Lower Cognitive Functioning Linked to Natural Cause Mortality in Schizophrenia

A new study revealed lower cognitive functioning was significantly associated with the risk of natural cause mortality among individuals with schizophrenia.¹

“An important implication of these findings is that cognitive functioning is an important measurement in individuals with schizophrenia,” wrote investigators, led by Faith Dickerson, PhD, MPH, from the Stanley Research Program at Sheppard Pratt in Baltimore. “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.”

Many people with schizophrenia have premature mortality from natural causes, dying 10 years younger, on average, than the general population. Research has identified reduced cognitive functioning as a determinant of mortality, but it was not studied specifically within a schizophrenia population.² Investigators sought to see whether lower cognitive functioning was a risk factor for natural cause mortality in schizophrenia.¹

The prospective cohort study included 844 individuals (mean age: 39.6 years) with schizophrenia or schizoaffective disorder who were enrolled at a nonprofit psychiatric system in Baltimore, Maryland, between February 1, 1999, and December 31, 2022. Among the sample, 63.2% were male, and 18.7% died of natural causes during a median follow-up of 14.4 years (range, 7.0 days to 23.9 days).

Investigators used Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and other clinical measures to determine whether lower cognitive functioning was a risk factor for natural cause mortality in this population. Other than lower cognitive function, investigators examined the association between natural cause mortality and obesity, tobacco smoking, and medical conditions.

The team discovered lower cognitive functioning was the most significant risk factor associated with mortality (Cox coefficient, −0.04; 95% confidence interval [CI], −0.05 to −0.03; adjusted P < .001). Other risk factors independently linked to mortality included an autoimmune disorder (hazard ratio [HR], 2.86; 95% CI, 1.83 – 4.47; adjusted P < .001), tobacco smoking (HR, 2.26; 95% CI, 1.55 – 3.30; P < .001), chronic obstructive pulmonary disease (HR, 3.31; 95% CI, 1.69 – 6.49; P = .006), body mass index [BMI] as a continuous variable (HR, 1.06; 95% CI, 1.02 – 1.09; P = .01), cardiac rhythm disorder (HR, 2.56; 95% CI, 1.40 – 4.69; P = .02), and being divorced or separated (HR, 1.80; 95% CI, 1.22 – 2.65; P = .02).

“There are several possible explanations for the association between cognitive functioning and mortality,” investigators wrote. “Worse cognitive functioning may indirectly contribute to survival by reducing persons’ abilities to identify somatic illness symptoms, seek medical treatment, and comply with treatment regimens, as has been suggested as an explanation for worse cancer outcomes of persons with schizophrenia than those in the general population.”

Investigators continued writing that reduced language abilities may impact interactions with medical professionals. Additionally, delayed memory may lower health literacy and patients may forget to follow through with recommended medical treatments.

“Our finding of a significant joint association of lower cognitive functioning and persistent somatic illnesses, such as COPD, as well as autoimmune and cardiac rhythm disorders is consistent with this possibility,” investigators wrote.

The study found participants with an RBANS score < 50ths percentile showed a joint association with being a smoker, having an increased BMI, and having a diagnosis of autoimmune or cardiac rhythm disorder.

Investigators highlighted many limitations, including:

• No data on medical interim data during follow-up period
• No data on who subsequently quit smoking
• Assessment of cognition using brief cognitive battery did not evaluate working memory or fully evaluate executive functioning
• Findings may not generalize to full schizophrenia population
• Sample size
• Not using additional methods other than LASSO to examine the contributions of many covariates

“In this cohort study, reduced cognitive functioning was associated with increased mortality in individuals with schizophrenia, particularly in those with additional risk factors,” investigators concluded. “Effective methods to improve cognitive functioning may result in a substantial reduction in mortality in this population.”

References

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

Hayat SA, Luben R, Dalzell N, et al. Understanding the relationship between cognition and death: a within cohort examination of cognitive measures and mortality. Eur J Epidemiol. 2018;33(11):1049-1062. doi:10.1007/s10654-018-0439-z