Stress-Related Disorders Linked to Higher Risk of Neurodegenerative Disease


Statistically significant associations between stress-related disorders were identified in those with Alzheimer disease, but not with Parkinson disease or amyotrophic lateral sclerosis.

Huan Song, MD, PhD

Huan Song, MD, PhD

Results from a comparative study suggest that individuals with stress related disorders are at a greater risk for neurodegenerative diseases compared to unexposed individuals. Notably, Huan Song, MD, PhD, lead researcher and colleagues, noted a greater risk of vascular neurodegenerative disorders as opposed to primary neurodegenerative disorders.

The study featured data from both a population-matched and sibling cohort, evaluating the association between stress-related disorders and the risk for neurodegenerative diseases. Overall, the population-matched cohort compared 61,748 exposed individuals with 595,335 matched unexposed individuals. Additionally, the sibling cohort analysis compared 44,839 exposed individuals to their 78,482 unaffected siblings.

Using the National Patient Register, neurodegenerative diseases were classified as either primary or vascular. Researchers also documented association between stress-related disorders and Alzheimer disease (AD), Parkinson disease (PD) and amyotrophic lateral sclerosis (ALS) in a separate analysis.

Stress-related disorders, such as post traumatic stress symdrome (PTSD), acute stress reaction, adjustment disorder, and other stress reactions, were much more prevalent in patients with a history of psychiatric disorders compared with their unexposed counterparts 19,178 (31.1%) vs 35,167 (5.9%). In the population-matched cohort, 4,314,225 person-years at risk were accrued with the median (interquartile range) follow-up of 4.7 (2.1-9.8) years.

Researchers found that neurodegenerative diseases were higher in individuals with a stress-related disorder (hazard ratio [HR], 1.57; 95% CI, 1.43-1.73). Additional analysis showed a greater risk 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 separate evaluation found a statistically significant association between stress-related disorders and AD (HR, 1.36; 95% CI, 1.12-1.67) but not PD (HR, 1.20; 95% CI, 0.98-1.47) or ALS (HR, 1.20; 95% CI, 0.74-1.96).

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“We found stronger associations for vascular neurodegenerative diseases than for primary neurodegenerative diseases, which may indicate the importance of cardiovascular factors in mediating the observed associations,” the study authors concluded.

Patients included in the study received their first diagnosis of stress-related disorders between January 1, 1987 and December 31, 2008. Exclusion criteria for the study contained individuals who had no data on family links, were aged 40 years or younger at the end of the study, had conflicting or missing information, or had a history of neurodegenerative diseases.

Individualized follow-ups occurred from the age of 40 years or 5 years after the diagnosis of stress-related disorders, whichever came later. This follow-up concluded after the first diagnosis of neurodegenerative disease, death, emigration, or end of final follow-up period (December 31, 2013).

“Vascular factors may also mediate the observed associations with primary neurodegenerative diseases, although to a lesser extent,” the Song and colleagues wrote. “The diminished magnitude of the association between stress-related disorders and vascular neurodegenerative diseases after additional adjustment for cardiovascular diseases supports such a hypothesis.”


Song H, Sieurin J, Wirdefeldt K, et al. Association of stress-related disorders with subsequent neurodegenerative diseases. JAMA Neurol. Published online March 9, 2020. doi:10.1001/jamaneurol.2020.0117

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