Wednesday, March 3, 2010

Wasted Funds??

Another way we can stretch our health care resources is to do away with the funding of useless research. This morning I heard a news report about a study linking "purpose in life" and Alzheimer's. Out of curiosity I looked up what I could about the study. I googled one of the authors (Patricia Boyle) and found a significant number of statistical studies have been funded by NIH which investigate various psychosomatic risk factors. Could we find better medical uses for the the allocated funds? Is this information of any value? -Joel

[The following is from:]

Effect of a Purpose in Life on Risk of Incident Alzheimer Disease and Mild Cognitive Impairment in Community-Dwelling Older Persons

Patricia A. Boyle, PhD; Aron S. Buchman, MD; Lisa L. Barnes, PhD; David A. Bennett, MD

Arch Gen Psychiatry. 2010;67(3):304-310.

Context Emerging data suggest that psychological and experiential factors are associated with risk of Alzheimer disease (AD), but the association of purpose in life with incident AD is unknown.

Objective To test the hypothesis that greater purpose in life is associated with a reduced risk of AD.

Design Prospective, longitudinal epidemiologic study of aging.

Setting Senior housing facilities and residences across the greater Chicago metropolitan area.

Participants More than 900 community-dwelling older persons without dementia from the Rush Memory and Aging Project.

Main Outcome Measures Participants underwent baseline evaluations of purpose in life and up to 7 years of detailed annual follow-up clinical evaluations to document incident AD. In subsequent analyses, we examined the association of purpose in life with the precursor to AD, mild cognitive impairment (MCI), and the rate of change in cognitive function.

Results During up to 7 years of follow-up (mean, 4.0 years), 155 of 951 persons (16.3%) developed AD. In a proportional hazards model adjusted for age, sex, and education, greater purpose in life was associated with a substantially reduced risk of AD (hazard ratio, 0.48; 95% confidence interval, 0.33-0.69; P < .001). Thus, a person with a high score on the purpose in life measure (score = 4.2, 90th percentile) was approximately 2.4 times more likely to remain free of AD than was a person with a low score (score = 3.0, 10th percentile). This association did not vary along demographic lines and persisted after the addition of terms for depressive symptoms, neuroticism, social network size, and number of chronic medical conditions. In subsequent models, purpose in life also was associated with a reduced risk of MCI (hazard ratio, 0.71; 95% confidence interval, 0.53-0.95; P = .02) and a slower rate of cognitive decline (mean [SE] global cognition estimate, 0.03 [0.01], P < .01).

Conclusion Greater purpose in life is associated with a reduced risk of AD and MCI in community-dwelling older persons.

Author Affiliations: Rush Alzheimer's Disease Center (Drs Boyle, Buchman, Barnes, and Bennett) and Departments of Behavioral Sciences (Drs Boyle and Barnes) and Neurological Sciences (Drs Buchman, Barnes, and Bennett), Rush University Medical Center, Chicago, Illinois.


Ira Glickstein said...

Thanks Joel for this new Topic. When I saw it on the news today, I too questioned the value of the research. I wondered if the cause and effect were reversed. Perhaps people in senior housing who are at higher risk for developing Altzheimers but have not yet been hit with clear symptoms of mild cognitive impairment are already suffering from less obvious pre-Altzheimers that also causes them to have less "purpose in life"?

On the news program this morning, an expert said the best approach would be to find some way to prevent the amyloid protein deposits typically found in the brains of Altzheimers patients.

On the other hand, having watched my mother-in-law during her "long goodbye", I wish there were better preventative treatments for this terrible disease. If it turns out that simple mental exercises, such as doing crossword puzzles or playing board games or video games, or physical and mental exercises such as square dancing or water aerobics, improved outcomes, that would be of value. Perhaps those with high "purpose in life" are fighting Altzheimers more successfully due to their enriched daily mental and physical activities.

Ira Glickstein

PS: On a related note, I have posted another Google Knol, this one on How to Keep Your PASSION Alive -Even in Retirement. This one is based on my Blog Topic Motivation and PASSION that I wrote in reply to one of Joel's coments on this Blog.

Howard Pattee said...

There is no longer much doubt that mental and physical activity delay or decrease many types of dementia including Alzheimer. For example. see Pub Med.

Ira Glickstein said...

How do you know, Howard, if all these studies and papers have the direction of causality correct?

Perhaps older people who say they have "no purpose in life" or who have reduced their exercises or crossword puzzles or reading or posting to this Blog and so on, have already been affected by amyloid build up in their brains that are short of the level for diagnosis of Mild Cognitive Impairment?

Perhaps those who are still mentally and physically active in old age may be exactly those without much amyloid build-ups?

The build-up of amyloids in the brain takes place over many years. Thus a study that finds less active, less purposed people are 2.4 times more likely to be diagnosed with Altzheimers within 5 to 10 years than those who are active and purposed may be confusing cause and effect.

On the other hand, since those of us on the Blog are all physically and mentally active and highly purposed, I would like to think our interests are helping to ward off Altzheimers. Like chicken soup, activity might not help, but "it wouldn't hurt".

Ira Glickstein

joel said...

I checked the reference that Howard provided. It is basically a long list of research papers. I tried a few to see what they were about. For the most part they were statistical studies with all the faults that such studies have. There is a principle of law that bad evidence does not increase in value when you increase the quantity of it. Lets look at a typical abstract as shown below.

"Life style interventions to reduce the risk of dementia.
by Flicker L.

Dementia has often thought to be unavoidable and incurable. In recent years, risk factors, including lifestyle attributes, have been associated with the two commonest forms of dementia, Alzheimer's Disease and vascular dementia. There is also new evidence that the adult brain maintains plasticity and response to external stimuli. Beside considerable observational data of the effect of lifestyle factors there is now increasing empirical evidence that alterations in lifestyle factors may decrease an individual's risk of developing dementia. The evidence is strongest for increasing an individual's level of physical activity, followed by the cessation of smoking. These interventions carry few risks and have many additional health benefits, so can be recommended for most of the older population. Other interventions such as increasing social engagement, cognitive stimulation and homocysteine lowering vitamin supplements also appear promising, with considerable observational evidence supporting their uptake, although there is still a lack of empirical evidence for these interventions."

Note the caveat at the end that empirical evidence is lacking. Why report something that has no empirical evidence? Here's another abstract illustrating the meager value of statistical studies.

"Abstract The interpretation of bone mineral densitometry results for a particular individual relies on valid reference data from a representative population sample. To establish local reference data, 411 Australian female volunteers had bone mineral densitometry performed at a single medical centre at the proximal femur and lumbar spine using a Hologic QDR 1000-W dual-energy X-ray absorptiometer. These data were compared with reference material from North American women compiled by Hologic. The Australian volunteers had, on average, 7% greater bone mineral density at the lumbar spine for the age range 25–55 years. Possible explanations for this include an actual population difference or the presence of a differential selection bias between the two samples."

Note that the last line negates the value of the study (which must have cost a pretty penny). I think we can do better. As Ira pointed out, in the case of Altzheimers we have chemical measure (amyloids). That means that we can attack the problem directly without resorting to statistical guessing. Can we doubt, based upon the overwhelming evidence of the past, that when a cure for Altzeimer's arrives it will be in the form of a pill rather than a change in behavior? Ronald Reagan and Charlton Heston were very active, but Altzheimer's got them anyhow.

Ira Glickstein said...

I'd be interested to hear Howard's response to Joels's comments and mine.

Joel is correct on some of the limitations of statistical sampling. However, that does not make all such research "wasted funds". (Next time you go for a blood test, ask them to test ALL your blood, not just a small sample :^)

Yes, there are good examples of active people, like President Reagan, who get Altzheimer's, but their activity levels may have delayed it by many years. Yes, a treatment that prevents the deposit of amyloids or dissolves them would be the best cure, but we do not yet have it. Nor do we have tests to determine amyloid levels in living brains.

I would not stop spending on this type of research, but, I would take the findings with a grain of salt. On the other hand, if these studies encourage more activity programs in senior housing, and if the residents think that will reduce their risk of Altzheimer's, what is the harm?

Ira Glickstein

Howard Pattee said...

Ira wants my response to Joel’s and his comments.

I have served on many NSF, NASA, and NIH study sections that review grant applications in a few areas where I have considerable knowledge, and I know how difficult it is to determine if a proposal is, as Joel suggests, a “waste of money” or a possible breakthrough. Consequently, in areas where I am not an expert, spreading my opinion isn't worth much, especially on a blog. I prefer to listen to people who know the subject.

I do know that the study of the brain is undergoing a revolution because of a combination of gene sequencing and non-invasive imaging techniques like fMRI. Ira’s question of the causal direction in correlated events is recognized by all the experts as the main issue. Only clever experiments will resolve it. For example, read the popular article by Stephen Pinker in the NY Times.

It appears from the literature that cognitive reserve models are well-supported. They admit both strong genetic and environmental causality. That means you may be predisposed to loss of functions in your genes, but that “use it or lose it” is still the best strategy.

Howard Pattee said...

I just looked up "Cognitive reserve" on Wikipedia, and it gives a short summary of what it explains.

Ira Glickstein said...

Thanks Howard for the links and the Wiki suggestion - I read them all through.

Brain Reserve and Cognitive Reserve are interesting concepts. They may explain why people with larger brains and greater mental activity may achieve higher age before genetically-linked Altzheimer's strikes in a clinically-observable way. The extra processing capacity of their brains ("hardware") and their better developed mental agility ("software") seem to find work-arounds to the amyloid deposits and thus delay the behavioral symptoms of Altzheimer's. Interestingly, once those behavioral symptoms appear, the decline is more rapid.

If this is true, then pushing people in senior housing to do more mental and physical activities may extend the non-symptomatic years of those with genetic susceptability to Altzheimer's. Since those of us without a family history of Altzheimer's do not know our genetic susceptability (and Steven Pinker who had a full genome workup specifically ordered them not to tell him about the Altzheimer's part), our best bet is to keep up our physical and mental activities. That will likely give us more "purpose in life" and thereby delay the behavioral symptoms of Altzeimer's by X years if we happen to have genetic susceptability.

Like chicken soup - it may not help but it wouldn't hurt.

The Pinker piece in the NY Times Mag was excellent in indicating how research can sometimed untangle multiple interacting causes. I also liked it because it reinforced my belief that nature/nurture tilts at least 60/40in favor of the former (assuming that both the nature and nurture are in the "normal" range). It may actually be 70/30 for most of us.

Bottom line: Though the types of research Joel suggests are "wasted funds" are full of snares and limitations, it is probably well worth the money to continue that research.

Ira Glickstein

joel said...

Ira said: Joel is correct on some of the limitations of statistical sampling. However, that does not make all such research "wasted funds". (Next time you go for a blood test, ask them to test ALL your blood, not just a small sample :^)

Joel responds: Ira's ironic remark gives me a chance to clarify my views about population studies. The reason a drawn sample of blood accurately represents the whole is scientific. The body is what is called a "well-stirred reactor" in chemistry. The circulation of the blood causes stirring. In addition, the draw takes place over about 20 seconds which is of the order of the circulation time. Hence, we have good theoretical reason to believe that the chemistry of the sample is the average of all of the rest of the arterial blood in the system. We would expect variations at the entrance and exits of various organs like the lungs (change of oxygen and CO2 levels), kidneys (change in urea level), etc. But we draw from the veins where the blood is returning from the lower arm. But, the details are not important here. The main point is that we have a good scientific reason to believe our sample is representative, because we have an understanding of the mechanisms involved. This is a far cry from having no understanding of Altzheimers and making wild guesses about connections and then doing population studies to try to find a slim correlation between variables. If we have infinite resources, I don't really care how researchers entertain themselves. However, our resources are finite and we need to expend them in a sensible way to maximize the probability of success. Mental and physical exercise is not like chicken soup, which can be bad for you if you don't skim off the fat. We don't need expensive studies to tell us that moderate exercise of both mind and body is a good thing. That money can be better spent. On the other hand, public fear of aluminum intake from aluminum pots and pans or aluminum based antacids is worth dealing with and does not require population studies. As in other toxicity studies, animals can receive controlled does , etc. That's science.

Thanks to Howard for a link to Pinker's excellent article. I'll make some comments tomorrow, because I believe it supports my view (naturally) :^)