Antihypertensive medications and risk for incident dementia and Alzheimer's disease: a meta-analysis of individual participant data from prospective cohort studies

Ding, Jie; Davis‐Plourde, Kendra; Sedaghat, Sanaz; Tully, Phillip J.; Wang, Wanmei; Phillips, Caroline; Pase, Matthew P.; Himali, Jayandra J.; Windham, B. Gwen; Griswold, Michael; Gottesman, Rebecca F.; Mosley, Thomas H.; White, Lon R.; Guðnason, Vilmundur; Debette, Stéphanie; Beiser, Alexa S.; Seshadri, Sudha; Ikram, M. Arfan; Meirelles, Osorio; Tzourio, Christophe; Launer, Lenore J.

doi:10.1016/s1474-4422(19)30393-x

Cited by 218 publications

(207 citation statements)

References 33 publications

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“…Investigations of neural exosomes and nanosomes revealed that AD patients exhibit metabolic disturbances many years before they develop AD [ 61 ]. Dysregulated insulin signaling is one of the main metabolic dysfunction that contributes to AD pathology [ 62 ]. Insulin is one of the hormones that affect every single cell in the body, and the insulin/insulin-like growth factor (IIS) signaling pathway interacts with other pathways and affects their functioning [ 63 ].…”

Section: The Mechanism Underlying Ad Developmentmentioning

confidence: 99%

Royal Jelly as an Intelligent Anti-Aging Agent—A Focus on Cognitive Aging and Alzheimer’s Disease: A Review

Ali

2020

Antioxidants

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The astronomical increase of the world’s aged population is associated with the increased prevalence of neurodegenerative diseases, heightened disability, and extremely high costs of care. Alzheimer’s Disease (AD) is a widespread, age-related, multifactorial neurodegenerative disease that has enormous social and financial drawbacks worldwide. The unsatisfactory outcomes of available AD pharmacotherapy necessitate the search for alternative natural resources that can target various the underlying mechanisms of AD pathology and reduce disease occurrence and/or progression. Royal jelly (RJ) is the main food of bee queens; it contributes to their fertility, long lifespan, and memory performance. It represents a potent nutraceutical with various pharmacological properties, and has been used in a number of preclinical studies to target AD and age-related cognitive deterioration. To understand the mechanisms through which RJ affects cognitive performance both in natural aging and AD, we reviewed the literature, elaborating on the metabolic, molecular, and cellular mechanisms that mediate its anti-AD effects. Preclinical findings revealed that RJ acts as a multidomain cognitive enhancer that can restore cognitive performance in aged and AD models. It promotes brain cell survival and function by targeting multiple adversities in the neuronal microenvironment such as inflammation, oxidative stress, mitochondrial alterations, impaired proteostasis, amyloid-β toxicity, Ca excitotoxicity, and bioenergetic challenges. Human trials using RJ in AD are limited in quantity and quality. Here, the limitations of RJ-based treatment strategies are discussed, and directions for future studies examining the effect of RJ in cognitively impaired subjects are noted.

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Section: The Mechanism Underlying Ad Developmentmentioning

confidence: 99%

Royal Jelly as an Intelligent Anti-Aging Agent—A Focus on Cognitive Aging and Alzheimer’s Disease: A Review

Ali

2020

Antioxidants

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“…Some of these abnormalities are probably mediated by indirect effects of intracerebral A␤ peptides. A␤ 40 induces vasoconstriction in isolated arteries and on application to mouse cortex [14][15][16]. Functional hyperemia and endothelium-dependent relaxation are attenuated by A␤ through a mechanism shown to involve Nox2-derived reactive oxygen species [17][18][19].…”

Section: Jc Palmer Et Al / Era Prevents Aβ-induced Hypertensionmentioning

confidence: 99%

“…Anti-hypertensive medications are being trialed to prevent cognitive decline [38]. The evidence is unclear as to whether a reduction in incident dementia is associated only with certain classes of anti-hypertensives: only calcium-channel blockers and renin-angiotensin system blockers had a significant effect in one analysis [39], but another meta-analysis found that people with hypertension had a reduced risk of developing dementia when taking any class of anti-hypertensive medication [40]. The direct vasodilatory effect on the cerebral vasculature of these commonly prescribed antihypertensive mediations is potentially a major confounder in studies investigating the impact of lowering BP on the AD risk.…”

Section: Jc Palmer Et Al / Era Prevents Aβ-induced Hypertensionmentioning

confidence: 99%

“…4-week infusion of either A␤ 40 (human A␤1-40; AnaSpec; San Jose, CA, USA) or saline into the brain parenchyma was performed using the Alzet ® osmotic pump model 2004 and Alzet ® brain infusion kit 1 (both Charles River). We directed infusions into the brain parenchyma as our previous study of A␤ 40 infusion into the right lateral ventricle indicated rapid clearance [35].…”

Section: Mini-osmotic Pump Implantationmentioning

confidence: 99%

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Zibotentan, an Endothelin A Receptor Antagonist, Prevents Amyloid-β-Induced Hypertension and Maintains Cerebral Perfusion

Palmer

Tayler

Dyer

et al. 2020

JAD

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Cerebral blood flow is reduced in Alzheimer's disease (AD), which is associated with mid-life hypertension. In people with increased cerebral vascular resistance due to vertebral artery or posterior communicating artery hypoplasia, there is evidence that hypertension develops as a protective mechanism to maintain cerebral perfusion. In AD, amyloid-␤ (A␤) accumulation may similarly raise cerebral vascular resistance by upregulation of the cerebral endothelin system. The level of endothelin-1 in brain tissue correlates positively with A␤ load and negatively with markers of cerebral hypoperfusion such as increased vascular endothelial growth factor. We previously showed that cerebroventricular infusion of A␤ 40 exacerbated preexisting hypertension in Dahl rats. We have investigated the effects of 28-day cerebral infusion of A␤ 40 on blood pressure and heart rate and their variability; carotid flow; endothelin-1; and markers of cerebral oxygenation, in the (normotensive) Wistar rat, and the modulatory influence of the endothelin A receptor antagonist Zibotentan (ZD4054). Cerebral infusion of A␤ caused progressive rise in blood pressure (p < 0.0001) (paired t-test: increase of 3 (0.1-5.6) mmHg (p = 0.040)), with evidence of reduced baroreflex responsiveness, and accumulation of A␤ and elevated endothelin-1 in the vicinity of the infusion. Oral Zibotentan (3 mg/kg/d, administered for 31 d) abrogated the effects of A␤ 40 infusion on baroreflex responsiveness and blood pressure, which declined, although without reduction in carotid blood flow, and Zibotentan caused uncoupling of the positive linear relationship between endothelin-1 and vascular endothelial growth factor, which as a sensor of tissue oxygenation would be expected to increase if there were hypoperfusion.

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“…Hypertension is recognized as a leading vascular risk factor for AD (Oveisgharan and Hachinski, 2010;Iadecola, 2014;Livingston et al, 2017) but studies on whether anti-hypertensive therapy can offer cognitive protection have had mixed results (Lithell et al, 2004;Peters et al, 2008;McGuinness et al, 2009;Perrotta et al, 2016). A recent meta-analysis of prospective cohort studies showed a reduced risk of dementia with use of any antihypertensive medication (Ding et al, 2019), suggesting a benefit that was independent of drug class. The recent SPRINT-MIND trial demonstrated a reduced incidence of cognitive impairment in the intensive blood pressure control group when compared to standard treatment group (Williamson et al, 2019), further supporting a direct relationship between neurodegenerative disease and elevated blood pressure.…”

Section: Introductionmentioning

confidence: 99%

Hypertension and Pathogenic hAPP Independently Induce White Matter Astrocytosis and Cognitive Impairment in the Rat

Levit

Cheng

Hough

et al. 2020

Front. Aging Neurosci.

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Hypertension is recognized as a risk factor for Alzheimer disease, but the causal link remains undetermined. Although astrocytes and microglia play an important role in maintaining the neurovascular unit, astrocytes and microglia have been understudied in comorbid models of hypertension and Alzheimer disease. In this study, male transgenic Fischer 344 rats (TgAPP21) overexpressing a pathogenic human amyloid precursor protein received 8 weeks of Angiotensin II infusion to increase blood pressure, and the rats were evaluated for astrocytosis, microgliosis, and cognitive function. A linear relationship between astrocytosis and blood pressure was observed in the corpus callosum and cingulum of wildtype rats, with hypertensive wildtype rats matching the elevated baseline astrocytosis seen in normotensive transgenic rats. In contrast, hypertensive transgenic rats did not demonstrate a further increase of astrocytosis, suggesting a deficient response. Angiotensin II infusion did not affect activation of microglia, which were elevated in the white matter and hippocampus of transgenic rats. Angiotensin II infusion did impair both wildtype and transgenic rats' executive functions in the Morris Water Maze. These results present important implications for the interaction between hypertension and pathogenic human amyloid precursor protein expression, as Angiotensin II infusion produced cognitive impairments in both genotypes, but transgenic rats were additionally impaired in developing a normal astrocytic response to elevated blood pressure.

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Antihypertensive medications and risk for incident dementia and Alzheimer's disease: a meta-analysis of individual participant data from prospective cohort studies

Cited by 218 publications

References 33 publications

Royal Jelly as an Intelligent Anti-Aging Agent—A Focus on Cognitive Aging and Alzheimer’s Disease: A Review

Royal Jelly as an Intelligent Anti-Aging Agent—A Focus on Cognitive Aging and Alzheimer’s Disease: A Review

Zibotentan, an Endothelin A Receptor Antagonist, Prevents Amyloid-β-Induced Hypertension and Maintains Cerebral Perfusion

Hypertension and Pathogenic hAPP Independently Induce White Matter Astrocytosis and Cognitive Impairment in the Rat

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