Michael Heneka applauds a sweeping survey of dementia that explores research, diagnosis and care.
The Fragile Brain: The Strange, Hopeful Science of Dementia
- Kathleen Taylor
The global rise in dementia should surprise no one. The figures — such as the 9.9 million new diagnoses each year — have been known for decades. As slow as we are to accept such vast changes on a personal, societal and political level, so research is slow to uncover why our brains become fragile with age.
Neuroscientist and writer Kathleen Taylor's The Fragile Brain is about that research. But it is much more than a simple reflection on the best published hypotheses. Taylor has crafted a personal, astonishingly coherent review of our current state of knowledge about the causes of Alzheimer's disease and dementia, as well as possible solutions, from lifestyle adjustments to drug developments.
Filled with elegant metaphors, her study covers the detail of molecular biology and larger-scale analysis, including epidemiological observations and clinical studies. It extends to dementia due to multiple sclerosis, stroke and encephalitis. For instance, some 5–30% of people who have a first stroke develop dementia. But the book's focus is Alzheimer's disease, and rightly so: it is what up to 80% of people with dementia are diagnosed with.
Taylor begins with a shocking juxtaposition, setting the costs of age-related disorders and of dementia alongside the scarcity in funding. In Britain, Australia and the United States, for example, funding for dementia research is a fraction of that for cancer — in the United States, just 18%. She contextualizes with reflections on the history of dementia research, deftly unravelling the roles of pioneering scientists Alois Alzheimer, Franz Nissl and Emil Kraepelin in describing the condition.
She then walks the reader through different brain elements and regions, from single neurons, transmitters and receptors to their complex interactions and function in cognition and behaviour. She describes the functional and structural loss of synapses as well as the many ways in which amyloid folds and abnormally accumulates in our brains.
Taylor's discussion of risk is especially rich. She explains how to interpret studies on risk factors for age-related dementia and Alzheimer's, such as carrying the APOE4 gene mutation. She emphasizes the influence of immune cells and their actions, such as clearing amyloid from the brain. She succinctly buries the long-fostered concept of the brain's immune privilege. And she isolates prime suspects in mediating further risks, from inflammation to the consequences of infection, vascular changes and production of reactive oxygen species such as hydrogen peroxide.
The big modifiable factors in early cognitive decline are, we now know, diabetes, obesity and smoking. Taylor's discussion here is sympathetic rather than hectoring, acknowledging the difficulties in shifting lifestyles. Likewise, her evidence on the influence of diet, food quality and habits is carefully handled, distilled to writer Michael Pollan's dictum: “Eat food. Not too much. Mostly plants.”
Factors harder to influence by ourselves — such as stress, depression, environmental pollution or poverty — she frames as needing consideration in the larger social context. She discusses interventions to delay or prevent dementia, such as physical fitness and good education. We know from studies that these can buffer genetic disadvantages such as carrying APOE4.
Taylor does not glide over the limitations of current interventions, such as drugs that at best offer transient improvement. Despite decades of intensive research on dementia, a therapeutic breakthrough is yet to come. Taylor counters gloom by revealing avenues of current and future research, for instance further analysis of molecular pathways.
Taylor's discussion of hypotheses about the nature of dementia points to the limitations of concepts such as the physiological function of the amino acids in amyloid plaques in the brain. She offers a forthright assessment of the amyloid-cascade hypothesis and its pros and cons — for example, evidence of genetic mutations and lack of therapeutic success, respectively — and examines it in the context of ideas about the role of inflammation in the brain, particularly in Alzheimer's.
She is critical of how dementia research is conducted, discussing, for instance, the limitations of mouse models in analysing disease mechanisms. Her constructive suggestions include not restricting animal models to studies of the brain, but rather looking at the animal as a whole, because peripheral events such as infection have a neurological impact. However, as she notes, such moves would demand significant funding increases.
Finally, The Fragile Brain addresses how people interact with those who have dementia, and how both information and respect are needed. This is of utmost importance: information can quell many fears.
Taylor has the talent to make complex biology easy, but not trivial. There are many gems, such as her comparison of the immune system's roles of “peacekeeping” and healing with the US Marshall Plan to aid Western Europe after the Second World War. She nicely avoids over-interpretation of findings where research has not yet progressed beyond guesswork. Her provocative questions about genetics, habits, attitudes and levels of knowledge should prompt readers to reason and hypothesize for themselves, and to learn — for instance, whether a particular type of surgery and a particular anaesthetic act together to induce or aggravate dementia.
The Fragile Brain, as a trove of accessible, up-to-date science, has something to offer caregivers and families of people with dementia; medical professionals in dementia diagnosis and treatment; and specialists in memory clinics. It calls for change that reaches to the foundations of our society, suggesting that we adapt lifestyles, workplaces and institutions “to prioritize not labour and cash, but health and well-being”. Some of this change has begun. We had better keep going.
See News Feature p.156
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Heneka, M. Neuroscience: Tide of forgetting. Nature 539, 166–167 (2016). https://doi.org/10.1038/539166a