Delirium is a common and costly problem, affecting up to half of hospitalized older adults, and resulting in substantial morbidity, cognitive decline, loss of functional independence, and increased mortality. Delirium is particularly problematic in patients with Alzheimer's dementia who have an increased risk for delirium, and in whom delirium accelerates the rate of cognitive decline. However, our understanding of the neurological basis of the risk for and effects of delirium in a given individual remains very limited. This project seeks to address this important knowledge gap by utilizing magnetic resonance imaging (MRI)-guided (neuronavigated) transcranial magnetic stimulation (TMS) with simultaneous electroencephalography (EEG) and electromyography (EMG) to evaluate cortical function in patients undergoing elective surgery. In a prospective cohort of 180 patients we will examine whether decreased brain network connectivity and altered mechanisms of cortical plasticity as characterized by TMS-EEG-EMG are associated with the risk of developing post-operative delirium. We will record TMS-evoked potentials (TEP) from dorsolateral prefrontal cortex, inferior parietal lobule, and primary motor cortex, before and after intermittent theta-burst stimulation (iTBS). We hypothesize that baseline EEG spectral power and connectivity, TMS-based measures of cortical reactivity and connectivity, and iTBS measures of cortical plasticity will be decreased in patients who subsequently develop delirium, and that patients with greater abnormalities in EEG features and TMS measures at baseline will have greater delirium severity and greater short-term cognitive decline after an episode of delirium. We will correlate neurophysiologic measures with changes in cognitive performance and subsequent cognitive decline in patients with versus without delirium. We hypothesize that EEG alpha power and connectivity, TMS reactivity, TEP cortical connectivity, and efficacy of the mechanisms of cortical plasticity will show greater decreases in patients with delirium than in those without, and will correlate with the magnitude of cognitive decline. Finally, in patients with a previously observed episode of delirium (in SAGES I) we will compare those with and without a history of delirium, and hypothesize that cortical physiology abnormalities will correlate with long-term cognitive decline after delirium (complicated delirium). Ultimately, our results will define neurophysiologic characteristics that can identify individuals with a vulnerable brain susceptible to delirium and subsequent cognitive decline, will provide novel tools to efficiently assess the effectiveness of interventions to help increase individual cerebral resilience and reduce the risk of delirium, and will guide development of therapeutic interventions to help normalize cerebral dysfunction and minimize long-term cognitive decline after delirium.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Program Projects (P01)
Project #
2P01AG031720-06A1
Application #
9567287
Study Section
Special Emphasis Panel (ZAG1)
Project Start
2018-09-15
Project End
2023-05-31
Budget Start
2018-07-15
Budget End
2019-03-31
Support Year
6
Fiscal Year
2018
Total Cost
Indirect Cost
Name
Hebrew Rehabilitation Center for Aged
Department
Type
DUNS #
030832075
City
Boston
State
MA
Country
United States
Zip Code
Mudge, Alison M; McRae, Prue; Hubbard, Ruth E et al. (2018) Hospital-Associated Complications of Older People: A Proposed Multicomponent Outcome for Acute Care. J Am Geriatr Soc :
Racine, Annie M; Gou, Yun; Fong, Tamara G et al. (2018) Correction for retest effects across repeated measures of cognitive functioning: a longitudinal cohort study of postoperative delirium. BMC Med Res Methodol 18:69
Inouye, Sharon K (2018) Delirium-A Framework to Improve Acute Care for Older Persons. J Am Geriatr Soc 66:446-451
Racine, Annie M; Fong, Tamara G; Gou, Yun et al. (2018) Clinical outcomes in older surgical patients with mild cognitive impairment. Alzheimers Dement 14:590-600
Fick, Donna M; Inouye, Sharon K; McDermott, Caroline et al. (2018) Pilot Study of a Two-Step Delirium Detection Protocol Administered By Certified Nursing Assistants, Physicians, and Registered Nurses. J Gerontol Nurs 44:18-24
Racine, Annie M; D'Aquila, Madeline; Schmitt, Eva M et al. (2018) Delirium Burden in Patients and Family Caregivers: Development and Testing of New Instruments. Gerontologist :
Vasunilashorn, Sarinnapha M; Fong, Tamara G; Albuquerque, Asha et al. (2018) Delirium Severity Post-Surgery and its Relationship with Long-Term Cognitive Decline in a Cohort of Patients without Dementia. J Alzheimers Dis 61:347-358
Kim, Dae Hyun; Mahesri, Mufaddal; Bateman, Brian T et al. (2018) Longitudinal Trends and Variation in Antipsychotic Use in Older Adults After Cardiac Surgery. J Am Geriatr Soc 66:1491-1498
Gross, Alden L; Tommet, Doug; D'Aquila, Madeline et al. (2018) Harmonization of delirium severity instruments: a comparison of the DRS-R-98, MDAS, and CAM-S using item response theory. BMC Med Res Methodol 18:92
Miao, Huihui; Dong, Yuanlin; Zhang, Yiying et al. (2018) Anesthetic Isoflurane or Desflurane Plus Surgery Differently Affects Cognitive Function in Alzheimer's Disease Transgenic Mice. Mol Neurobiol 55:5623-5638

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