497. THE EFFECTIVENESS OF VAGUS NERVE STIMULATION IN THE TREATMENT OF ALZHEIMER’S AND PARKINSON’S DISEASE: A SYSTEMATIC REVIEW

Abstract Background Alzheimer’s disease (AD) and Parkinson’s disease (PD) are the two most common age-related neurodegenerative disorders, and their increasing prevalence highlights the need for novel treatments. Recent evidence points to the role of neuroinflammation in the early progression of both diseases. This is thought to be linked to a dysfunction of the locus coeruleus (LC)-noradrenergic pathway which normally has anti-inflammatory effects. Vagus nerve stimulation (VNS) has been shown to modulate this pathway by stimulating the release of noradrenaline from the LC which can reduce neuroinflammation. Therefore, it is hypothesised that VNS could be an effective treatment in preventing or slowing the pathological processes involved in AD and PD. Aims & Objectives This systematic review aimed to determine the effectiveness of VNS as a treatment for AD and PD. Method Medline, EMBASE, PsycINFO and Cochrane Library databases were searched for studies examining VNS use in AD and PD populations. The inclusion criteria encompassed human and preclinical animal studies, and the primary outcomes were cognitive function for AD and motor function for PD. Biochemical markers of neuroinflammation were set as secondary outcomes. Data was extracted and narratively synthesised. A quality assessment was subsequently conducted through the completion of risk of bias tables summarised using the RevMan 5.4.1 software. Results 21 studies met the inclusion/exclusion criteria: 5 AD studies (2 human, 3 animal) and 16 PD studies (8 human, 8 animal). Their collective results highlighted short-term cognitive improvements in AD patients, supported by preclinical evidence. Mixed effects were seen on PD patients with consistently significant improvements in gait but limited effects on tremor. These findings are attributable to VNS' significant effects in shifting the AD and PD brain environments to a more anti-inflammatory condition for example by decreasing activated glial and pro-inflammatory cytokine populations. Specifically, the superiority of a phasic, rather than chronic, VNS intervention was noted in producing greater effects. Discussion & Conclusions To our knowledge, this is the first systematic review looking at the use of VNS in AD and PD participants. Overall, the evidence shows the positive effects of VNS in modulating neuroinflammation suggesting its role in restoring LC function. This supports the potential of VNS as a disease-modifying treatment for AD and PD which leads to the reported improvements in clinical characteristics. The greater effects of phasic VNS, hypothesised to be due to its resemblance to the natural activity of the LC, are of particular interest. This systematic review also identified research gaps suggesting directions for furture studies. The significant heterogeneity in VNS methodologies and limited clinical data emphasise the need for further standardised clinical trials to establish optimal protocols and long-term efficacy, especially in human AD populations. This would pave the way to a better understanding of how, theoretically, VNS may be implemented into future clinical practice.