Researchers still don’t know all the reasons people go on to develop dementia, and why. What they do know, however, is that 5% to 8% of the world’s population over 60 suffers severe cognitive decline with age, with some 10 million new cases every year.
Earlier this week, researchers from the University of Nottingham published a study suggesting that a common class of medications, called anticholinergics, may be one risk factor for developing dementia. The link is eye-catching because these drugs are so common among older adults. And yet, from the current research, it’s still impossible to say if these drugs are actually causing more cases of dementia—in part because dementia is so hard to diagnose. In order to actually make conclusions about these drugs and their potential risks, researchers need to first find ways to detect dementia in its earliest stages.
It’s certainly possible that anticholinergics contribute to dementia, says Donna Wilcock, a researcher who focuses on physiology and aging at the University of Kentucky and was not affiliated with the recent paper. Anticholinergics work by blocking the neurotransmitter acetylcholine, which helps regulate a variety of organ systems. In the brain, this neurotransmitter helps us form new memories and later retrieve them. It also helps our muscles relax. Often, blocking acetylcholine can alleviate symptoms caused by other conditions, including incontinence, asthma, or even seizures.
In Alzheimer’s, the most common form of dementia, it seems like the neurons in the brain that produce acetylcholine are disproportionately damaged, compared to the neurons that produce other kinds of neurotransmitters, Wilcock says. Perhaps by blocking acetylcholine, anticholinergic drugs are making the brain more vulnerable to the pathologies that cause dementia—the amyloid buildups associated with Alzheimer’s, perhaps, or the misshapen clumps of TDP-43 that characterize the newly-minted condition called LATE.
However, in a study that looks back on patients’ health records over time like this one, it’s hard to isolate other confounding factors that could have contributed to higher dementia rates.
The work, which appeared in the journal JAMA Internal Medicine, looked at the health records of over 285,000 people over 50, about 58,000 of whom developed dementia later in life. Researchers also looked at which of these patients had been prescribed any kind of anticholinergic, which can treat anything from allergies to overactive bladder to depression to Parkinson’s disease. Controlling for other factors like smoking, 16.7% of the patients with dementia had been taking some kind of anticholinergic drug daily for at least three years, a decade before the study’s start time. In the group of healthy participants, that figure was only 12.2%. These figures reflect previous work that has shown associations between these drugs and dementia.
There are alternative explanations for their results, though. Some of the conditions that require anticholinergics may put a person at higher risk of developing dementia. Additionally, it’s possible that for some patients, the drugs were being prescribed for very early symptoms of dementia, Carol Coupland, an epidemiologist at the University of Nottingham and lead author of the paper said in an email to Quartz.
In order to definitively say that these drugs contributed to dementia, researchers would have to see an uptick in diagnoses as soon as patients started taking these drugs, and also show exactly how they change the brain. Right now, that kind of real-time diagnosis of dementia is still a pipe dream.
Currently, dementia is diagnosed only when a person’s cognitive impairment has gotten in the way of their daily life. It requires a trip to a primary care physician, and then a neurological specialist, and, in some cases, a brain scan. But even before a person starts to show symptoms of dementia, the brain has already begun to deteriorate. In the case of Alzheimer’s, the brain may show signs of the disease as early as two decades before a person starts to experience any cognitive decline. By the time symptoms do show up, it’s too late to reverse them. The damage has been done. Until researchers come up with better ways to identify the earliest stages of mental decline, studies like this will stay inconclusive.