Alzheimer's and Anesthesia

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I've seen many caregivers worried about the potential effects of anesthesia if their loved ones who have dementia must undergo surgery. I looked into this issue in great detail when a friend who has FTD was facing the need for knee replacement surgery.

First, let me say that I had been under the impression that the idea that anesthesia could cause dementia was fairly new and that few studies had been done. THIS IS NOT TRUE. Researchers have been studying this possibility for more than 50 years.

The only type of *surgery* that has been shown to cause dementia or make it worse is major cardiac surgery. However, this is probably due to the adverse effects of cardiopulmonary bypass on the brain, not to anesthesia. I did not include studies on cardiac surgery in this blog, but I will address them in a future blog.


A *short-term* decline in cognitive function is relatively common in elderly patients after major surgery -- and likely to cause the caregiver to panic! For example, in a large study of 225 patients ≥ 65 years of age undergoing non-cardiac surgery, 15% had "post-operative cognitive dysfunction (POCD)" in the two days following surgery.

However, POCD usually resolves within a few days or weeks. The risk of long-term cognitive dysfunction from non-cardiac surgery is relatively low. For example, in a large study involving 262 elderly patients who underwent total knee replacement, only ~5% had any decrease in cognitive function (compared to each patient's own pre-surgery baseline) six months after surgery.

Does the type of anesthesia used during surgery affect the risk of developing long-term (lasting 3 to 6 months) POCD? No. In the study above, the frequency of POCD at six months post-surgery was the same in patients who received general anesthesia as those who received regional anesthesia (~5%). Studies on other types of major non-cardiac surgery have come to the same conclusion: for example, an extensive review of the literature, performed in 2006, covering 16 trials which involved a total of 2,708 patients, did not find any significant difference in the incidence of POCD when general anesthesia and local anesthesia were compared.

In fact, many researchers believe that there are no "permanent" effects on cognitive function (i.e., lasting more than a year), from any type of non-cardiac surgery or anesthesia. Most studies that *appeared* to find a long-term effect failed to take into account the effect of aging, itself, on the patient. When studies were designed to compare surgery patients with matching non-surgery controls, both types of patients had the same level of cognitive decline 1-2 years later.

Other studies that appeared to find a link between anesthesia and cognitive decline failed to consider other risk factors associated with surgery and/or just the hospital environment itself. Some of these *actual* risk factors -- including certain pre- and post-operation medicines -- can be avoided, or their impact minimized. For a more detailed discussion on these, see below.

Nevertheless, there is still a lingering concern that the anticholinergic, pro-inflammatory and pro-amyloidogenic impact of anesthesia and/or surgery itself may have an impact on the dementia process. Alzheimer's is associated with a loss of cholinergic neurons; and the central cholinergic system is involved in the action of general anesthesia agents. From this point of view, patients with Alzheimers represent a particular case in which the choice of anesthesia drugs might be expected to have a negative effect on the postoperative outcome. There is also concern that individuals with vascular dementia or microvascular lesions associated with Alzheimer's disease may be at risk from reduced regional oxygen saturation.

Caregivers might therefore be concerned about the recent studies done with cell cultures and animals exposed to isoflurane. Cell culture and animal studies are *not* reliable indicators of what might happen in humans. Still, the cell culture studies found that isoflurane triggered death in some cells, causing a build up of beta-amyloid, and increasing the harmful clumping (oligomerization) of beta-amyloid. Desflurane did not contribute to cell death or the production of amyloid-beta protein in brain cell cultures unless it was combined with low oxygen conditions, and might appear to be a better choice. Other scientists point out that studies on isolated cell types are of questionable value; and that these particular studies did not use normal cells.

Researchers at University of Pennsylvania's School of Medicine have discovered that common anesthetics that are delivered by inhalation increase the number of amyloid plaques in the brains of middle-aged mice. However, mice do not naturally develop Alzheimer's, so the animals used in these tests had to be genetically engineered to produce the human protein amyloid beta. The mice were exposed to the anesthetics for two hours per day over a total of five days. Compared to controls, the anesthesia did *not* appear to worsen cognitive ability, which was already considerably compromised at this age, although it did accelerate amyloid beta aggregation and the appearance of plaques. And the HBO "The Alzheimer's Project" notes that aged human brains can have lots of plaques and tangles, without the person showing any signs of dementia. Ergo, the relevance of these mouse studies is questionable.

Moreover, isoflurane has had a long history of safety in all ages of patients, from premature babies to octogenarians. And a 2007 review of the data on knee and hip surgery done on 36,025 patients over 90 years of age, and on 687 patients over 100 years of age, showed that even patients this old could benefit from major surgery, with significantly improved quality of life, despite the very high prevalence of moderate to severe pre-operative cognitive impairment.


If the type of anesthesia used during surgery apparently does not affect the likelihood of developing or exacerbating cognitive decline, even short-term, are there any known risk factors that do? Yes -- and many of them can be avoided, or their effects minimized. For example:

>> Talk with the surgeon, the anesthesiologist, and the doctor who will monitor post-op recovery. Make sure they understand your loved one has Alzheimer's, and that anticholinergic drugs should be avoided. Diazepam should not be used as a pre-operation medicine. Benzodiazepines and meperidine should not be used for pain control after the surgery.

>> Dehydration is a risk factor for developing all sorts of health problems, including delirium and POCD, so do what you can to ensure that your loved one has plenty of liquids while in the hospital -- before and after surgery.

>> There was a recent report that surgery (either the stress of the surgery or the effect of the anesthetics on liver metabolism) could affect thyroid function. Make sure that the medical team keeps an eye on post-surgery thyroid hormone and vitamin B12 levels.

>> If at all possible, avoid the use of physical restraints, and the use of bladder catheters.

>> Many elderly patients -- even those without dementia -- go into a decline simply because the hospital environment confuses, tires, and upsets them. Factors such as sleep deprivation, immobility, sensory overloading (too much noise and confusion, too many bright lights at night) and lack of a home environment have been linked with delirium, which is a risk factor for POCD.

* Some studies have found that pre-surgery psychiatric counseling can help.

* Family members can help by making sure that a loved one is not left alone for long periods, especially when coming out of anesthesia. If possible, arrange to stay overnight at the hospital -- this way, someone who knows how the patient normally acts can quickly alert hospital staff to any changes in behavior.

* Some hospitals will arrange for sitters to stay with the Alzheimer's patient at times when family members can't be there. If that type of service isn't available, see if you can arrange for a private aide to come in.

* After the surgery, the entire medical team and family should make sure that patients are kept oriented and hydrated, that they are up and walking as soon as possible, and that they avoid the use of sleep medications.

* Sleep deprivation can be a serious problem in a hospital. Making sure that the hospital room is well lit and that curtains are open during the day, and that the room is dark at night, can help patients maintain a sense of time, and get back to a regular schedule of sleeping at night and staying awake during the day. Give the patient a warm drink (milk or herbal tea), relaxation tapes or music, and back massage at bedtime. Ask the nursing staff to make adjustments to the patient's schedule to allow regular, uninterrupted periods of sleep (e.g., reschedule medications and procedures if necessary).

* If your loved one needs eyeglasses and hearing aids, make sure they are worn.

* Use techniques that help orient the patient and keep the patient mentally stimulated. For example, use a bulletin board or white board with the names of care-team members and the day's schedule. Hospital staff and family should talk with the patient to help the patient remember where s/he is and why. (The greater the level of dementia, the more often this should be done.) In addition, staff and/or family should engage the patient in cognitively stimulating activities (e.g., discussion of current events, structured reminiscence, word games, maybe a sing-along -- whatever your loved one can do), preferably two or three times a day.

* Familiar objects from home such as a favorite sweater, blanket, pillow, books, or family photos can help patients maintain orientation and awareness while they are in the hospital.

In other words, if the doctors, nurses, and family all work together to help your loved one understand where s/he is and what is going on, keep your loved one mentally active during the day, help your loved one sleep at night, and avoid noise and confusing bustle and activity, your loved one will have far less risk of developing problems.

>> If the surgery involves something like knee or hip replacement, a good rehabilitation program can also help. This includes twice daily physiotherapy and daily activities, more intense nursing care (which could be provided by family), and common rehabilitation interventions such as occupational therapy and speech therapy.



The National Institutes of Health has published an excellent little booklet, called "Hospitalization Plans - A Guide to Hospital Visits for Individuals with Memory Loss", which you can download for free at:

http://www.nia.nih.gov/Alzheimers/Publications/happens.htm