Jay Ingram - The End of Memory: A Natural History of Aging and Alzheimers

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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

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 Alzheimers disease could exhibit the same disruptions of brain metabolism as patients with Alzheimers 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 Alzheimers. At the same time, the brains of children of fathers with Alzheimers 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, Alzheimers 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 Alzheimers, 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.

Ive had what I think is a pretty typical exposure to Alzheimers. I learned most from helping take care of my favourite aunt as she dwindled away. My aunt, my mothers sister, visited all the familiar checkpoints: forgetting to eat, not being able to use the pill minder because she didnt 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 loudlyrefused actuallyif 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 didnt write this book because Ive had family members die of dementia (likely Alzheimers). Most people have had some sort of experience with the diseaseand many have been eloquent about the experience, some of them giving first-person accounts of what its actually like, others telling their stories from a caregivers or family members point of view. As I began to think more about Alzheimers, I wanted an anatomy of the disease, a natural history. Not a guide to caregiving or diet recommendations or a description of an individuals 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 Alzheimers 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 Alzheimers patients worldwide accelerates have combined to place enormous pressure on Alzheimers science to come up with a treatment. Alzheimers is, after all, the plague of the twenty-first century.

But, of course, it isnt just of the twenty-first century. Long before Alois Alzheimers 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 Alzheimers disease about a hundred years ago, and while that coinage created a brief flurry of interest at the time, it wasnt until the mid-1970s that it became recognized as a disease, rather than a common companion of old age. Since that time, weve 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. Alzheimers? Just $480 millionnothing compared to the cost of care, which is rising inexorably.

So where do we stand? What exactly is the nature of the beast? Thats 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 Alzheimers, 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 Alzheimers disease, from Auguste Deter, the first patient, through some quiet decades until the 1970s, when Alzheimers 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, youll meet, likely for the first time, Abraham Trembley, a genius scientist who grabbed everyones 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 naturallynot with dementia, just healthy aging (assuming these processes are actually different). In Chapter 8, we return to Alzheimers lab and look over his shoulder to see what he saw in Auguste Deters brainthe crucial differences that set it apart from healthy aging brains, the differences that are still the basis of an Alzheimers diagnosis (called plaques and tangles). They dominated Alzheimers 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 Alzheimers is a complex disease. What might look simple at first glance (if there are plaques in the brain, there is Alzheimers) 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 Alzheimers 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 Alzheimers 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 concepta mysterious something that protects some individuals from dementia. It turns out theres 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.