Many of us have seen an elder in the family or amongst relatives losing their minds. And we fear it might happen to us too as we age. As expected, a whole industry has grown up to feed on that fear. In this superb piece, physician William Meller uses the stories of two famous actors to lay out what dementia is and what it is not, what medicine can and cannot offer when it comes to dementia.
He begins with Robin Williams, who in his last two years, Meller writes, “was being hunted by a stealthy predator.” The early signs were easy to ignore – “stubborn constipation, trouble sleeping, a sense of smell that had quietly faded, and the usual ‘senior moments.'” Then came a tremor, a walk that “grew stiff and stooped,” and, for the fastest comic mind alive, the terror of being on a film set “unable to hold a single line in his head.” His doctors did their best. “In May of 2014, he was diagnosed with Parkinson’s, with an accompanying dose of depression. It was a careful reading of the evidence before them. It was also wrong. In August, Williams took his own life.”
The real culprit revealed itself only at autopsy. “The pathologist who examined his brain found it riddled with microscopic deposits called Lewy bodies – a case so severe it was, in the examiner’s estimation, among the worst he had ever encountered.” His widow, Susan Schneider Williams, later wrote about it in the journal Neurology and called the disease “the terrorist inside my husband’s brain.” As Meller notes, it is a clinically apt phrase: “The disease worked in the unseen dark, struck with a confusing pattern, and was identified only after it had finished bringing down one of the most creative verbal minds of our generation.”
The lesson is a hard one: “Even with the best of care, we cannot always diagnose the true cause of dementia while the patient is alive.” The case of Bruce Willis, diagnosed first with aphasia and later with frontotemporal dementia, is “a fitting contrast, illustrating the variety of conditions lumped in the general media under the term dementia.” Progressive aphasia, Meller explains, “is not a separate illness that later becomes dementia; it is most often the presenting symptom of frontotemporal degeneration itself.”
Which brings us to a distinction most of us get wrong. “The first thing to understand is that ‘dementia’ is not a disease. It is a syndrome – a description of a problem rather than its cause… Saying a person ‘has dementia’ is like saying they ‘have a fever’: it tells you something is wrong, not what.” Beneath the umbrella sit several very different diseases – Alzheimer’s, frontotemporal dementia, Lewy body dementia, vascular dementia – which “behave differently, are diagnosed differently, respond to treatment differently, and – as we will see – are exploited differently.”
That last word, “exploited,” is where this piece hits you hard. For thirty years, the dominant theory has held that a protein called amyloid is the primary villain of Alzheimer’s, and the money followed the theory: “the National Institutes of Health spent roughly $1.6 billion on amyloid research in 2022 alone, close to half of its entire Alzheimer’s budget for the year.” At its heart sat a celebrated 2006 paper in Nature – which, sixteen years later, a Vanderbilt neuroscientist showed to contain doctored images. After a two-year investigation, it was retracted.
Meller is careful not to overclaim, and that restraint is what makes him worth reading: “The honest conclusion is subtler and more disquieting: a celebrated pillar of the field’s leading theory appears to have been fabricated; a vast research enterprise was built around it for two decades; competing ideas were starved of attention and money. Skepticism, properly understood, is not cynicism. It is the insistence that even the reigning paradigm be made to show its work.”
If the science is shaky, the marketing is not. New blood tests can now predict Alzheimer’s pathology with roughly 90 percent accuracy, and “after decades of diagnostic darkness, we suddenly hold something like a searchlight.” But, Meller warns, “accuracy is not the same as usefulness, because the value of knowing depends entirely on what the knowledge lets you do.” Picture a worried, symptom-free sixty-year-old who tests positive: guidelines don’t endorse the test for them, and they wouldn’t even qualify for the drugs. “We have handed someone a frightening result, threatening them with a disease they may never develop and for which we have little to offer. We have manufactured dread and called it ‘early detection.”
And the drugs? Two anti-amyloid antibodies are now approved; they clear plaque and did slow decline in trials. “But read that sentence carefully. Slowing the rate of decline does not mean improving. It means it got worse more slowly.” The benefit was so slight that “many of the scientists and doctors on the FDA panel did not want to approve the drugs at all,” and against it “sits an immodest risk” of brain swelling and bleeding: “In the lecanemab trial, swelling or hemorrhage appeared in about 17 percent of treated patients, against 9 percent on placebo.” Their predecessor, aducanumab, was “approved by the FDA in 2021 over the explicit objection of its own scientific advisory committee,” and quietly pulled from the market in 2024.
If the prescription drugs offer modest benefit at real cost, the supplement aisle offers, in Meller’s tart phrase, “no benefit at enormous profit.” The market for brain-health supplements is around eleven billion dollars and climbing, because “fear is a superb business model, and little frightens an aging population like the prospect of losing its mind.” Its bestseller, Prevagen, is built on a protein from a glowing jellyfish that supposedly “survives digestion intact, crosses into the brain, and improves memory” – a premise that “collides with the basic biology of the gut.”
So what works? Mellor’s test for when ageing tips into something worse is worth memorising: “Forgetting where you left your keys is normal. Forgetting what keys are for is not. Occasionally losing a name is normal; getting lost driving home from a store you have visited for twenty years is not.” As for prevention, there is no magic pill – only the unglamorous truth that “what is good for the heart is good for the brain.” One finding surprised us: treating hearing loss “ranks among the more promising things a person can do for the aging brain, presumably because a brain starved of input declines faster.” None of this, he notes drily, ” will sell eleven billion dollars of jellyfish protein, because it is unpatentable, unprofitable, and demands actual effort. It is also, unlike most of what is marketed to the frightened, true.”
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