Field of Science

Miles to go before...

A New York Times article describes a study conducted by the NIH that basically asked scientists to simply sift through the massive evidence of the past twenty years to answer one question; what factors can cause or prevent Alzheimer's disease? The answer is unsurprisingly depressing- there is basically no proven therapy, personal habit, dietary supplement or mental task that correlates with the prevention of AD. AD is still as much a disease without a cure or preventative remedy as it ever was. We have almost as much work to do as Alois Alzheimer would have in 1908.

The bad news about AD has just kept on coming in over the last few years. Part of the reason is the very disappointing verdict on the role of beta-amyloid, reached after dozens of clinical trials which targeted the clump of protein in AD brains and failed to reverse the debilitating effects of the disease. Along with these studies, there has been a panoply of articles suggesting everything from crossword puzzle solving to Gingko biloba extracts that could possibly prevent the disease.

But as the NYT article reports, most of these recommendations are based on faulty 'studies' which are typically called "observational" studies. These studies are essentially accounts of observations made after someone has started on a measure that's assumed to be preventative. In addition, most of these observations are self-reported. Thus, evidence from such observations is spotty at best and is a far cry from the double-blind controlled clinical trials required to establish efficacy. After sifting through the evidence, the NIH study group concluded that they were sure only about one measure- Gingko biloba. And here the verdict was that Gingko biloba does not prevent AD. Apart from this, most other factors touted as preventive measures- including cognitive stimulation, vitamin E and antioxidants- could not be correlated with decreased incidence of AD with any degree of certainty. There's just no good evidence.

Part of the problem is simply the amount of time patients enrolled in trials would have to be observed in order to draw any conclusion about prevention. AD typically emerges around age 50, but its effects become apparent only in the late 60s and early 70s. A true clinical trial to study prevention would probably have to start during the young years and subjects would have to be followed for at least two to three decades, an expensive and complicated endeavor.

Yet the reports cited in the NYT should not be as depressing as they appear. For one thing, many people now think that the real reason none of the therapies for AD are working is simply because they are administered too late. Two new promising studies based on PET scans and spinal taps could make it easier to detect AD earlier and start treatment immediately. Plus, it's precisely the fragmented nature of the reported observations that provides opportunity for studying them further. Also, as depressing as the amyloid-targeting trials were, at least they provide good evidence of something that does not seem to be working. In science, the misses are almost as important as the hits. Finally, it's not like long-term studies cannot be attempted; the famous Framingham study followed the inhabitants of a small Massachusetts town not just over years but over generations to establish the connection between high cholesterol and heart disease. Perhaps a Framingham-style study for Alzheimer's is due.

Until these deep questions are resolved though, AD patients and their families will keep on living their private version of hell and will keep on trying to stave off the terrible malady by trying anything that remotely seems to work. The least we can all do is keep on searching.

1 comment:

  1. There is some evidence that higher cognitive abilities in the 20s is protective. The following is certainly a long term study.

    [ J. Am. Med. Assoc. vol. 275 pp. 528 - 532 '96 ] 93 Nuns ages 75 - 95 were studied. All had written an autobiographical essay at age 22 to get into the order. 14 died and some had Alzheimer's disease. Those with low idea density and low grammatical complexity in their autobiographies had the neuropathology of Alzheimer's disease, while those with high idea density were free of Alzheimer's disease. Of the living 79 patients the smart ones at age 22 remained smart (for the most part) at 75+, while the less intellectually gifted ones stayed the same. All of these women were college educated and were teachers for most of their lives. Thus the study wasn't confounded by education or occupation. The sociology of the sisters prior to entry was the same.

    However, all sorts of smart people have died of it -- Claude Shannon for one. A fascinating example of someone with high intelligence of another type is Willem de Kooning, who continued to paint as he declined from the disease. The esthetic value of these later paintings is under considerable debate. I'll have to ask more prospective daughter in law, who writes (anonymous) gallery reviews for the New Yorker.

    Closer to home is a college classmate, former president of a county medical society (the county has a population of 350,000), and the late husband of a violinist friend of mine, who was a biology professor. Both women think the cognitive decline started at least 10 - 15 years before the end (or the present in the case of my classmate).

    So the best advice I can give is that of my late centenarian father, who, when asked for the secret of his long (and quite healthy) life said "I chose my parents carefully".



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