Insulin, cognition, and dementia.
Cognitive disorders of aging represent a serious threat to the social and economic welfare of current society. It is now widely recognized that pathology related to such conditions, particularly Alzheimer's disease, likely begins years or decades prior to the onset of clinical dementia symptoms. This revelation has led researchers to consider candidate mechanisms precipitating the cascade of neuropathological events that eventually lead to clinical Alzheimer's disease. Insulin, a hormone with potent effects in the brain, has recently received a great deal of attention for its potential beneficial and protective role in cognitive function. Insulin resistance, which refers to the reduced sensitivity of target tissues to the favorable effects of insulin, is related to multiple chronic conditions known to impact cognition and increase dementia risk. With insulin resistance-associated conditions reaching epidemic proportions, the prevalence of Alzheimer's disease and other cognitive disorders will continue to rise exponentially. Fortunately, these chronic insulin-related conditions are amenable to pharmacological intervention. As a result, novel therapeutic strategies that focus on increasing insulin sensitivity in the brain may be an important target for protecting or treating cognitive decline. The following review will highlight our current understanding of the role of insulin in brain, potential mechanisms underlying the link between insulin resistance and dementia, and current experimental therapeutic strategies aimed at improving cognitive function via modifying the brain's insulin sensitivity.
Department of Psychiatry and Behavioral Science, University of Washington School of Medicine, Seattle, WA, USA; Geriatric Research, Education, and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, WA, USA.
Brenna
B
Cholerton
Department of Internal Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina, Winston-Salem, NC 27157-1207, USA.
Laura D
LD
Baker
Department of Internal Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina, Winston-Salem, NC 27157-1207, USA. Electronic address: suzcraft@wakehealth.edu.
Suzanne
S
Craft
D000544:Alzheimer Disease / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000503:physiopathology; D003071:Cognition / Q000187:drug effects; D003704:Dementia / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D006801:Humans; D007328:Insulin / Q000378:metabolism* / Q000494:pharmacology / Q000627:therapeutic use; D007333:Insulin Resistance
D007328:Insulin
Aging; Alzheimer's disease; Cognition; Diabetes; Insulin