Stress-Related Disorders Tied to Future Neurodegenerative Disease

Megan Brooks

March 12, 2020

Stress-related disorders are tied to an increased risk of neurodegenerative disease later in life, results from a large observational study show.

The association between stress-related disorders and subsequent increased risk of neurodegenerative diseases was stronger for neurodegenerative diseases with a primary vascular component (80% increased risk) vs primary neurodegenerative disease (30% increased risk).

"This may indicate an important mediating role of vascular factors," investigator Huan Song, MD, PhD, of Sichuan University in Chengdu, China, told Medscape Medical News.

"Therefore, close surveillance on, or finding a way to reduce, the risk of cardiovascular diseases may subsequently reduce the risk of developing neurodegenerative diseases among patients with stress-related disorders," said Song.

The study was published online March 9 in JAMA Neurology.

New Insights

Posttraumatic stress disorder (PTSD) has been associated with increased risk for dementia, but less is known about the potential link between other stress-related disorders and neurodegenerative diseases.

Using a nationwide population-matched and sibling-matched cohort design, investigators examined the association between a range of stress-related disorders, including PTSD, acute stress reaction, adjustment disorder, and subsequent risk for dementia, parkinsonian disorders, and amyotrophic lateral sclerosis (ALS).

Participants included 61,748 individuals with stress-related disorders and 595,335 matched unexposed individuals from the general population. The sibling cohort analysis included 44,839 exposed individuals and their 78,482 unaffected full siblings.

Follow-up began at age of 40 (median age, 47 years) or 5 years after a diagnosis of stress-related disorders, whichever came later, until the first diagnosis of a neurodegenerative disease, death, emigration, or the end of follow-up.

During median follow-up of 4.7 years, the researchers found that, compared with unexposed individuals, those with a stress-related disorder were at an increased risk of neurodegenerative diseases (hazard ratio [HR], 1.57; 95% confidence interval [CI], 1.43 - 1.73).

The risk increase was significantly greater for vascular neurodegenerative diseases (HR, 1.80; 95% CI, 1.40 - 2.31) than for primary neurodegenerative diseases (HR, 1.31; 95% CI, 1.15 - 1.48).

A statistically significant association was found for Alzheimer's disease (HR, 1.36; 95% CI, 1.12 - 1.67) but not Parkinson disease (HR, 1.20; 95% CI, 0.98 - 1.47) or ALS (HR, 1.20; 95% CI, 0.74 - 1.96).

Results from the sibling cohort corroborated results from the population-matched cohort, which suggest that the association between stress-related disorders and neurodegenerative diseases cannot be explained by familial factors shared by siblings, the researchers note.

Modifiable Risk Factor?

Weighing in on the results for Medscape Medical News, Brittany LeMonda, PhD, senior neuropsychologist at Lenox Hill Hospital in New York City, said it's well known that stress is bad for the brain but that research in this area has been limited.

"This study really sheds light on what we may have 'thought' but didn't really have the scientific data to back," said LeMonda, who wasn't involved in the research.

She also noted that most of the research examining stress tends to focus on individuals with PTSD, mainly in veterans.

"This study looks at civilians with a range of stress-related disorders and a number of common neurodegenerative disorders. This is a very large-scale, population-based study, so the results are very important in that they are generalizable to some degree," said LeMonda.

She noted that it's also not surprising that the strongest link was between stress-related disorders and neurodegenerative conditions with a vascular component.

"This really highlights the importance of cerebrovascular health and that life stressors and how one handles these stressors can impact our brains years later, not only in terms of physiological response — that is, by causing a cascade of events that results in chronic neuroinflammation — but also via our behaviors, lifestyle choices, and coping mechanisms when faced with high stress.

"We can make poor choices, like smoking, consuming high fat foods, not sleeping well. These behaviors can have a real effect on our brain and vascular well-being," said LeMonda.

The finding that stressful events and stress disorders can result in neurodegenerative disorders is significant and may offer an opportunity for prevention.

"These findings suggest that we may be able to identify those at risk for dementia based on stress disorders earlier in life," LeMonda explained. "If we can identify these individuals much earlier, then we can try to provide appropriate interventions and try to change the brain and body's response to stress — from both physiological and behavioral perspectives."

She also noted that the study underlines the need for early detection of stress disorders to provide an opportunity for early intervention.

"Also, from a public health perspective, it would be important that the general population is made aware of these findings so that they can seek the appropriate treatments in the context of chronic stress or trauma," LeMonda concluded.

Th e study was funded by grants from the Swedish Research Council, the Icelandic Research Fund, the European Research Council, the Karolinska Institutet, the Swedish Initiative for Research on Microdata in the Social and Medical Sciences, and West China Hospital, Sichuan University. Song and LeMonda have disclosed no relevant financial relationships.

JAMA Neurology. Published online March 9, 2020. Abstract

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