Alzheimer's disease and neurodegenerative diseases in France

Bakhta, Kenza; Cecillon, Eléonore; Lacombe, Emma; Lamy, Marie; Leboucher, Aziliz; Philippe, Jeanne

doi:10.1016/s0140-6736(19)31633-2

Cited by 11 publications

(5 citation statements)

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“…RAGE mediates Aβ-induced perturbations in the BBB, neurons, and microglia in AD [21], in which sporadic onset accounts for 95% of cases [42]. The infection has the potential to play a role in sporadic cases of AD [43].…”

Section: Discussionmentioning

confidence: 99%

Receptor for Advanced Glycation End Products (RAGE) Mediates Cognitive Impairment Triggered by Pneumococcal Meningitis

et al. 2021

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Pneumococcal meningitis is a life-threatening infection of the central nervous system (CNS), and half of the survivors of meningitis suffer from neurological sequelae. We hypothesized that pneumococcal meningitis causes CNS inflammation via the disruption of the blood-brain barrier (BBB) and by increasing the receptor for advanced glycation end product (RAGE) expression in the brain, which causes glial cell activation, leading to cognitive impairment. To test our hypothesis, 60-day-old Wistar rats were subjected to meningitis by receiving an intracisternal injection of Streptococcus pneumoniae or artificial cerebrospinal fluid as a control group and were treated with a RAGE-specific inhibitor (FPS-ZM1) in saline. The rats also received ceftriaxone 100 mg/kg intraperitoneally, bid, and fluid replacements. Experimental pneumococcal meningitis triggered BBB disruption after meningitis induction, and FPS-ZM1 treatment significantly suppressed BBB disruption. Ten days after meningitis induction, surviving animals were free from infection, but they presented increased levels of TNF-α and IL-1β in the prefrontal cortex (PFC); high expression levels of RAGE, amyloid-β (Aβ 1-42 ), and microglial cell activation in the PFC and hippocampus; and memory impairment, as evaluated by the open-field, novel object recognition task and Morris water maze behavioral tasks. Targeted RAGE inhibition was able to reduce cytokine levels, decrease the expression of RAGE and Aβ 1-42 , inhibit microglial cell activation, and improve cognitive deficits in meningitis survivor rats. The sequence of events generated by pneumococcal meningitis can persist long after recovery, triggering neurocognitive decline; however, RAGE blocker attenuated the development of brain inflammation and cognitive impairment in experimental meningitis.

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Section: Discussionmentioning

confidence: 99%

Receptor for Advanced Glycation End Products (RAGE) Mediates Cognitive Impairment Triggered by Pneumococcal Meningitis

et al. 2021

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“…Numerous and varied attempts have been made to develop a disease-modifying approach, but none have shown clinical benefits in patients due to the complex pathological mechanism of AD [ 11 ]. Even in August 2018, France’s health insurance system refused to pay for 4 medications for AD (donepezil, lisdexamfetamine, galantamine, and memantine hydrochloride) due to lack of efficacy and a variety of adverse effects [ 12 ]. The vulnerability of ADRD patients is magnified by the morbidity and mortality of COVID-19, as well as the indirect impact of the pandemic on social support and health care systems[ 13 ].…”

Section: Introductionmentioning

confidence: 99%

Effect of Alzheimer Disease on Prognosis of Intensive Care Unit (ICU) Patients: A Propensity Score Matching Analysis

Zhu¹,

Chen

et al. 2022

Med Sci Monit

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Background The growing number of patients with Alzheimer disease worldwide has become a leading public concern. Whether Alzheimer disease has an impact on the outcomes of critically ill patients remains unclear; therefore, we conducted this study to evaluate comorbid Alzheimer disease in patients in the Intensive Care Unit (ICU). Material/Methods Data were extracted from the Medical Information Mart for Intensive Care-III database, version 1.4. Patients were divided into an Alzheimer disease group and a non-Alzheimer disease group. Differences in all-cause mortality, length of hospital stay, mechanical ventilation rate, and mechanical ventilation duration were analyzed. Propensity score matching (PSM) was performed to compensate for differences in baseline characteristics. The differences in prognosis were compared between groups after PSM. Survival analyses in patients were performed and Cox regression analyses were used to predict prognoses. Results We included 33 935 patients, among which 433 patients were comorbid with Alzheimer disease. After PSM, there were no significant differences in 7-day mortality, but there were significant differences in 28-day mortality ( P =0.047) and 90-day mortality ( P =0.012) between the 2 groups. There was also a significant difference in the 4-year cumulative survival between the 2 groups ( P <0.001). In all patients undergoing surgery, multivariate Cox regression analysis showed that Alzheimer disease comorbidity was significantly associated with 90-day mortality and 4-year mortality. Conclusions Critical ill patients with Alzheimer disease had higher 28-day and 90-day mortality. Especially for patients undergoing surgery, Alzheimer disease is an independent risk factor affecting long-term survival.

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“…The prevalence of cognitive dysfunction and dementia, particularly AD, is on the rise in Europe due to the aging population (5)(6)(7)(8). The pathophysiology of AD is complex and involves various mechanisms, including oxidative stress, in ammatory responses, and amyloid β-protein deposition (9)(10).…”

Section: Introductionmentioning

confidence: 99%

Causal relationship between cholesterol-lowering therapy and Alzheimer Disease: evidence from genetic correlation and Mendelian randomization study

Sheng

Gao

Yin

2023

Preprint

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The objective of this study was to investigate the causal relationship between cholesterol-lowering therapy and Alzheimer's disease (AD) using Mendelian Randomization (MR) with two sets of genetic instruments derived from UK Biobank, GLGC, and GWAS ATLAS. Instrumental variables were selected based on SNPs that were significantly associated with lipid-lowering drugs or targets, but not with outcome or confounding factors. The primary analysis was conducted using inverse variance weighted (IVW), MR-PRESSO, WM. Cochran Q, and MR pleiotropy tests to assess heterogeneity or pleiotropy. The results revealed that cholesterol-lowering drugs did not show a significant effect on AD risk with IVW (Atorvastatin: OR = 0.943, 95% CI = 0.612–1.453, p = 0.789; Pravastatin: OR = 6.857, 95% CI = 0.514–90.864, p = 0.144; Rosuvastatin: OR = 2.466, 95% CI = 0.333–18.278, p = 0.377; Simvastatin: OR = 1.138, 95% CI = 0.976–1.328, p = 0.098; Ezetimibe: OR = 1.292, 95% CI = 0.239-6,969, p = 0.766). Further multivariable and target MR analyses (HMGCR, NPC1L1, and PSCK9) also demonstrated that the combination of statins and ezetimibe, or their pharmacological targets, did not show a significant causal relationship with AD. Therefore, based on the current evidence, it can be concluded that there is no causal relationship between cholesterol-lowering drugs and AD.

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Alzheimer's disease and neurodegenerative diseases in France

Cited by 11 publications

References 0 publications

Receptor for Advanced Glycation End Products (RAGE) Mediates Cognitive Impairment Triggered by Pneumococcal Meningitis

Receptor for Advanced Glycation End Products (RAGE) Mediates Cognitive Impairment Triggered by Pneumococcal Meningitis

Effect of Alzheimer Disease on Prognosis of Intensive Care Unit (ICU) Patients: A Propensity Score Matching Analysis

Causal relationship between cholesterol-lowering therapy and Alzheimer Disease: evidence from genetic correlation and Mendelian randomization study

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