Urinary Incontinence and Alzheimer’s Disease: Insights From Patients and Preclinical Models

Abstract

Alzheimer’s disease effects a large percentage of elderly dementia patients and is diagnosed on the basis of amyloid plaques and neurofibrillary tangles (NFTs) present in the brain. Urinary incontinence (UI) is often found in the elderly populations and multiple studies have shown that it is more common in Alzheimer’s disease patients than those with normal cognitive function. However, the link between increased UI and Alzheimer’s disease is still unclear. Amyloid plaques and NFTs present in micturition centers of the brain could cause a loss of signal to the bladder, resulting in the inability to properly void. Additionally, as Alzheimer’s disease progresses, patients become less likely to recognize the need or understand the appropriate time and place to void. There are several treatments for UI targeting the muscarinic and β3 adrenergic receptors, which are present in the bladder and the brain. While these treatments may aid in UI, they often have effects on the brain with cognitive impairment side-effects. Acetylcholine esterase inhibitors are often used in treatment of Alzheimer’s disease and directly oppose effects of anti-muscarinics used for UI, making UI management in Alzheimer’s disease patients difficult. There are currently over 200 pre-clinical models of Alzheimer’s disease, however, little research has been done on voiding disfunction in these models. There is preliminary data suggesting these models have similar voiding behavior to Alzheimer’s disease patients but much more research is needed to understand the link between UI and Alzheimer’s disease and discover better treatment options for managing both simultaneously.

Personality traits and the risk of urinary incontinence: Evidence from three longitudinal samples

“…Indeed, higher neuroticism and lower conscientiousness, and to a lesser extent lower extraversion, openness, and agreeableness, are associated with a higher risk of cognitive impairment and dementia, 19 which are implicated in elevated risk of UI. 31 These traits may also contribute to UI through biological factors. Higher neuroticism and lower conscientiousness, for example, are associated with higher inflammation, 32 which in turn is related to overactive bladder.…”

“…Cognitive function may also be a potential pathway that links personality to UI. Indeed, higher neuroticism and lower conscientiousness, and to a lesser extent lower extraversion, openness, and agreeableness, are associated with a higher risk of cognitive impairment and dementia, 19 which are implicated in elevated risk of UI 31 . These traits may also contribute to UI through biological factors.…”

Understanding neuropsychiatric symptoms in Alzheimer’s disease: challenges and advances in diagnosis and treatment

“…Once thought to primarily occur in only late-stage disease, many studies have shown emergence of these symptoms in many individuals quickly after diagnosis ( Lyketsos et al, 2011 ). As progression continues, individuals become less able to perform basic activities of daily living (ADLs) and instrumental activities of daily living (IADLs) and become increasingly reliant on caregivers as they develop incontinence and express extrapyramidal symptoms ( Tsolaki et al, 2001 ; Bartolone et al, 2021 ). Once diagnosed, AD will continue to increase in severity over a span of 3–10 years ( Zanetti et al, 2009 ).…”

Central nervous system sulfatide deficiency as a causal factor for bladder disorder in Alzheimer's disease

“…Lower urinary tract dysfunction (LUTD) such as urinary incontinence is prevalent in middle-to late-stage AD. [4][5][6] Although cognitive impairment has been proposed to be associated with abnormal urinary incidents, 7 the underlying mechanistic connection between AD development and the associated bladder disorders is unknown. Recent studies have brought to attention the involvement of spinal cord in AD pathogenesis.…”