Wearables-and Blood-based Biomarkers-incorporated Modernisation of Circadian Rhythm Disruption Management in People Living With Alzheimer's Dementia: A Stepwise Study From Digital Inclusivity, Digital Therapy, to Digital Phenotyping and Biomarker Exploration

In 2025, Taiwan will become a super-aged society, with a continuous rise in the number of people living with Alzheimer's dementia. The majority of these patients will experience "behavioural and psychological symptoms of dementia (BPSD)," such as agitation and sleep disturbances. Among these symptoms, nighttime sleep disorders and circadian rhythm disruptions not only deteriorate patients' quality of life but also impose substantial caregiving and medical costs on society, significantly increasing caregiver burden.

Currently, the assessment of such symptoms relies heavily on caregiver-reported questionnaires, which are often subjective and can only offer cross-sectional information. In Taiwan, this challenge is compounded by the fact that caregivers are often elderly individuals with cognitive decline themselves, making it difficult to accurately evaluate symptoms and develop effective treatment plans. Our previous research conducted in the UK revealed that even patients with late-stage dementia can accept to wear research-grade actigraphy with good compliance. Utilizing wearable devices for symptom assessment provides a more objective and continuous evaluation, with the analysis of emerging variables potentially contributing to a better understanding of dementia progression and the mechanisms underlying patients' circadian rhythm disturbances.

On the other hand, the treatment of circadian rhythm disruptions and sleep disorders in dementia patients heavily depends on medication. Many of these drugs lack proper indications for such use, and may increase the risk of falls and mortality. Near-infrared photobiomodulation (PBM) is a novel therapy emerged in recent years. Our team recently collaborated with Harvard University under a project funded by the Taiwanese National Science and Technology Council, successfully publishing the first findings on a "wearable PBM device" designed for home use in treating depression. The study demonstrated that the device might help improve sleep problems in elderly individuals with depression. If dementia patients can simultaneously use this device along with actigraphy devices, it could not only alleviate their sleep and circadian rhythm disturbances but also provide objective, continuous multi-dimensional symptom assessments through actigraphy and its build-in sensors.

This four-year project aims to begin with exploring "digital inclusivity," first validating the feasibility of using research-grade actigraphy among people living with Alzheimer's dementia in Taiwan, and establishing a research platform incorporating wearable devices data in this population. The investigators will then continue collaborating with Harvard University to conduct a double-blind randomized clinical trial, confirming the efficacy of wearable PBM devices in improving sleep, circadian rhythm disturbances, and other BPSD among these patients. Additionally, the investigators will assess the experiences of both patients and caregivers using a combined "digital therapy" approach involving both devices.

Finally, through the integration of the data across the four years from wearable devices, clinical symptom assessments, and the latest validated blood-based biomarkers for Alzheimer's disease, the investigators will conduct a longitudinal analysis. Collaborating with the largest European remote dementia care team, RADAR-AD, the investigators will explore potential digital phenotypes for dementia and examine the interactions between circadian rhythm disturbances, cognitive decline progression, and biomarkers. The ultimate goal is to establish a novel three-dimensional management model for dementia patients encompassing "clinical symptoms (cognitive and non-cognitive)," "lifestyle and functionality," and "biological markers."