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Lower Urinary Tract Symptoms in Subjects with Subclinical Cerebral White Matter Lesions

Lower Urinary Tract Symptoms in Subjects with Subclinical Cerebral White Matter Lesions Hindawi Journal of Aging Research Volume 2018, Article ID 1582092, 5 pages https://doi.org/10.1155/2018/1582092 Research Article Lower Urinary Tract Symptoms in Subjects with Subclinical Cerebral White Matter Lesions 1,2 1,3 1,3 1,3 1,3 Chi-Hang Yee , Ching Leung, Yuki Yu-Ting Wong, Sylvia Lee, Jenny Li, 1,4 1,5 1,4 Pauline Kwan, Winnie Chiu-Wing Chu, Vincent Chung-Tong Mok , 1,2 and Chi-Fai Ng Prince of Wales Hospital, 30-32 Ngan Shing Street, Shatin, New Territories, Hong Kong Department of Surgery, SH Ho Urology Centre, %e Chinese University of Hong Kong, Hong Kong %e Chinese University of Hong Kong, Hong Kong Department of Medicine and %erapeutics, %e Chinese University of Hong Kong, Hong Kong Department of Imaging and Interventional Radiology, %e Chinese University of Hong Kong, Hong Kong Correspondence should be addressed to Chi-Hang Yee; yeechihang@surgery.cuhk.edu.hk Received 7 March 2018; Revised 2 July 2018; Accepted 9 July 2018; Published 30 July 2018 Academic Editor: Carmela R. Balistreri Copyright © 2018 Chi-Hang Yee et al. *is is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Aim. We assessed the impact of cerebral white matter lesions (WMLs) on lower urinary tract symptoms in subjects with normal neurological and cognitive function.Methods. A cohort of community-dwelling subjects aged≥65 years were recruited to undergo MRI brain assessment. WMLs were graded using the Fazekas scale from 0 to 3. A separate telephone interview was carried out to assess the urinary symptoms in these subjects using the questionnaire Overactive Bladder-Validated 8-Question Awareness Tool (OAB-V8). Results. 800 community-dwelling elderly subjects were recruited to undergo MRI brain. In this cohort, 431 subjects responded to the telephone interview concerning their urinary symptoms. Among the respondents, 21.1% did not exhibit any WML on their MRI brain. Most of the subjects (52.6%) exhibited grade 1 WML. On logistic regression, age was found to be positively correlated with the Fazekas score (correlation coefficient 0.203, p≤ 0.01). Using a cutoff of 8 on OAB-V8, 22% of the respondents experienced OAB. Presence of WML, hypertension, or diabetes mellitus was not found to be correlated with storage urinary symptoms or OAB-V8 total score. Multiple logistic regression analysis did not show the presence of WML to be associated with the diagnosis of OAB (adjusted OR 1.13, 95% CI 0.65–1.96, p � 0.659). Conclusions. WML is associated with age and is common in the elderly population. Mild WML is subclinical, with no obvious neurological and urinary symptoms. Our cohort did not demonstrate a relationship between WML and lower urinary tract symptoms. that causes a generalized, nerve-mediated, excitation of the 1. Introduction detrusor muscle [6]. On aging, there is an increased risk of Overactive bladder (OAB) syndrome is defined as “urgency, atherosclerosis [7]. It brings bladder ischaemia. Subsequent with or without urge incontinence, usually with frequency reperfusion injures nerves, resulting in smooth muscle and nocturia” [1], and its incidence is high in population damage and impaired contractility. Overactive bladder above 40 years [2, 3]. While aging is an underlying factor for syndrome would be a consequence [8]. OAB syndrome, there are multiple ways which can con- Atherosclerosis is also a systemic condition that can affect cerebral arteries supplying the brain. Cerebral white tribute to the happening of these lower urinary tract symptoms. *ese include altered lower urinary tract sensory matter lesion (WML) on magnetic resonance imaging (MRI) input [4], overactive detrusor contractions resulting from is a common finding in the elderly, signifying chronic bi- increased excitability and spread of contraction within the lateral ischaemic brain injury [9]. WML progression has muscle [5], and an abnormality in the central nervous system been associated with cognitive decline and dementia, motor 2 Journal of Aging Research male. *e total score ranges from 0 to 42 points, with dysfunction, and depression. Longitudinal studies consis- tently reported a relationship between WML progression a score above 8 points reflecting that the patient may have OAB. and decline in cognitive performance [10, 11]. Furthermore, WML in the context of cognitive and motor impairment is Descriptive statistics were used to characterize the de- reported to be associated with urinary incontinence [12]. mographic data. *e generalized linear model of binomial *ese dysfunctions were grouped as geriatric syndromes of regression with a robust estimator was used to evaluate vascular dementia, vascular parkinsonism, and vascular whether there were any predictors for urinary symptoms of incontinence. However, the impact of total subclinical WML urgency and frequency, as well as OAB-V8 total score. on the urinary system, that is, WML without any cognitive Multiple logistic regression analysis to investigate the cor- and motor symptoms, is seldom studied. We report a pro- relation between OAB and different potential predictive spective study on urinary symptoms in a group of otherwise factors was done, with p< 0.05 being considered as statis- tically significant. SPSS software version 22.0 (SPSS Inc, healthy community-dwelling elders with WML, in the ab- sence of any previously documented stroke and dementia. Chicago, IL, USA) was used for calculations. 3. Results 2. Materials and Methods Between September 2011 and August 2014, 800 community- A cohort of subjects for brain MRI were recruited by means dwelling elderly subjects were recruited to undergo MRI of recruitment notices placed in housing estates and com- brain. In this cohort, 431 subjects responded to the telephone munity centers in Hong Kong. In order to avoid under- interview concerning their urinary symptoms, with a re- sampling of the subjects of the more advanced age, stratified sponse rate of 53.9% (Table 1). *e mean age of the re- sampling was adopted in order to have around 33% of spondents was 71± 5.1 years. Only 9 patients were on subjects in each of the following age strata: 65–69, 70–74, anticholinergics for their OAB symptoms. None was on and≥75 years. Inclusion criteria were as follows: (1) age≥65 beta-3 agonist. Among the 431 subjects, 91 (21.1%) of them years, (2) community-dwelling elderly, and (3) sufficient did not exhibit any WML on their MRI brain. Most of the language competency for cognitive testing. Exclusion cri- subjects exhibited a mild degree of WML, yielding grade 1 teria were as follows: (1) history of clinical stroke or transient on the Fazekas scale. On logistic regression, age was found to ischaemic attack and (2) dementia determined by the be positively correlated with the Fazekas score (correlation published cutoff values of the Chinese Mini-Mental State coefficient 0.203, p≤ 0.01). Examination or medical history [13]. In our cohort of respondents, most of the subjects ex- Recruited subjects would undergo mini-mental state perienced no or very mild urinary symptoms of OAB examination after data on demographics and basic medical (Table 2). When we broke down the questions of OAB-V8 health background had been collected. Brain MRI was then into different domains, 67.3% of the respondents did not performed for all eligible subjects with a 3Tscanner (Achieva experience any urgency and 26.5% experienced mild ur- X-series; Medical Systems, Best, Netherlands). To comply gency symptoms; 74.7% did not experience any frequency with the VCI harmonization standard [14], 3D/T1- and and 13.7% experienced mild frequency symptoms; 49.4% did proton-density/T2 and fluid-attenuated inversion recovery not experience any nocturia and 31.8% experienced mild (FLAIR) sequences were obtained for WML measurement, nocturia symptoms; and 68.9% did not experience any urge which was determined as ill-defined hyperintensities≥5 mm incontinence and 26.7% experienced mild urge on FLAIR but isointense with normal brain parenchyma on incontinence. T1-weighted images. Using the Fazekas scale, deep white Binomial regression with a robust estimator was used to matter hyperintense signals were rated as 0 � absence, evaluate whether there were any predictors for urinary 1 � punctate foci, 2 � beginning confluence of foci, or symptoms of urgency and frequency, as well as OAB-V8 3 � large confluent areas [15]. total score (Table 3). Age was found to be statistically sig- A separate telephone interview was carried out to nificantly correlated with the frequency symptom. Presence assess the urinary symptoms in these subjects with MRI of WML, hypertension, or diabetes mellitus was not found to brain performed. *e questionnaire Overactive Bladder- be correlated with storage urinary symptoms or OAB-V8 Validated 8-Question Awareness Tool (OAB-V8) was total score. Using the OAB-V8 total score of >8 as a cutoff used to assess the urinary symptoms of the subjects. *e point for the diagnosis of OAB, multiple logistic regression OAB-V8 is a self-administered tool directed toward analysis did not show the presence of WML to be associated detecting patients suffering from OAB [16]. It contains the with the diagnosis of OAB (adjusted OR 1.13, 95% CI original 8 items from the OAB-q symptom bother scale 0.65–1.96, p � 0.659) (Table 4). with modified instructions. To assess a subject’s urinary symptoms, the OAB-V8 asks how bothered one is by the four hallmark symptoms of OAB: urinary frequency, 4. Discussion urgency, nocturia, and urge incontinence. Items are measured on a 6-point Likert scale (0 � not at all to 5 � a *e first pathological description of WML in the brain of very great deal), plus a dichotomous question about the elderly dates back to Durand-Fardel in 1854 [17]. In 1987, patient’s gender, which would add 2 points if the subject is Hachinski introduced the descriptive term “leukoaraiosis” to Journal of Aging Research 3 Table 1: Questionnaire response characteristics. implication and pathological features are diverse. Barber et al. looked into MR images of patients with Alzheimer’s Subjects in the cohort (n) 800 disease and dementia with Lewy bodies [23]. Periventricular Respondents (n) 431 hyperintensities were found to independently correlate with Male 159 atrophic processes involving ventricular enlargement. On Female 272 Median age, years (IQR) 70 (8) the contrary, deep white matter hyperintensities did not Patients on anticholinergics (n) 9 correlate with measures of brain atrophy, but they were Patients on beta-3 agonists (n) 0 associated with ischaemic risk factors. Furthermore, histo- Deep white matter Fazekas score pathological studies have shown that deep white matter 0 (n) 91 hyperintensity is related to the severity of ischaemic tissue 1 (n) 227 damage [24]. As we postulated that lower urinary tract 2 (n) 89 symptoms in the context of pelvic arterial insufficiency and 3 (n) 24 ischaemia-related bladder degeneration were correlated to IQR � interquartile range. chronic ischaemic brain disease in the elderly, deep white matter hyperintensity on MRI was adopted for analysis in this study. It has been proposed that WML is the pathoanatomic Table 2: Respondents’ OAB-V8 results. substrate in the brain aetiology of OAB [25]. However, Respondents (n) overall data on the association between lower urinary tract OAB-V8 Nil Mild Moderate to severe dysfunction and WML are scarce and contradictory. A few studies have been attempted to assess the correlation be- Urgency (Q2 + Q3 + Q7) (n) 290 114 27 Frequency (Q1) (n) 322 59 50 tween WML and lower urinary tract symptoms. In a smaller Nocturia (Q5 + Q6) (n) 213 137 81 scale study by Sakakibara et al., they studied the urinary Incontinence (Q4 + Q8) (n) 297 115 19 symptoms and WML of sixty-three subjects [26]. Among OAB-V8 � Overactive Bladder-Validated 8-Question Questionnaire. them, 33 subjects had urodynamic studies. WML was Question scores and classification: urgency: nil (0), mild (1–6), and classified from grade 0 to grade 4 according to Brant- moderate to severe (7–15); frequency: nil (0), mild (1-2), and moderate to Zawadzki et al. [22]. In subjects with grade 1–4 WML, severe (3–5); nocturia: nil (0), mild (1–4), and moderate to severe (5–10); detrusor overactivity was more common (82%) than in those incontinence: nil (0), mild (1–4), and moderate to severe (5–10). with grade 0 WML (9%). A similar result could not be demonstrated by our study probably due to quite a different define WML without specifying the pathology or aetiology composition of the cohort. In our study, most of the subjects [18]. *e prevalence of WML increases with age. *e most had no or very mild WML. In contrast, the cohort of accepted opinion on the aetiology of WML is the conse- Sakakibara et al. had more subjects with more significant WML. In their study, 11 subjects belonged to grade 0, 15 quence of ischaemia, which is representing a vascular process linked with cerebral small vessel changes. *ese subjects belonged to grade 1, 12 subjects belonged to grade 2, 14 subjects belonged to grade 3, and 11 subjects belonged to changes may also lead to a damaged blood-brain barrier, resulting in a chronic leakage of fluid and macromolecules in grade 4. Furthermore, the mean mini-mental state exami- nation score was in the lower normal range in their cohort. the white matter [19]. WMLs are frequent findings on brain imaging. *ese factors might signify that if there is a correlation Zimmerman et al. reviewed 365 consecutive MRIs with age between WML and LUTS, such a relationship would only be ranging from 6 to 84 years [20]. WMLs were found in 93.5% obvious if there were significant WMLs accompanied by of the patients regardless of the diagnosis. Eighty-seven some degree of neurological symptoms. symptom-free volunteers aged 31–83 years were recruited *e association between urinary symptoms and WML by Fazekas, and MRI was performed for assessment. WML was also investigated in the Leukoaraiosis And DISability (LADIS) study [27]. *e LADIS study was a longitudinal, increased from 11% in the 4th decade to 83% in those over 70 years of age [21]. In our study, 79% of our subjects were multicenter, observational study which primarily aimed at assessing the role of WML as an independent predictor of found to have WML. Age was also found to be correlated with WML severity. Having a mean age of 71 years in our the transition to disability in initially nondisabled elderly persons. Six hundred thirty-nine subjects aged between 65 cohort, the prevalence and trend were comparable to the results by Fazekas. and 84 years were enrolled. Concerning urinary complaints, Fazekas et al. introduced a grading system for WML its assessment was done by 4 questions with the di- assessment [15], which was a modification of the system chotomous answer yes or no. *ese questions were on proposed by Brant-Zawadzki et al. [22] and Zimmerman nocturia, frequency, incontinence, and urgency. Except for et al. [20]. *e system involves the assessment of both urgency, no statistically significant difference was found periventricular hyperintensity and deep white matter between severity of WML and symptoms of nocturia, fre- quency, and incontinence. In fact, these few symptoms were hyperintensity. In our current study, we focused on deep white matter hyperintensity. *e difference between peri- found to be more prominent in those with mild WML than in those with moderate WML. Such contradictory findings ventricular and deep white matter lesions has yet to be well defined. Some studies have proposed that their clinical could again be explained by the fact that the LADIS study 4 Journal of Aging Research Table 3: Generalized linear model of factors affecting lower urinary tract symptoms. OAB-V8 total score OAB-V8 urgency score OAB-V8 frequency score Coefficient SE p Coefficient SE p Coefficient SE p Age −0.012 0.013 0.379 <0.001 0.020 0.982 −0.072 0.026 0.005 Male 0.243 0.153 0.112 −0.323 0.282 0.253 0.373 0.252 0.139 Fazeka score >0 −0.126 0.189 0.504 −0.202 0.293 0.491 0.309 0.306 0.314 Hypertension 0.081 0.154 0.600 −0.111 0.232 0.632 0.194 0.241 0.422 Diabetes mellitus −0.082 0.158 0.604 −0.110 0.279 0.694 −0.077 0.259 0.765 Hyperlipidaemia −0.024 0.151 0.875 −0.192 0.239 0.421 −0.155 0.250 0.534 Alpha blocker 0.287 0.194 0.139 0.097 0.432 0.822 0.932 0.322 0.004 OAB-V8 � Overactive Bladder-Validated 8-Question Questionnaire; SE � standard error; p � p value. Table 4: Multiple logistic regression analysis of factors predicting WML is associated with age and is common in the el- OAB (OAB-V8 score >8). derly population. Mild WML is usually subclinical, with no obvious neurological and urinary symptoms. Our study on Predictor Adjusted OR 95% CI p value a cohort of 431 community-dwelling healthy elderly did not Age 0.99 (0.94, 1.04) 0.632 show any relationship between WML and LUTS. Further Male 1.29 (0.80, 2.09) 0.296 study would be needed to confirm the sequential symptoms Fazeka score >0 1.13 (0.65, 1.96) 0.659 manifestation with respect to an increasing severity of WML. Hypertension 1.22 (0.74, 1.99) 0.433 Diabetes mellitus 0.94 (0.56, 1.58) 0.827 Hyperlipidaemia 1.19 (0.73, 1.93) 0.495 Data Availability Alpha blocker 1.55 (0.73, 3.27) 0.253 OAB-V8 � Overactive Bladder-Validated 8-Question Questionnaire. *e data of this study are not openly available to the public. had its cohort composition lying between our study and the Consent study by Sakakibara et al. [26]. In our cohort, the majority of subjects (67%) with WML belonged to Fazekas grade 1. In Informed consent was obtained from all individual partic- comparison, the cohort of Sakakibara et al. had 29% of the ipants included in this study. subjects belonging to mild WML, and the cohort in the LADIS study had 44% of the subjects belonging to mild Conflicts of Interest WML. Furthermore, the urological assessment in the LADIS study was not based on a validated questionnaire. Rather, it *e authors declare that there are no conflicts of interest. was based on 4 questions only. On the contrary, our study using a validated questionnaire of OAB-V8 offered a more References proper assessment of the urological symptoms. *e results of our study were echoed by Wehrberger [1] A. J. Wein and E. S. Rovner, “Definition and epidemiology of et al. [28]. Both the studies could not demonstrate a clear overactive bladder,” Urology, vol. 60, no. 5, pp. 7–12, 2002. [2] I. Milsom, W. Stewart, and J. *uroff, “*e prevalence of relationship between WML and LUTS. 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Lower Urinary Tract Symptoms in Subjects with Subclinical Cerebral White Matter Lesions

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Hindawi Publishing Corporation
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Copyright © 2018 Chi-Hang Yee et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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2090-2204
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10.1155/2018/1582092
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Abstract

Hindawi Journal of Aging Research Volume 2018, Article ID 1582092, 5 pages https://doi.org/10.1155/2018/1582092 Research Article Lower Urinary Tract Symptoms in Subjects with Subclinical Cerebral White Matter Lesions 1,2 1,3 1,3 1,3 1,3 Chi-Hang Yee , Ching Leung, Yuki Yu-Ting Wong, Sylvia Lee, Jenny Li, 1,4 1,5 1,4 Pauline Kwan, Winnie Chiu-Wing Chu, Vincent Chung-Tong Mok , 1,2 and Chi-Fai Ng Prince of Wales Hospital, 30-32 Ngan Shing Street, Shatin, New Territories, Hong Kong Department of Surgery, SH Ho Urology Centre, %e Chinese University of Hong Kong, Hong Kong %e Chinese University of Hong Kong, Hong Kong Department of Medicine and %erapeutics, %e Chinese University of Hong Kong, Hong Kong Department of Imaging and Interventional Radiology, %e Chinese University of Hong Kong, Hong Kong Correspondence should be addressed to Chi-Hang Yee; yeechihang@surgery.cuhk.edu.hk Received 7 March 2018; Revised 2 July 2018; Accepted 9 July 2018; Published 30 July 2018 Academic Editor: Carmela R. Balistreri Copyright © 2018 Chi-Hang Yee et al. *is is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Aim. We assessed the impact of cerebral white matter lesions (WMLs) on lower urinary tract symptoms in subjects with normal neurological and cognitive function.Methods. A cohort of community-dwelling subjects aged≥65 years were recruited to undergo MRI brain assessment. WMLs were graded using the Fazekas scale from 0 to 3. A separate telephone interview was carried out to assess the urinary symptoms in these subjects using the questionnaire Overactive Bladder-Validated 8-Question Awareness Tool (OAB-V8). Results. 800 community-dwelling elderly subjects were recruited to undergo MRI brain. In this cohort, 431 subjects responded to the telephone interview concerning their urinary symptoms. Among the respondents, 21.1% did not exhibit any WML on their MRI brain. Most of the subjects (52.6%) exhibited grade 1 WML. On logistic regression, age was found to be positively correlated with the Fazekas score (correlation coefficient 0.203, p≤ 0.01). Using a cutoff of 8 on OAB-V8, 22% of the respondents experienced OAB. Presence of WML, hypertension, or diabetes mellitus was not found to be correlated with storage urinary symptoms or OAB-V8 total score. Multiple logistic regression analysis did not show the presence of WML to be associated with the diagnosis of OAB (adjusted OR 1.13, 95% CI 0.65–1.96, p � 0.659). Conclusions. WML is associated with age and is common in the elderly population. Mild WML is subclinical, with no obvious neurological and urinary symptoms. Our cohort did not demonstrate a relationship between WML and lower urinary tract symptoms. that causes a generalized, nerve-mediated, excitation of the 1. Introduction detrusor muscle [6]. On aging, there is an increased risk of Overactive bladder (OAB) syndrome is defined as “urgency, atherosclerosis [7]. It brings bladder ischaemia. Subsequent with or without urge incontinence, usually with frequency reperfusion injures nerves, resulting in smooth muscle and nocturia” [1], and its incidence is high in population damage and impaired contractility. Overactive bladder above 40 years [2, 3]. While aging is an underlying factor for syndrome would be a consequence [8]. OAB syndrome, there are multiple ways which can con- Atherosclerosis is also a systemic condition that can affect cerebral arteries supplying the brain. Cerebral white tribute to the happening of these lower urinary tract symptoms. *ese include altered lower urinary tract sensory matter lesion (WML) on magnetic resonance imaging (MRI) input [4], overactive detrusor contractions resulting from is a common finding in the elderly, signifying chronic bi- increased excitability and spread of contraction within the lateral ischaemic brain injury [9]. WML progression has muscle [5], and an abnormality in the central nervous system been associated with cognitive decline and dementia, motor 2 Journal of Aging Research male. *e total score ranges from 0 to 42 points, with dysfunction, and depression. Longitudinal studies consis- tently reported a relationship between WML progression a score above 8 points reflecting that the patient may have OAB. and decline in cognitive performance [10, 11]. Furthermore, WML in the context of cognitive and motor impairment is Descriptive statistics were used to characterize the de- reported to be associated with urinary incontinence [12]. mographic data. *e generalized linear model of binomial *ese dysfunctions were grouped as geriatric syndromes of regression with a robust estimator was used to evaluate vascular dementia, vascular parkinsonism, and vascular whether there were any predictors for urinary symptoms of incontinence. However, the impact of total subclinical WML urgency and frequency, as well as OAB-V8 total score. on the urinary system, that is, WML without any cognitive Multiple logistic regression analysis to investigate the cor- and motor symptoms, is seldom studied. We report a pro- relation between OAB and different potential predictive spective study on urinary symptoms in a group of otherwise factors was done, with p< 0.05 being considered as statis- tically significant. SPSS software version 22.0 (SPSS Inc, healthy community-dwelling elders with WML, in the ab- sence of any previously documented stroke and dementia. Chicago, IL, USA) was used for calculations. 3. Results 2. Materials and Methods Between September 2011 and August 2014, 800 community- A cohort of subjects for brain MRI were recruited by means dwelling elderly subjects were recruited to undergo MRI of recruitment notices placed in housing estates and com- brain. In this cohort, 431 subjects responded to the telephone munity centers in Hong Kong. In order to avoid under- interview concerning their urinary symptoms, with a re- sampling of the subjects of the more advanced age, stratified sponse rate of 53.9% (Table 1). *e mean age of the re- sampling was adopted in order to have around 33% of spondents was 71± 5.1 years. Only 9 patients were on subjects in each of the following age strata: 65–69, 70–74, anticholinergics for their OAB symptoms. None was on and≥75 years. Inclusion criteria were as follows: (1) age≥65 beta-3 agonist. Among the 431 subjects, 91 (21.1%) of them years, (2) community-dwelling elderly, and (3) sufficient did not exhibit any WML on their MRI brain. Most of the language competency for cognitive testing. Exclusion cri- subjects exhibited a mild degree of WML, yielding grade 1 teria were as follows: (1) history of clinical stroke or transient on the Fazekas scale. On logistic regression, age was found to ischaemic attack and (2) dementia determined by the be positively correlated with the Fazekas score (correlation published cutoff values of the Chinese Mini-Mental State coefficient 0.203, p≤ 0.01). Examination or medical history [13]. In our cohort of respondents, most of the subjects ex- Recruited subjects would undergo mini-mental state perienced no or very mild urinary symptoms of OAB examination after data on demographics and basic medical (Table 2). When we broke down the questions of OAB-V8 health background had been collected. Brain MRI was then into different domains, 67.3% of the respondents did not performed for all eligible subjects with a 3Tscanner (Achieva experience any urgency and 26.5% experienced mild ur- X-series; Medical Systems, Best, Netherlands). To comply gency symptoms; 74.7% did not experience any frequency with the VCI harmonization standard [14], 3D/T1- and and 13.7% experienced mild frequency symptoms; 49.4% did proton-density/T2 and fluid-attenuated inversion recovery not experience any nocturia and 31.8% experienced mild (FLAIR) sequences were obtained for WML measurement, nocturia symptoms; and 68.9% did not experience any urge which was determined as ill-defined hyperintensities≥5 mm incontinence and 26.7% experienced mild urge on FLAIR but isointense with normal brain parenchyma on incontinence. T1-weighted images. Using the Fazekas scale, deep white Binomial regression with a robust estimator was used to matter hyperintense signals were rated as 0 � absence, evaluate whether there were any predictors for urinary 1 � punctate foci, 2 � beginning confluence of foci, or symptoms of urgency and frequency, as well as OAB-V8 3 � large confluent areas [15]. total score (Table 3). Age was found to be statistically sig- A separate telephone interview was carried out to nificantly correlated with the frequency symptom. Presence assess the urinary symptoms in these subjects with MRI of WML, hypertension, or diabetes mellitus was not found to brain performed. *e questionnaire Overactive Bladder- be correlated with storage urinary symptoms or OAB-V8 Validated 8-Question Awareness Tool (OAB-V8) was total score. Using the OAB-V8 total score of >8 as a cutoff used to assess the urinary symptoms of the subjects. *e point for the diagnosis of OAB, multiple logistic regression OAB-V8 is a self-administered tool directed toward analysis did not show the presence of WML to be associated detecting patients suffering from OAB [16]. It contains the with the diagnosis of OAB (adjusted OR 1.13, 95% CI original 8 items from the OAB-q symptom bother scale 0.65–1.96, p � 0.659) (Table 4). with modified instructions. To assess a subject’s urinary symptoms, the OAB-V8 asks how bothered one is by the four hallmark symptoms of OAB: urinary frequency, 4. Discussion urgency, nocturia, and urge incontinence. Items are measured on a 6-point Likert scale (0 � not at all to 5 � a *e first pathological description of WML in the brain of very great deal), plus a dichotomous question about the elderly dates back to Durand-Fardel in 1854 [17]. In 1987, patient’s gender, which would add 2 points if the subject is Hachinski introduced the descriptive term “leukoaraiosis” to Journal of Aging Research 3 Table 1: Questionnaire response characteristics. implication and pathological features are diverse. Barber et al. looked into MR images of patients with Alzheimer’s Subjects in the cohort (n) 800 disease and dementia with Lewy bodies [23]. Periventricular Respondents (n) 431 hyperintensities were found to independently correlate with Male 159 atrophic processes involving ventricular enlargement. On Female 272 Median age, years (IQR) 70 (8) the contrary, deep white matter hyperintensities did not Patients on anticholinergics (n) 9 correlate with measures of brain atrophy, but they were Patients on beta-3 agonists (n) 0 associated with ischaemic risk factors. Furthermore, histo- Deep white matter Fazekas score pathological studies have shown that deep white matter 0 (n) 91 hyperintensity is related to the severity of ischaemic tissue 1 (n) 227 damage [24]. As we postulated that lower urinary tract 2 (n) 89 symptoms in the context of pelvic arterial insufficiency and 3 (n) 24 ischaemia-related bladder degeneration were correlated to IQR � interquartile range. chronic ischaemic brain disease in the elderly, deep white matter hyperintensity on MRI was adopted for analysis in this study. It has been proposed that WML is the pathoanatomic Table 2: Respondents’ OAB-V8 results. substrate in the brain aetiology of OAB [25]. However, Respondents (n) overall data on the association between lower urinary tract OAB-V8 Nil Mild Moderate to severe dysfunction and WML are scarce and contradictory. A few studies have been attempted to assess the correlation be- Urgency (Q2 + Q3 + Q7) (n) 290 114 27 Frequency (Q1) (n) 322 59 50 tween WML and lower urinary tract symptoms. In a smaller Nocturia (Q5 + Q6) (n) 213 137 81 scale study by Sakakibara et al., they studied the urinary Incontinence (Q4 + Q8) (n) 297 115 19 symptoms and WML of sixty-three subjects [26]. Among OAB-V8 � Overactive Bladder-Validated 8-Question Questionnaire. them, 33 subjects had urodynamic studies. WML was Question scores and classification: urgency: nil (0), mild (1–6), and classified from grade 0 to grade 4 according to Brant- moderate to severe (7–15); frequency: nil (0), mild (1-2), and moderate to Zawadzki et al. [22]. In subjects with grade 1–4 WML, severe (3–5); nocturia: nil (0), mild (1–4), and moderate to severe (5–10); detrusor overactivity was more common (82%) than in those incontinence: nil (0), mild (1–4), and moderate to severe (5–10). with grade 0 WML (9%). A similar result could not be demonstrated by our study probably due to quite a different define WML without specifying the pathology or aetiology composition of the cohort. In our study, most of the subjects [18]. *e prevalence of WML increases with age. *e most had no or very mild WML. In contrast, the cohort of accepted opinion on the aetiology of WML is the conse- Sakakibara et al. had more subjects with more significant WML. In their study, 11 subjects belonged to grade 0, 15 quence of ischaemia, which is representing a vascular process linked with cerebral small vessel changes. *ese subjects belonged to grade 1, 12 subjects belonged to grade 2, 14 subjects belonged to grade 3, and 11 subjects belonged to changes may also lead to a damaged blood-brain barrier, resulting in a chronic leakage of fluid and macromolecules in grade 4. Furthermore, the mean mini-mental state exami- nation score was in the lower normal range in their cohort. the white matter [19]. WMLs are frequent findings on brain imaging. *ese factors might signify that if there is a correlation Zimmerman et al. reviewed 365 consecutive MRIs with age between WML and LUTS, such a relationship would only be ranging from 6 to 84 years [20]. WMLs were found in 93.5% obvious if there were significant WMLs accompanied by of the patients regardless of the diagnosis. Eighty-seven some degree of neurological symptoms. symptom-free volunteers aged 31–83 years were recruited *e association between urinary symptoms and WML by Fazekas, and MRI was performed for assessment. WML was also investigated in the Leukoaraiosis And DISability (LADIS) study [27]. *e LADIS study was a longitudinal, increased from 11% in the 4th decade to 83% in those over 70 years of age [21]. In our study, 79% of our subjects were multicenter, observational study which primarily aimed at assessing the role of WML as an independent predictor of found to have WML. Age was also found to be correlated with WML severity. Having a mean age of 71 years in our the transition to disability in initially nondisabled elderly persons. Six hundred thirty-nine subjects aged between 65 cohort, the prevalence and trend were comparable to the results by Fazekas. and 84 years were enrolled. Concerning urinary complaints, Fazekas et al. introduced a grading system for WML its assessment was done by 4 questions with the di- assessment [15], which was a modification of the system chotomous answer yes or no. *ese questions were on proposed by Brant-Zawadzki et al. [22] and Zimmerman nocturia, frequency, incontinence, and urgency. Except for et al. [20]. *e system involves the assessment of both urgency, no statistically significant difference was found periventricular hyperintensity and deep white matter between severity of WML and symptoms of nocturia, fre- quency, and incontinence. In fact, these few symptoms were hyperintensity. In our current study, we focused on deep white matter hyperintensity. *e difference between peri- found to be more prominent in those with mild WML than in those with moderate WML. Such contradictory findings ventricular and deep white matter lesions has yet to be well defined. Some studies have proposed that their clinical could again be explained by the fact that the LADIS study 4 Journal of Aging Research Table 3: Generalized linear model of factors affecting lower urinary tract symptoms. OAB-V8 total score OAB-V8 urgency score OAB-V8 frequency score Coefficient SE p Coefficient SE p Coefficient SE p Age −0.012 0.013 0.379 <0.001 0.020 0.982 −0.072 0.026 0.005 Male 0.243 0.153 0.112 −0.323 0.282 0.253 0.373 0.252 0.139 Fazeka score >0 −0.126 0.189 0.504 −0.202 0.293 0.491 0.309 0.306 0.314 Hypertension 0.081 0.154 0.600 −0.111 0.232 0.632 0.194 0.241 0.422 Diabetes mellitus −0.082 0.158 0.604 −0.110 0.279 0.694 −0.077 0.259 0.765 Hyperlipidaemia −0.024 0.151 0.875 −0.192 0.239 0.421 −0.155 0.250 0.534 Alpha blocker 0.287 0.194 0.139 0.097 0.432 0.822 0.932 0.322 0.004 OAB-V8 � Overactive Bladder-Validated 8-Question Questionnaire; SE � standard error; p � p value. Table 4: Multiple logistic regression analysis of factors predicting WML is associated with age and is common in the el- OAB (OAB-V8 score >8). derly population. Mild WML is usually subclinical, with no obvious neurological and urinary symptoms. Our study on Predictor Adjusted OR 95% CI p value a cohort of 431 community-dwelling healthy elderly did not Age 0.99 (0.94, 1.04) 0.632 show any relationship between WML and LUTS. Further Male 1.29 (0.80, 2.09) 0.296 study would be needed to confirm the sequential symptoms Fazeka score >0 1.13 (0.65, 1.96) 0.659 manifestation with respect to an increasing severity of WML. Hypertension 1.22 (0.74, 1.99) 0.433 Diabetes mellitus 0.94 (0.56, 1.58) 0.827 Hyperlipidaemia 1.19 (0.73, 1.93) 0.495 Data Availability Alpha blocker 1.55 (0.73, 3.27) 0.253 OAB-V8 � Overactive Bladder-Validated 8-Question Questionnaire. *e data of this study are not openly available to the public. had its cohort composition lying between our study and the Consent study by Sakakibara et al. [26]. In our cohort, the majority of subjects (67%) with WML belonged to Fazekas grade 1. In Informed consent was obtained from all individual partic- comparison, the cohort of Sakakibara et al. had 29% of the ipants included in this study. subjects belonging to mild WML, and the cohort in the LADIS study had 44% of the subjects belonging to mild Conflicts of Interest WML. Furthermore, the urological assessment in the LADIS study was not based on a validated questionnaire. Rather, it *e authors declare that there are no conflicts of interest. was based on 4 questions only. On the contrary, our study using a validated questionnaire of OAB-V8 offered a more References proper assessment of the urological symptoms. *e results of our study were echoed by Wehrberger [1] A. J. Wein and E. S. Rovner, “Definition and epidemiology of et al. [28]. Both the studies could not demonstrate a clear overactive bladder,” Urology, vol. 60, no. 5, pp. 7–12, 2002. [2] I. Milsom, W. Stewart, and J. *uroff, “*e prevalence of relationship between WML and LUTS. 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