It's stressful, worrying about dementia

Remember the big news just a few months ago about the declining incidence of dementia?  There was a story in the New York Times, and many other sites, about a couple of papers in The Lancet (papers here and here.)  We blogged about it at the time.  Gina Kolata in the NYT said this:

A new study has found that dementia rates among people 65 and older in England and Wales have plummeted by 25 percent over the past two decades, to 6.2 percent from 8.3 percent, a trend that researchers say is probably occurring across developed countries and that could have major social and economic implications for families and societies. 

Another recent study, conducted in Denmark, found that people in their 90s who were given a standard test of mental ability in 2010 scored substantially better than people who had reached their 90s a decade earlier. Nearly one-quarter of those assessed in 2010 scored at the highest level, a rate twice that of those tested in 1998. The percentage of subjects severely impaired fell to 17 percent from 22 percent.

Er, but now a study published in BMJ Open this week reports that the more stress women experience in middle age, the higher their risk of dementia as they get older.  This was a prospective study of 800 Swedish women born in 1914, 1918, 1922 and 1930, who underwent a psychiatric examination in 1968, and who were re-examined in 1974, 1980, 1992, 2000 and 2005. They were asked whether they had undergone any of 18 major stressors, including divorce, widowhood, work-related stress and illness of a relative.

Anonymous German picture puzzle, 19th C; source

In the 37 years of follow-up, 19.1% or 153 women developed dementia (425 of the subjects had died over the course of the study), and number of stressors was found to be associated with risk.  And, importantly, risk and number of psychosocial stressors was "independent of long-standing perceived distress." 

Our study shows that common psychosocial stressors may have severe and long-standing physiological and psychological consequences. However, more studies are needed to confirm these results and investigate whether more interventions such as stress management and behavioural therapy should be initiated in individuals who have experienced psychosocial stressors.

What's the mechanism?  The idea is that long-standing exposure to stress hormones may cause "dysregulation in neuroendocrine systems".   But the researchers don't find a one-to-one correlation between stress in midlife and dementia -- that is, not everyone who reported stress became demented and not everyone with dementia had reported major stresses.  The investigators suggest that that is because individuals respond differently to stress.

Well, that's a bit hand-wavy.  Of course, it's always difficult, or even impossible, to apply associations found at the population level to individuals.  Not everyone with high cholesterol levels has a heart attack, and not everyone with high stress will become demented, even if cholesterol and stress are real risk factors.  It means that there are other, unmeasured risk factors involved, that the effect of stress or cholesterol depends on or interacts with unknown variables. So, of course more research is needed (she said snidely).  Or... a different approach to understanding causation. 

But, let's go back to the Lancet papers of July, that reported that incidence of dementia is going down.  Yes, that's on a population level, and it's possible that everyone with dementia in these studies (samples in Denmark, England and Wales) experienced more stress in midlife than those without.   But, if stress is a strong risk factor for dementia, and we were to accept that rates of dementia are really going down, then this would mean that levels of stress in midlife are declining as well.  That is, by the measures in the BMJ Open study, less work-related stress, less divorce, less family illness and fewer parents dying.  Not likely.

Now, it's possible that the younger cohorts in the Swedish study will or did experience less dementia than those born earlier, as in the Danish and British studies, but that question wasn't asked of the data, and anyway the sample size is too small to show a reliable effect if it's stratified by birth cohort.  So, we don't know if incidence of dementia is falling in Sweden as it seems to be elsewhere.  But if it is, that means, to us at least, that something is overriding the effect of stress as a risk factor. 

Do we know more now than we did last year about predicting who'll get dementia in old age?  Another way to put this is: will we know more in 6 months than we do now?  And yet another way is: at what point should we start believing any of these stories?  More generally, is there a better way to understand causation?  At present, for whatever reason, we seem to be doing little more than groping for a black cat in the dark.