Introduction: Alzheimer’s disease (AD) is the most prevalent type of dementia. Pathological changes in the AD brain include Amyloid ß-protein (Aß) plaques. In addition to cognitive decline in AD patients, urinary incontinence (UI) is more prevalent in AD patients than in the general geriatric population, for which there is no biological explanation. Hepatocyte Growth Factor (HGF) is present in Aß plaques and is modulated by synaptic activity in hippocampal neurons. In addition, HGF phosphorylates the NMDA receptor, which regulates urinary bladder activity. HGF levels have been found to be increased in cerebrospinal fluid and serum of AD patients but urinary levels have yet to be assessed. We hereby hypothesize the potential of increased HGF detection in urine for assessment of AD with UI at a single AD Center of Excellence.
Methods: With IRB approval, patients’ demographic information, urological symptoms (OABSS; score 0-15), cognitive function (MMSE; score 0-30), and urine samples were collected for analysis. The three groups being compared were: 1. AD with UI; 2. AD without UI, 3. UI without AD. Urine was collected with a room-temperature preservative and HGF was measured using Luminex assays following manufacturer’s instructions.
Results: Age distribution, mini-mental state exam (MMSE) and overactive bladder symptom score (OABSS) were reported for three groups. HGF levels were compared in the different patient groups using One-Way ANOVA followed by Tukey’s post-hoc test. HGF is significantly increased in urine of AD patients with reported UI symptoms compared to those with UI only (p=0.014).
Conclusions: We have, for the first time, described elevated HGF in the urine of AD patients with UI. Increased levels of HGF in AD patients with UI in comparison to non-AD patients with UI may indicate that the cause of UI in AD patients may be distinct from that in non-AD UI patients. UI in AD patients may have different disease progress course or require different treatment. More research remains to be done, however, this study reports a novel utility of urine protein to understand the link of increase urinary incontinence symptoms in the Alzheimer Disease population.
Source of Funding: Support from the Aikens Research Center at Beaumont Research Institute.