Contributions of Sleep and Pain to Alzheimer's Disease Related Biomarkers: Identifying Modifiable Risk Factors in Women with Normal to Mildly Impaired Cognitive Function

PROJECT SUMMARY This supplement will increase understanding of modifiable Alzheimer?s disease related risk factors (sleep, pain, arousal), and their associations and interactions with Alzheimer?s disease related biomarkers, cognition, and daytime functioning in three groups of middle-to-older aged women characterized by: fibromyalgia and insomnia (FMI), subclinical sleep and pain complaints (SPC), or mild cognitive impairment (MCI).

Women are at greater risk (2x) of Alzheimer?s disease, and the vast majority (2/3rds) of Americans with Alzheimer?s disease are women.

Chronic pain, poor sleep, and MCI are independently associated with greater risk of neurodegenerative disorders, and increased levels of biomarkers associated with Alzheimer?s disease (amyloid beta-A?, tau) and inflammation (C-reactive Protein-CRP, IL-6).

Thus, these groups are ideal for studying these factors and addressing the lack of understanding of the mechanisms underlying their association and the degree to which modifiable factors (sleep, pain, arousal) may interact to mitigate Alzheimer?s disease risk, onset or progression.

The parent study, a NIH/NINR funded randomized clinical trial (RCT), focuses on the mechanistic roles of sleep and arousal in chronic pain and pain-related neural plasticity.

Our team does not currently conduct Alzheimer?s disease focused research, and the parent trial does not have an Alzheimer?s disease focus.

Nonetheless, it offers a unique opportunity to examine the associations and interactions amongst the modifiable Alzheimer?s disease related factors measured in the parent trial (sleep, pain, arousal) and the Alzheimer?s disease related biomarkers, cognition, and daytime functioning measures proposed in this supplement.

This supplement is an important first step for our team to develop an Alzheimer?s disease research focus based on a biopsychosocial model in which the associations of sleep, pain, and arousal with Alzheimer?s disease related biomarkers, cognition, and daytime functioning are moderated by sex hormones, APOE genotype, age, and education.

This supplement takes advantage of the parent trial?s infrastructure, data, and well-characterized samples of FMI and SCP. 30 women with FMI and 60 with SCP will be recruited for the supplement from the parent trial?s baseline screening phase. Additionally, a new sample of 30 women with MCI will be recruited.

This supplement tests two specific aims: Aims 1 and 2 examine the associations and interactions amongst sleep, pain, arousal, and Alzheimer?s related biomarkers, cognition, and daytime functioning, and their moderation by sex hormones, APOE genotype, age, and education in women with FMI, SPC, or MCI.

While these aims involve data collected during the screening phase of the parent trial, the parent trial also examines the impact of cognitive behavioral treatment for insomnia (CBT-I) on sleep, pain, arousal, central sensitization, and neural plasticity in women with FMI.

Thus, an Exploratory Aim investigates CBT-I?s potential to mitigate the impact of sleep, pain, and arousal on the Alzheimer's related biomarkers in the proposed biopsychosocial model. Results will be used to support future R01 proposals focused on Alzheimer?s disease.

Public Health Implications: Identification of sleep, pain, and arousal as intervention targets with high potential to mitigate Alzheimer?s disease risk, onset or progression has important implications for persons with or at risk for dementia, their families, and the US healthcare system.