This study investigated the relationships of cardiovascular risk factors with verbal learning and memory in patients with schizophrenia. Our findings provide evidence for a link between MetS and more severe memory impairment in schizophrenia. In addition, alcohol dependence or abuse also showed a significant relationship, whereas tobacco was not associated with memory impairment. These findings suggest that modifiable risk factors should be sought in patients with schizophrenia, as their optimal treatment may improve these patients' cognitive performance or keep the existing deficits from progressing.
First, we have found an association between the number of MeTS criteria present and memory impairment. Our findings confirm the link between cognitive impairments associated with MeTS in schizophrenia [3
], and suggest that interventions to reduce cardiovascular risk factors may have positive effects on memory deficits. Our results are also in line with previous studies' findings showing that metabolic syndrome contributes to cognitive impairment in elders [4
]. Indeed, we found that among the different components of MeTS, hypertriglycerides, abdominal obesity, low HDL cholesterol were the most important features associated with memory impairment. These three factors are well-established risk factors for atherosclerosis [19
], suggesting that atherosclerosis may be linked to cognitive impairment in schizophrenia. Several authors have also proposed nonvascular mechanisms involving actions of adiposity on neuronal tissue through neurochemical mediators, such as leptin [20
]. Surprisingly, other factors such as hyperglycaemia and hypertension were not statistically associated with cognitive impairment in our study. These results contradict some previous studies [6
], specifically the study performed by Friedman et al., who found that hypertension increased the risk for cognitive impairment [13
]. One explanation could be the differences between populations, especially the relatively young average age in our study (36.6 years) compared with previous studies (47.3 years in Friedman's study). Future studies are necessary to explore the influence of the length of exposure to each component of MetS on memory impairment.
In accordance with several previous studies, alcohol dependence or abuse [25
] was associated with cognitive impairment. Alcohol may worsen the already decreased cholinergic transmission involved in cognitive impairment in schizophrenia [27
]. The neurotoxic action of alcohol, which is exerted via accelerated cerebral atrophy and reduced acetylcholine synthesis, has been described previously [29
]. Interestingly, a recent study supports that alcohol use may exacerbate an existing neurobiological alteration associated with schizophrenia [30
]. In practice, patients with coexisting mental and substance use disorders, such as alcohol abuse, have rarely received necessary treatments and have generally experienced poor outcomes [31
]. Hence, doctors should consider the possible existence of alcohol dependence or abuse when planning cognitive rehabilitation programs with these patients, and they should develop better coordination between addiction and mental health services in the treatment of these patients.
Surprisingly, our findings did not support the existence of a relationship between smoking and memory. Nicotine is a cholinergic agonist that can counteract the cholinergic dysfunction in cognitive impairment [33
]. However, previous studies found a relationship with smoking only for working memory, spatial organization, attention, and inhibitory function [28
]. In addition, nicotine can also desensitize/inactivate nicotinic acetylcholine receptors induced by repeated nicotine exposure [35
]. Our findings should however be interpreted with caution because nicotine consumption was not precisely measured in our study (i.e., amount consumed, duration of consumption/abstinence, passive smoking).
Limitations and Perspectives
- The sample may not be representative of the entire population of patients with schizophrenia. Patients were mostly middle-aged males with more than 5 years of illness duration. Thus, we need confirmation for more diverse and larger groups of patients.
- This study is limited by being cross-sectional in design rather than prospective in design. No causal inference can be made formally between MeTS, alcohol and memory, and our models should be interpreted from an associational point of view. Future longitudinal studies are needed to confirm that the sequence MeTS/alcohol→Memory is temporally verified.
- We only studied memory function because it is among the most commonly affected cognitive domains in patients with schizophrenia. Future studies should investigate other cognitive composites such as attention and executive function. Considering just one composite would not have been a perfect reflection of a global cognitive function. It would have been misleading to assume that our patients were not suffering from other neuropsychological deficits.
- Several important data were not available, such as eating habits, alcohol use, and smoking details (i.e., amount and duration of consumption). Another potential weakness is related to the different medications used by patients. It appears that antipsychotics may have an impact on metabolic syndrome and cognition [36, 37]. In particular, atypical antipsychotics differ markedly in their potential to cause metabolic disturbances  or to improve cognition . Further studies should thus investigate the complex interactions of antipsychotics, MeTS, and cognition, and examine the role of antipsychotics precisely.
- Future studies will need to address whether preventing or lowering MeTS and alcohol use will improve cognitive impairment.
- Finally, multiple tests were performed in our study and we cannot exclude false-positive results.