Researchers Find Potential New Risk Factors and Early Signs of Alzheimer’s

How early is too early to think about your risk of Alzheimer’s? A new study found that certain health conditions could potentially help predict an Alzheimer’s diagnosis two to 10 years before the condition develops.

The researchers found that several conditions—such as anxiety, hearing loss, and constipation—are associated with a higher chance of being later diagnosed with Alzheimer’s. The findings—published in The Lancet Digital Health—are just a start in helping providers better identify early warning signs of Alzheimer’s or potential new risk factors for the disease.

“The ultimate goal is to learn what’s happening before the disease," Thomas Nedelec, PhD, a postdoctoral researcher at Institut du Cerveau-Paris Brain Institute in France and lead author of the study, told Verywell. “One specificity that this disease has is that it can take a very long time to appear and so by building a cluster of health conditions we get a better understanding of what is affecting the disease.”

According to the Center for Disease Control and Prevention (CDC), people typically notice Alzheimer’s symptoms starting at age 60, and the risk of Alzheimer’s doubles every five years after age 65. However, Alzheimer’s effects on the brain can start years before symptoms set in, leaving a window of opportunity to intervene early enough and delay its onset.

What the Research Shows

The team collected medical records for 20,214 people living in the United Kingdom and 19,458 people living in France diagnosed with Alzheimer’s between 1996 and 2020. By crunching the data, they hoped to find if there was a particular diagnosis that providers should look closer at because it could be predictive of Alzheimer’s disease years before it appeared.

Of the 123 medical conditions found in people two to 10 years before their Alzheimer's diagnosis, 10 health conditions or symptoms were significantly associated with Alzheimer’s. These included:

• Major depressive disorder
• Anxiety
• Reaction to severe stress and adjustment disorders
• Hearing loss
• Constipation
• Spondylosis (degeneration of bones in the spine from aging)
• Unexplained or abnormal weight loss
• Malaise and fatigue
• Memory loss
• Fainting and collapsing events

Depression and anxiety were the top conditions connected to Alzheimer’s. Most patients with Alzheimer’s showed symptoms of depression and anxiety nine years prior to their diagnosis. The research team linked constipation and abnormal weight loss to Alzheimer’s disease seven years later as well.

Still in Early Stages

Previous studies have shown a growing link between symptoms such as depression, anxiety, and hearing loss, but Nedelec said there were others that surprised him.

He explained that spondylosis and constipation were unexpected, as there is not much research linking these two with Alzheimer’s.

However, none of the above symptoms will automatically lead to an Alzheimer’s diagnosis.

“There’s a bunch of reasons to wonder why that happened in the analysis and it becomes a kind of chicken or egg type of question,” Scott Kaiser, MD, a geriatrician and director of geriatric cognitive health for the Pacific Neuroscience Institute at Providence Saint John’s Health Center who was not involved in the study, told Verywell. “Is this a symptom of Alzheimer’s or is this a risk factor that increases your chances of Alzheimer’s?”

It’s also hard to make any definitive conclusions when other factors such as your socioeconomic status, genetics, and body mass index (BMI) carry their own risks for Alzheimer’s.

“Family history is something that can increase your odds of Alzheimer’s but then there are a bunch of other things like how active you are, how much second smoke or air pollution you’re exposed to, loneliness, and social isolation,” Kaiser explains. Having this information could create a more complete picture of what leads to an Alzheimer’s diagnosis.

Additionally, the study authors gathered medical records from when patients visited their primary care provider rather than a specialist. Earlier signs of Alzheimer’s could have been inaccurate or missed until symptoms worsened and became more apparent.

Nedelec explained that their findings are a statistical association reporting on the small differences of patients that develop Alzheimer’s in 10–15 years and should not be thought of as a definite risk factor for Alzheimer’s.

“If you read this and think constipation causes Alzheimer’s disease, that is not what this research demonstrates,” Kaiser explained. “The whole idea is trying to ‌have enough associations in a clear enough pattern that can help us better predict risk [in the future] and intervene early.”

Despite the limitations, there is value in identifying conditions that with more research could show a potential early risk factor for Alzheimer’s. In the meantime, Nedelec says his team is working to identify the reason why ‌conditions such as constipation are linked to an Alzheimer’s diagnosis nearly a decade later. They are also looking to apply this model to other neurodegenerative diseases such as Parkinson’s.

“It’s a modern and different approach taking advantage of improvements in computing power and predictive modeling,” Kaiser said. “I think this is a great study because in taking care of patients we might better predict the possibility that they’re on track to develop Alzheimer’s disease.”