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Article

Cognitive Impairment in Frail Hypertensive Elderly Patients: Role of Hyperglycemia

by
Pasquale Mone
1,2,3,*,
Jessica Gambardella
3,4,
Antonella Pansini
1,
Antonio de Donato
2,
Giuseppe Martinelli
5,
Eugenio Boccalone
6,
Alessandro Matarese
7,
Salvatore Frullone
1 and
Gaetano Santulli
3,4,8,*
1
ASL Avellino, 83100 Avellino, Italy
2
Department of Mental and Physical Health and Preventive Medicine, University of Campania “Luigi Vanvitelli”, 80121 Naples, Italy
3
Department of Medicine (Cardiology), Wilf Family Cardiovascular Research Institute, Fleischer Institute for Diabetes and Metabolism (FIDAM), Albert Einstein College of Medicine, New York, NY 10461, USA
4
International Translational Research and Medical Education Consortium (ITME), University “Federico II” of Naples, 80131 Naples, Italy
5
ASL Naples, 80100 Naples, Italy
6
ASL Caserta, 81100 Caserta, Italy
7
Cardarelli Hospital, 80131 Naples, Italy
8
Department of Molecular Pharmacology, Einstein Institute for Aging Research, Einstein-Sinai Diabetes Research Center (ES-DRC), Albert Einstein College of Medicine, New York, NY 10461, USA
*
Authors to whom correspondence should be addressed.
Cells 2021, 10(8), 2115; https://doi.org/10.3390/cells10082115
Submission received: 8 June 2021 / Revised: 11 August 2021 / Accepted: 13 August 2021 / Published: 17 August 2021
(This article belongs to the Special Issue Cellular Senescence in Age-Related Diseases: Molecular Bases and Therapeutic Interventions)
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Abstract

Endothelial dysfunction is a key hallmark of hypertension, which is a leading risk factor for cognitive decline in older adults with or without frailty. Similarly, hyperglycemia is known to impair endothelial function and is a predictor of severe cardiovascular outcomes, independent of the presence of diabetes. On these grounds, we designed a study to assess the effects of high-glucose and metformin on brain microvascular endothelial cells (ECs) and on cognitive impairment in frail hypertensive patients. We tested the effects of metformin on high-glucose-induced cell death, cell permeability, and generation of reactive oxygen species in vitro, in human brain microvascular ECs. To investigate the consequences of hyperglycemia and metformin in the clinical scenario, we recruited frail hypertensive patients and we evaluated their Montreal Cognitive Assessment (MoCA) scores, comparing them according to the glycemic status (normoglycemic vs. hyperglycemic) and the use of metformin. We enrolled 376 patients, of which 209 successfully completed the study. We observed a significant correlation between MoCA score and glycemia. We found that hyperglycemic patients treated with metformin had a significantly better MoCA score than hyperglycemic patients treated with insulin (18.32 ± 3.9 vs. 14.94 ± 3.8; p < 0.001). Our in vitro assays confirmed the beneficial effects of metformin on human brain microvascular ECs. To our knowledge, this is the first study correlating MoCA score and glycemia in frail and hypertensive older adults, showing that hyperglycemia aggravates cognitive impairment.
Keywords: aging; antidiabetic drugs; metformin; endothelial cells; cognitive impairment; frailty; hypertension; hyperglycemia; anti-aging research; therapeutic strategies; age-related disease; metabolism aging; antidiabetic drugs; metformin; endothelial cells; cognitive impairment; frailty; hypertension; hyperglycemia; anti-aging research; therapeutic strategies; age-related disease; metabolism

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MDPI and ACS Style

Mone, P.; Gambardella, J.; Pansini, A.; de Donato, A.; Martinelli, G.; Boccalone, E.; Matarese, A.; Frullone, S.; Santulli, G. Cognitive Impairment in Frail Hypertensive Elderly Patients: Role of Hyperglycemia. Cells 2021, 10, 2115. https://doi.org/10.3390/cells10082115

AMA Style

Mone P, Gambardella J, Pansini A, de Donato A, Martinelli G, Boccalone E, Matarese A, Frullone S, Santulli G. Cognitive Impairment in Frail Hypertensive Elderly Patients: Role of Hyperglycemia. Cells. 2021; 10(8):2115. https://doi.org/10.3390/cells10082115

Chicago/Turabian Style

Mone, Pasquale, Jessica Gambardella, Antonella Pansini, Antonio de Donato, Giuseppe Martinelli, Eugenio Boccalone, Alessandro Matarese, Salvatore Frullone, and Gaetano Santulli. 2021. "Cognitive Impairment in Frail Hypertensive Elderly Patients: Role of Hyperglycemia" Cells 10, no. 8: 2115. https://doi.org/10.3390/cells10082115

APA Style

Mone, P., Gambardella, J., Pansini, A., de Donato, A., Martinelli, G., Boccalone, E., Matarese, A., Frullone, S., & Santulli, G. (2021). Cognitive Impairment in Frail Hypertensive Elderly Patients: Role of Hyperglycemia. Cells, 10(8), 2115. https://doi.org/10.3390/cells10082115

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