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Meta-Analysis
. 2021 May 1;78(5):510-518.
doi: 10.1001/jamapsychiatry.2021.0015.

Association Between Cardiovascular Risk Factors and Cognitive Impairment in People With Schizophrenia: A Systematic Review and Meta-analysis

Katsuhiko Hagi  1 , Tadashi Nosaka  1 , Dwight Dickinson  2 , Jean Pierre Lindenmayer  3 , Jimmy Lee  4   5   6 , Joseph Friedman  7 , Laurent Boyer  8 , Mei Han  9   10 , Nur Amirah Abdul-Rashid  4 , Christoph U Correll  11   12   13   14
Affiliations
Meta-Analysis

Association Between Cardiovascular Risk Factors and Cognitive Impairment in People With Schizophrenia: A Systematic Review and Meta-analysis

Katsuhiko Hagi et al. JAMA Psychiatry. .

Abstract

Importance: Schizophrenia is associated with cognitive dysfunction and cardiovascular risk factors, including metabolic syndrome (MetS) and its constituent criteria. Cognitive dysfunction and cardiovascular risk factors can worsen cognition in the general population and may contribute to cognitive impairment in schizophrenia.

Objective: To study the association between cognitive dysfunction and cardiovascular risk factors and cognitive impairment in individuals with schizophrenia.

Data sources: A search was conducted of Embase, Scopus, MEDLINE, PubMed, and Cochrane databases from inception to February 25, 2020, using terms that included synonyms of schizophrenia AND metabolic adversities AND cognitive function. Conference proceedings, clinical trial registries, and reference lists of relevant publications were also searched.

Study selection: Studies were included that (1) examined cognitive functioning in patients with schizophrenia or schizoaffective disorder; (2) investigated the association of cardiovascular disease risk factors, including MetS, diabetes, obesity, overweight, obesity or overweight, hypertension, dyslipidemia, and insulin resistance with outcomes; and (3) compared cognitive performance of patients with schizophrenia/schizoaffective disorder between those with vs without cardiovascular disease risk factors.

Data extraction and synthesis: Extraction of data was conducted by 2 to 3 independent reviewers per article. Data were meta-analyzed using a random-effects model.

Main outcomes and measures: The primary outcome was global cognition, defined as a test score using clinically validated measures of overall cognitive functioning.

Results: Twenty-seven studies involving 10 174 individuals with schizophrenia were included. Significantly greater global cognitive deficits were present in patients with schizophrenia who had MetS (13 studies; n = 2800; effect size [ES] = 0.31; 95% CI, 0.13-0.50; P = .001), diabetes (8 studies; n = 2976; ES = 0.32; 95% CI, 0.23-0.42; P < .001), or hypertension (5 studies; n = 1899; ES = 0.21; 95% CI, 0.11-0.31; P < .001); nonsignificantly greater deficits were present in patients with obesity (8 studies; n = 2779; P = .20), overweight (8 studies; n = 2825; P = .41), and insulin resistance (1 study; n = 193; P = .18). Worse performance in specific cognitive domains was associated with cognitive dysfunction and cardiovascular risk factors regarding 5 domains in patients with diabetes (ES range, 0.23 [95% CI, 0.12-0.33] to 0.40 [95% CI, 0.20-0.61]) and 4 domains with MetS (ES range, 0.15 [95% CI, 0.03-0.28] to 0.40 [95% CI, 0.20-0.61]) and hypertension (ES range, 0.15 [95% CI, 0.04-0.26] to 0.27 [95% CI, 0.15-0.39]).

Conclusions and relevance: In this systematic review and meta-analysis, MetS, diabetes, and hypertension were significantly associated with global cognitive impairment in people with schizophrenia.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Lindenmayer reports grants from Roche, Alkermes, Astellas, Takeda, Lundbeck, Otsuka, Neurocrine, and, Intra-Cellular Therapies during the conduct of the study; consulting for Janssen, Lundbeck, and Newron; and has a patent to Multi Health Systems issued and with royalties paid. Dr Lee reports grants from Ministry of Health National Medical Research Council in Singapore during the conduct of the study. Dr Correll reports 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; provided expert testimony for Janssen, Otsuka, and Bristol Myers Squibb; served on a data safety monitoring board for Boehringer Ingelheim, Lundbeck, Rovi, Supernus, and Teva; is a stock option holder of LB Pharma; and received royalties from UpToDate. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Flow Diagram
Figure 2.
Figure 2.. Forest Plot of Global Cognitive Differences Between Patients With Schizophrenia With and Without Cognitive Dysfunction and Cardiovascular Risk Factors (CVRF)
BMI indicates body mass index (calculated as weight in kilograms divided by height in meters squared); CVD, cardiovascular disease; MetS, metabolic syndrome; NA, not applicable.
See this image and copyright information in PMC

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