The Last Battle

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rita hayworth

For every year since 1840, life expectancy in the Western world has lengthened by three months. Many more of us can look forward to a full retirement and, in the Commonwealth countries, a letter from the Queen on our 100th birthdays. It’s worth asking, though, whether large-scale longevity is worth pursuing if more than half of us will become demented before that century mark.

In The End of Memory: A Natural History of Aging and Alzheimer’s, released in Canada to coincide with Alzheimer’s Awareness Month (out September in the US), Jay Ingram sketches a biography of the disease and assesses where exactly we stand with the search for a cure. Depending on your outlook, the news is either thoroughly dispiriting – and be warned, cynicism is linked to dementia – or strangely uplifting. The latter because ephemeral attributes such as conscientiousness and erudition seem suddenly to become medical realities in this bizarre research field. Some people also appear to transcend the biology of the disease, dying with brains full of tangles and plaques, their cognition intact.

For the longest time, the disease identified by Alois Alzheimer in 1905 was what we think of as the “early onset” form, distinct from senile dementia, which itself was mostly dismissed as a normal part of aging – not inevitable, but par for the course. Public perception changed when actress Rita Hayworth died of Alzheimer’s at age 68, after several years of being dismissed as a drunk. Photos had appeared in the press of a scarecrow-like Hayworth, disoriented and distraught in Heathrow Airport. The latest surge in attention, of course, derives from the aging baby boomers, who will soon be elderly in record numbers and bring the authority of their purchasing power to bear on the problems of that life stage.

The predominant model of Alzheimer’s progression is called the amyloid cascade hypothesis. It starts at least a decade before symptoms with an excess of beta amyloid, as measured in the spinal fluid. The amyloid aggregates into senile plaques outside brain cells and then somehow triggers the release of tau (the strengthening agent in neuron membranes) from the cell walls. These tau molecules form neurofibrillary tangles inside the cells. Synapses, the points of communication between neurons, are destroyed and then the brain cells themselves die, and the process spreads through the brain in much the same way that prion diseases like Mad Cow Disease travel, following a characteristic path from the entorhinal cortex on through the memory centers, actually shrinking the brain.

A significant minority of researchers contest this model, given that beta amyloid plaques first congregate in the default areas of the brain – those most active during daydreaming – and then distribute themselves evenly, whereas tangle formation matches the progress of the brain’s destruction, cropping up wherever there has been brain damage. This has resulted in two research camps, says Ingram: Tauists versus BAptists. Both are likely important agents (particularly their precursors, as the plaques and tangles themselves may be tombstones of damage done), and it’s crucially important to understand the mechanisms better if we’re to select an appropriate target for treatment.

My imagination flares at every mention of longitudinal studies, those research projects that follow a set of subjects for decades of their lives. So I’m naturally drawn to the Nun Study that Ingram brings up in support of the idea of “cognitive reserve” an illusive ingredient that fends off the cognitive effects of Alzheimer’s. In the 1990s, a whopping 678 American nuns between 75 and 107 years of age agreed to cognitive testing for the rest of their lives and a brain autopsy afterward. The study is ongoing at the University of Kentucky, but I’ll skip to one of the most startling findings so far – a good predictor of which nuns would go on to develop Alzheimer’s disease was found in evidence collected decades before any age-related decline: the essays they had written at age 20.

In 1930, the School Sisters of Notre Dame began to require novices to write a short piece about their life and calling. Of the nuns who went on to develop Alzheimer’s, 90% had written essays that scored low when analyzed for “idea density” – an average of 3.86 ideas per ten words, compared with an average of 4.78 in those who remained without dementia. Only 13% of the healthy elderly nuns had scored low in idea density as young women. Another protective factor was the degree of positive emotion in their essay. In the general population, education, conscientiousness and a challenging job are all correlated with lower risk of Alzheimer’s symptoms.

The only effective treatments so far are unrelated to slowing the disease’s progression. They prop up failing neurotransmitters for a few months by recycling what the brain produces, but once the supply runs dry the medication loses all effect. We’re many years away from a long-term treatment, because we simply don’t understand what’s going on at the root of it all. Pharma seems stuck on the idea of plaque-busting, even though results have been dispiriting. Some promising interventions include deep brain stimulation and precisely-timed estrogen replacement.

Ingram points to a branch of research that calls Alzheimer’s “Type 3 diabetes” because of its glucose metabolism malfunction in the brain. In fact, though various dietary theories on the disease (danger from aluminum, benefits from turmeric) have petered out through conflicting results, Alzheimer’s risk increases with every increment of ones glucose consumption. That, vegetables and exercise seem to be our best bets for avoiding the fate ourselves, though some of us will be the victims of our genes no matter our lifestyle.

The current diagnosis is called “suspected Alzheimer’s” – only an autopsy can properly label the disease – but new diagnostic tools include everything from a combination of twenty biomarkers to the loss of our left nostril’s ability to smell peanut butter. In the years when we still pick up that nutty aroma, we’d be well advised to follow the lead of Sister Mary, a lively centenarian from the Nun Study with an atrophied brain yet intact cognition. Her biology-defying philosophy: “I only retire at night.”

 

Image: Rita Hayworth in the trailer for Gilda (via Wikimedia Commons)

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