CVD Risk Factors May Further Impair Cognition in Schizophrenia

Risk factors for cardiovascular disease (CVD) are strongly associated with global cognitive impairment in patients with schizophrenia in new findings that suggest the need for an aggressive management approach.

Investigators found that metabolic syndrome (MetS), hypertension, and diabetes were associated with poorer performance in specific cognitive domains, including attention/vigilance, reasoning and problem solving, speed of processing, verbal learning, and visual learning.

“Given our findings of the relationship between cardiovascular risk factors and poorer cognition, the focus on monitoring and promoting cardiovascular health is not only relevant for physical health purposes but also for psychiatric reasons, making it even more important for psychiatric clinicians to pay more attention to monitoring and health promotion and selection of medications with lower cardiovascular risk,” senior investigator Christoph Correll, MD, professor of psychiatry and molecular medicine, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, New York, told Medscape Medical News.

The study was published online March 3 in JAMA Psychiatry.

“Floor Effect?”

“We know from the general population that people with metabolic problems also have worse cognition,” Correll said. “People with schizophrenia have a lower level of cognition, at a degree of 1.5 or 2 standard deviations below the population norm, and also have worse cardiometabolic health compared to the general population.”

The goal of the study was to determine whether greater CVD risk further lowers cognitive ability or whether there was a type of “floor” such that cognition would not drop beyond a certain point, “meaning, if cognition is already very low, does the presence of cardiovascular risk factors lower it further?” said Correll.

A prior systematic review and meta-analysis of 12 studies showed an association between MetS and diabetes and cognitive impairment in patients with schizophrenia, but the researchers believed that to determine the clinical importance of this required a much more “expansive set of data consisting of all studies investigating the association of risk factors for CVD with cognitive function in schizophrenia.”

To investigate, they identified 27 studies (n = 10,174 patients with schizophrenia; mean [SD] age, 42.1 [8.7] years) that met inclusion criteria. To be included, studies had to have examined cognitive functioning in patients with schizophrenia or schizoaffective disorder; investigated the association of CVD risk factors with outcomes; and compared cognitive performance of those with vs those without these risk factors in patients with schizophrenia/schizoaffective disorder.

Over half (63.8%) of study participants were male, and most (70.5%) were non-White. The mean duration of illness was 14.1 years, and the mean number of years of education was 11.8 (1.7) years.

Most (nine) studies were conducted China, followed by the United States (seven studies), Europe (seven studies), Singapore, India, and Egypt (one study each).

Compromised Vasculature

For all CVD risk factors with the exception of dyslipidemia, effect sizes between patients with schizophrenia who had cognitive dysfunction in comparison with those who did not have cognitive dysfunction ranged from -0.20 to 0.70 for global cognition, “indicating poorer cognition for patients with specific cognitive dysfunction and CVD risk factors,” the authors write.

The following table shows significant findings regarding the association between specific CVD risk factors and cognitive impairment.

There were also greater deficits among those with obesity (eight studies; n = 2779; P = .20), overweight (eight studies; n = 2825; P = .41), and insulin resistance (one study; n = 193; P = .18) in comparison with patients who did not have these risk factors. However, the results did not reach significance.

The researchers found different associations in CVD risk factors and specific cognitive domains in patients with schizophrenia.

Those with MetS had greater deficits in global cognition in comparison with those without MetS. Cognitive domains specifically associated with MetS were reasoning/problem solving, speed of processing, verbal learning, and attention/vigilance.

Similarly, global cognition was significantly associated with greater impairment among patients with diabetes. Specific domains that were affected were attention/vigilance, reasoning/problem solving, processing speed, verbal learning, and visual learning.

Compared to patients who did not have arterial hypertension, those with hypertension had poorer global cognition as well as poorer reasoning, speed of processing, verbal learning, and working memory.

There was no significant difference in global cognition between patients with schizophrenia and comorbid obesity or overweight in comparison with those in whom these were not present. However, one study showed significantly poorer visual learning among patients with obesity and overweight in comparison with those without obesity or overweight.

There were no significant cognitive differences between those with and those without dyslipidemia or insulin resistance.

There are several possible reasons for the link between poorer cognition and CVD risk factors in individuals with schizophrenia, Correll said.

“Some people with obesity also have sleep apnea, and therefore not enough oxygen reaches the brain, which can affect cognition, and some people with cardiovascular illness have more inflammation, and we know that inflammation is bad for brain function,” he said.

Moreover, hypertension, metabolic syndrome, and diabetes may “compromise the vasculature in the brain, so people might have mini-strokes or insufficient blood supply in certain brain areas, which can affect cognition,” he said.

Aggressive Approach Needed

Commenting on the study for Medscape Medical News, Henry Nasrallah, MD, professor of psychiatry, neurology, and neuroscience, University of Cincinnati College of Medicine, Cincinnati, Ohio, said that the “practical clinical implications of this study are that hypertension and diabetes must be aggressively treated in patients with schizophrenia to reduce the burden on their cognition, which can lead to further functional impairment.”

Nasrallah, who is also the director of the Neuropsychiatry and Schizophrenia Programs, said that because weight gain and obesity may lead to hypertension and type 2 diabetes, “diet and exercise should be routinely prescribed to patients with schizophrenia.”

Weight loss and exercise “can reduce hypertension and hyperglycemia and can therefore be a useful nonpharmacologic approach to avoiding further cognitive dysfunction in schizophrenia and in the general population as well,” Nasrallah said.

Correll added, “Paying attention to the body and mind helps not only the body but the mind as well.”

The study was funded by Sumitomo Dainippon Pharma. Correll has received grants and personal fees from Janssen/Johnson & Johnson and Takeda outside the submitted work; personal fees from Acadia, Alkermes, Allergan, Angelini, Axsome, Boehringer Ingelheim, Gedeon Richter, Gerson Lehrman Group, Indivior, Intra-Cellular Therapies, LB Pharmaceuticals, Lundbeck, MedAvante-ProPhase, Medscape, Merck, Neurocrine, Noven, Otsuka, Pfizer, Recordati, Rovi, Sumitomo Dainippon, Sunovion, Supernus, Teva, and Servier outside the submitted work; has provided expert testimony for Janssen, Otsuka, and Bristol-Myers Squibb; has served on a data safety monitoring board for Boehringer Ingelheim, Lundbeck, Rovi, Supernus, and Teva; holds stock options in LB Pharma; and has received royalties from UpToDate. The other authors’ relevant financial relationships are listed in the original article. Nasrallah has disclosed no such relationships.

JAMA Psychiatry. Published online March 3, 2021. Abstract

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