The End of Memory: A Natural History of Aging and Alzheimer's

250 Pages·2015·1.28 MB·English

by  Jay Ingram

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Table of Contents
About the Author
Copyright Page
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To my father, Ralph Ingram, for demonstrating dignity, patience and love in
caring for my mother through her years of dementia
Introduction
I forget exactly what I was looking for when I came across an editorial in the
journal Neurology titled, “Mom and Me.” It referenced a really cool piece of
research showing that people whose mothers had had Alzheimer’s disease could
exhibit the same disruptions of brain metabolism as patients with Alzheimer’s
and yet be cognitively intact. That is, in the absence of symptoms of any kind,
their brains nonetheless seemed to be on the way to Alzheimer’s. At the same
time, the brains of children of fathers with Alzheimer’s were ticking along just
fine. This convinced the researchers that because the mitochondria (the so-called
power plants of the cell) are inherited through the maternal line, Alzheimer’s is a
disease of the mitochondria. It was good science, but it was more than that.
Those data hit home for me because at the end of her life, my mother was
bedridden and unaware. She was said to have Alzheimer’s, but since no autopsy
was done, that was pretty much a guess. A guess with the odds on its side, true,
but not a diagnosis. Not that it would really have mattered. With the exception of
some drugs that slow the process for a year, more or less, there is no way of
delaying the cognitive decline that is dementia. And now it seemed as if I was
running the risk of getting the same thing.
I’ve had what I think is a pretty typical exposure to Alzheimer’s. I learned
most from helping take care of my favourite aunt as she dwindled away. My
aunt, my mother’s sister, visited all the familiar checkpoints: forgetting to eat,
not being able to use the pill minder because she didn’t know today was
Tuesday, wandering when first moved into a home because we had waited too
long to move her. But she would have protested loudly—refused actually—if we
had tried to move her any earlier. Eventually, even her good humour deserted
her. My father-in-law declined a little faster but in roughly the same way.
But I didn’t write this book because I’ve had family members die of dementia
(likely Alzheimer’s). Most people have had some sort of experience with the
disease—and many have been eloquent about the experience, some of them
giving first-person accounts of what it’s actually like, others telling their stories
from a caregiver’s or family member’s point of view. As I began to think more
about Alzheimer’s, I wanted an anatomy of the disease, a natural history. Not a
guide to caregiving or diet recommendations or a description of an individual’s
experience. But a scientific account: Where does it come from? What causes it?
Is it a natural part of aging? How are we trying to combat it?
The science of Alzheimer’s disease is complex and extremely challenging. As
fascinating as any medical mystery, it is unique among them. The emotionally
draining personal experience of the disease and the very real threat to health care
systems as the numbers of Alzheimer’s patients worldwide accelerates have
combined to place enormous pressure on Alzheimer’s science to come up with a
treatment. Alzheimer’s is, after all, “the plague of the twenty-first century.”
But, of course, it isn’t just of the twenty-first century. Long before Alois
Alzheimer’s name was attached to the disease, the medical world was aware of
dementia and described it in terms that are immediately familiar to us. It was
first called “Alzheimer’s disease” about a hundred years ago, and while that
coinage created a brief flurry of interest at the time, it wasn’t until the mid-1970s
that it became recognized as a disease, rather than a common companion of old
age. Since that time, we’ve been living in a nearly unprecedented era of
concentration on a single illness. Or at least it felt that way to me until I saw the
stats. In the U.S., the National Institutes of Health (NIH) spends over $6 billion a
year on cancer research, $4 billion on heart disease and $3 billion on HIV/AIDS.
Alzheimer’s? Just $480 million—nothing compared to the cost of care, which is
rising inexorably.1
So where do we stand? What exactly is the nature of the beast? That’s what
this book is about.
The first chapter takes a step back to give a sense of how people have thought
about aging and death in the past. Sinning was a recurrent theme; dementia was
the punishment. On the other hand, your honest striving for salvation could earn
you a long and vibrant life and a virtual lock on a place in heaven. Today, we
dread Alzheimer’s, but in the past, it was usually considered to be a normal part
of aging for some. Chapters 2 and 3 tell the story of the beginnings of
Alzheimer’s disease, from Auguste Deter, the first patient, through some quiet
decades until the 1970s, when Alzheimer’s was finally recognized as a
worldwide threat.
Chapter 4 takes an extremely rare look at dementia from both the outside and
the inside; in both cases, the “patient” is Jonathan Swift. In Chapter 5, you’ll
meet, likely for the first time, Abraham Trembley, a genius scientist who
grabbed everyone’s attention with his “immortal” hydra and helped kick-start
studies of the biology of aging. Then, in Chapter 6, a closer look at one amazing
phenomenon, the inexorable increase in life expectancy over the last 175 years,
and James Fries’ theory of the “compression of morbidity.”
Chapters 7 and 8 are paired. The first is a look at what happens as the brain
ages naturally—not with dementia, just healthy aging (assuming these processes
are actually different). In Chapter 8, we return to Alzheimer’s lab and look over
his shoulder to see what he saw in Auguste Deter’s brain—the crucial
differences that set it apart from healthy aging brains, the differences that are
still the basis of an Alzheimer’s diagnosis (called “plaques” and “tangles”). They
dominated Alzheimer’s description of what he saw on his slides, and they
dominate thinking about the disease today.
I introduce the Nun Study in Chapter 9, partly because it is one of my
favourites (a brilliant idea for a long-term study) and partly because its results
underline the fact that Alzheimer’s is a complex disease. What might look
simple at first glance (if there are plaques in the brain, there is Alzheimer’s)
turns out not to be (many completely healthy, whip-smart elders have brains
absolutely ridden with plaques). The most astonishing result from the Nun Study
is that essays written by young novitiates in their early twenties predicted with
surprising accuracy who among them would get Alzheimer’s sixty years later.
The Nun Study has added enormously to our understanding of the disease.
The significance of the Nun Study is made crystal clear by contrasting the
apparently inexorable spread of Alzheimer’s in the brain, as I do in Chapter 10,
with the resistance to damage that has been labelled “brain reserve” (described in
Chapter 11). Much is known about where neurons begin to break down in the
brain and how plaques and tangles apparently conspire to spread in all directions
from those initial sites. But brain autopsies conducted as part of the Nun Study
revealed that many cognitively intact nuns had plaques and tangles in their
brains when they died. This observation, combined with those from other
studies, led to the brain reserve concept—a mysterious something that protects
some individuals from dementia. It turns out there’s a long list of factors that
might be part of brain reserve, a list that will likely grow over time. Education is
one of the most important, and education is thought to be an important player in
the small number of studies now emerging which suggest that in some places,
especially Europe, the incidence of dementia might be decreasing. This is the
subject of Chapter 12; it is a surprising and important, though early, trend that
bears watching.
With the shadow of Alzheimer’s over all of us, we want to know our chances
of getting it and what sorts of treatments will be available if we do. That is the
subject of Chapter 13. In a way, the study of the genetics of Alzheimer’s is in its
infancy, but it’s already clear that some genes are important for both early-and