Pain and Nutrition in Dementia and Alzheimer’s Phase 1: a cross-sectional, observational study design

Background: Neurodegenerative diseases such as Alzheimer's Disease and related dementias (ADRDs) as well as chronic pain have increased in prevalence as the population ages. In fact, recent epidemiological research suggests that having chronic pain may increase one's risk of all-cause dementia. There are mechanistic factors that overlap in both ADRD and chronic pain progression, including epigenetic dysregulation that could lead to increased inflammation. Previously, our group presented evidence that dietary patterns impact inflammatory potential and epigenetic modifications, and accelerate epigenetic aging. Here, we hypothesize that diet- induced inflammation and epigenetic alterations may be underexplored mechanistic pathways connecting chronic pain and ADRD risk. Methods: The Pain and Nutrition in Dementia and Alzheimer's Phase 1 (PANDA-1) study is a cross-sectional, observational study, which will recruit 90 individuals ≥55 years of age with and without painful knee osteoarthritis (OA). Biological samples will be collected to assess study eligibility, blood-based inflammatory markers, and epigenetic age using the epigenetic clock DNAmGrimAge. A 24-h dietary recall will be completed to determine nutrition status via the Dietary Inflammation Index (DII). Pain and psychosocial questionnaires will be employed to determine pain phenotypes. Quantitative Sensory Testing will be conducted to determine responses to noxious mechanical and thermal stimuli. Lower-extremity function and mobility measures will also be obtained. Finally, height, weight, pain history, medical history, medication use, and demographic variables will be collected as covariates. Hierarchical regression, mediation and moderation analyses, as well as ANOVAs will be conducted to evaluate relationships among the DII, epigenetic aging, cognition status, and pain. Conclusion: This study will integrate dietary, epigenetic, and cognitive assessments in a chronic pain population, to lay the groundwork of a possible associations linking chronic pain and ADRDs. PANDA-1 aims to determine potential relationships of dietary patterns on interindividual variability of cognitive status and pain outcomes in older adults deemed cognitively intact. Subsequent phases of this study will include individuals with mild cognitive impairment and ADRDs. Findings from this work will inform future studies targeting dietary intervention approaches to mitigate overlapping neurodegenerative and pain-related aging processes.