) Alzheimer's disease (AD) causes alterations in sensory systems ?such as olfaction or hearing-, and motor domains that sometimes precede cognitive symptoms, as shown in longitudinal studies. However, it remains largely unknown the specific role of sensory and motor disruptions within the AD neurodegeneration process and its clinical use for predicting future dementia onset. In this proposal, we focus on the network nature of sensory and motor changes in the aging brain. We postulate that AD neurodegeneration transversally affects connectivity streams across neuronal systems involving multiple domains of network integration, from sensory-motor to high-order cognitive brain centers. Thus, we will investigate the functional streams connecting sensory and motor regions with associative cortex to disentangle the role of sensory-motor disruption in the disease and its relationship with tau and amyloid accumulation at the brain circuit level. Particularly, we will use functional connectivity MRI, multimodal PET neuroimaging (tau and amyloid tracers), and graph theory metrics to reliably quantify the sensory and motor circuit changes in the cerebral tissue of preclinical and clinical AD samples from our local Harvard Aging Brain Study at Massachusetts General Hospital. Our preliminary data has demonstrated that network analysis can provide a highly accurate quantitative map of the sensory-motor systems connectivity in aging populations, offering a firm basis for assessment of AD related changes in brain function. In this multi-disciplinary investigation we will 1) quantify sensory and motor functional streams in aging and AD (Aim 1); 2) investigate the association of sensory and motor functional streams with tau and amyloid deposits (Aim 2); and 3) investigate the sensory and motor connectivity changes in the follow-up (Aim 3).

Public Health Relevance

This project focuses on a combined effort in which we will 1) investigate the sensory and motor streams in preclinical and clinical Alzheimer's disease (AD) cohorts using functional connectivity MRI and graph theory approaches; 2) analyze the cortical intersection between sensory and motor connectivity changes and tau and amyloid deposits in preclinical and clinical AD populations using multimodal PET neuroimaging; 3) characterize sensory and motor connectivity changes over time (from 2 to 4 years follow-up) and its associations with longitudinal variations in clinical, neuropsychological and PET profiles.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
5R01AG061811-02
Application #
9997775
Study Section
Sensorimotor Integration Study Section (SMI)
Program Officer
St Hillaire-Clarke, Coryse
Project Start
2019-09-01
Project End
2024-05-31
Budget Start
2020-06-01
Budget End
2021-05-31
Support Year
2
Fiscal Year
2020
Total Cost
Indirect Cost
Name
Massachusetts General Hospital
Department
Type
DUNS #
073130411
City
Boston
State
MA
Country
United States
Zip Code
02114