Abstract
Diabetes and cognitive dysfunction, ranging from mild cognitive impairment to dementia, often coexist in individuals over 65 years of age. Vascular contributions to cognitive impairment/dementia (VCID) are the second leading cause of dementias under the umbrella of Alzheimer’s disease and related dementias (ADRD). Over half of dementia patients have VCID either as a single pathology or a mixed dementia with AD. While the prevalence of type 2 diabetes in individuals with dementia can be as high as 39% and diabetes increases the risk of cerebrovascular disease and stroke, VCID remains to be one of the less understood and less studied complications of diabetes. We have identified cerebrovascular dysfunction and compromised endothelial integrity leading to decreased cerebral blood flow and iron deposition into the brain, respectively, as targets for intervention for the prevention of VCID in diabetes. This review will focus on targeted therapies that improve endothelial function or remove iron without systemic effects, such as agents delivered intranasally, that may result in actionable and disease-modifying novel treatments in the high-risk diabetic population.
Highlights
The global incidence of diabetes has more than tripled in the last 20 years (International Diabetes Federation; IDF, 2019)
There is increasing recognition that cognitive impairment, ranging from mild cognitive dysfunction to dementia, is another neurological complication of diabetes with vascular origins (Gorelick et al, 2017; van Sloten et al, 2020) as numerous studies have shown that decreased cerebral blood flow (CBF) and increased blood brain barrier (BBB) permeability precede the development of neuronal pathologies and overt cognitive deficits (Iadecola, 2017; Sweeney et al, 2019a)
We have identified cerebrovascular dysfunction and compromised neurovascular unit (NVU) as therapeutic targets and started testing multiple pharmacological interventions to correct these pathologies for the prevention and treatment of Vascular contributions to cognitive impairment/dementia (VCID) in diabetes
Summary
Reviewed by: Kristen Zuloaga, Albany Medical College, United States Ami P. Diabetes and cognitive dysfunction, ranging from mild cognitive impairment to dementia, often coexist in individuals over 65 years of age. While the prevalence of type 2 diabetes in individuals with dementia can be as high as 39% and diabetes increases the risk of cerebrovascular disease and stroke, VCID remains to be one of the less understood and less studied complications of diabetes. We have identified cerebrovascular dysfunction and compromised endothelial integrity leading to decreased cerebral blood flow and iron deposition into the brain, respectively, as targets for intervention for the prevention of VCID in diabetes. This review will focus on targeted therapies that improve endothelial function or remove iron without systemic effects, such as agents delivered intranasally, that may result in actionable and disease-modifying novel treatments in the high-risk diabetic population
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