Mass Genl researchers look at anesthesia and cognitive dysfunction

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This post may be of interest to those who have a loved one with dementia, or those contemplating surgery with general (inhaled) anesthesia.

A Boston Globe newspaper article I circulated back in 2007 was about hospital-induced delirium.  In that article, Massachusetts General Hospital researchers drew attention to the anesthetic isoflurane as part of the cause of delirium.

Last week Massachusetts General Hospital distributed a press release on isoflurane; it causes Alzheimer’s-like changes in mammalian brains.  Researchers mention an anesthetic that may be safer — desflurane.

The full press release is copied below.

Robin

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www.massgeneral.org/about/pressrelease.aspx?id=1443

Massachusetts General Hospital Press Release
Study reveals how anesthetic isoflurane induces Alzheimer’s-like changes in mammalian brains
MGH researchers find desflurane may be safer anesthetic option for patients with Alzheimer’s disease
01/Mar/2012

The association of the inhaled anesthetic isoflurane with Alzheimer’s-disease-like changes in mammalian brains may by caused by the drug’s effects on mitochondria, the structures in which most cellular energy is produced.  In a study that will appear in Annals of Neurology and has received early online release, Massachusetts General Hospital (MGH) researchers report that administration of isoflurane impaired the performance of mice on a standard test of learning and memory – a result not seen when another anesthetic, desflurane, was administered.  They also found evidence that the two drugs have significantly different effects on mitochondrial function.

“These are the first results indicating that isoflurane, but not desflurane, may induce neuronal cell death and impair learning and memory by damaging mitochondria,” says Yiying (Laura) Zhang, MD, a research fellow in the MGH Department of Anesthesia, Critical Care and Pain Medicine and the study’s lead author. “This work needs to be confirmed in human studies, but it’s looking like desflurane may be a better anesthetic to use for patients susceptible to cognitive dysfunction, such as Alzheimer’s patients.”

Previous studies have suggested that undergoing surgery and general anesthesia may increase the risk of Alzheimer’s, and it is well known that a small but significant number of surgical patients experience a transient form of cognitive dysfunction in the postoperative period.  In 2008, members of the same MGH research team showed that isoflurane induced Alzheimer’s-like changes – increasing activation of enzymes involved with cell death and generation of the A-beta plaques characteristic of the disease – in the brains of mice.  The current study was designed to explore the underlying mechanism and behavioral consequences of isoflurane-induced brain cell death and to compare isoflurane’s effects with those of desflurane, another common anesthetic that has not been associated with neuronal damage.

In a series of experiments, the investigators found that the application of isoflurane to cultured cells and mouse neurons increased the permeability of mitochondrial membranes; interfered with the balance of ions on either side of the mitochondrial membrane; reduced levels of ATP, the enzyme produced by mitochondria that powers most cellular processes; and increased levels of the cell-death enzyme caspase.  The results also suggested that the first step toward isoflurane-induced cell death was increased generation of reactive oxygen species – unstable oxygen-containing molecules that can damage cellular components. The performance of mice on a standard behavioral test of learning and memory declined significantly two to seven days after administration of isoflurane, compared with the results of a control group.  None of the cellular or behavioral effects of isoflurane were seen when the administered agent was desflurane.

In another study by members of the same research team – appearing in the February issue of Anesthesia and Analgesia and published online in November – about a quarter of surgical patients receiving isoflurane showed some level of cognitive dysfunction a week after surgery, while patients receiving desflurane or spinal anesthesia had no decline in cognitive performance.  That study, conducted in collaboration with investigators from Beijing Friendship Hospital in China, enrolled only 45 patients – 15 in each treatment group – so its results need to be confirmed in significantly larger groups.

“Approximately 8.5 million Alzheimer’s disease patients worldwide will need anesthesia and surgical care every year,” notes Zhongcong Xie, MD, PhD, corresponding author of both studies and director of the Geriatric Anesthesia Research Unit in the MGH Department of Anesthesia, Critical Care and Pain Medicine.  “Developing guidelines for safer anesthesia care for these patients will require collaboration between specialists in anesthesia, neurology, geriatric medicine and other specialties.  As the first step, we need to identify anesthetics that are less likely to contribute to Alzheimer’s disease neuropathogenesis and cognitive dysfunction.”  Xie is an associate professor of Anesthesia at Harvard Medical School (HMS)

Additional co-authors of the Annals of Neurology study are Zhipeng Xu, MD, PhD, Hui Wang, MD, and Yuanlin Dong, MD, MGH Anesthesia; Rudolph Tanzi, PhD, MGH Neurology; Hai Ning Shi, DVM, PhD, MGH Pediatrics; Deborah Culley, MD, and Greg Crosby, MD, Brigham and Women’s Hospital;  and Edward Marcantonia, MD, MS, Beth Israel Deaconess Medical Center.  The study was supported by grants from the National Institutes of Health, the American Geriatrics Society, the Alzheimer’s Association and the Cure Alzheimer’s Fund.

Massachusetts General Hospital, founded in 1811, is the original and largest teaching hospital of Harvard Medical School. The MGH conducts the largest hospital-based research program in the United States, with an annual research budget of more than $750 million and major research centers in AIDS, cardiovascular research, cancer, computational and integrative biology, cutaneous biology, human genetics, medical imaging, neurodegenerative disorders, regenerative medicine, reproductive biology, systems biology, transplantation biology and photomedicine.

“Mind, Mood & Memory” booklet

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This terrific booklet, Parkinson’s Disease: Mind, Mood & Memory, was published several years ago by the National Parkinson Foundation (parkinson.org).  I hand it out to all newcomers to our Lewy Body Dementia caregiver-only support group meetings.  It has a wonderful chapter (five) focused on Dementia with Lewy Bodies.

The booklet makes the important point that there’s a delicate balance between treating psychosis (hallucinations and delusions) and treating parkinsonian motor symptoms.

Here’s a link to it:

www3.parkinson.org/site/DocServer/Mind_Mood_Memory.pdf?docID=191

I hope you value this booklet as much as I do!

Robin

Now 2 Autonomic Dysfunction Specialists in Northern CA

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Finally, there’s a neurologist who is an autonomic specialist in the Bay Area.  His name is Safwan Jaradeh, MD.  He’s at Stanford.  (Neurology appointment phone is 650-723-6469.  New patient appointment phone is 650-725-5792.  New patients will need a referral from a neurologist.)  He used to be at the Medical College of Wisconsin.  A patient’s family who saw him in WI wrote a very positive review of him on POTSplace (www.potsplace.com/physicians.htm).

The only other MD in the Bay Area who sees patients with autonomic dysfunction is a cardiologist named Karen Friday, MD.  She’s at Stanford (Cardiology) and the Palo Alto VA.  A couple of years ago one of our MSA group members was receiving inadequate treatment for OH (orthostatic hypotension) from a movement disorder specialist.  The group member took her husband to see Dr. Friday and was very impressed with the care received.  Also, someone wrote a positive review of her on POTSplace.

Years ago, someone told me:  “Many of the autonomic specialists are cardiologists rather than neurologists, because of the close association between the autonomic system and blood pressure.”

If any of you are dealing with or have dealt with SEVERE symptoms of orthostatic hypotension and you are receiving excellent care for these challenging symptoms from your neurologist, please let me know.  Thus far, I’ve only heard negative stories about neurologists and OH treatment.

Robin

PS. There are three directories of autonomic specialists in the US:

www.potsplace.com/physicians.htm
www.ndrf.org/physicia.htm
www.mc.vanderbilt.edu/gcrc/aas/AAS_referals_by_state.htm#CA

MDs know limits of treatment and the need to plan

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Some of us were talking at last night’s caregiver support group meeting about whether MDs, in general, seem in favor of or opposed to feeding tubes, and whether MDs will honestly answer a family’s question as to their advice as to what they’d do if their family member lost the ability to swallow.

There’s an article in last Saturday’s Wall Street Journal (wsj.com) about one person’s view of these matters.  The author, a retired physician, believes that doctors tend to choose less treatment at the end of life for themselves, and are reluctant to impose their “views on the vulnerable” when families ask “what would you do?”

Here’s an interesting statistic about CPR from the article:  “A study by Susan Diem and others of how CPR is portrayed on TV found that it was successful in 75% of the cases and that 67% of the TV patients went home. In reality, a 2010 study of more than 95,000 cases of CPR found that only 8% of patients survived for more than one month. Of these, only about 3% could lead a mostly normal life.”

Here’s a link to the article:  (there may be a charge to view the full article)

online.wsj.com/article/SB10001424052970203918304577243321242833962.html

Life & Culture
Why Doctors Die Differently
Careers in medicine have taught them the limits of treatment and the need to plan for the end
By Ken Murray
Wall Street Journal
February 25, 2012

It’s worth reading.

“Never too soon to talk about the future; it can be too late quite suddenly”

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Local support group member and volunteer Denise is reading the book How to Care for Aging Parents. She is offering occasional reports on the highlights of the book. She has read the first chapter, which is about starting the conversation about future care. Here are Denise’s take-aways, which are not specific to adult children talking with aging parents about the future.

Robin

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Denise’s Notes to

Chapter one – “Get Ready, Get Set”
of the book “How to Care for Aging Parents”
by Virginia Morris and Robert Butler
2004

“It is never too soon to talk about the future, although it can become too late quite suddenly.”

Wise words from the authors. Chapter one, ‘”Get Ready, Get Set,’” begins by addressing how hard it can be to get these conversations started with any family member.

If you’re having difficulty, they suggest several ways of coming at the topic indirectly. Try, for example: “There was an interesting article in the paper about in-home care. Have you thought about what kind of help you’d feel comfortable with or where you’d like to live?”

It’s usually necessary to revisit topics you’ve already discussed. It’s not worth arguing between you. If you are repeatedly unsuccessful, ask another family member or professional to speak with them. As frustrating as it is, sometimes a person is more willing to have that conversation with another of their offspring, a sibling or in-law, even someone outside the family like a doctor, lawyer, or clergy.

If you get them talking, remember it’s all about them. Understand that they have fears about growing old, feeble, incompetent, and being a burden. Don’t be judgmental or dismiss their hopes. Instead, find out where they see themselves living, how they want to handle daily life when they can no longer drive, cook, bathe or dress, and if they are okay with relocating. Try to get a picture of their expectations. Your ultimate goal is to make decisions they will feel comfortable with so transitions will be easier for them to accept and adapt to.

You won’t be able to cover everything in one go or finalize some arrangements until a crisis occurs. If you’re already facing a crisis and haven’t yet made arrangements, the authors do an excellent job of identifying local resources to put services in place. Of course, they would prefer you familiarize yourself with these ahead of time.

* Area Agency on Aging – Call the Eldercare Locator 800-677-1116 or www.eldercare.gov

* Local Senior Centers, Community Groups and Religious organizations (Jewish Family Services, United Way)

* Local Hospital Discharge Planner

* Employee Assistance Plan eldercare information and referral (check with your HR department)

* State Long-Term Care Ombudsman’s Office represents residents of nursing homes and their families

* Medicare’s web site and hotline 877-267-2323 or www.medicare.gov

* Foundations and Organizations for a particular disease

* Geriatric Care Manager to assess needs or take over care almost entirely

* 211 – Many states are establishing human service information lines contacted by dialing 211.

If you’’re wise enough to be talking ahead of time you are in a good position to purchase long term care insurance, get on wait lists for special services, nursing facilities or senior housing communities; file paperwork requiring lead time, like VA benefits; prepare wills, powers of attorney, advance directives; protect assets; sign HIPAA forms; choose a health care proxy; or remodel a home to prevent falls.

All that advance planning produces a mountain of paper. The authors have an extensive checklist of documents and information to gather and file where family members can lay hands on them easily. Someone should organize them and keep them that way – and it doesn’t have to be you! Enlist the help of anyone you trust with personal documents who has the inclination and ability.

The remainder of the chapter are practical tips for keeping track of someone else’s healthcare details. This is especially important for long-distance caregivers. With at least 1/3 of family caregivers at least an hour away (usually more), their special circumstances are specifically addressed. Amid the list of good advice there are several suggestions as to who might be enlisted to keep an eye on things, including neighbors or relatives living nearby; post office, gas and electric companies, and people who deliver home-bound meals are sometimes trained to watch for trouble at homes where elderly people live alone; even a bank manager who could call you if accounts are being drained or sitting idle (indicating bills are not being paid).

Primary of this practical advice is to have a back-up plan for the primary caregiver. Arrange for someone else to step in on short notice, for your parent to go to a senior center or adult day-care center, or for her to go to a senior residence for a temporary stay. Too many caregivers don’t have a Plan B and are caught in dire straights when life takes an unexpected turn.