α7 Nicotinic Acetylcholine Receptor: A Potential Target in Treating Cognitive Decline in Schizophrenia.

PURPOSE: The aim of this article is to review the recent trials of α7 nicotinic acetylcholine receptor (α7 nAChR) agonists and positive allosteric modulators (PAMs) on the treatment of cognitive decline in schizophrenia. α7 Nicotinic acetylcholine receptor abnormalities in schizophrenia and clinical implications of α7 nAChR agonists and PAMs are also discussed.

PROCEDURES: Studies were searched on PubMed with keywords "nicotinic," "alpha7," and "schizophrenia" over a 2-year period: January 1, 2016, to December 1, 2017. Cognition was not included in key terms in order to broaden the results. Inclusion criteria included (1) article categorization as a clinical study, review, or journal article; (2) schizophrenia diagnosis based on Diagnostic and Statistical Manual of Mental Disorders criteria; (3) article in English; (4) objective measure of cognition from effects of α7 nAChR agonists/PAMs; and (5) article currently published.

FINDINGS: A total of 76 studies were found over the past 2 years. Fifteen of these studies were included in this review. Human studies were limited. Cognitive-related improvements in rodent models were found across the 6 cognitive constructs: perception, executive functioning, social and affective processes, working memory, and long-term memory.

IMPLICATIONS: These results support the potential of nAChR agonists and PAMs to improve cognitive decline in patients with schizophrenia as an adjunct treatment to antipsychotics. However, these results were found primarily in rodent models of schizophrenia, and further primate/human studies are necessary to support this conclusion in humans.