Alzheimers disease finds a different voice

AP has a story about Peter Bristol, one of the first subjects of the A4 Study – shorthand for the Anti-Amyloid in Asymptomatic Alzheimer’s Study – a test of whether a drug that targets amyloid will change the rate of cognitive decline in adults. Every four weeks, Mr. Bristol and 999 other cognitively normal adults aged 65 to 85 will receive an infusion of either bapineuzumab or a placebo. Random assignment, not a clinician’s choice, will determine the 500 who receive the drug and the 500 who receive the placebo concocted to look just like the drug. After three years, the data will tell whether affecting amyloid can change the way Alzheimer’s disease speaks to us.

And the Philadelphia Inquirer has a January 2015 story on the A4 study with particular attention to the ethical issues in how to approach telling a cognitively normal person he has elevated amyloid.


Amyloid is one of the pathological signatures of Alzheimer’s disease. Pathologists describe it as a plaque, a sharply demarcated object that sits between neurons. One of the first pathologists to observe hundreds of these throughout the cortex of a human’s brain, Alois Alzheimer’s, called it a “special substance.” He wrote in his 1907 case report On an Unusual Illness of the Cerebral Cortex, “Distributed all over the cortex, but especially in the upper layers, there are minute military foci which are caused by the deposition of a special substance in the cortex.”

A4 is a bold experiment. To enroll, a person must undergo a PET scan that uses a radioactive dye and a CAT scan to detect whether this special substance is in a person’s brain. I’m quoted talking about how the study will tell us not only whether we can change the course of cognitive decline seen in persons who have amyloid accumulated in their cortex, but also how after an older adult learns this image of their brain, they will reimagine their sense of self. It will narrow the gap between the brain and the mind.

Peter Bristol’s mother and brother had Alzheimer’s disease dementia. The disease spoke through them, like it did through Auguste Deiter, the woman Alzheimer’s cared for. But Peter Bristol is a “healthy senior.” He does not have a history of illness, but a lament about a future illness. If the A4 study works, meaning cognitive change in the group of persons receiving the drug is slower than in the group of persons who do not receive it, this result will begin work like a cleaver. It will separate the symptoms of Alzheimer’s disease – namely disabling cognitive impairments – from the pathology of the disease.

That pathology will begin to speak to us in a different voice than when it first spoke to Alois Alzheimer’s some 100 years ago. No longer will it speak through patients like Auguste Deiter and her distraught and exhausted husband who brought her to the asylum in Frankfurt. Instead, it will speak through an image of itself and a drug.