incretins and Cognition-Disorders

We performed a PRISMA systematic review of incretin-based therapies and effects on neurocognitive function in humans. There was observational evidence to support dipeptidyl peptidase-IV inhibitors in improving cognition, whilst glucagon-like peptide-1 had positive effects on cerebral glucose metabolism. Powered clinical trials are now needed in patients with- and without diabetes.

Topics: Adult; Aged; Brain; Cognition; Cognition Disorders; Dipeptidyl Peptidase 4; Dipeptidyl-Peptidase IV Inhibitors; Female; Glucagon-Like Peptide-1 Receptor; Glucose; Humans; Incretins; Male; Middle Aged; Treatment Outcome

Parkinson's disease is a chronic neurodegenerative disorder characterized by a progressive loss of dopaminergic neurons. The pathophysiological mechanisms underlying Parkinson's are still unknown. Mitochondrial dysfunction, abnormal protein aggregation, increased neuroinflammation and impairment of brain glucose metabolism are shared processes among insulinresistance, diabetes and neurodegeneration and have been suggested as key mechanisms in development of Parkinson's and cognitive impairment.. To review experimental and clinical evidence of underlying Parkinson's pathophysiology in common with diabetes and cognitive impairment. Anti-diabetic agents and recent patents for insulin-resistance that might be repositioned in the treatment of Parkinson's also have been included in this review.. A narrative review using MEDLINE database.. Common antidiabetic treatments such as DPP4 inhibitors, GLP-1 agonists and metformin have shown promise in the treatment of Parkinson's disease and cognitive impairment in animals and humans. Study of the pathophysiology of neurodegeneration common between diabetes and Parkinson's disease has given rise to new treatment possibilities. Patents published in the last 5 years could be used in novel approaches to Parkinson's treatment by targeting specific pathophysiology proteins, such as Nurr1, PINK1 and NrF2, while patents to improve penetration of the blood brain barrier could allow improved efficacy of existing treatments.. Further studies using GLP-1 agonists and DPP-4 inhibitors to treat PD are warranted as they have shown promise.

Topics: Animals; Antiparkinson Agents; Brain; Cognition; Cognition Disorders; Diabetes Mellitus; Dipeptidyl-Peptidase IV Inhibitors; Drug Discovery; Drug Repositioning; Humans; Hypoglycemic Agents; Incretins; Insulin Resistance; Neuroprotective Agents; Parkinson Disease; Patents as Topic

Mood disorders may be conceptualized as progressive neurodegenerative disorders associated with cognitive decline. Novel treatments capable of preserving and/or enhancing cognitive function represent an area of priority for research in the future. Insulin, insulin-like growth factor (IGF)-1 and incretins may play a critical role in both physiological and pathophysiological processes of the CNS. An emerging paradigm regarding the pathophysiology of mood disorders posits that alterations in biological networks that mediate stress compromise optimal neuronal and glial function. A growing body of evidence indicates that central administration of insulin may enhance cognitive function in both healthy and cognitively impaired individuals. The neuroactive peptides, insulin, IGF-1 and incretins, or agents that facilitate their central effects (e.g. insulin-sensitizing agents), may constitute novel and possibly disease-modifying neurocognitive treatments.

Topics: Animals; Central Nervous System; Cognition Disorders; Homeostasis; Humans; Incretins; Insulin; Insulin-Like Growth Factor I; Mental Disorders