Sleep Apnoea and Memory (SAM): Protocol for a prospective study of prevalence and symptoms of sleep apnoea in memory clinics

The Sleep Apnoea and Memory (SAM) study is a prospective multi-site observational trial designed to determine the prevalence of sleep apnoea in NHS memory clinic patients, evaluate optimal screening methods, and inform future interventional trials aimed at improving cognitive outcomes through sleep apnoea treatment.

The Gist

Imagine your brain is a busy city that needs to be cleaned every night while you sleep. The "garbage trucks" (your brain's cleaning crew) work best when the city is quiet and the streets are clear.

Sleep Apnoea is like a traffic jam in your throat. Every time you breathe, your airway gets blocked, causing you to stop breathing for a few seconds. This happens over and over again all night. It's like someone repeatedly slamming the brakes on a car while trying to drive to work. Your brain wakes up slightly to gasp for air, disrupting the "cleaning crew" and leaving behind a mess of toxic waste.

Over time, this mess can make your memory fuzzy and increase the risk of dementia.

The Problem: The "Silent" Traffic Jam

Here's the tricky part: Many people with memory problems go to special "Memory Clinics" to get help for their forgetfulness. But doctors there rarely ask, "Do you snore?" or "Do you stop breathing at night?"

It's like a mechanic looking at a car with a flat tire but never checking the air pressure. They treat the flat tire (the memory loss) but miss the real cause (the lack of air).

The Solution: The SAM Study

The Sleep Apnoea and Memory (SAM) study is a new project designed to fix this blind spot. Think of the researchers as detectives trying to solve a mystery: How many people in memory clinics actually have this "traffic jam" in their throats, and can fixing it help their brains?

Here is how they are doing it, broken down simply:

1. The "Home Detective" (The Device)
Instead of making patients sleep in a hospital with wires everywhere (which is scary and expensive), the study uses a special home sleep test.

• The Metaphor: Imagine a high-tech smartwatch that doesn't just count your steps, but also acts like a night-time air traffic controller. It sits on your finger and wrist, watching your breathing and heart rate while you sleep in your own bed.
• The Goal: They want to see how many people have this breathing problem without them even knowing it.

2. The "Questionnaire Map"
The researchers are also testing different questionnaires (like a roadmap).

• The Metaphor: They are trying to figure out which questions are the best "GPS" to find the problem. Do we ask, "Do you snore?" or "Do you feel tired?" They want to find the most accurate map to spot sleep apnoea in older people, whose symptoms might look different than in younger people (like just feeling confused or needing to pee at night).

3. The "Brain Fuel" Check (The Blood Test)
For some participants, they are also taking blood samples.

• The Metaphor: Think of this as checking the oil quality in the car's engine. They are looking for specific chemicals in the blood that show if the brain is getting damaged.
• The Big Question: If they treat the sleep apnoea (fix the traffic jam), will the "oil" get cleaner? Will the brain stop getting damaged? This is a pilot test to see if treating sleep apnoea could actually slow down dementia.

Why This Matters

If this study proves that sleep apnoea is common in memory clinics, and that treating it helps, it could change medicine forever.

• Current situation: We treat the memory loss like a broken engine part that can't be fixed.
• Future hope: We might realize the engine is fine, but the fuel line is clogged. If we just clear the clog (treat the sleep apnoea), the memory might get better, or at least stop getting worse.

In short: The SAM study is a mission to wake up the medical world to the idea that fixing your breathing at night might be the key to saving your memory. They are going to every memory clinic to find the hidden "traffic jams" and see if clearing them out can help people live better, sharper lives.

Technical Summary

Based on the provided preprint, here is a detailed technical summary of the Sleep Apnoea and Memory (SAM) study protocol.

1. Problem Statement

Sleep apnoea (SA), particularly Obstructive Sleep Apnoea (OSA), is a highly prevalent condition in older adults and is increasingly recognized as a modifiable risk factor for cognitive decline, Mild Cognitive Impairment (MCI), and Alzheimer's Disease (AD). Despite this link:

• Under-diagnosis: SA is rarely assessed in memory clinics, leading to a significant gap in understanding its prevalence among patients presenting with cognitive symptoms.
• Screening Limitations: Standard screening tools (e.g., STOP-Bang, Epworth Sleepiness Scale) have limited predictive performance in older adults and those with cognitive impairment, as classic symptoms (like snoring) may be absent or attributed to aging/neurodegeneration.
• Diagnostic Barriers: The gold standard for diagnosis, in-laboratory Polysomnography (PSG), is resource-intensive and impractical for large-scale screening. Home Sleep Apnoea Tests (HSAT) offer a scalable alternative but require validation in memory clinic populations.
• Therapeutic Gap: It remains unclear whether treating SA in patients with cognitive impairment can slow neurodegeneration or improve clinical outcomes.

2. Methodology

The SAM study is a prospective, observational, multi-site study designed to assess prevalence, screening efficacy, and feasibility.

• Study Design & Setting:

  • Type: Pragmatic, prospective, observational.
  • Sites: Multiple NHS memory clinics across the UK (Bristol, London, Cornwall, Northumbria, Bradford).
  • Recruitment: Adults (≥18 years) attending memory or cognitive disorder services. No exclusion based on diagnosis; patients with existing SA diagnoses are included to assess treatment adherence.
  • Sample Size: Target of 453 participants (to yield 385 analyzable cases), calculated to estimate a 50% prevalence rate and model 16 predictors without overfitting.

• Data Collection Procedures:

  • Primary Diagnostic Tool: A single night of Home Sleep Apnoea Testing (HSAT) using the WatchPAT™ 300 device (Type III respiratory polygraphy). This device measures peripheral arterial tone (PAT), heart rate, oximetry, actigraphy, body position, snoring, and chest motion.
  • Questionnaires: Participants complete validated tools including the STOP-Bang (SA risk), Epworth Sleepiness Scale (ESS), and bespoke NICE-recommended symptom/risk factor questionnaires.
  • Delivery: Primarily remote (device mailed, data uploaded to CloudPAT®), with telephone/face-to-face options to minimize digital exclusion.
  • Sub-study (Blood Biomarkers): A subset of participants at the lead site (North Bristol NHS Trust) with new SA diagnoses will undergo blood draws at 4–8 week intervals (pre- and post-treatment).
    • Biomarkers: Amyloid-beta (Aβ40/42), phosphorylated tau (p-tau 181, p-tau 217), glial fibrillary acidic protein (GFAP), and neurofilament light chain (NfL).

• Outcomes:

  • Primary: Prevalence of at least mild SA (defined as Oxygen Desaturation Index [ODI] ≥ 5 at 3% desaturation).
  • Secondary:
    • Prevalence stratified by cognitive diagnosis (e.g., AD, Lewy Body Disease).
    • Diagnostic accuracy of STOP-Bang and ESS in this specific population.
    • Feasibility of remote screening (completion rates, user experience).
    • Change in blood biomarkers following SA treatment.

• Analysis Plan:

  • Descriptive statistics for prevalence with 95% confidence intervals.
  • ROC curve analysis and LASSO regression to identify the best predictors of SA.
  • Interrupted time series analysis to evaluate changes in biomarkers pre- and post-intervention.

3. Key Contributions

• Protocol Development: Establishes a rigorous framework for integrating SA screening into routine memory clinic workflows using scalable, remote HSAT technology.
• Validation of Screening Tools: Aims to determine if standard questionnaires (STOP-Bang/ESS) are effective predictors of SA in cognitively impaired populations, where symptom presentation differs from the general population.
• Biomarker Pilot: Introduces a novel pilot methodology to investigate the causal link between SA treatment and neurodegenerative biomarkers (Aβ, p-tau, NfL), potentially identifying a mechanism for disease modification.
• Patient-Centric Design: Incorporates Patient and Public Involvement (PPI) from inception, ensuring protocols are accessible to those with cognitive difficulties and their caregivers.

4. Results

• Status: This document is a study protocol. No empirical results (data collection, prevalence rates, or biomarker changes) are reported yet.
• Anticipated Findings: The study expects to quantify the high burden of undiagnosed SA in memory clinics and determine the feasibility of remote testing. The sub-study aims to provide preliminary evidence on whether treating SA alters the trajectory of AD biomarkers.

5. Significance

• Clinical Impact: If SA is found to be highly prevalent and treatable in memory clinics, it could lead to immediate improvements in patient quality of life, sleep, and potentially cognitive function.
• Public Health: Identifying SA as a modifiable risk factor could shift dementia prevention strategies, reducing the overall burden of cognitive decline.
• Future Research: The data generated will inform the design of a definitive randomized controlled trial (RCT) to test whether treating SA slows the progression of dementia.
• Healthcare Efficiency: Validating remote HSAT in this population could reduce the need for expensive in-lab PSG, making SA diagnosis more accessible and cost-effective within the NHS.

Funding & Ethics: The study is funded by the NIHR Research for Patient Benefit programme (NIHR207185) and supported by the Goldman Foundation. It has received favorable ethical opinion from the Health Research Authority (Ref: 25/NW/0221).