As if to shoot down my emerging optimism about diet and lifestyle changes as prevention strategies for Alzheimer's disease, a comprehensive analysis by an independent government panel has found there is not enough scientific evidence to support these strategies. The study, published in the June 14, 2010 issue of the Annals of Internal Medicine, summarized results from 165 scientific papers published from 1984-2009.

The good news is that the study supported the view that smoking, diabetes, depression, and metabolic syndrome are all associated with an increased risk of Alzheimer's disease,  while lifestyle changes such as eating a Mediterranean diet, exercising, and fostering extensive social relationships are linked to a lower risk. But the bad news is that none of these relationships are particularly robust. The authors conclude that better designed and lengthier studies need to be done, and that "the current literature does not provide adequate evidence to make recommendations for interventions."

My feeling is that since we can't control our age and our family history, it certainly doesn't hurt to improve our diets and lifestyles, and as better studies are conducted we will hopefully find that our efforts have paid off in the long term.

This past Wednesday's New York Times had a fascinating and lengthy page one article on a new study that will examine whether treating young people without symptoms but with a genetic mutation predisposing them to Alzheimer's disease can delay or prevent the onset of dementia.

Most of the family members come from one Andes region of Columbia, Antioquia. Over three centuries, many in this lineage of 5,000 people have inherited a single genetic mutation guaranteeing that they will develop Alzheimer's. The mutation is an altered protein on the presenilin 1 gene on chromosome 14. Mutations on three genes have been linked to familial, early-onset Alzheimer's disease. These genes have been labeled PS1, PS2 and APP by researchers. Although home genetic testing for Alzheimer's and other diseases has recently been in the news, it is the people at high risk of the familial, early-onset Alzheimer's disease who really are appropriate for genetic testing and counseling.

The study itself is intriguing on many levels. First of all, it involves families where often the elderly parent is the caregiver for her children suffering from Alzheimer's disease in their 40's. An 82 year old mother of 4 children afflicted with Alzheimer's describes the horror: "I wouldn't wish this on a rabid dog. It is the most terrifying illness on the face of the earth." Secondly, it will involve treating patients who don't yet have any symptoms. As one of the researchers states: "The nightmare scenario is obviously that there is a serious side effect." Finally, only recently has an area of Columbia near Medellin, a former murder capital of the world, been safe enough for such research to be conducted.

In another blow to past optimism about remedies for memory loss and Alzheimer's disease, a large randomized trial recently published found no improvement in slowing cognitive decline in older adults receiving gingko biloba compared with people receiving placebo. Gingko is one of the oldest living tree species, and the extract of its leaves is one of the most popular medicinal herbs in North America.

Of the many reasons people use gingko, several relate to memory and Alzheimer's disease: improving mental function, preventing age-related memory decline, and slowing or preventing Alzheimer's disease. The recent study, known as the Gingko Evaluation of Memory study, was published in the December 23, 2009 Journal of the American Medical Association. Conducted by researchers at six academic medical centers in the U.S., it tracked over 3000 community-dwelling subjects ages 72-96 and followed them for an average of 6 years. Cognition was measured with several standard assessment tools, and included aspects of memory, attention, visuo-spatial construction, language, and executive functions.

There now appears to be ample evidence that gingko biloba is not effective in either preventing dementia or slowing the rate of decline in older adults without dementia. These results add to other recent disappointments in dementia interventions, including statins, NSAIDS (non-steroidal anti-inflammatory drugs), and estrogen. At least for the immediate future, focusing on exercise, diet, and other lifestyle changes appear to be the way to go.

The theme of a recent blog post here, the growing number of people with Alzheimer's disease , has another dark side: namely, the equally worrisome increase in antipsychotic medication use. Despite my belief that when used appropriately and judiciously these medications may be beneficial and even outweigh their risks, I have to admit the problem has spiraled out of control. In 2007 nearly one in three nursing home residents in the U.S. received an antipsychotic drug, the highest reported level of use in more than a decade. A large 2006 study involving over 16,000 patients showed that 41% of nursing home residents with dementia but no psychosis received antipsychotics, despite the FDA's black box warning issued in 2005 that these drugs are associated with excess mortality in elderly patients with dementia.

Of course, the reasons for the increase are obvious: behavioral problems in dementia are challenging to manage, and most nursing homes have too few staff with training and education in managing agitation and aggression without medications. Many nursing homes have a culture of medicating problems rather than getting to the bottom of them, despite growing evidence that behavior management strategies work. Symptoms such as wandering, repetitive verbalizations, and resistance to personal care should rarely if ever be treated with antipsychotics.