July 10th, 2019
Alzheimer’s Disease (AD), a type of dementia that results in memory loss and cognitive decline, is one of the most feared diseases in the US. Unfortunately, the many efforts to develop medications to cure AD (146 clinical trials from 1998 to 2017) have not proved successful thus far.
With no leads on developing Alzheimer’s drugs for symptomatic patients, many are turning to preventive measures to try and detect and ward off dementia. This shift toward Alzheimer’s prevention, while well-intentioned, creates significant potential for overtreatment, write University of Michigan physicians Dr. Kenneth Langa and Dr. James Burke, in JAMA Internal Medicine.
Doctors may diagnose patients with “preclinical AD” if they have no demonstrated cognitive decline but show elevated levels of brain amyloid. Having high levels of the protein beta-amalyoid correlates with Alzheimer’s, making it a potential risk factor for the disease. The problem is, an estimated 30% of adults over age 50 meet the criteria for preclinical AD, but most of these people will never develop dementia in their lifetime. However, once a patient has been diagnosed, it is likely they will be prescribed medications like cholinesterase inhibitors, even though these have not been proven effective in reducing dementia risk or slowing cognitive decline.
Langa and Burke also warn against widespread use of amyloid-inhibitors which are currently in development. Given the high cost of newer preventive medications for cholesterol (which debuted at $14,000 a year), Langa and Burke estimate that AD-prevention drugs would cost our health care system more than $100 billion each year, even if just half of eligible people with preclinical AD were to take them.
It’s also not clear that reducing amyloid buildup actually prevents Alzheimer’s Disease, making the benefits of preventive drugs for AD even more ambiguous. Proponents of the “amyloid model” of Alzheimer’s research have been criticized for refusing to consider other potential causes of AD, even after evidence showed that the amyloid hypothesis is flawed. As Sharon Begley writes in a STAT investigation of AD research, many researchers believe that amyloid buildup in the brain may be a marker of AD, but not the cause. There could be other reasons, such as an infection, inflammation, or something else, that causes both cognitive decline and elevated amyloid levels. Unfortunately, little is known about these other potential causes of AD, because leading researchers effectively silenced those who disagreed with the “pro-amyloid camp.”
Before we jump the gun on testing and treating everyone’s amyloid levels, we need better information on the biology of AD and dementia, the effectiveness of potential preventive drugs, and how to target these treatments toward those who are most likely to be helped.