There is more to life than increasing its speed.
Mahatma Gandhi, attributed
IN HIS TRAILBLAZING work The Stress of Life, published in 1956, endocrinologist Hans Selye explained how stressful experiences can make us sick. Before Selye, the notion that stress could influence our biology was practically unheard of. Today, we’re all too familiar with the toll modern-life stress exerts on our health. Depression and anxiety, headaches, insomnia, heart disease: the evidence linking them to stress is overwhelming. Whether stress also contributes to Alzheimer’s isn’t as clear-cut, but once scattered and now mounting reports are giving weight to the idea.
Superficially it makes sense. The brain is the main organ controlling how we cope with stressful experiences, and all stresses lead to some kind of change in neuronal circuitry. In the short term these changes are good: they promote resilience, personal growth and learning. In the long term, however, when a person is repeatedly exposed to stress, they lead to neuronal wear and tear. And I mean that literally: animal studies show that repeated stress exposure shrinks neuronal dendrites, strips synapses, and even stunts the brain’s ability to grow new neurons.1
Human brain imaging mirrors this sorry state. People with low social standing–that is, how a person ranks themselves within society–who report chronic stress have less grey matter in their prefrontal cortex.2 There’s even a report suggesting that three years after the 9/11 terrorist attacks, people who lived closer to the disaster had less grey matter in their hippocampus–the part of the brain that controls memory.3
Of course, the dimensions of human life are complex and multifarious. And the behavioural responses often associated with stress–diet, smoking, drinking, et cetera–make for a tangled web of cause and effect. That said, the evidence connecting stress to Alzheimer’s is growing, not fading. Indeed, veterans who suffer post-traumatic stress disorder (PTSD) are nearly twice as likely to succumb to dementia, mostly as a result of Alzheimer’s.4 And Alzheimer’s patients with higher levels of the stress hormone cortisol actually deteriorate faster.5
In the early 2000s a neuropsychologist named Robert S. Wilson at the Rush Alzheimer’s Disease Center in Chicago devised a study to explore the link further. Wilson interviewed over 6,000 elderly volunteers from south Chicago using what psychologists call the ‘neuroticism scale’, a test where people are asked to rate their level of agreement on a five-point scale: ‘strongly disagree’, ‘disagree’, ‘neutral’, ‘agree’, ‘strongly agree’. He then asked them to score a series of statements related to stress, such as, ‘I am not a worrier’, ‘I often feel tense and jittery’, ‘I often get angry at the way people treat me’, ‘I often feel helpless and want someone else to solve my problems’. At the same time, Wilson assessed the participants using a battery of cognitive and memory tests.
Three years later he repeated the test on the same volunteers (bar the small proportion who had died), and three years after that began fishing for statistical evidence linking stress proneness to Alzheimer’s risk.
The connection checked out. Of the 170 people who eventually developed Alzheimer’s, the vast majority scored highest on the neuroticism scale. The data suggested that a stress-prone person is 2.4 times more at risk.6 This finding was significant even after accounting for age, sex, race, education, medical history and possession of the APOE4 gene. When Wilson carried out another similar study a few years later, the result was the same, only the odds rose to 2.7 times higher risk.7 But how stress increases the risk of Alzheimer’s remains a mystery.
In an attempt to demystify the link, researchers at the University of California, Irvine, led by behaviour expert Frank LaFerla, took mice and concocted a method to stress them out in a human, ‘lifelike’ way. LaFerla argued that early attempts to understand stress in Alzheimer’s had failed because they’d looked at its effect over short time periods–minutes–or extremely long periods–days and weeks. This doesn’t really reflect the reality of stress for humans, he said. So his team sought to ‘mimic a short-term modern-life stressful experience, such as in car accidents and shooting events, which often last for hours rather than minutes or days/weeks’.8
LaFerla also pointed out that stress doesn’t just arise psychologically; it’s the result of physical trauma as well. He therefore wanted to stress the mice mentally and physically simultaneously. To do this, the mice were confined to small spaces and put on fast-moving platforms, all the while exposed to loud noise in a brightly lit room for five hours. Though these kinds of experiments do not sit well with me ethically, they have proved to be somewhat informative.
LaFerla’s researchers then looked in the animals’ brains. As expected, the mice’s dendrites and synapses had shrunk compared to non-stressed mice. Unexpectedly, however, the stress also raised beta-amyloid levels and caused severe memory impairments that lasted up to eight hours. Translating those findings to the human world, LaFerla’s team suggested that day-to-day stressful experiences–especially ones lasting several hours or more–might somehow accelerate Alzheimer’s or at the very least worsen the disease in its early stages.
Over half a century ago Hans Selye wrote:
Such expressions as, ‘This work gives me a headache’ or ‘drives me crazy’, grow out of experience… but there are imperceptible transitions [italics mine] between the healthy, the slightly disturbed, and the insane personality… it is often the stress of adjustments to life under difficult circumstances that causes a change from healthy to disturbed, or from disturbed to insane.9
No doubt his choice of words is outdated. But the idea, for mental health and now Alzheimer’s, perhaps resonates today more than ever: in our ceaseless endeavour to do and be more, we unconsciously integrate stress into the fabric of our everyday lives; we grant it acceptance and allow it to accrue; we forget that there are events in life where stress really is unavoidable (losing a job, getting a divorce, the death of a spouse). It’s critical, therefore, to recognise when stress is avoidable and do our best to control it–because Alzheimer’s is born of imperceptible transitions.