, analysis of risk
ratio or multivariate analysis was performed only be-
tween controls and cases with vascular dementia.
Relative risks were expressed in odds ratios after
controlling for age and sex by the Mantel-Haenszel x2
test, in which continuous variables were categorized as
follows: systolic blood pressure £160 mm Hg and/or
diastolic blood pressure £95 mm Hg was defined as
hypertension, serum total cholesterol £180 mg/dl as
hypercholesterolemia, body mass index £25.4 as obe-
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1,000 for men and 70.0/1,000 for women, with the
female: male ratio of 1:2 not significant in difference.
We examined the brain morphology of 50 cases with
dementia out of 59 (85%) by postmortem examination
or CT scan during the 54-month period from January
1986 to July 1990 (Table 2). Thirty-four patients died,
32 of whom were autopsied; CT examination only was
performed in the remaining 18 cases. Table 2 demon-
strates coincidence rates of clinical diagnoses of dis-
eases causing dementia at the screening compared with
those determined by brain morphology. An agreement
between the two was obtained in 19 of 21 patients with
vascular dementia (90.5%) and in five of eight with
senile dementia of the Alzheimer type (62.5%) but only

sity, and hematocrit £45% as high hematocrit.
To evaluate an independent risk factor of vascular
dementia, we used the multiple logistic regression
model of Walker and Duncan,31 in which appropriately
determined scores were assigned for ordinal variables
(males, 1; females, 2; absence, 0; presence, 1), and
continuous variables were entered directly into the
equation. Two-tailed probability of <0.01 or <0.05 was
judged as the significance level for statistics.
Results
Table 1 presents the age- and sex-specific prevalence
of dementia in Hisayama residents aged 65 years and
older at the screening. Prevalence progressively in-
creased with advancing age for both sexes and showed
prominently high rates beyond the age of 80 years; more
than one third of the surviving patients aged 85 years or
older suffered from dementia. After the age composi-
tion of the study population was adjusted to that of the
whole of Japan, the prevalence of dementia among the
Hisayama residents aged 65 years and older was 57.4/
in six of 21 (28.6%) with dementia classified as other
(including mixed type). Fifteen cases initially diagnosed
as other were confined to the clinical diagnosis of mixed
type because there was a lack of definite episodes of
stroke or the degree of dementia was not severe enough
for diagnosis as senile dementia of the Alzheimer type
(Hasegawa's score >10.0). Eight cases of mixed type
were classified into vascular dementia and seven into
senile dementia of the Alzheimer type afterward on the
basis of the morphological diagnosis. Vascular dementia
accounted for 56% of the morphologically diagnosed
cases of dementia in both sexes, senile dementia of
Alzheimer's type for 26%, and other for 18%, with a
ratio of vascular dementia to senile dementia of the
Alzheimer type of 2.2 for both sexes. Two patients with
subdural hematoma, two with head injury, one with
normal-pressure hydrocephalus, and one with Parkin-
son's disease were included in the category of other.
Of the 28 patients finally determined to have vascular
dementia, 20 had clinical episodes that were considered
cerebral stroke. Using clinical histories, CT scan, or

TABLE 2. Coincidence Rates of Type Diagnosis for Dementia Between Clinical Scales and Brain Pathology in
Hisayama, Japan, 1985-1990
Final (morphological) diagnosis
No. cases Coincidence
Clinical diagnosis examined Vascular dementia SDAT Other rates (%)
Vascular dementia 21 19* 0 2 90.4
SDAT 8 2 5* 1 62.5
Other 21 7 8 6* 28.6

Total 50 28 13 9
'Coincidence rates: asterisked numbers/examined cases. SDAT, senile dementia of the Alzheimer type.
 Ueda et al Dementia: Prevalence and Risk Factors 801

TABLE 3. Types of Cerebral Stroke Observed in Cases of Vascular TABLE 5. Odds Ratios of Risk Factors for Vascular Dementia
Dementia in Hisayama, Japan Compared With Those for Control Cases in Hisayama, Japan
Age Risk factor Odds ratio 95% CI
65-79 years £80 years Total Hypertension (SBP a 160 mm Hg
Type of stroke (n-8) («=20) (n=28) and/or DBP a 95 mm Hg) 3.09* 1.24-7.73
Small multiple in fa rets 2 11 13 Obesity (BMI 2:25.4) 1.69 0.50-5.71
Cerebral embolism 4 3 7 ECG abnormalities (Minnesota code
Large cortical infarcts 0 3 3
m, and/or rv,.3) 3.11' 1.23-7.88
Serum total cholesterol (2:180 mg/dl) 1.96 0.63-6.06
Single small infarcts 1 1 2
Binswanger's disease Cigarette smoking (2:10 a day) 0.45 0.07-2.75
0 2 2
Alcohol consumption (234 g ethanol
Intracerebral hemorrhage 1 0 1
a day) 0.72 0.09-5.64
Hematocrit (2:45%) 4.88* 1.55-15.33
autopsy findings, the type of cerebral infarction was Glucose intolerance 1.86 0.51-6.72
determined (Table 3). Small multiple infarcts were SBP, systolic pressure; DBP, diastolic pressure; BMI, body mass
present in 13 cases (46%), cerebral embolism in seven index; ECG, electrocardiographic; CT, confidence interval.
(25%), large infarcts in three, small solitary infarcts in *p<0.05 versus control by Mantel-Haenszel x2 test, adjusted for
two, Binswanger's disease in two, and intracerebral age and sex.
hemorrhage in one case. Binswanger's disease was
diagnosed by findings of extensive periventricular lu-
cency on CT scan, rapid deterioration of clinical course, abnormalities (especially Minnesota codes III, and/or
and severe small intracerebral vascular lesions at au- IVi-3), and high hematocrit.
topsy. Small multiple infarcts were much more frequent Table 6 shows standardized coefficients of multiple
in those aged 80 years or older, totaling 62 lesions. Their logistic regression analysis for each variable and their
location on the brain was as follows, in order of fre- probability values to distinguish patients with vascular
quency: 24 in the basal ganglia, nine in the temporal dementia from control subjects. In the case of systolic or
lobe, nine in the frontal lobe, seven in the occipital lobe, diastolic pressure, mean blood pressure was selected as
three on thalamus, and 10 in other regions. a variable. Age, electrocardiographic abnormalities, and
Data obtained before the onset of dementia were high hematocrit were considered independent and sig-
available in 27 of 28 patients with vascular dementia and nificant risk factors for vascular dementia. The stan-
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in 12 of 13 patients with senile dementia of the Alzhei-
mer type. In addition, data at the regular examination in
1973-1974 or in 1978 were obtained in 789 of 828
control subjects (95%). Table 4 presents the average
values and standard deviations of several parameters
with continuous quantity for vascular dementia, senile
dementia of the Alzheimer type, and control groups.
The average age was significantly higher for patients
with senile dementia of the Alzheimer type or vascular
dementia than for control subjects. Average blood pres-
sures (including systolic, diastolic, and mean) were
significantly greater in patients with vascular dementia
than in control subjects.
Table 5 demonstrates risk ratio (odds ratio) and a
95% confidence interval for vascular dementia for each
variable (transformed into numerical variables as previ-
ously mentioned) compared with controls after control-
ling for age and sex. A significant odds ratio (>2.0) was
perceived in cases of hypertension, electrocardiographic
dardized coefficient of mean blood pressure was rela-
tively large, and its probability value showed borderline
significance.
Discussion
The prevalence rate of dementia for those ^65 years
of age in our study was 6.7%, which included severe
dementia in 2.4% and mild dementia in 4.3%. Our
figures are relatively similar to those previously report-
edi-io.12,13 except the study of Pfeffer et al," which
reported a higher prevalence rate. This study was,
however, designed for persons in the retirement com-
munity and was recently criticized for its acceptance of
some cases on the basis of psychometric tests only,
which artificially elevated the rates in that population.12
Surveillance of dementia has been carried out in
several municipalities in Japan since 1980,2232"34 in
which Karasawa's criteria for clinical evaluation of
elderly dementia is commonly or widely used. With the

TABLE 4. Comparison of Risk Factors Between Patients With Dementia and Control Subjects in Hisayama, Japan
Control subjects Vascular dementia SDAT
Variable (n=789) (n=27)
Age (years) 73.3 ±6.0 81.3+9.1* 85.7±4.5*
Systolic blood pressure (mm Hg) 140.6±22.7 151.4+21.2* 147.9±21.9
Diastolic blood pressure (mm Hg) 78.5±11.1 85.1 ±9.4* 74.3±9.7
Mean blood pressure (mm Hg) 99.2±13.9 107.4+10.4* 98.9±12.0
Body mass index 22.0±3.2 21.9+2.9 21.4±2.3
Scrum total cholesterol (mg/dl) 197.0±39.3 195.2±35.5 191.0±27.3
Hematocrit (%) 40.0±4.3 40.9+5.3 38.8±3.3
Values are mean±SD. n, number of cases; SDAT, senile dementia of the Alzheimer type. *p<0.0\ versus control by
Bonferroni's multiple comparison and analysis of covariance; corrected for age and sex.
 802 Stroke Vol 23, No 6 June 1992
TABLE 6. Risk Factors for Vascular Dementia in Hisayama, Japan,
Analyzed by Multiple Logistic Regression
Standardized
Risk factor coefficients
Age 1.672
Sex 0.176
Mean blood pressure 0.452
ECG abnormalities 0.524
Body mass index 0.131
Serum total cholesterol -0.231
Hematocrit 0.706
Alcohol consumption 0.090
Cigarette smoking -0.313
Glucose intolerance -0.166
ECG, electrocardiographic.
age composition of the study populations in the previous
surveys adjusted to that of the Hisayama population,
the prevalence of all types of dementia appearing in the
five reports from the Japanese communities ranges from
5.1% to 6.0%.
The relative importance of rates of vascular dementia
and senile dementia of the Alzheimer type differed
significantly from one study to another. Two Finnish
studies1-6 showed rates of senile dementia of the Alz-
heimer type higher than those of vascular dementia.
Jorm et al35 reported from the integration of the liter-
ature that the US studies showed no significant differ-
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ence, whereas many studies from other western coun-
tries revealed a higher rate of senile dementia of the
Alzheimer type than vascular dementia. The prevalence
rates of dementia by etiology obtained from Japanese
surveys14-22-32-34-36 were very similar, with those of vas-
cular dementia higher than those of senile dementia of
the Alzheimer type. It is uncertain whether the higher
prevalence of vascular dementia derives from the spec-
ificity of the Japanese. In our study, approximately 50%
of the cases initially diagnosed as other (including
mixed type) fell into the categories of vascular dementia
and senile dementia of the Alzheimer type, according to
brain morphology. They were at first considered to be
mixed type because of the lack of clear episodes of
cerebral stroke, low grade on Hachinski's ischemic
scores and greater number of aged subjects with mod-
erately impaired dementia. More than 60% of those
were found to have multiple infarcts at autopsy or on
CT scan. It is doubtful whether multiple infarcts have
contributed to the development of dementia, even
though morphological evidence of senile dementia of
the Alzheimer type, such as senile plaques or neu-
rofibrillary tangles, was absent. Infarcts were localized
in the cortex or subcortex in the frontal, temporal, and
occipital lobes and in the thalamus and putamen, but
there was no systematic or regulatory distribution.
Tomlinson37 suggested that the loss of 50 ml or more of
cerebral volume as a result of infarction could cause
dementia. A clinical and autopsy study of dementia in
Olmsted County, Minnesota,38 indicated that when ce-
rebral infarction was suggested as the cause of demen-
tia, in very few cases was there autopsy evidence of
cerebral infarction large or extensive enough to cause
dementia. Hachinski et al27 stressed the importance of
the existence of leukoaraiosis on the CT scan as evi-
dence of vascular dementia, which suggests demyelina-
tion in this area resulting from poor perfusion. It was
P originally and generally held39 that the combination of
0.001 the severe penetrating vessel disease with hypoperfu-
sion in the watershed area produced the pathological
0.605
picture of Binswanger's disease, which is associated with
0.051 recurrent brief focal neurological deficits and features a
0.005 progressive dementia. However, a recent report40 indi-
0.611 cated that leukoaraiosis was observed in approximately
0.361 30% of patients identified as having senile dementia of
0.013 the Alzheimer type. It is possible, therefore, that in one
0.766
third or more of elderly patients identified as having
senile dementia of the Alzheimer type, a vascular
0.374
process is affecting the white matter and contributing to
0.548 the recognition of the occurrence of dementia (mixed
type). Intracerebral small vascular lesions, particularly
on perforating arteries, are probably caused by angione-
crosis41 (which is more closely related to hypertension)
and by lipohyalinosis (probably induced by the arterio-
sclerotic process42). However, pathological examination
could not necessarily differentiate hypertensive lesions
from arteriosclerotic process43 because there is an over-
lapping of pathological findings between the two.
In the present study, aging, hypertension, electrocar-
diographic ST-T changes, and high hematocrit were
perceived to be risk factors for vascular dementia. These
factors can be associated with developments of both
hypertensive and arteriosclerotic lesions. Risk factors
for lacunar infarction of the autopsy series from
Hisayama residents were aging, hypertension, high R or
ST-T electrocardiographic changes, atrial fibrillation,
and glucose intolerance.44 These are relatively similar to
the risk factors for vascular dementia. High hematocrit
possibly induces hypoperfusion because of increased
viscosity of blood, and atrial fibrillation does so through
decreased cardiac output. Long-term exposure to hy-
pertension or diabetes mellitus results in not only the
acceleration of atherosclerosis but also the enhance-
ment of arteriolar lesions. From this aspect, the ques-
tion of measures to prevent vascular dementia might
come back to the question of how to prevent arterio-
sclerosis, a disorder for which no successful procedures
have yet been discovered.
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