Is stress a risk factor for dementia?

Gosh, this is a hard one to study. I have to hand it to the people at Southampton University who have just announced this project funded by the Alzheimer’s Society. It is clearly a massively important topic. To look retrospectively at stress is challenging because we all remember past events in a rather filtered way, and if the participants’ memories are impaired, doubly so. To look at it prospectively involves very long time periods and large cohorts (although as the Whitehall II cohort ages, this becomes a possible source of longitudinal data with a specific focus on both biological and experiential stress markers).

What interests me most of all is confounding – the close relationship between stress, lifestyle and socio-economic (dis)advantage. How can we really tease them apart to get the true effect that stress has, independent of the others? There are tools in the box, such as multiple regression and propensity score analysis, but they depend on having quantitative measures of stress and all the other factors that we believe really represent the underlying factor for each individual.

How will this measure against Austin Bradford Hill’s considerations for finding cause-and-effect?

  1. Strength of effect – it may not be terribly strong, especially if there are stronger determinants such as smoking mixed up with it
  2. Consistency across studies – this is the first study, others will be needed to try to confirm it.
  3. Specificity – this is a problem because we are far from lab conditions, and looking at the many varied sources of stress, how people deal with it, and what happens to their cognitive function, although at a molecular biology level it might be possible to be quite specific
  4. Temporality – the cause has to happen before the effect; this one at least should be OK
  5. Dose-repsonse – if we believe the markers of stress provide numbers at least in the right ballpark, then this could be one of the big arguments in favour of a link
  6. A plausible mechanism of action, and…
  7. …coherence between lab and field data – there have been animal studies so this one is a possibility.
  8. Experiment – I don’t think that one is getting past the ethics committee any time soon!
  9. Analogy with other risk factors – if the stress effect is hormonal then people with pathological hormone imbalances might be a useful population, if it is an effect of neuron-environment interaction (harmful plasticity) then it is going to be much harder to tease apart from the confounders.

So, a mixed bag, but certainly worth trying out. I wish them luck, but I’m glad I’m not trying to crunch the numbers for them.


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