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Stress-Related Disorders Are Associated with Increased Risk of Neurodegenerative Disease

People with stress-related disorders had an increased risk of neurodegenerative diseases compared with individuals who were not subject to psychiatric reactions induced by trauma or other life stressors, according to a population-matched and sibling cohort study published in JAMA Neurology on March 9.

The increased risk was more pronounced for vascular disease—at 80 percent (HR, 1.80; 95% CI, 1.40-2.31)—than  for other primary neurodegenerative diseases—at 31 percent  (HR,1.31; 95% CI 1.15-1.48), reported Huan Song, MD, PhD, of West China Hospital in Chengdu, China, and colleagues. "These findings suggest that stress-related disorders may be associated with the subsequent risk of neurodegenerative diseases, possibly through a cerebrovascular pathway," the researchers wrote.

The investigators said their research supports the hypothesis that people with a stress-related disorder diagnosis have an increased risk of developing a neurodegenerative disease later in life, regardless of multiple confounders like familial factors. "The underlying mechanisms behind this association, primarily the role of cerebrovascular factors, warrant further studies," they concluded.

Prior research on the general population and male veterans has shown that posttraumatic stress disorder is linked with increased risk of dementia. One investigation with limited control for familial factors also supported the link between dementia and all stress-related disorders, the investigators noted.

Notably, the findings from the sibling group corroborated findings from the population-matched group, the researchers pointed out.

The population-matched cohort consisted of 595,335 matched unexposed individuals and 61,748 exposed individuals, and the sibling cohort study included 44,839 exposed individuals and their 78,482 unaffected full siblings. The general population and participants with stress-related disorders were compared in a matched cohort design, and participants were also compared with a sibling cohort. 

Follow-up started five years after the diagnosis of stress-related disorder or the age of 40 years depending on whichever came later, until the end of follow-up, death, the first diagnosis of a neurodegenerative disease, and emigration, whichever happened first.

Dr. Song's group used Swedish registers to identify individuals who were initially diagnosed with a stress-related disorder between January 1, 1987, and December 31, 2008. Participants that had missing or conflicting data, no information on family links, history of neurodegenerative disease, and were aged 40 years or younger at the end of the study were excluded.  

The researchers did not find a  statistically significant association between stress-disorders and amyotrophic lateral sclerosis (HR, 1.20; 95% CI 0.74-1.96) or Parkinson's disease (HR, 1.20; 95% CI 0.98-1.47). However, the association was significant  for Alzheimer disease (HR, 1.36; 95% CI 1.12-1.67).

Limitations of the study included surveillance bias and reverse causation. Other limitations included the lack of outpatient specialist care information in the National Patient Register (NPR) until 2001, the dearth of validation studies for the diagnosis of stress-related disorder in the NPR, and residual confounding due to the lack of detailed information on potential risk factors of neurodegenerative diseases and stress-related disorders.

Disclosures: Dr. Song reported no disclosures. 

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