Pathophysiology Associated with Diabetes-induced Tauopathy and Development
of Alzheimer’s Disease

Sarkar, Poulami; Banu, Sharmin; Bhattacharya, Sanchari; Bala, Asis; Sur, Debjeet

doi:10.2174/1573399818666220513142030

Cited by 5 publications

(1 citation statement)

References 74 publications

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“…Among people older than 60 years with type 2 diabetes (T2D), up to 20% of them might develop dementia [ 7 ]. Brain insulin resistance [ 8 ], neuro-inflammatory disorders [ 9 ], oxidative stress [ 7 ], sympathovagal imbalance [ 10 ] and impaired dynamic cerebral autoregulation [ 11 ] have been proposed to explain cerebrovascular disease and cognitive dysfunction in T2D individuals [ 6 , 7 , 12 ]. More specifically, executive function [ 13 ], in particular cognitive flexibility and verbal fluency [ 14 ], and verbal episodic memory [ 14 ] are decreased in individuals with T2D with Cohen’s d ranged from −0.22 to −0.51 compared to healthy controls [ 12 , 14 , 15 ].…”

Section: Introductionmentioning

confidence: 99%

Acute Effects of a Maximal Cardiopulmonary Exercise Test on Cardiac Hemodynamic and Cerebrovascular Response and Their Relationship with Cognitive Performance in Individuals with Type 2 Diabetes

Besnier

Gagnon

Monnet

et al. 2023

IJERPH

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Cardiovascular and cerebrovascular diseases are prevalent in individuals with type 2 diabetes (T2D). Among people with T2D aged over 70 years, up to 45% might have cognitive dysfunction. Cardiorespiratory fitness (V˙O2max) correlates with cognitive performances in healthy younger and older adults, and individuals with cardiovascular diseases (CVD). The relationship between cognitive performances, V˙O2max, cardiac output and cerebral oxygenation/perfusion responses during exercise has not been studied in patients with T2D. Studying cardiac hemodynamics and cerebrovascular responses during a maximal cardiopulmonary exercise test (CPET) and during the recovery phase, as well as studying their relationship with cognitive performances could be useful to detect patients at greater risk of future cognitive impairment. Purposes: (1) to compare cerebral oxygenation/perfusion during a CPET and during its post-exercise period (recovery); (2) to compare cognitive performances in patients with T2D to those in healthy controls; and (3) to examine if V˙O2max, maximal cardiac output and cerebral oxygenation/perfusion are associated with cognitive function in individuals with T2D and healthy controls. Nineteen patients with T2D (61.9 ± 7 years old) and 22 healthy controls (HC) (61.8 ± 10 years old) were evaluated on the following: a CPET test with impedance cardiography and cerebral oxygenation/perfusion using a near-infrared spectroscopy. Prior to the CPET, the cognitive performance assessment was performed, targeting: short-term and working memory, processing speed, executive functions, and long-term verbal memory. Patients with T2D had lower V˙O2max values compared to HC (34.5 ± 5.6 vs. 46.4 ± 7.6 mL/kg fat free mass/min; p < 0.001). Compared to HC, patients with T2D showed lower maximal cardiac index (6.27 ± 2.09 vs. 8.70 ± 1.09 L/min/m2, p < 0.05) and higher values of systemic vascular resistance index (826.21 ± 308.21 vs. 583.35 ± 90.36 Dyn·s/cm5·m2) and systolic blood pressure at maximal exercise (204.94 ± 26.21 vs. 183.61 ± 19.09 mmHg, p = 0.005). Cerebral HHb during the 1st and 2nd min of recovery was significantly higher in HC compared to T2D (p < 0.05). Executive functions performance (Z score) was significantly lower in patients with T2D compared to HC (−0.18 ± 0.7 vs. −0.40 ± 0.60, p = 0.016). Processing speed, working and verbal memory performances were similar in both groups. Brain tHb during exercise and recovery (−0.50, −0.68, p < 0.05), and O2Hb during recovery (−0.68, p < 0.05) only negatively correlated with executive functions performance in patients with T2D (lower tHb values associated with longer response times, indicating a lower performance). In addition to reduced V˙O2max, cardiac index and elevated vascular resistance, patients with T2D showed reduced cerebral hemoglobin (O2Hb and HHb) during early recovery (0–2 min) after the CPET, and lower performances in executive functions compared to healthy controls. Cerebrovascular responses to the CPET and during the recovery phase could be a biological marker of cognitive impairment in T2D.

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Section: Introductionmentioning

confidence: 99%

Acute Effects of a Maximal Cardiopulmonary Exercise Test on Cardiac Hemodynamic and Cerebrovascular Response and Their Relationship with Cognitive Performance in Individuals with Type 2 Diabetes

Besnier

Gagnon

Monnet

et al. 2023

IJERPH

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High glucose- or AGE-induced oxidative stress inhibits hippocampal neuronal mitophagy through the Keap1–Nrf2–PHB2 pathway in diabetic encephalopathy

Xu,

Gao,

Jiang

et al. 2024

Sci Rep

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Diabetic encephalopathy (DE) is a severe complication of diabetes, but its pathogenesis remains unclear. This study aimed to investigate the roles and underlying mechanisms of high glucose (HG)- and advanced glycosylation end product (AGE)-induced oxidative stress (OS) in the cognitive decline in DE. The DE mouse model was established using a high-fat diet and streptozotocin, and its cognitive functions were evaluated using the Morris Water Maze, novel object recognition, and Y-maze test. The results revealed increased reactive oxygen species (ROS) generation, mitophagy inhibition, and decreased prohibitin 2 (PHB2) expression in the hippocampal neurons of DE mice and HG- or AGE-treated HT-22 cells. However, overexpression of PHB2 reduced ROS generation, reversed mitophagy inhibition, and improved mitochondrial function in the HG- or AGE-treated HT-22 cells and ameliorated cognitive decline, improved mitochondrial structural damage, and reversed mitophagy inhibition of hippocampal neurons in DE mice. Further analysis revealed that the Kelch-like ECH-associated protein 1 (Keap1)–nuclear factor erythroid 2-related factor 2 (Nrf2) pathway was involved in the HG- or AGE-mediated downregulation of PHB2 in HT-22 cells. These results demonstrate that HG- or AGE-induced OS inhibits the mitophagy of hippocampal neurons via the Keap1–Nrf2–PHB2 pathway, thereby contributing to the cognitive decline in DE.

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Novel Strategy for Alzheimer’s Disease Treatment through Oral Vaccine Therapy with Amyloid Beta

Matsuzaka

Yashiro

2023

Biologics

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Alzheimer’s disease (AD) is a neuropathology characterized by progressive cognitive impairment and dementia. The disease is attributed to senile plaques, which are aggregates of amyloid beta (Aβ) outside nerve cells; neurofibrillary tangles, which are filamentous accumulations of phosphorylated tau in nerve cells; and loss of neurons in the brain tissue. Immunization of an AD mouse model with Aβ-eliminated pre-existing senile plaque amyloids and prevented new accumulation. Furthermore, its effect showed that cognitive function can be improved by passive immunity without side effects, such as lymphocyte infiltration in AD model mice treated with vaccine therapy, indicating the possibility of vaccine therapy for AD. Further, considering the possibility of side effects due to direct administration of Aβ, the practical use of the safe oral vaccine, which expressed Aβ in plants, is expected. Indeed, administration of this oral vaccine to Alzheimer’s model mice reduced Aβ accumulation in the brain. Moreover, almost no expression of inflammatory IgG was observed. Therefore, vaccination prior to Aβ accumulation or at an early stage of accumulation may prevent Aβ from causing AD.

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Pathophysiology Associated with Diabetes-induced Tauopathy and Development of Alzheimer’s Disease

Cited by 5 publications

References 74 publications

Acute Effects of a Maximal Cardiopulmonary Exercise Test on Cardiac Hemodynamic and Cerebrovascular Response and Their Relationship with Cognitive Performance in Individuals with Type 2 Diabetes

Acute Effects of a Maximal Cardiopulmonary Exercise Test on Cardiac Hemodynamic and Cerebrovascular Response and Their Relationship with Cognitive Performance in Individuals with Type 2 Diabetes

High glucose- or AGE-induced oxidative stress inhibits hippocampal neuronal mitophagy through the Keap1–Nrf2–PHB2 pathway in diabetic encephalopathy

Novel Strategy for Alzheimer’s Disease Treatment through Oral Vaccine Therapy with Amyloid Beta

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