Project - Delineating relationships between sleep-wake disturbances, brain changes, dementia risk factors and the accumulation of dementia pathology
All Chief investigators and associate investigators
CIA- McKinnon; AI – Sharon Naismith; AI – Jurgen Fripp; AI – Stephanie Rainey-Smith
Research Project Abstract
Understanding potential modifiable risk factors for dementia is critical, with approximately one-third of all Alzheimer’s Disease cases and up to 40% of all dementia cases attributable to modifiable risk factors such as physical inactivity, hypertension and depression. Accordingly, comprehensively characterising the role and significance of sleep-wake disturbance (SWD) in cognitive decline and how it relates to brain pathology and other risk factors, is crucial for determining the degree to which SWD itself may confer additional dementia risk. Indeed addressing SWD, along with other modifiable risk factors, may prove to be a viable primary prevention approach for dementia. (Project 07/04/2021 – 07/04/2024)
Dementia, AD, Sleep disorders, Ageing
Challenges within the field
This project will deliver novel insights regarding the role of sleep-wake disturbances (SWDs) such as OSA to not only advance the understanding of biological mechanisms contributing to dementia risk, but also to inform clinical diagnostics at varying stages of cognitive decline.
This project will be the first to comprehensively characterise SWDs in older adults regarding their interrelationships with dementia pathology progression, other modifiable risk factors, brain structure and function alterations, and cognitive changes.
In doing so, it is projected to strengthen the evidence-base for SWDs to be formally recognised as a modifiable risk factor for dementia, highlighting the importance of early screening and intervention for those with sleep concerns.
It will also produce the type of meaningful translational outcomes that are presently largely lacking in this research area. Clinical tools will be used to produce individualised reports for each participant about their risk of dementia or further cognitive decline. Clinicians can utilise these to implement appropriate treatment pathways.
Research Project Description
Sleep-wake disturbance (SWD) has the potential to be targeted as a modifiable risk factor for dementia as it is evident early in the disease course, with SWD present in around two thirds of those with Mild Cognitive Impairment (MCI). MCI is an ‘at-risk’ stage whereby 45% of individuals with MCI will progress to AD within five years. Understanding potential modifiable risk factors is critical, with approximately one-third of all AD cases and up to 40% of all dementia cases attributable to modifiable risk factors such as physical inactivity, hypertension and depression.
Accordingly, comprehensively characterising the role and significance of SWD in cognitive decline and how it relates to brain pathology and other risk factors, is crucial for determining the degree to which SWD itself may confer additional dementia risk. Indeed, addressing SWD, along with other modifiable risk factors, may prove to be a viable primary prevention approach for dementia.
To target SWD as a modifiable risk factor for dementia, we must further delineate the underlying pathophysiological mechanisms by which SWD causes neurodegeneration. Recent evidence has highlighted the deleterious effects of SWD, particularly the nocturnal hypoxaemia present in obstructive sleep apnoea (OSA).
1. To determine in an older adult cohort either at risk for or in the early stages of dementia how sleep-wake disturbances (derived from actigraphy and oximetry) measured at two timepoints (2 years apart) relate to:
a) The accumulation and progression of amyloid beta and tau pathology.
b) The accumulation of other modifiable risk factors (including vascular, genetic, mood).
c) Brain structure, function, and cognition
2. To develop and validate statistical and machine learning models that quantify weighted risk composites of measures from Aim 1 that can be used to produce clinical reports to inform individualised risk assessment and dementia prediction.
These validated risk composites will also be able to be implemented in clinics more broadly, giving clinicians access to crucial, personalised information about an individual’s projected cognitive trajectory. These outcomes would reflect a substantial breakthrough in dementia research, with significant impacts including providing guidance for targeted and early interventions, and informing primary prevention of dementia approaches.
- *NB* I made this about HBA overall, not my project, as that is what the form seemed to infer
- Research shows that mood, sleep and lifestyle factors (such as exercise, diet and cognitive activity), as well as vascular conditions (including high blood pressure, diabetes, heart disease and high cholesterol), can contribute to cognitive decline and depression in later life.
- Research undertaken by The Healthy Brain Ageing Program targets these modifiable risk factors by providing early identification, intervention and prevention programs for older adults at risk for dementia. Through the ForeFront Healthy Brain Ageing Research Clinic, our multifaceted team of neurologists, geriatricians, sleep physicians, clinical neuropsychologists, general physicians, psychiatrists, nurses, exercise physiologists, dietitians, nutritionists, research assistants and students work together to evaluate the effects of interventions designed to modify these risk factors in older adults.
- A multimodal approach is taken, whereby we collect longitudinal data from a number of sources including MRI, PET, PSG, actigraphy, oximetry, blood-based biomarkers, and clinical and cognitive data, to produce research outputs that inform, produce, and refine these interventions.