Cortisol, Cognition, and Brain Volume

In 2015 when I was first told that I had Alzheimer's disease, my care team advised me to make various lifestyle changes, including reducing stress.  Earlier this year, when my cognitive test scores were less than what we'd hoped for, my neuropsychologist and neurologist advised that I should reduce my commitments -- which I have done.  But why would that be important?

It's widely accepted that cortisol, the hormone that rises most prominently when we experience stress, attacks the hippocampus.  The hippocampus appears often to be the first part of the brain affected by Alzheimer's disease, and there have been efforts to correlate stress with Alzheimer's disease.  While stress may not cause Alzheimer's disease, there is certainly evidence that it aggravates the symptoms.  It likely also interferes with the healing that I've experienced through improved exercise, diet, sleep, and social connection.  It appears to do this by inhibiting neurogenesis -- the generation of new brain cells from stem cells.

Case in point -- a study published in the November 2018 issue of the journal Neurology correlated blood cortisol levels in younger and middle-aged adult Americans of European ancestry with cognitive test scores, brain volume, and other markers.  The study population excluded anyone with evidence of Alzheimer's disease.  The study found that "[h]igher serum cortisol was associated with lower brain volumes and impaired memory in asymptomatic younger to middle-aged adults, with the association being evident particularly in women."  (It did not attempt to correlate stress with the subsequent development of Alzheimer's disease.)  

In 2018, Scientific American carried a report on the study, which you can read here.  It featured an interview with one of the investigators.

The study used about 2,000 participants in the Framingham Heart Study, which has now been in progress since 1948.  To arrive at their conclusions, the investigators measured morning blood cortisol levels and then administered various tests of memory, abstract reasoning, visual perception, attention, and executive function. Test subjects also received brain MRIs to assess an array of physical parameters.  As near as I can tell, this was done one time.

What the investigators did not attempt to explain is why cortisol levels had a much greater impact on women than men.  For example, the brain volume associations occurred almost entirely in women.  Another uncontrolled variable was the nature of the lifestyles of the test subjects.  They were all people with the freedom to devote hours to the test, suggesting that their baseline stress levels may be consistent with each another and relatively low.  The question would then be whether they represented the general population.