Impairments in cognitive function represent a consistent, non-specific, and clinically significant
feature in metabolic, mood, and dementing disorders. The foregoing observation is instantiated by evidence
demonstrating that these disorders share pathophysiological mechanisms including, but not limited to, aberrant
insulin signaling, inflammation, and glucocorticoid activity. Moreover, these mechanisms have been
consistently reported to increase vulnerability to and/or exacerbate impairments in cognitive function.
Notwithstanding evidence suggesting a bidirectional relationship between disturbances in the metabolic milieu,
mood, and increased risk for dementia, efficacious treatments that target cognitive impairments in these
populations do not presently exist. Taken together, it is proposed that anti-diabetic agents may aid the
management of mood disorders and future risk for dementia through disease modification by targeting
underlying pathophysiological mechanisms (e.g., aberrant metabolic function) rather than focusing solely on
symptom mitigation. The current aim is to provide a brief narrative review of extant studies that report on the
potential neurotherapeutic effects of anti-diabetic agents on disturbances in mood and impairments in cognitive
Keywords: Depression, bipolar, diabetes, dementia, Alzheimer’s disease, insulin, insulin resistance, GLP-1,
incretin, thiazolidinedione, metformin, cognition.
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