Peri-Anesthetic Imaging of Cognitive Dysfunction
Condition: Postoperative Cognitive Dysfunction; Delirium; Dementia; Neurotoxicity
MeSH terms: Delirium; Postoperative Cognitive Complications; Cognitive Dysfunction
Study type: Observational

Summary: 
      Recent data suggests that anesthetics can have prolonged effects on gene expression, protein
      synthesis and processing as well as cellular function in ways that the investigators are only
      beginning to understand, especially in the very young and the elderly. Within moments to days
      of emerging from anesthesia - cardiac or non-cardiac - some patients experience mild to very
      severe disorientation and changes in memory and thinking ability without apparent cause. For
      the vast majority of patients, this Post-Operative Cognitive Dysfunction (POCD), generally
      subsides, but for some with "diminished cognitive reserve" - especially the elderly, those
      with less education or prior CNS events such as stroke or early dementia - changes in memory
      and executive function may persist. If prolonged for more than three months, POCD has been
      linked to an increased risk of death. In 1-2% of elderly patients, the problem may ultimately
      continue for more than a year, leading to a loss of ability to care for themselves and early
      demise. Though this may seem like a small percentage, seniors will comprise up to 40% of the
      50-75 million surgical procedures performed annually over the next 20-30 years. This amounts
      to 70,000 - 200,000 elder affected, and for them and their families, the cost of POCD in
      longer-term care, lost wages, and extended suffering will remain very high.
    

Detailed description: 
      For more than 160 years, "modern" anesthesia has provided immense benefit to patients of all
      ages. However, over the past several years, concern has been growing that for patients at the
      extremes of age, some anesthetic agents may harbor subtle, previously minimally examined,
      serious neurotoxic effects which can cause lasting decline in the function of the central
      nervous system (CNS). For the elderly, these effects may manifest in lasting post-operative
      deterioration of memory and the capacity for normal information processing that can result in
      the inability to perform the activities of daily living (ADLs) with eventual early demise.
      Unfortunately, even though our ability to evaluate anesthetic risk has grown asymptotically
      for virtually every organ system, the brain remains neglected. And even though we know a good
      deal about effect sites for general anesthetic agents, we still have an incomplete
      understanding of the potential toxic effects of anesthetics on the brain. Therefore,
      employing a human surgical model (endoscopic prostatectomy), we propose a pilot study of 15
      otherwise neurologically intact, ASA I - III, males, 65+ year of age. After pre-enrollment
      screening (MMSE & BDI) and standard pre-op evaluation, subjects will undergo both anatomic
      and functional MRI studies plus a battery of neurocognitive tests (NCT) at two time points
      approximately 2-3 weeks apart prior to surgery. These pre-op studies will establish both a
      "non-surgical control" for the study as well as a baseline for post-op studies. 2-3 weeks
      after surgery, MRI and NCT will be repeated. The study aims to determine if MRI can
      demonstrate changes in the CNS pre-op vs post-op that relate to anesthesia and surgery and
      how those changes might correlate with NCT over the same interval.
    

Observational model: Case-Only
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Subjects will be non-rheumatoid, non-immune-compromised, males and females, 65+ years old,
        scheduled for open abdominal surgery under general anesthesia of 3+ hour's duration.
      
Keywords: Anesthetic Agents; POCD; Delirium; Cognitive Testing; Aging; Surgery; fMRI; Diffusion Tensor Imaging; White Matter