Cognitive Decline Linked With Premature Death in Schizophrenia

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Individuals with schizophrenia who have lower cognitive functioning are at a significantly higher risk of dying from natural causes, according to a recent study published in JAMA Network Open. The research found that cognitive decline, combined with factors like smoking, obesity, and chronic health conditions, sharply increased the likelihood of premature death, highlighting the urgent need for interventions that improve both mental and physical health in this patient population.

The association between schizophrenia and reduced lifespan has been well-studied though it’s predominantly been attributed to natural causes, with factors such as poor physical health, unhealthy lifestyle habits, and socioeconomic challenges playing a role. This study analyzed the role of cognitive decline, which is recognized as a risk factor for mortality in the general population, but few studies have specifically examined this relationship in the context of schizophrenia.

Investigators aimed to address that gap, exploring how cognitive functioning impacts natural cause mortality among people diagnosed with schizophrenia or schizoaffective disorder. The primary objective of this study was to determine whether lower cognitive functioning serves as a significant risk factor for natural cause mortality in individuals with schizophrenia or schizoaffective disorder. The study also investigated other contributing factors, including obesity, tobacco smoking, and underlying medical conditions, to provide a comprehensive understanding of mortality risk in this population.

This prospective cohort study, spanning more than 2 decades, enrolled participants from a nonprofit psychiatric system in Baltimore, Maryland. Between February 1999 and December 2022, 844 individuals diagnosed with either schizophrenia or schizoaffective disorder were recruited. The participants (mean age of 39.6 years) were followed for a median period of 14.4 years, though follow-up times ranged from as little as 7 days to nearly 24 years.

Cognitive functioning was assessed using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), a tool commonly used to measure cognitive deficits in various domains such as memory, attention, and language. In addition to cognitive assessments, data were collected on factors including obesity, smoking habits, and the presence of medical conditions, all of which were evaluated for their potential impact on mortality.

The study’s primary outcome was the association between cognitive function and natural cause mortality. Additional factors evaluated included obesity, tobacco smoking, and the presence of chronic medical conditions such as autoimmune disorders, chronic obstructive pulmonary disease (COPD), and cardiac rhythm disorders. The Cox proportional hazards models were adjusted for confounding factors to isolate the independent effect of each variable.

Results showed that out of 844 participants, 158 (18.7%) died of natural causes during the follow-up period. The analysis revealed that lower cognitive functioning, as measured by the RBANS, was the most significant predictor of mortality. The Cox regression coefficient for cognitive functioning was −0.04 (95% CI, −0.05 to −0.03; z = −5.72; P < .001), indicating that for each unit decrease in cognitive score, the risk of mortality increased.

In addition to cognitive function, several other factors were independently associated with higher mortality risk. These included:

• Autoimmune disorders (HR, 2.86; 95% CI, 1.83-4.47; z = 4.62; P < .001)
• Tobacco smoking (HR, 2.26; 95% CI, 1.55-3.30; z = 4.23; P < .001)
• COPD (HR, 3.31; 95% CI, 1.69-6.49; z = 3.48; P = .006)
• Elevated BMI as a continuous variable (HR, 1.06; 95% CI, 1.02-1.09; z = 3.30; P = .01)
• Cardiac rhythm disorders (HR, 2.56; 95% CI, 1.40-4.69; z = 3.06; P = .02)
• Divorce or separation (HR, 1.80; 95% CI, 1.22-2.65; z = 2.97; P = .02)

Investigators noted that individuals with RBANS scores below the 50th percentile were more likely to experience early mortality if they also smoked, had a higher BMI, or had been diagnosed with autoimmune or cardiac rhythm disorders.

“An important implication of these findings is that cognitive functioning is an important measurement in individuals with schizophrenia,” the authors wrote. “Another implication is that compensation may need to be made for cognitive deficits in this population in terms of explanation and instructions accompanying medical interventions.”

Overall, the study provides insight into the critical role of cognitive functioning in predicting mortality from natural causes among individuals with schizophrenia. The findings suggest lower cognitive function, alongside physical health issues such as autoimmune disorders, smoking, obesity, and chronic medical conditions, significantly increases the risk of death.

Reference

Dickerson F, Khan S, Origoni A, et al. Risk Factors for Natural Cause Mortality in Schizophrenia. JAMA Netw Open. 2024;7(9):e2432401. doi:10.1001/jamanetworkopen.2024.32401