Humans are getting better at delaying death. On average, people can expect to live beyond 71, five years longer than in 2000. What we haven’t yet figured out is how to beat one of the worst afflictions of aging: Alzheimer’s disease. The brain-shrinking progressive illness has emerged as one of the planet’s biggest public health challenges. More than a century after the tell-tale signs of Alzheimer’s were first seen under a microscope, a few drugs treat the disease's symptoms, but there are still none that slow, let alone reverse, its progression. Researchers estimate there are 46.8 million people worldwide living with dementia, with Alzheimer's the cause in up to 80 percent of cases. The number is expected to almost double every 20 years in the absence of medical breakthroughs on preventions or cures. The cost of dementia care, estimated at about $818 billion in 2015, represents 1.09 percent of global gross domestic product.
Drug companies working to combat the underlying disease have long targeted the protein amyloid, which clumps in the brain of Alzheimer's patients. Biogen, Eli Lilly, Merck and Roche have amyloid-targeting drugs in various stages of testing. Biogen’s Aducanumab reduced amyloid levels and cognitive decline in an early-stage trial, but later data showed the drug didn't have a cognitive benefit in all doses tested, raising questions about its prospects. Data from Eli Lilly in late 2016 or early 2017 will show whether its amyloid-targeting drug works in early-stage patients after previous, disappointing results with the drug. Researchers don't know whether amyloid triggers Alzheimer's or is a minor contributor. As numerous therapies targeting the protein have fizzled in testing, interest has grown in new approaches, especially in those focused on an aberrant protein called tau. As Azheimer's progresses, tau spreads through the brain, accumulating in tangles that strangle brain cells. Among the companies testing tau strategies are Eli Lilly, Johnson & Johnson, Biogen, AbbVie and TauRx Pharmaceuticals.
German psychiatrist Alois Alzheimer was the first to connect dementia to abnormal protein deposits in brain tissue, in 1906. Research into the symptoms, causes, risk factors and treatment of the disease later named for him has taken place largely in the last 30 years, yet the precise chemistry remains largely unknown. Until recently, the only way doctors could be certain patients had Alzheimer’s disease was to check their brain tissue under a microscope for amyloid deposits. The exam wasn’t especially helpful because the patient was already dead. A breakthrough came in 2012, when the U.S. Food and Drug Administration approved a dye used in scans to detect the plaques. For the first time, live people could be reliably diagnosed. The scans also enabled doctors to track plaque growth with the progression of dementia, and to observe that the plaques emerge decades before symptoms. More important, the scans enabled people with other forms of dementia to be excluded from drug trials, producing more reliable results, and plaques could be used to measure the efficacy of drugs.
Science moves at its own pace. Sufferers can’t wait. Lacking a cure, more than 20 national governments have set forth a jumble of formal dementia-fighting plans that include commitments to pay more for research, build residential care centers, increase awareness of palliative measures and draw up ethical guidelines for caregivers. France was the first in Europe, in 2001. The U.S. released its version in 2012. Alzheimer’s advocates are in a contest for resources against groups representing heart disease, cancer and other maladies that kill many more people. Financial challenges overlap with cultural ones. China mandates that children take care of the aged to protect Confucian values. In Japan, there is fear that the strain on the welfare system will conflict with an obligation to care for the elderly. A rape prosecution in Iowa against the husband of a woman with Alzheimer’s raised disquieting questions about sexual consent. Studies reporting behavioral improvement from treatment with turmeric and green tea vex skeptics of dietary nostrums. Stigma is a concern. The country-music singer Glen Campbell cited it as a reason for making his own struggle with Alzheimer’s disease public. Julianne Moore portrayed an attractive, comparatively young Alzheimer’s patient in the movie “Still Alice.” She won an Oscar.
The Reference Shelf
- The World Health Organization lists 10 facts that show the magnitude of the global dementia challenge and an infographic to illustrate the response needed.
- The National Institute on Aging aggregates information on Alzheimer’s disease, its symptoms, diagnosis and treatment.
- Alzheimer’s Disease International provides an analysis of protective and modifiable risk factors in its World Alzheimer Report 2014.
- Alzforum is a web-based scientific community dedicated to understanding Alzheimer’s disease and related disorders.
Jason Gale contributed to the original version of this article.
First published March 19, 2015
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