Hypothesis / aims of study
The maintenance of continence is not an automatic process, but rather one which relies on the coordination of multiple areas of the brain, collating and processing sensory input from the bladder. Sensory input from the lower urinary tract is conveyed by the pudendal and hypogastric nerves to the periaqueductal grey matter, the hypothalamus, and the insula cortex, and the anterior cingulate cortex (ACC) in the medial frontal lobe [1]. The ACC has multiple functions, but is believed to be largely involved in the the “context-driven modulation of arousal states”. The ACC is also involved in executive function, an aspect of cognition functioning covering a broad range of cognitive tasks, divided into “volition, planning, purposive action, and action monitoring” [2].
Urinary incontinence (UI) and lower urinary tract symptoms (LUTS), including urinary urgency, frequency, and nocturia are highly prevalent amongst the general population; this prevalence rises in association with increasing age.
Given the involvement of the brain in continence, it has been suggested that OAB in older people may be as much a brain disease as a disorder of the bladder, with evidence from imaging studies that older people with OAB have structural and functional changes to the brain.
There is a well-recognised but ooorly-understood association between falls and LUTS in older adults. Older people with urinary urgency or UUI are significantly more likely to fall and sustain injury compared to age-matched controls, with estimates of the odds ratio for falls ranging from 1.5 to 2.3 [3]. Changes in the brain such as accumulation of white matter hyperintensities affect not only the ability to suppress the urge to void but also the ability to safely walk and manage executive functions. Performing simultaneous tasks, both of which require executive function, such as walking and talking, can impair performance of one or both of those tasks.
We hypothesised that older adults with OAB demonstrate impairment in executive function compared to their peers who do not have OAB.
Study design, materials and methods
This was an exploratory cross-sectional study comparing the performance of adults aged 65 and over with and without OAB on two cognitive tests.
Potential participants were recruited from a specialist geriatric continence clinic and by advertising in local newsletters. Inclusion criteria were: aged 65 or older and community-dwelling, without a diagnosis of cognitive impairment or dementia syndrome. Exclusion criteria included urinary catheter use (indwelling or intermittent), dialysis, a neurodegenerative disease potentially causing cognitive impairment, and inability to complete cognitive testing due to sensory impairment such as blindness, protanopia, or inability to hold a pen.
We defined the OAB group as having urinary urgency, as per the International Continence Society definition, a 24 urinary frequency of 8 or more, and at least one episode of urinary incontinence per week. The “non-OAB” control group were defined by a Bladder Symptom Assessment Questionnaire (BSAQ) score of 4 or less.
No participants reported any subjective change in their memory or cognition prior to recruitment.
Following informed consent, participants voided their bladder, then completed two tests of cognition, the Trail Making B Test (TMT-B) and a computer-based test of reaction time. The TMT-B is a validated test of cognition, testing visual search, scanning, mental flexibility, and executive (frontal lobe) function. Subjects were asked to link in sequence a series of 25 circles, each containing one of the letters A to L or the numbers 1 to 12, and the time taken to complete and number of errors made recorded. For reaction time, we used an online test (https://www.humanbenchmark.com/tests/reactiontime). Participants were asked to click a mouse as quickly as possible following a visual stimulus (an on-screen image changing from red to green). Participants performed the TMT-B test twice and the reaction time test five times. Mean time for each test and number of errors on the TMT-B were used for analysis.
Demographic information, known comorbidities, and prescribed medication were also recorded, and a Charlson Comorbidity Index (CCI) and Anticholinergic Burden Score (ACB) were calculated for each participant.
Time was recorded for each cognitive test and compared between groups using an independent samples T test (normally-distributed data) or Mann-Whitney U-test (non-normally distributed data). Statistical significance was pre-defined at p<0.05. Data were analysed using SPSS v25 (IBM Corp, USA).
This is the first trial to compare trail making tests and reaction times in OAB, and as such no pilot data are available. Based on similar work comparing TMT-B times in older adults with normal cognition to those with mild cognitive impairment, a required sample size of 26 per group for a two-tailed T test was calculated.
Results
56 people were recruited, of whom 35 had a diagnosis of OAB. The OAB group contained more women than the control group (85% vs 61% respectively, p<0.05) but there were no significant differences in age, Charlson Comorbidity Index, number of prescribed medications, or Anticholinergic Burden Score. These data are summarised in Table 1.
Those with OAB took significantly longer to complete the TMT-B (103 seconds vs 77 seconds, 26%), but made no more errors than those without OAB. No difference in the reaction times between the groups was observed. These data are summarised in Table 2.
Interpretation of results
In this study, the performance on the TMT-B was significantly slower in those with a diagnosis of OAB than in those without. There were no significant differences in age, comorbidity, or polypharmacy between the two groups, and the participants did not describe subjective cognitive impairment.
The time taken to complete the TMT-B test is known to be a marker of frontal lobe dysfunction. It has been hypothesised that the bladder is in a state of inhibition by the frontal lobes, through pre-frontal cortices activating the periaqueductal grey matter and in turn the pontine micturition centre, it could be hypothesised that urgency, and in turn OAB, can be as a result of changes in the function of the frontal lobes. Studies using fMRI have identified changes in frontal lobe activation in patients with OAB.
This would therefore suggest that OAB is associated with measurable frontal lobe dysfunction in the absence of overt cognitive impairment. This result could also partially account for the observed association between falls and LUTS in older adults, given that walking is considered to be an executive function. Additionally, although as a cross-sectional study a direction of causality cannot be inferred, these results may suggest that in those with identified executive dysfunction may be at higher risk of developing LUTS, and active case finding and prophylactic bladder health education may be of benefit.