# The Aging Brain Under General Anesthesia: Neurophysiology, Neuroimaging Biomarkers of Aging and Alzheimer's Disease, and Post-Operative Cognitive Outcomes

> **NIH NIH R01** · MASSACHUSETTS GENERAL HOSPITAL · 2020 · $639,246

## Abstract

In the United States, nearly 100,000 patients receive general anesthesia and sedation daily to safely
undergo surgical and non-surgical procedures. A high proportion of the patients receiving anesthesia care are
elderly, and in addition may have pre-existing conditions such as Alzheimer's disease or cerebrovascular
disease. As such, elderly patients have a higher risk of post-operative delirium and cognitive dysfunction.
Anesthesiologists know that management of older patients requires different approaches compared with that of
younger patients. For example, the dose required to achieve the same anesthetic state in elderly patients can
be 50% lower than that for younger patients. Unfortunately, at present we know little about the fundamental
neurophysiology of how anesthetic drugs influence the aging brain. This represents a major knowledge gap
that prevents us from developing novel approaches to more safely administer anesthesia and sedation in
elderly patients. In recent years, aided largely by non-invasive imaging methods, significant progress has been
made in understanding systems-level neurophysiology of anesthetic effects in humans. In parallel, imaging
biomarkers have advanced to enable the identification of two of the most common “silent” pathologies that may
put older adults at higher risk for poor post-anesthesia/surgical outcomes: Alzheimer's disease (AD) and
cerebrovascular disease (CVD). We propose here to bring these two lines of research together with a study
employing imaging markers of preclinical AD (amyloid PET, cortical atrophy) and CVD (FLAIR MRI, DTI)
alongside sophisticated computational analysis of intra-operative EEG, with the goal of using these measures
to better understand variability in response to anesthesia and post-operative outcomes. As we accomplish the
aims of this grant, the data generated should lead to fundamental new insights into the neurophysiology of
anesthesia in aging patients. These insights will advance knowledge about how to assess patients for risks of
anesthesia and reduce those risks through improved brain monitoring, improved drug dosing, and a precision-
medicine approach to tailoring anesthesia to the individual's brain.

## Key facts

- **NIH application ID:** 9904463
- **Project number:** 5R01AG056015-04
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** EMERY N BROWN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $639,246
- **Award type:** 5
- **Project period:** 2017-04-15 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9904463

## Citation

> US National Institutes of Health, RePORTER application 9904463, The Aging Brain Under General Anesthesia: Neurophysiology, Neuroimaging Biomarkers of Aging and Alzheimer's Disease, and Post-Operative Cognitive Outcomes (5R01AG056015-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9904463. Licensed CC0.

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