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Recent clinical and epidemiological observations point to a correlation between disorders of energy metabolism, such as obesity and diabetes, and cognitive decline and dementia. Many studies indicate that these age-related conditions closely interact with each other, but the underlying molecular and physiological mechanisms for such correlations are largely unknown. Insulin and leptin, hormones classically implicated in diabetes and obesity, are gaining increasing attention for their participation in cognitive processes and memory. Disrupted signaling by those hormones is associated with impaired brain function. The current review discusses how restoration of insulin and leptin signaling in the brain may attenuate neuronal damage and promote cognition. We further discuss potential therapeutic approaches involving the use of insulin and leptin as cognitive enhancers in the context of metabolic disorders and Alzheimer's disease.
This article is part of the special issue entitled ‘The Quest for Disease-Modifying Therapies for Neurodegenerative Disorders’.
•Insulin and leptin share molecular links related to memory and synaptic plasticity.•Insulin plays a significant role in cognition by modulating brain physiology.•Leptin therapy rescues learning and memory in a mouse model of Alzheimer's disease.•Intranasal delivery of insulin and leptin comprises an effective non-invasive approach to ameliorate cognitive impairment.