Brain ageing may be involved in the pathophysiology of overactive bladder (OAB) and account for the increasing incidence of storage and voiding symptoms in older patients. Age‐related white matter hyperintensities (ARWMHs) on brain magnetic resonance imaging (MRI) have been suggested as a marker of brain ageing and have been associated with lower urinary tract symptoms/dysfunction (LUTS/LUTD), namely OAB and detrusor overactivity. The LADIS (Leukoaraiosis and Disability) study showed that patients with moderate to severe ARWMHs reported more urinary urgency than patients with mild ARWMHs [1]. Despite the high number of patients included, the LADIS Study, similarly to other previous studies [2,3], lacked a detailed urological and pelvic assessment, thus undermining the possible causes of this finding. The present study is the first to assess systematically a broad spectrum of possible concurrent causes for storage LUTS in older patients to allow a better understanding of the relationship between ARWMHs and OAB. The main aim is to evaluate the presence and severity of LUTS/LUTD in patients according to ARWMHs severity.

An observational open-label cohort study was performed, and patients were recruited according to the following inclusion criteria: age above 55 years, cerebral small vessel disease findings on MRI (T1- and T2-weighted, proton density and diffusion-weighted), being autonomous on daily life activities (Instrumental Activity of Daily Living with no changes or a minimum change in only one item) and ability to understand and sign an informed consent form. Exclusion criteria included pre-existent major neurologic disease, particularly those potentially involved in neurogenic LUTD (e.g. dementia, post-stroke patients with Rankin>1, Parkinson’s Disease or multiple system atrophy, vertebral trauma, etc), dependency on third party or inability to understand and participate in the study. 
An informed consent form was obtained for all participants. Potential candidates were identified during a neurological appointment and the study described; during this appointment, the patient underwent clinical evaluation including IADL scale, Montreal Cognitive Assessment scale (MoCA) and physical examination, including  neurological exam were also performed. Data from brain MRI was also reviewed and ARWMHs classified according to Fazekas scale (1,2 or 3, respectively mild, moderate and severe). During the second visit, after a complete history including concomitant medication and past medical history, patients filled a list of validated questionnaires (OABq Short Form - OABqSF, Vaizey scale for faecal incontinence and, in men, International Prostate Symptom Score-IPSS and International Index of Erectile Function - IIEF-5), performed pelvic exam and a flow test with post-void residual urine (both women and men), as well as a prostate ultrasound measurement in male patients. Patients were also instructed to fill in a validated 3-day bladder diary during the following month. 
Statistical analysis was performed per‐protocol with SPSS® (ver. 29), using a nonparametric Mann–Whitney U test (0.05 significance level) for numeric variables when a non‐normal distribution was confirmed with Kolmogorov–Smirnov test or one-sample t-test if a normal distribution was observed.

A total of 46 participants were included, 18 male and 28 female. 21 (45.6%) showed mild ARWMHs on brain MRI (Fazekas 1) and 25 (54.4%) moderate-to-severe (Fazekas 2 and 3). Mean patient age in the two groups was, respectively, 70.7 ± 1.5 and 75.6 ± 1.6 years (p=0.03).
No significant differences were found in body mass index, caffeine consumption, smoking, diabetes mellitus, relevant concurrent medications (anticholinergic, B3 agonists and diuretics use), vaginal atrophy and urethral hypermobility in women or prostate volume in men (Table 1).
An age-adjusted analysis was performed when comparing all remaining data, since the group of patients with moderate-to-severe ARWMHs had a mean age superior to the group with mild ARWMHs.
Validated questionnaires, OABqSF scores (both symptom bother and health related quality of life) were similar between groups. IPSS for male LUTS, Vaizey scale for faecal incontinence and IIEF-5 for erectile function also showed no significant differences between the mild and moderate-to-severe ARMHs groups. The 3-day bladder diaries revealed frequent nocturia (1.5 ± 0.2 vs. 1.2 ± 0.2, p=0.660) and moderate to strong urgency episodes (2.0 ± 0.7 vs. 1.6 ± 0.4, p=0.820) in both groups. The same trend was noted for urgency urinary incontinence (0.7 ± 0.3 vs. 0.7 ± 0.2, p=0.620) and mean voiding volume (204 ± 18 vs. 221 ± 13, p=0.655).
Considering voiding function, the maximum flow in mL/s (Qmax) was significantly different between the mild and moderate-to-severe ARWMHs groups (respectively, 20.8 ± 3.1 vs. 17.0 ± 3.1, p=0.03). The differences in voided volume and post-void residual urine in mLS were also statistically significant (respectively, 235 ± 35 vs. 149 ± 26, p<0.001 and 11 ± 4 vs. 63 ± 21, p=0.05, borderline) (Table 2).

Participants were referred to the study due to presence of ARWMHs of any degree in MRI of presumed vascular etiology and no other relevant neurological diagnosis except vascular disease and no dementia, and irrespective of the presence of urinary symptoms. Participants were grouped into mild and moderate-to-severe ARWMHs according to the primary endpoint. The groups were similar concerning most of their baseline characteristics (including sex, BMI, habits, and physical examination findings), with a slight but statistically significant difference in age, with the moderate-to-severe ARWMHs patients being older, in accordance to previous knowledge. The lack of differences between groups in all validated questionnaires, adjusting for age, may be due to a general lack of self-perceived symptoms. However, objective and semi-objective measurements were also used and clearly demonstrated underlying lower urinary tract dysfunction. Participants, in general, showed high levels of urinary urgency (with a mean of 2 to 3 episodes per day), including urgency incontinence and low mean volumes, with no significant differences according to ARWMHs.
The voiding function parameters showed interesting differences between groups. Patients with moderate-to-severe ARWMHs presented statistically significant lower Qmax, lower voided volume and higher post-void residual urine, suggesting that voiding dysfunction, frequently overlooked in these patients, may play a relevant role.

Lower urinary tract dysfunction in elderly patients is most likely multifactorial and involvement of both storage and voiding functions should be clearly considered. Patients and clinicians should never assume LUTD to be normal and a complete clinical history, pelvic exam and non-invasive assessment (including bladder diary, flowmetry and post-void residual urine measurement) should be routinely offered to patients despite of the severity of ARWMHs.

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Tadic SD, Griffiths D, Murrin A, Schaefer W, Aizenstein HJ, Resnick NM. Brain activity during bladder filling is related to white matter structural changes in older women with urinary incontinence. Neuroimage. 2010;51(4):1294–302

Continence 12S (2024) 101562
DOI: 10.1016/j.cont.2024.101562