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 late-onset Alzheimer's, and more are being announced all the time. In the long run, the hope is that some of these will lead to preventive treatments. Sadly, at the moment, none of those exist. However, as I describe in Chapter 14, there is a rush of clinical trials underway at the moment, most of which-so far anyway-have come up empty. But to an optimist, every failed trial at least yields inform-ation you didn't have before. That's the way it works.

Chapters 15 through 18 depart somewhat from the mainstream by taking four individual features of the disease and exploring each one. There are two female Alzheimer's patients for every male, and while superior female longevity accounts for much of this, other, not-well-characterized influences are in the picture, connected, perhaps, to differences in the male and female brains. One of them might be the female hormone estrogen, but again, its role isn't perfectly clear. Once thought to be the key to maintaining cognitive health through menopause and beyond, experts now generally believe that its beneficial actions are much more limited.

Many will remember the aluminum scare, the idea popular in the 1980s and 1990s that aluminum was the cause of Alzheimer's and all aluminum kitchenware should be thrown out immediately. A substantial body of science lay behind the initial worries about aluminum, but inconsistent research results eventually turned most scientists away. All the same, that trend is a lovely example of how a scientific idea can rise-and then fall.

Alzheimer's is by no means the only form of dementia, although it probably represents 75 per cent of the total. The majority are subtle variations on a theme, with rogue proteins (eerily similar to the infectious prions of mad cow disease) accumulating in different parts of the brain and playing a central role in many of those parts. But the most puzzling-and therefore the most scientifically attractive-is the mysterious dementia found on the island of Guam. Is it caused by dietary toxins? Are those toxins delivered in extreme doses by the consumption of bats? This too is ongoing research.

Chapter 18 focuses on where you live and what you eat. It is simply impossible, and would be very tedious, to review the support for every single claim on behalf of a "dementia-protective" food. There are just too many, and the evidence is scattered and scant. But two are worth examining: one is the assertion that turmeric is responsible for the extremely low rates of Alzheimer's found in India; the other, the incontrovertible evidence that large amounts of sugar in the diet are not good. Today, this evidence is considered so central to the problem of Alzheimer's that some are calling the disease type 3 diabetes.

I've tried to describe the state of our knowledge of Alzheimer's as broadly and evenly as I could. I'm sure there will be researchers who won't like my emphasis on this or that or the fact that I didn't write about their approach to the disease. I'm also confident that those who advocate a particular set of vitamin supplements or dietary guidelines will find my omission of them scandalous. My hope is that when you read this book, you'll gain a much broader and deeper understanding of this disease, which preoccupies us so much. Knowing more might even help in that most difficult of tasks: caring for those who are struggling with the affliction.

And by the way, shortly after I read "Mom and Me," I was fortunate enough to come across another article, this one titled "Exceptional Parental Longevity Associated with Lower Risk of Alzheimer's Disease and Memory Decline."2 Well, that was a pick-me-up! My mother, demented as she was, lived to ninety-four and my dad, a month shy of ninety-eight. In this study, anything over the age of eighty-five was considered exceptional longevity, putting me in a somewhat safer zone. But it would be so simplistic to think that my risk of becoming demented is slightly higher because of my mother and lower because of my mother and my father because those are only two risk factors out of dozens if not hundreds. My experience illustrates a point: in the twenty-first century, we face aging in a way that has never happened before-one eye on the clock and the other on Alzheimer's.



Copyright © 2014 by Jay Ingram