Dementia and neurodegeneration affect more and more individuals across the world, especially in Latin American (LA) countries. Currently there is no cure for dementia. A new focus is on identifying the risk factors or early signs for dementia that are modifiable and can be the targets for preventing or delaying the onset of dementia. The main goal of this project is to establish the involvement of circadian disturbance in the development/progression of Alzheimer’s disease (AD) and frontotemporal dementia (FTD) in Latin America. To prepare the body for anticipated daily changes in behaviors and in metabolic needs, the circadian system generates/orchestrates daily/circadian rhythms in almost all biological functions/processes including sleep and brain function. Disturbances in circadian rhythms and/or their synchronization with the day-night or light-dark cycle, as occurred during shift work, are linked to numerous adverse health outcomes such as sleep disorders, cardiometabolic diseases, and cognitive impairment. Recent studies including ours provided evidence for a bi-directional relationship between circadian disturbance and the development/progression of AD. For instance, using a longitudinal design, we showed that circadian regulation of motor activity was degraded with aging, and the aging process was accelerated after the onset of mild cognitive impairment and further accelerated after the onset of dementia; circadian disturbance was also correlated with amyloid pathology in preclinical AD; and circadian disturbance also predicted the risk for Alzheimer’s dementia in older adults with normal cognition, independent of cognition and APOE-ε4 status (see Preliminary Data). However, these circadian studies were mainly performed in high-income countries such as the US and EU countries, and circadian health and its link to dementia and neurodegeneration in Latin America are unknown. The main hypothesis behind this project is that circadian health in Latin America countries is affected by specific sample features (such as age, gender, social determinants of health [SDOH], socioeconomic status [SES]), and contributes to neurocognition and dementia. To test the hypothesis, we will leverage the database of the ReDLat (Multi-Partner Consortium to Expand Dementia Research in Latin America) project, in which three groups of participants (AD, FTD, and controls) aged between 40 and 80 years old undergo a multidimensional assessment including SES, neurocognition, neuroanatomical changes (MRI), and whole-genome sequencing. We propose to perform non-invasive assessment of circadian disturbance in ReDLat participants using daily motor activity recordings (~7 days). We will analyze motor activity recordings to derive a number of measures that reflect multiscale regulatory function of the circadian system and have been used to demonstrate the link of circadian disturbance to Alzheimer’s disease and related dementia in other populations (not Latin America).
PIs: Agustín Ibáñez / Claudia Duran Aniotz
Support: National Institutes of Health (NIH), USA
