Dementia is associated with chronic rhinosinusitis: A

population-based case-controlled study

Shiu-Dong Chung, M.D., Ph.D.,1,2 Shih-Han Hung, M.D.,3 Herng-Ching Lin, Ph.D.,1,4 and
Jiunn-Horng Kang, M.D.1,5,6

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ABSTRACT

Background: Cardiovascular diseases are reported to be associated with both chronic rhinosinusitis (CRS) and dementia. Nevertheless, whether dementia
is associated with CRS is still unknown. In the present study, we explored the association between dementia with prior CRS using a population-based data
set.
Methods: This study used the Taiwan Longitudinal Health Insurance Database 2000 as the source of data for a case control study. We included 8768
subjects with dementia as cases and 8768 age- and sex-matched subjects as controls. We identified cases who had received a diagnosis of CRS before having
received a diagnosis of dementia. Conditional logistic regression analyses were performed to examine the association of dementia with previously diagnosed
CRS.
Results: Results showed that of all sampled subjects, 875 (5.0%) had been previously diagnosed with CRS. A chi-squared test showed that there was a
significant difference in the prevalences of prior CRS between cases and controls (6.0% versus 4.0%; p 0.001). The adjusted odds ratio (OR) of prior CRS
for subjects with dementia was 1.44 (95% CI, 1.251.66) compared with controls. Furthermore, compared with controls, the OR of prior CRS was similar
for subjects with dementia for both sexes (the OR for male subjects was 1.48 and OR for female subjects was 1.41).
Conclusion: We concluded that subjects with dementia had a higher odds of having had prior CRS than controls. This study implies a potential association
between CRS and dementia.
(Am J Rhinol Allergy 29, 44 47, 2015; doi: 10.2500/ajra.2015.29.4113)

ementia is a prevalent problem worldwide.1,2 The increased

burden of dementia has recently drawn greater attention.2,3
The types and etiology of dementia vary and Alzheimers dementia
and vascular dementia are two of the most common dementias.
Although the etiology of dementia is still not well understood, some
risk factors are recognized. Although ones genetic background and
environmental factors are associated with neurodegeneration in dementia, it is worth noting that dementias, including Alzheimers
dementia and vascular dementia, share some risk factors such as
hypertension, diabetes mellitus, hyperlipidemia, obesity, and cigarette smoking with cardiovascular diseases (CVDs).4 Therefore, it was
suggested that a vascular etiology may play an important role in
dementia.
Chronic rhinosinusitis (CRS) is one of the most prevalent respiratory diseases and can affect all ages.5 It is estimated that 216% of
the general population may have CRS.5,6 Chronic inflammatory process occurs in the mucosa of the paranasal sinus, which is associated
with stasis of secretion, and secondary infection may be noted in CRS
patients. CRS has been reported to be associated with significant
functional limitation and workdays lost.7 Recently, CRS was reported
to increase the risk of CVDs and stroke.8,9 Although the pathomechanism is still unknown, the chronic inflammatory status, sleep loss,
cerebral vasculopathy, and related treatments were proposed as contributing to the association of CRS with CVDs.7
Because there is evidence showing a theoretical linkage among
CRS, dementia, and CVDs, we hypothesized that CRS might also be
associated with an increased risk of dementia. Large-scale epidemio-

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From the 1Sleep Research Center, Taipei Medical University, Taipei, Taiwan, 2Division
of Urology, Department of Surgery, Far Eastern Memorial Hospital, New Taipei City,
Taiwan, 3 Department of Otolaryngology, 4School of Health Care Administration,
5
Department of Physical Medicine and Rehabilitation, and 6Department of Physical
Medicine and Rehabilitation, School of Medicine, College of Medicine, Taipei Medical
University, Taipei, Taiwan
The authors have no conflicts of interest to declare pertaining to this article
Address correspondence to Jiunn-Horng Kang, M.D., Department of Physical Medicine
and Rehabilitation, Taipei Medical University Hospital, 252 Wu-Hsing Street, Taipei
110, Taiwan
E-mail address: jhk@tmu.edu.tw
Copyright 2015, OceanSide Publications, Inc., U.S.A.

44

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logical data are needed to verify our hypothesis. To evaluate the

association between CRS and dementia, we conducted a large-scale
retrospective casecontrol study in Taiwan.

METHODS
Database
The study sample for this casecontrol study was taken from the
Longitudinal Health Insurance Database 2000 (LHID2000). Taiwan
inaugurated its National Health Insurance (NHI) program in 1995 to
provide comprehensive and easily accessible medical care for all of its
citizens. The LHID2000 includes claims data and registration files of
1,000,000 individuals randomly sampled from the 2000 Registry for
Beneficiaries (n 23.72 million) of the Taiwan NHI program. The
LHID2000 allows researchers in Taiwan to follow-up the medical
services of these 1,000,000 individuals since initiation of the Taiwan
NHI program. Some researchers and the Taiwan National Health
Research Institute have established the high validity of the data
derived from the Taiwanese NHI program.

Selection of Cases and Controls

As for the selection of cases in this study, we first identified 14,538
subjects who had received a first-time diagnosis of dementia (ICD9-CM codes 290.0290.4, 294.1, 331.0331.2, or 331.82) during ambulatory care visits in January 2004 to December 2011. Because administrative data sets are criticized for their low diagnostic validity, this
study only included those subjects who had been diagnosed with
dementia at least twice in the period 20042011, with at least one
diagnosis being made by a certified neurologist or psychiatrist. We
then excluded selected subjects aged 45 years, because this age
group has a very low prevalence of dementia (n 291). Thereafter,
we designated their first dementia diagnosis as the index date in this
study. We also excluded those who had a history of major psychosis
or a substance-related disorder (ICD-9-CM codes 291299 or
303305), stroke (ICD-9-CM codes 430438), or traumatic brain injury (ICD-9-CM codes 801804 or 850854) before the index date (n
5479). Ultimately, 8768 subjects with dementia were included as cases.
We retrieved 8768 controls from the remaining beneficiaries of the
LHID2000. Controls were matched by gender, age, and index year.

JanuaryFebruary 2015, Vol. 29, No. 1

Although for subjects with dementia, the year of the index date was
the year in which they received their first dementia diagnosis, for
controls, the year of the index date was simply a matched year in
which the controls had a medical use. For controls, we also defined
the date of their first use of ambulatory care occurring during that
matched year as the index date. Furthermore, we ensured that none of
the included controls had received a diagnosis of dementia, major
psychosis, a substance-related disorder, stroke, or traumatic brain
injury before their index date.

Table 1. Demographic characteristics of subjects with dementia

and controls in Taiwan (n 17,536)

Exposure Assessment

Variable

This study attempted to explore the odds of having previously been

diagnosed with CRS between cases and controls. Therefore, we first
identified all cases who had ever received a diagnosis of CRS (ICD9-CM codes 473, 473.0, 473.1, 473.2, 473.3, 473.8, and 473.9) during
ambulatory care visits (including outpatient departments of hospitals
and clinics). We only included those CRS subjects who were diagnosed by certified otolaryngologists. In addition, this study only
included those CRS cases with at least one diagnosis of CRS in a
medical claim before the index date.

Statistical Analysis
All analyses were conducted using the SAS system (SAS System for
Windows, Version 8.2; SAS Institute, Cary, NC). Chi-squared tests
were used to compare differences in sociodemographic characteristics
including monthly income (New Taiwan dollars, NT$015,840;
NT$15,84125,000; NT$25,001; in 2011, the average exchange rate
was U.S. dollars, US$1 NT$29), geographic location (northern,
central, eastern, and southern Taiwan), and urbanization level of the
patients residence (five levels, with level 1 being the most urbanized
and level 5 being the least) between cases and controls. In addition,
we took medical comorbidities including hyperlipidemia, diabetes,
hypertension, tobacco use disorder, alcohol abuse, Parkinsons disease, and obesity into consideration in this study. We also adjusted for
the number of medical visits within 1 year before the index date in the
regression models. Finally, conditional logistic regression analyses
(conditioned on sex, age, and index year) were performed to examine
the association of dementia with previously diagnosed CRS. The
conventional value of p 0.05 was adopted to assess the statistical
significance.

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RESULTS

Of the 17,536 sampled subjects, the mean age was 76.1 years with
an SD of 9.9 years. After matching for sex and age, Table 1 shows that
there was no significant difference in urbanization level or geographic
region between cases and controls. However, cases had higher prevalences of comorbidities including hyperlipidemia (30.6% versus
29.0%; p 0.020), diabetes (32.3% versus 26.3%; p 0.001), hypertension (67.4% versus 65.1%; p 0.001), and alcohol abuse (3.0%
versus 1.0%; p 0.001) than controls. In addition, cases were more
likely to have monthly incomes of NT$15,841 (p 0.001) compared
with controls. There was a significant difference in the number of
medical visits within 1 year before the index date between cases and
controls. The mean number of medical visits within 1 year before the
index date was 31.2 25.9 and 24.9 22.5 for cases and controls,
respectively (p 0.001).
Table 2 shows the prevalence of prior CRS between cases and
controls. Of the 17,536 sampled subjects, 875 (5.0%) had a CRS diagnosis before the index date. The chi-squared test revealed that there
was a significant difference in the prevalences of prior CRS between
cases and controls (6.0% versus 4.0%; p 0.001). Correspondingly, the
conditional logistic regression analysis suggested that the odds ratio
(OR) of prior CRS for cases was 1.56 (95% CI, 1.361.80) compared
with controls. Furthermore, after adjusting for subjects monthly income, geographic location, urbanization level, hyperlipidemia, diabe-

American Journal of Rhinology & Allergy

Gender
Male
Female
Urbanization level
1 (most urbanized)
2
3
4
5 (least urbanized)
Monthly income
NT$115,841
NT$15,84125,000
NT$25,001
Geographic region
Northern
Central
Eastern
Southern
Hyperlipidemia
Diabetes
Hypertension
Tobacco use disorder
Parkinsons disease
Obesity
Alcohol abuse

O
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Patients with
Dementia
(n 8768)

Controls
(n 8768)

Total
no.

Percent

Total
no.

3942
4826

44.9
55.1

3942
4826

44.9
55.1

2233
2203
1234
1585
1513

25.5
25.1
14.1
18.1
17.2

2155
2199
1314
1528
1572

24.6
25.1
15.0
17.4
17.9

5376
3021
371

61.3
34.5
4.2

5115
3269
384

58.3
37.3
4.4

3714
2249
2530
275
2686
2828
5912
445
629
18
250

42.4
25.6
28.9
3.1
30.6
32.3
67.4
5.0
7.2
0.2
3.0

3681
2233
2558
296
2545
2308
5704
415
151
12
60

41.9
25.5
29.2
3.4
29.0
26.3
65.1
5.0
1.7
0.1
1.0

p Value

Percent

Y
P
1.000

0.194

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0.001

0.770

0.020
0.001
0.001
0.646
0.001
0.438
0.001

$NT New Taiwan dollars.

tes, hypertension, alcohol abuse, and Parkinsons disease and the

number of medical visits within 1 year before the index date, cases
were more likely than controls to have been diagnosed with CRS
before the index date (OR, 1.44; 95% CI, 1.251.66; p 0.001).
We further analyzed the relationship between dementia and CRS
according to sex. Table 3 shows that compared with controls, the OR
of prior CRS was similar for cases for both sexes (the OR for men was
1.48 and for women was 1.41).

DISCUSSION
We found that dementia patients had a significantly higher prevalence and risk of having had prior CRS in a large-scale casecontrol
study in Taiwan. To our best knowledge, this is the first study to
indicate a potential link between CRS and dementia. Although CRS is
a chronic disease that can significantly hamper the quality of life and
cause a great medical burden,10 it is generally considered to be a
benign disease that rarely results in serious complications. Nevertheless, recently growing data showed that the impacts and consequences of CRS may be greater than previously thought. Our study
adds new evidence that CRS is associated with dementia, a serious
neurological disease, which causes significant disability and economic burdens. Furthermore, there is currently no curative treatment
for most dementia patients. Prevention is still one of most effective
strategies to reduce the burden of dementia.11 Therefore, recognizing
risk factors of dementia is fundamental for public health.
As a casecontrol study, directly proposing a cause-and-effect relationship between CRS and dementia, should be performed with
special caution. Several explanations regarding the association between CRS and dementia are proposed. First, it is worth noting that

45

Table 2. Prevalence, crude ORs, and 95% CIs for CRS among sampled subjects
Total (n 17,536)

Presence of CRS

Yes
No
Crude OR* (95% CI)
Adjusted OR# (95% CI)

875
16,661

5.0
95.0

Controls (n 8768)

Subjects with
Dementia
(n 8768)
n

529
6.0
8239
94.0
1.56 (1.361.80)
1.44 (1.251.66)

346
8422

4.0
96.0

p Value

0.001

Y
P

1.00
1.00

*The crude OR was calculated by a conditional logistic regression, which was conditioned on gender, age group, and the year of the index date.
#Adjusted OR was calculated by a conditional logistic regression, which was conditioned on gender, age group, and the year of the index date and adjusted
for patients urbanization level, monthly income, geographic region, hypertension, diabetes, hyperlipidemia, tobacco use disorder, alcohol abuse, and
Parkinsons disease and the number of medical visits within 1 yr before the index date.
p 0.001.
CRS chronic rhinosinusitis; OR odds ratio.

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Table 3. Prevalence, crude ORs, and 95% CIs for CRS among sampled subjects by gender
Presence of CRS

Yes
No
Crude OR* (95% CI)
Adjusted OR# (95% CI)

Male

Female

Subjects with Dementia

(n 3942) n (%)

Controls (n 3942)
n (%)

235 (6.0)
3707 (94.0)
1.55 (1.261.90)
1.48 (1.201.83)

157 (4.0)
3785 (96.0)
1.00
1.00

Subjects with Dementia

(n 4826)n (%)

Controls (n 4826)
n (%)

294 (6.1)
4532 (93.9)
1.60 (1.321.92)
1.41 (1.171.71)

189 (3.9)
4637 (96.1)
1.00
1.00

*The crude OR was calculated by a conditional logistic regression which was conditioned on age group and the year of the index date.
#Adjusted OR was calculated by a conditional logistic regression, which was conditioned on gender, age group, and the year of the index date and adjusted
for patients urbanization level , monthly income, geographic region, hypertension, diabetes, hyperlipidemia, tobacco use disorder, alcohol abuse, and
Parkinsons disease and the number of medical visits within 1 yr before the index date.
p 0.001.
CRS chronic rhinosinusitis; OR odds ratio.

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CRS and dementia share some common risk factors, such as cigarette
smoking and diabetes mellitus.1215 This fact may partially contribute
to the association we observed. Second, it is recognized that CRS is
associated with vasculopathy of the brain and stroke in epidemiological studies7,9 and therefore could directly lead to an increased risk of
vascular dementia.
In addition, some consequences of CRS may increase the risk of
dementia. Poor sleep is a common problem among patients with
CRS.1618 Sleep loss has been reported to be associated with increased
proinflammatory cytokines and prothrombotic biomarkers.19 Strong
association between sleep disturbance and CVDs has been recognized.20 Moreover, sleep deprivation is associated with significant
impairment of memory consolidation and cognitive consequence.21
Neuronal degeneration and apoptosis in sleep-deprived rats has been
established.22 Therefore, chronic sleep disturbance was proposed as
being associated with dementia.23,24 Studies also found that emotional
distress and depression are frequently comorbid with CRS.25,26 Depression is also a recognized risk for dementia that has recently
drawn increased attention.2729 Finally, some usual treatments of CRS
may theoretically exacerbate controlling the risk of dementia in patients with CRS. For example, decongestion medications acting as
sympathomimetic medications can elevate the blood pressure, and
corticosteroids may worsen the control of diabetes and lipid profiles.
A more critical clinical issue is whether CRS is a modifiable risk
factor for dementia. Before additional studies explore the pathomechanism of the association between these two conditions, no conclusions can be drawn. However, physicians should at least be aware
of this possibility in patients with clinically diagnosed CRS. Regular

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46

monitoring of a patients cognitive status may be required. A comprehensive survey and aggressive interventions of other known risk
factors such as diabetes mellitus, hypertension, and hyperlipidemia
for dementia are advised for patients with CRS, because these patients are at higher risk for dementia. Timely referral to a specialist is
recommended if cognitive decline is recognized early in patients with
CRS.
Although a gender difference was found in the prevalence of
dementia,30 we did not find a gender difference in the association
between dementia and prior CRS. Both men and women with dementia had significantly higher risks of having had prior CRS, and the
general risk was comparable in the two sexes. Interestingly, CRS
patients may have olfactory dysfunction, which is also a common
finding in the patients with neurodegeneration diseases such as dementia and Parkinsons disease.31 Nevertheless, the causes of olfactory dysfunction from two conditions depend on the sites of involvement in olfactory neuropathway. Whether olfactory loss in CRS plays
a role in dementia needs to be further studied.
As an explorative epidemiological study, our study provides a
potential association between CRS and dementia. However, some
disadvantages should be noted in our study. First, a concern regarding coding accuracy in medical registries can be argued. The LHID
was created based on the National Insurance Bureau in Taiwan. The
data quality is generally considered useful and suitable for epidemiological surveys, and a body of sound studies has been published
based on this database. Nevertheless, it is possible that some patients
with CRS and dementia who did not seek medical services were
un-coded. Therefore, biased risk estimation may have occurred in our

JanuaryFebruary 2015, Vol. 29, No. 1

9.

study. Second, some potentially confounding variables were not

available in our database such as cigarette smoking, physical activity,
family history, and the body mass index. These factors may have had
unequal distributions between the two conditions and should be
adjusted for in future studies. Third, the diagnostic criteria for dementia may have been heterogeneous in our database. This problem
needs to be further clarified, because the standards and criteria for a
clinical diagnosis of dementia are still not well established. Fourth, in
the present study, we treated the comorbidity profiles as binary
variables. However, the disease control status may modify the risk of
dementia. For example, adequate control versus poor control of hypertension may have different risks for subsequent dementia. Bisecting the comorbid status into a presence and absence may lead to a
misestimation of the adjusted risk in the regression model. Fifth, from
a statistical view, data from medical registries may suffer from an
ascertainment bias. CRS patients may have had greater medical attention and follow-up than the general population that would have
increased the chance of discovering other diseases, even those that
were unrelated to CRS. In summary, to explore the pathomechanism
of association between CRS and dementia, a prospective cohort study
with more detail demographic variables and comorbidity profiles
should be considered. Furthermore, whether the risk of dementia in
CRS is modifiable with adequate treatment of CRS is also critical in
clinical practice.

10.
11.
12.

13.
14.
15.

16.

17.

18.

19.

CONCLUSIONS
We found that patients with dementia were significantly associated
with prior CRS in this casecontrol study in Taiwan. Additional study
is advised to confirm our findings and explore the pathomechanism.

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