There is an urgent need to hasten the identification of novel strategies and preventative targets to mitigate the occurrence, progression and attendant adverse health outcomes of Alzheimer’s disease (AD). The role of sleep and circadian disruption is emerging as a potential novel interventional target for the treatment of AD. For example, recent data has revealed the critical role of sleep in regulating the clearance of the brain tissue beta-amyloid, a toxic protein implicated in AD. Furthermore, several studies have identified a relationship between sleep deficits and circadian disruption and the underlying biology of AD.Collaborative work from our group has also revealed moderately strong associations of cerebrospinal fluid (CSF) levels of P-tau and T-tau, recognized biomarkers of neurodegeneration, in relation to actigraphy-based biomarkers of sleep and circadian dysregulation. We now seek to extend this provocative work to characterize a potential causal role for circadian rhythm disruption in the progression of Alzheimer’s disease-associated neurodegeneration. This developing interdisciplinary, clinical and translational program is a collaborative effort across the Neurologic Institute Sleep Disorders Center and the Center of Brain Health.
Innovative investigation of approaches to quantitative analysis of REM sleep without atonia are being conducted to develop methodology and apply this algorithm to a prospective cohort of REM sleep behavior disease and isolated REM sleep without atonia.
Immune Mechanisms Underlying the Neuroprotective Effects of Physical Activity in Human and Mouse Models of Genetic Risk for Alzheimer's Disease” (R01AG022304-12; Rao, Stephen PI; Lamb, Bruce MPI)
Genetics and Epigenetics of Sleep and Circadian Disorders and Neurodegeneration. Accelerator Lerner Research Institute funding (Multi PI: R Mehra, Sujata Rao, Stephen Rao)Lou Ruvo Center for Brain Health Keep Memory Alive Scholar
Young Scientist Award: Quantitative Analysis of REM Sleep Without Atonia: Methods Development, Diagnostic Thresholds for Synucleinopathies, and Associations with Disease Markers (PI: Winnie Pao)
REM Sleep Behavior Disorder: A Review of the Literature and Update on Current Concepts. Chest. Chest.LIN;152(3):650-662. Rodriguez CL, Budur K, Jaimchariyatam N.
Polysomnographic findings in dementia with Lewy bodies. Neurologist. 2013 Jan;19(1):1-6. WC, Boeve BF, Ferman TJ, Lin SC, Smith GE, Knopman DS, Graff-Radford NR, Petersen RC, Parisi JE, Dickson DW, Silber MH.
Objective Sleep Indices Relative to Neurocognitive Function and Cerebrospinal Fluid Biomarkers in Patients with Mild Cognitive Impairment and Alzheimer’s Disease SLEEP 2018. R, Bena J, Pillai J, Leverenz J, Mehra R.
Alteration of Unique Neuroinflammatory Mediators Relative to Sleep Dysfunction in Alzheimer ’s disease with Mild Cognitive Impairment. American Neurological Association 2018. Pillai JA, Mehra R, Bena J, Nawabit R, Bekris LM, Rao SM and Leverenz JB.