A Pilot Clinical Trial Investigating Deep Brain Stimulation of the Pedunculopontine Nucleus for the Treatment of Alzheimer's Disease

Intervention Feasibility - Recruitment Rates

Time Frame: Study Initiation to End of Study Enrolment Period (36 month period)

Determined by assessing recruitment trends. The effectiveness of recruitment strategies will be assessed by monitoring the rate at which eligible participants are enrolled.

Intervention Feasibility - Adherence to Study Protocol

Time Frame: Study Initiation to Final Participant Study Completion (3 years)

To ensure procedural consistency across participants, adherence to the study protocol will be systematically monitored. Any protocol deviations will be documented and evaluated for their potential impact on study outcomes, ensuring the reliability and reproducibility of findings

Intervention Feasibility - Attrition Rates

Time Frame: Study Initiation to Final Participant Study Completion by (3 years)

Participant retention will be assessed through an analysis of attrition rates, with particular attention to identifying the causes of dropout.

Intervention Feasibility - Participant Evaluation of Intervention

Time Frame: Participants will complete the exit interview at the final follow-up visit (month 12).

Exit interviews will be conducted with participants and their caregivers to gather quantitative and qualitative information on their subjective experience and evaluation of the study intervention. Quantitative feedback on six items assessing satisfaction (e.g., understanding of study protocol, follow-up schedule manageability, likelihood of participating in future studies with same procedure) are measured on a a 5-point Likert scale (1 - "Very Dissatisfied" to 5 - "Very Satisfied"). Total score on quantitative items ranges from 6 - 30, with a higher score representing a more positive participant and caregiver evaluation of the study intervention.

Intervention Safety - Adverse Events (AEs) and Serious Adverse Events (SAEs)

Time Frame: Assessed at DBS implantation (Month 0) and at regular follow-up visits 1-month, 3-months, 6-months, 9-months, and 12-months post-DBS surgery.

Possible adverse events (AEs), serious adverse events (SAEs), or unanticipated problems related to the DBS device, related surgery and/or stimulation will be closely monitored and managed as per standard of care and definitions and classifications set forth in the following subsections. An AE is any untoward medical occurrence, unintended disease or injury, or untoward clinical signs (including abnormal laboratory findings) in subjects, users or other persons, whether or not related to the investigational devices or procedures. An SAE is an event that: Led to death; Led to serious deterioration in the health of the subject Led to foetal distress, foetal death or a congenital abnormality or birth defect Could have led to death or a serious deterioration were it to recur.

Intervention Safety - AE Severity

Time Frame: Assessed at DBS implantation (Month 0) and at regular follow-up visits 1-month, 3-months, 6-months, 9-months, and 12-months post-DBS surgery.

All AEs will be assessed by the study team using The Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 published by the U.S. Department of Health and Human Services (November 27, 2019) grading system. For AEs not included in the CTCAE defined grading system, the following guidelines will be used to describe severity: Grade 1, Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated; Grade 2, Moderate; minimal, local or non-invasive intervention indicated; limiting age- appropriate instrumental activities of daily life (ADL)\*; Grade 3, Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care ADL\*\*; Grade 4, Life-threatening consequence; urgent intervention indicated; or Grade 5, Death related to AE.

Intervention Safety - AE Relationship to Study Intervention

Time Frame: Assessed at DBS implantation (Month 0) and at regular follow-up visits 1-month, 3-months, 6-months, 9-months, and 12-months post-DBS surgery.

Team will determine AE's causality based on categories below: Definitely Related - There is clear evidence to suggest a causal relationship, and other possible contributing factors can be ruled out. Probably Related - There is evidence to suggest a causal relationship, and the influence of other factors is unlikely. Possibly Related - There is some evidence to suggest a causal relationship (e.g., the event occurred within a reasonable time. However, other factors may have contributed to the event (e.g., the participant's clinical condition, other concomitant events). Unlikely to be related - A clinical event whose temporal relationship to implantation/use of the study device makes a causal relationship improbable and in which other drugs, devices or underlying disease provides plausible explanations. Not Related - The AE is completely independent of implantation/use of the study device, and/or evidence exists that the event is definitely related to another etiology.

Intervention Safety - AE Outcome

Time Frame: Assessed at final follow-up visit 12-months post-DBS surgery, or at the last time of observation.

The outcome of the AE will be defined according to the following: Recovered/ Resolved: The event has fully resolved at the end of the study\*; Recovering/ Resolving: The event is improving but has not fully resolved at the end of the study\*; Recovered/ Resolved with sequelae: The event has resolved, but retained pathological conditions resulting from the prior disease or injury; Not recovered/ not resolved: The event is ongoing at the end of the study\*; Fatal: This event is determined to be the cause of death; and Unknown: Outcome information could not be obtained.