M48. IS METABOLIC SYNDROME RELATED TO COGNITIVE PERFORMANCE IN PATIENTS WITH SCHIZOPHRENIA? RESULTS FROM A DOUBLE-BLIND, ACTIVE-CONTROLLED, LURASIDONE STUDY
Authors: Hagi Katsuhiko , Nosaka Tadashi , Pikalov Andrei 
Published: May 2020

Abstract

Background
Schizophrenia is associated with cognitive dysfunction as well as cardiovascular disease (CVD).
A central risk factor for CVD is the metabolic syndrome (MetS), which is of special concern in schizophrenia.
The prevalence of MetS in U.S. patients with schizophrenia is higher versus general population (32.5% versus 23%). The prevalence of MetS and diabetes mellitus (DM) in those with schizophrenia double that of the general population. Adverse events of some antipsychotics used to treat schizophrenia include weight gain, obesity and other MetS complications, particularly abnormal glucose and lipid metabolism. Patients with schizophrenia have low rates of treatment for MetS and its components.
Furthermore, components of MetS are risk factors for cognitive impairment and dementia in the general population. Cognitive impairment is a hallmark feature of schizophrenia, and the level of community functioning is strongly correlated with the degree of cognitive impairment.
Given the importance of cognitive impairment in schizophrenia, the potential role of MetS in contributing to cognitive dysfunction is important.
The objective of this post-hoc analysis was to examine cross-sectional relationships between metabolic syndrome and cognitive performance in patients with schizophrenia treated with lurasidone or quetiapine XR for 6-weeks.

Methods
This post hoc analysis utilized data from 6-week, double-blind, placebo-controlled trial of patients with an acute exacerbation of schizophrenia who were randomized to fixed, once-daily oral doses of lurasidone 80 mg (LUR 80 n=125), lurasidone 160 mg (LUR 160, n=121), quetiapine XR 600 mg (QXR, n=120) and placebo (PBO, n=122). Patients with metabolic syndrome (MetS) at baseline were identified based on the National Cholesterol Education Program – Adult Treatment Panel III criteria (NCEP-ATP-III).
Cognitive performance and functional capacity were assessed by the CogState computerized cognitive battery at baseline and 6 weeks.

Results
In the acute 6-week period, LUR160 was significantly superior on the cognitive composite score to PBO (p&lt;0.05, d=0.37), while LUR 80 and QXR did not separate from PBO in the evaluable analysis sample (excluding subjects with non-evaluable composite Z-scores; n=267).
A total of 45/267 (16.9%) patients met criteria for MetS.
Treatment of patients with MetS group with LUR 160 (vs placebo) was associated with significantly greater week 6 improvement in the cognitive composite score (p&lt;0.05, d=1.15), while LUR 80 and QXR did not separate from PBO.
In the group without MetS, LUR dose groups and QXR did not differ from PBO in the CogState composite score.
In the analysis of cognitive domain scores, LUR 80 was significantly superior to PBO on working memory in the group with MetS (p&lt;0.05, d=1.01) and reasoning/problem solving in the group without MetS (p&lt;0.05, d=0.46).
LUR 160 was significantly superior to PBO on processing speed in the group with MetS (p&lt;0.05, d=1.20), reasoning/problem solving (p&lt;0.05, d=0.45) and social cognition (p&lt;0.05, d=0.46) in the group without MetS.
QXR was significantly superior to PBO on verbal learning and reasoning/problem solving in the group without MetS (p&lt;0.05, d=0.38 and p&lt;0.05, d=0.37, respectively).

Discussion
Patients with MetS responded to treatment with lurasidone with significantly improved CogState composite and domain scores. No improvement on cognition was seen in patients with MetS treated with QXR. Evaluation of potential for MetS and improvements in cognition should be important elements in the algorithm of optimization of treatment in patients with schizophrenia.