Anxiety May Raise the Risk of Alzheimer's in Some People

Doctors have warned about the toll of anxiety for a long time. High blood pressure, heart disease, diabetes, obesity, depression, stomach trouble, even asthma: all of these have shown up in connection with elevated stress and worry. And you don't need a formal diagnosis of Generalized Anxiety Disorder to feel it. Many people carry pieces of the condition without ever being labeled.

Given everything pressing on people right now, the odds of hitting a stretch of stress, or even real anxiety, are not small. It reaches everyone. Age, race, income level: none of that offers protection. For most people the state passes, and they recover without getting trapped in a repeating loop. Still, plenty of factors can keep anxiety switched on longer than it should be. Therapy and medication exist to carry someone through a rough patch. What happens inside the body during a prolonged high-stress period, though, can reshape a person not only in the mind but in the tissue itself.

A study from the Rotman Research Institute at Baycrest Health Sciences in Toronto looked at this directly. The researchers found that people already diagnosed with mild cognitive impairment, or MCI, who also showed anxiety symptoms faced a sharply higher chance of their thinking declining faster. Depression raised the risk too, and it did so on its own, separate from the anxiety.

Among patients with the amnestic form of MCI, anxiety symptoms were tied to a quicker slide into Alzheimer's disease, beyond what depression, memory loss, or brain shrinkage accounted for on their own. Anxiety also predicted a faster rate of atrophy in the entorhinal cortex. Put together, these findings point away from the idea that anxiety is simply an early sign or a side feature of Alzheimer's. It appears instead to push the decline along, acting directly or indirectly on the volume of that brain region. Other work has linked anxiety in MCI to unusual levels of plasma amyloid protein and of T-tau proteins in cerebrospinal fluid, both of which are markers used to track Alzheimer's.

The Baycrest team drew on the Alzheimer's Disease Neuroimaging Initiative, a large population-based data set, and tracked 376 adults between the ages of 55 and 91 across three years. They watched anxiety, depression, cognitive performance, and shifts in brain structure. The pattern that emerged was clear. For MCI patients with mild anxiety, the risk of conversion to Alzheimer's rose by 33 percent. With moderate anxiety it climbed to 78 percent, and with severe anxiety it reached 135 percent. In other words, the worse the anxiety, the faster amnestic MCI tipped over into Alzheimer's, even after the researchers accounted for depression and for cognitive decline itself.

Participants were checked every six months, and the team logged whatever changed. Everyone carried a clinical diagnosis of amnestic MCI, yet each scored low on the depression scale, which meant the anxiety was not just a symptom of clinical depression wearing a different name. The researchers also saw that patients who reported anxiety at any point during follow-up lost tissue faster in the medial temporal lobe. That part of the brain is where memories get built, and it turns up again and again in Alzheimer's research.

A growing body of work has flagged depression in this same group as a meaningful risk marker as well. The difference in practice is how the two are handled. Memory clinics screen for depression as a matter of routine during assessment and follow-up. Anxiety usually gets no such check. For years it was filed under general psychiatry rather than treated as a category of its own. Telling apart whether a patient has anxiety, depression, or both clearly matters.

Dr. Linda Mah, a principal investigator on the study, put it plainly: clinicians should screen for anxiety in anyone with memory problems, because that anxiety flags a greater risk of developing Alzheimer's. She was careful about the limits of what follows from that. No published evidence yet shows whether the anti-anxiety drugs used in psychiatry would help manage symptoms in people with mild cognitive impairment or lower their odds of converting. Even so, she said, behavioral stress management programs could reasonably be recommended at a minimum.

MCI counts as a warning sign that a person may convert to Alzheimer's within a few years. But not everyone does. Some people hold steady, and a few even recover some of their cognitive ground. What the Baycrest study offers, in Mah's words, is solid evidence that anxiety works as a predictive factor for which direction an MCI patient will go.

The short version: anxiety may speed a patient's decline toward Alzheimer's through direct or indirect effects on the brain. The American Journal of Geriatric Psychiatry released the findings online ahead of the print edition, which was set for May 2015.

By Laura A. Wells. Sources: Baycrest Centre for Geriatric Care, "Anxiety can damage brain, research shows," ScienceDaily, November 10, 2014. Mah, L., Binns, M., Steffens, D., "Anxiety symptoms in amnestic mild cognitive impairment are associated with medial temporal atrophy and predict conversion to Alzheimer's disease," The American Journal of Geriatric Psychiatry, October 29, 2014. Nauert, R. (Ed.), "Anxiety Increases Risk of Alzheimer's Disease," PsychCentral, November 11, 2014.