Title: White Matter Lesions or Alzheimer's Disease: Which Contributes More to Overactive Bladder and Incontinence in Elderly Adults with Dementia?
Abstract: To the Editor: Age-related white matter lesions (WMLs, also called vascular dementia) and Alzheimer's disease (AD) are common causes of dementia and are known to be independent risk factors for overactive bladder (OAB, urinary urgency and frequency) and urinary incontinence, but it remains uncertain which disease is a more significant contributor to OAB and incontinence in elderly adults with dementia. Herein lower urinary tract symptoms (LUTS) and urodynamic findings in AD are compared with those in WMLs. Forty-nine individuals with mild to moderate dementia irrespective of OAB were recruited (21 men, 28 women; mean age 76). The underlying diseases were AD alone in nine, AD + WMLs in 15, and WMLs alone in 25. AD was diagnosed according to National Institute of Neurological and Communicative Diseases and Stroke/Alzheimer's Disease and Related Disorders Association and Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria. To augment diagnostic accuracy, the magnetic resonance imaging (MRI)-based voxel-based specific regional analysis system for AD was used. WMLs were diagnosed according to the National Institute of Neurological Disorders and Stroke and Association Internationale pour la Recherché et l'Enseignement en Neurosciences criteria. All cases had greater than Grade 2 WMLs on the Brant-Zawadzki MRI grading scale.1 Dementia with Lewy bodies and other dementia etiologies were excluded clinically and according to metaiodobenzylguanidine myocardial scintigraphy. Mini-Mental State Examination (MMSE) and Alzheimer's Disease Assessment Scale cognitive subscale (ADAS cog) scores were mildest in WMLs alone (16.8 and 23.7 in AD alone, 17.1 and 21.6 in AD + WMLs, 27.5 and 7.7 in WMLs alone). The Lower Urinary Tract Symptoms questionnaire1 was administered, and a urodynamic study was performed according to International Continence Society standards. Before participating in the study, informed consent was obtained from all participants and their families. The local ethics committee approved the study. The urinary questionnaire showed that daytime urinary frequency (>8 times), nighttime urinary frequency (>twice), and urinary incontinence (>1/wk) was most common in WMLs alone (33%, 44%, 33% in AD alone; 40%, 60%, 27% in AD + WMLs; 68%, 84%, 40% in WMLs alone, respectively (Figure 1)). The urodynamic study showed that frequency of detrusor overactivity was almost the same in the three groups (77.8% in AD alone, 77.3% in AD + WMLs, 60.0% in WMLs alone). In contrast, first sensation volume was smallest (greater bladder sensation) in WMLs alone but not statistically significantly so (256 mL in AD alone; 276 mL in AD + WMLs, and 248 mL in WMLs alone). Whereas previous studies measured bladder function in AD or WMLs separately, the incidence of urinary frequency was 75% in WMLs1 (not mentioned in AD), urinary incontinence was 10% to 90% in AD (data vary because totally dependent persons are inevitably functionally incontinent2) and 57% in WMLs,1 and detrusor overactivity was 40% in AD3, 4 and 91% in WMLs.1 A comparison of AD and WMLs in the present study indicated that WMLs are a more significant contributor to OAB and incontinence than AD in elderly adults with dementia. In addition, with WMLs, bladder dysfunction occurs independent of dementia. The pathological mechanisms for bladder dysfunction in AD and WMLs remain obscure, but experimental and neuroimaging studies have shown that the prefrontal cortex is crucial for the higher control of micturition. Greater bladder sensation might also result from an altered central micturition circuit.5 A single-photon emission computed tomography study showed that frontal hypoperfusion is common in WMLs, whereas parietal-temporal hypoperfusion is common in AD.6 Like vascular dementia and parkinsonism, incontinence in elderly adults due to ischemic WMLs is called “vascular incontinence,”7 because OAB could predate parkinsonism and dementia in WMLs.1, 7 In conclusion, the results of the present study indicated that WMLs are a more significant contributor to OAB and incontinence than AD in elderly adults with dementia. Conflict of Interest: None of the authors have any conflicts of interest to declare. Author Contributions: Osamu Takahashi and Fuyuki Tateno: acquisition, analysis, and interpretation of data. Ryuji Sakakibara: study concept and design, acquisition of participants and data, analysis and interpretation of data, and preparation of manuscript. Jalesh Panicker and Clare J. Fowler: critical review of manuscript. Masahiko Kishi, Yohei Tsuyusaki, Hitoshi Yano, Megumi Sugiyama: acquisition of participants and data. Tomoyuki Uchiyama and Tatsuya Yamamoto: review of data. Sponsor's Role: No sponsors.