This week will in all likelihood be an important one historically in the world of Alzheimer's Disease. As I pointed out in a September blog post, the realization that in Alzheimer's disease damage to the brain begins years or even decades before symptoms begin to show themselves has led to the first major changes in how Alzheimer's is diagnosed in 27 years. On April 16 the documents describing these new criteria were made public, published in the journal Alzheimer's and Dementia.

The key differences between how Alzheimer's disease has been diagnosed since 1984 and how it will be diagnosed going forward reflect much of what's been learned since then. First of all, it's now well known that some people may have many amyloid plaques in their brain, but no symptoms of illness. Second, the fact that people often have mixed  dementias (Alzheimer's, vascular disease, Lewy Body disease) has only recently become widely appreciated. And third, five widely studied biomarkers of Alzheimer's disease are now formally incorporated into the new diagnostic criteria.

Although some of the new criteria, like the use of these biomarkers, have caveats that for now they are "recommended for research use only," they are still sending a critical message. As one of the authors of the guidelines and director of the National Institute on Aging's Alzheimer's Disease Centers Program, Creighton Phelps, put it in the New York Times' article today, "We're redefining Alzheimer's disease and looking at this in a different way than had ever been done. I think we're going to start to identify it earlier and earlier."

One promising avenue disclosed today that I had been unaware of is the fact that a bill was introduced in Congress this month that would create specific Medicare billing codes for Alzheimer's diagnosis, including discussions between providers and caregivers. Since much of what I have heard from readers, patients and caregivers reflects the frustration they feel when it comes to communication with their doctors, I think this is a very welcome development. Hopefully it is also a sign that even though we don't yet have effective treatments for most people with Alzheimer's disease, getting people with preclinical disease and mild cognitive impairment into research studies will expedite the drug development process.

Of all the Alzheimer's drugs currently approved by the FDA, memantine is the only one that is in a class of drugs called NMDA receptor antagonists, drugs which act to regulate the brain chemical glutamate. The others (Aricept, Exelon, and Razadyne) are all cholinesterase inhibitors, which act to increase levels of acetylcholine in the brain. Memantine (trade name Namenda) is approved for use in patients with moderate to severe Alzheimer's disease, but many doctors also prescribe it "off-label" for use in people with only mild or mild-moderate disease. One way researchers and clinicians characterize disease severity in this way is by scores on the Mini-Mental State Exam, or MMSE.

But in an article published April 11 in the on-line edition of the Archives of Neurology , Lon Schneider, MD and colleagues found that in fact evidence is lacking for a benefit of memantine in mild Alzheimer's disease. The study, done as a meta-analysis, synthesized data from three trials of memantine that included 431 patients with mild Alzheimer's (MMSE scores of 20-23) and 697 patients with moderate Alzheimer's (MMSE scores of 10-19). The memantine patients with mild Alzheimer's did no better than placebo on any of the measures looked at, including cognition, daily functioning, and behaviors. As far as the patients with moderate Alzheimer's,  there were small but significant improvements over placebo in measures of cognition and caregiver impressions of improvement.

In my view this study merely confirms what most of us who treat patients see in our practices: memantine is potentially helpful for some patients with moderate and moderate-severe Alzheimer's disease, but it is by no means a "miracle drug." It continues to be most important to identify and treat patients as early as possible, before most of the damage in the brain is done.

After a few weeks without a front page story about Alzheimer's disease, the New York Times was back with an important one today. The piece described two large studies which analyzed the genes of over 50,000 people in the United States and Europe. The discoveries double the number of genes known to be involved in Alzheimer's from 5 to 10, and shed new light on contributing factors such as cholesterol, inflammation, and the concept of innate immunity.

While having the newly discovered genes don't seem to increase a person's risk of developing Alzheimer's nearly as much having one or two copies of  the APOE 4 gene, they are likely to be very helpful in understanding the disease and hopefully developing therapies.

One of the most fascinating aspects of the article was the reference to the genetic study done by American researchers (the second study was done by British, French and others). In the American study, which was funded by the National Institutes of Health and involved 44 universities and research institutes, "nearly every Alzheimer's center and Alzheimer's geneticist in the country cooperated." This cooperation, in a highly competitive field where researchers were used to "jealously guarding their data," enabled data to be gathered on over 50,000 people, which was absolutely essential in concluding that these newly discovered genes were truly associated with Alzheimer's disease.

Now the two groups of researchers will be combining their data in search of more information, which will hopefully yield even more useful information in the coming months.

The relationship between depression and dementia has never been completely understood, although clearly depression has become more and more accepted as a risk factor for Alzheimer's disease. What hasn't been clear is whether having depression actually worsens cognitive decline in people with dementia.
A recent study, just published in the April 2011 American Journal of Geriatric Psychiatry, sheds more light on this interesting relationship. In a study of over 300 elderly nursing home residents, cognitive decline was measured over 36 months using the Mini-Mental State Examination (MMSE), a commonly used dementia screening test. The findings were most interesting. Those residents who had both dementia and depression showed a much steeper cognitive decline than those suffering from dementia alone. Since other variables like age, gender, and level of education were factored in, the authors concluded that "in dementia, the presence of depression correlates to accelerated cognitive decline beyond gender and level of education, suggesting a unique influence of depression on the rate of cognitive decline in dementia."

This finding certainly makes sense to me and others who treat dementia in nursing homes, since having depression in and of itself poses a large burden to one's overall health and well-being.