Synergism of antihypertensives and cholinesterase inhibitors in Alzheimer's disease

Hu, Ziheng; Wang, Lirong; Ma, Shifan; Kirisci, Levent; Feng, Zhiwei; Xue, Ying; Klunk, William E.; Kamboh, M. Ilyas; Sweet, Robert A.; Becker, James T.; Lv, Qianzhou; López, Oscar L.; Xie, Xiang‐Qun

doi:10.1016/j.trci.2018.09.001

Cited by 10 publications

(8 citation statements)

References 103 publications

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“…Despite the fact that substantial progress has been made over the last decade, the AD-related molecular and cellular pathogenesis remain poorly understood [2], and no pharmacologic therapies are available to stop the disease progression [3]. Moreover, the currently available treatments have extremely limited therapeutic effect [4]. Therefore, further investigation into the pathophysiology and molecular mechanisms underlying AD is urgently required.…”

Section: Introductionmentioning

confidence: 99%

Association of gut microbiota composition and function with a senescence-accelerated mouse model of Alzheimer’s Disease using 16S rRNA gene and metagenomic sequencing analysis

Peng

Yang

et al. 2018

Aging

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Although an intriguing potential association of the gut microbiome with Alzheimer's disease (AD) has attracted recent interest, few studies have directly assessed this relationship or underlying mechanism. Here, we compared the gut microbiota composition and functional differentiation of senescence-accelerated mouse prone 8 (SAMP8) mice with control senescence-accelerated mouse resistant 1 (SAMR1) mice using 16S rRNA gene and metagenomic sequencing analysis, respectively. Specifically, 16S sequencing results showed that the SAMP8 mice displayed a characteristic composition of the gut microbiome that clearly differed from that of the SAMR1 mice. Moreover, network analysis revealed that the gut microbiota of SAMP8 mice had decreased correlation density and clustering of operational taxonomic units. Metagenomic results revealed that the predominant Cluster of Orthologous Groups functional category related to these changes was the metabolism cluster in SAMP8 mice. The Kyoto Encyclopedia of Genes and Genomes (KEGG) annotation further demonstrated enrichment of the relative abundance of some dominant metabolism-related KEGG pathways in the SAMP8 mice, consistent with the suggested pathogenic mechanisms of AD. In conclusion, this study suggests that perturbations of the gut microbiota composition and the functional metagenome may be associated with AD. Further studies are warranted to elucidate the potential new mechanism contributing to AD progression.

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Section: Introductionmentioning

confidence: 99%

Association of gut microbiota composition and function with a senescence-accelerated mouse model of Alzheimer’s Disease using 16S rRNA gene and metagenomic sequencing analysis

Peng

Yang

et al. 2018

Aging

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“…Indeed, beta‐blocker therapy has been shown to cause a significant decrease in PWD 33 ; patients treated with acetylcholinesterase inhibitors were not included to avoid confounding effects on cognitive function. 34 , 35 PWD was assessed via a digital computerized system, confirmed by manual measurements on paper.…”

Section: Methodsmentioning

confidence: 99%

Global cognitive function correlates with P‐wave dispersion in frail hypertensive older adults

Mone

Pansini

Calabrò

et al. 2022

J of Clinical Hypertension

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P-Wave Dispersion (PWD) is an ECG parameter defined as the difference between the longest and the shortest P-Wave duration. PWD has been associated with hypertension, a leading cause of age-related cognitive decline. Moreover, hypertension is associated with vascular dementia and Alzheimer's Disease. Based on these considerations, we evaluated PWD and global cognitive function in frail hypertensive older adults with a previous diagnosis of cognitive decline. We evaluated consecutive frail hypertensive patients ≥65-year-old with a Mini-Mental State Examination (MMSE) score <26. Patients with evidence of secondary hypertension, history of stroke, myocardial infarction, or therapy with beta-blockers or acetylcholinesterase inhibitors were excluded. Beta-blocker therapy causes a significant decrease in PWD; patients treated with acetylcholinesterase inhibitors were not included to avoid confounding effects on cognitive function. By examining 180 patients, we found that PWD significantly correlated with MMSE score. Strikingly, these effects were confirmed in a linear multivariate analysis with a regression model. To our knowledge, this is the first study showing that PWD correlates with global cognitive function in frail hypertensive older adults.

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“…Among veterans with cardiovascular disease, individuals prescribed an ARB that developed AD were slower to require assisted living than AD control patients (Li et al, 2010). Furthermore, a combination of diuretics, calcium channel blockers and ARBs slow cognitive decline (Hu et al, 2018), indicating the potential for synergistic interventions targeting multiple systems. In fact, there is evidence that ARBs may be more effective than ACEIs in regard to cognitive outcomes, independent of their ability to lower blood pressure (Hajjar et al, 2020).…”

Section: Early Studies Of Ras-affecting Compounds In Pre-clinical Andmentioning

confidence: 99%

Angiotensin (1–7) Expressing Probiotic as a Potential Treatment for Dementia

et al. 2021

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Increasing life expectancies are unfortunately accompanied by increased prevalence of Alzheimer's disease (AD). Regrettably, there are no current therapeutic options capable of preventing or treating AD. We review here data indicating that AD is accompanied by gut dysbiosis and impaired renin angiotensin system (RAS) function. Therefore, we propose the potential utility of an intervention targeting both the gut microbiome and RAS as both are heavily involved in proper CNS function. One potential approach which our group is currently exploring is the use of genetically-modified probiotics (GMPs) to deliver therapeutic compounds. In this review, we specifically highlight the potential utility of utilizing a GMP to deliver Angiotensin (1–7), a beneficial component of the renin-angiotensin system with relevant functions in circulation as well as locally in the gut and brain.

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Synergism of antihypertensives and cholinesterase inhibitors in Alzheimer's disease

Cited by 10 publications

References 103 publications

Association of gut microbiota composition and function with a senescence-accelerated mouse model of Alzheimer’s Disease using 16S rRNA gene and metagenomic sequencing analysis

Association of gut microbiota composition and function with a senescence-accelerated mouse model of Alzheimer’s Disease using 16S rRNA gene and metagenomic sequencing analysis

Global cognitive function correlates with P‐wave dispersion in frail hypertensive older adults

Angiotensin (1–7) Expressing Probiotic as a Potential Treatment for Dementia

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