The relationship of hypertension in the elderly to AD, vascular dementia, and cognitive function

Posner, Holly; Tang, Mingxin; Luchsinger, José A.; Lantigua, Rafael; Stern, Yaakov; Mayeux, Richard

doi:10.1212/wnl.58.8.1175

Cited by 279 publications

(186 citation statements)

References 40 publications

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“…Mid-life hypertension increases the risk of AD in later life [93][94][95]. Accordingly, hypertension medications including angiotensin converting enzyme (ACE) inhibitors, calcium channel blockers (CCBs), and angiotensin-1 receptor blockers (ARBs) have been tested as potential therapeutics for AD.…”

Section: Antihypertensive Drugsmentioning

confidence: 99%

Drug Repositioning Approaches for the Discovery of New Therapeutics for Alzheimer's Disease

Kim

2015

Neurotherapeutics

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Summary Alzheimer's disease (AD) is the most common cause of dementia and represents one of the highest unmet needs in medicine today. Drug development efforts for AD have been encumbered by largely unsuccessful clinical trials in the last decade. Drug repositioning, a process of discovering a new therapeutic use for existing drugs or drug candidates, is an attractive and timely drug development strategy especially for AD. Compared with traditional de novo drug development, time and cost are reduced as the safety and pharmacokinetic properties of most repositioning candidates have already been determined. A majority of drug repositioning efforts for AD have been based on positive clinical or epidemiological observations or in vivo efficacy found in mouse models of AD. More systematic, multidisciplinary approaches will further facilitate drug repositioning for AD. Some experimental approaches include unbiased phenotypic screening using the library of available drug collections in physiologically relevant model systems (e.g. stem cell-derived neurons or glial cells), computational prediction and selection approaches that leverage the accumulating data resulting from RNA expression profiles, and genome-wide association studies. This review will summarize several notable strategies and representative examples of drug repositioning for AD.

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Section: Antihypertensive Drugsmentioning

confidence: 99%

Drug Repositioning Approaches for the Discovery of New Therapeutics for Alzheimer's Disease

Kim

2015

Neurotherapeutics

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“…In community-based studies among the general population, older age, female gender, low education, race and ethnicity, diabetes, hypertension, lipids, stroke, anemia, history of head trauma, mid-life obesity, inflammatory factors, the APOE4 allele and other genetic markers have been identified as risk factors for Alzheimer's disease or vascular cognitive impairment in community-based studies of the general community population (17)(18)(19)(20)(21)(22)(23). Dietary intake (fruits, vegetables, Omega 3's, Mediterranean diet) and physical activity appear to be protective, and hormone replacement therapy and homocysteine are still controversial; there is also an interactive effect between some risk factors and the APOE-4 allele (24).…”

Section: Risk Factors For Cognitive Impairment In Hemodialysis Patientsmentioning

confidence: 99%

“…However, in contrast to the general population, the roles of aging and non-vascular factors are overshadowed by stroke and the high prevalence of cardiovascular risk factors (18)(19)(20). In addition, the contributions of factors secondary to kidney failure such as uremia, anemia, metabolic disturbances and hemodynamic instability during dialysis are still to be defined (4,25).…”

Section: Risk Factors For Cognitive Impairment In Hemodialysis Patientsmentioning

confidence: 99%

“…Most hemodialysis patients are vasculopaths, with high rates of hypertension (80%), diabetes (60%) (14), markedly elevated levels of inflammatory markers and homocysteine (27), vascular endothelial dysfunction (28), cardiovascular events including stroke (29,30), and carotid atherosclerosis (31), all of which contribute to vascular cognitive impairment (23) and neurodegenerative diseases such as Alzheimer's disease (18,32). Ischemic cerebrovascular disease and underlying vascular endothelial pathology however appear to play the largest roles in the genesis of cognitive impairment in CKD and hemodialysis patients.…”

Section: Risk Factors For Cognitive Impairment In Hemodialysis Patientsmentioning

confidence: 99%

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Cognitive Impairment in the Aging Dialysis and Chronic Kidney Disease Populations: An Occult Burden

Murray

2008

Advances in Chronic Kidney Disease

348

241

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The heavy burden of cognitive impairment in hemodialysis and chronic kidney disease patients has only recently become recognized. Up to 70 percent of hemodialysis patients ages 55 years and older have moderate to severe chronic cognitive impairment, yet it is largely undiagnosed. Recent studies describe the strong graded relation between estimated glomerular filtration rate (eGFR) and cognitive function in CKD patients. The process of conventional hemodialysis may induce recurrent episodes of acute cerebral ischemia, which in turn may contribute to acute decline in cognitive function during dialysis. Thus the worst time to communicate with dialysis patients may be during the hemodialysis session. Both symptomatic and occult, subclinical ischemic cerebrovascular disease appear to play a large role in a proposed model of accelerated vascular cognitive impairment in these populations. Severe cognitive impairment or dementia among hemodialysis patients is associated with an approximately two-fold increased risk of both mortality and dialysis withdrawal. Pre-dialysis cognitive screening and adding dementia to the list of comorbidities on Form 2728 would provide critical information regarding the benefit versus risks of receiving dialysis. It could also improve quality of care and outcomes by raising clinician's awareness of the potential effects of cognitive impairment on medication, fluid, and dietary compliance, and ability to make advance directive decisions among dialysis patients. While much remains to be learned regarding the pathophysiology of cognitive impairment in kidney disease, the public health implications of this substantial burden are immediate.

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“…Intimale Hyperplasie, hyaline Degeneration und fibrinoide Nekrose der Media und Kalzifikationen der Adventitia intrazerebraler Arteriolen führen zu einer Rechtsverschiebung der zerebralen Autoregulation [7], wodurch das Risiko einer kritischen Hypoperfusion bei niedrigeren Perfusionsdrücken zunimmt [75]. Eine eingeschränkte Reservekapazität verursacht darüber hinaus eine Störung in der Anpassung eines raschen, bedarfsgerechten regionalen Blutflusses [64]. Leu …”

Section: Pathophysiologieunclassified

Arterielle Hypertonie und Demenz

Scheid

Voigt

2005

Nervenarzt

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Die arterielle Hypertonie ist unabhän-gig von ihrer Genese als wichtigster beeinflussbarer Risikofaktor für den Schlaganfall etabliert. Ätiologisch werden 26-49% aller Schlaganfälle auf eine arterielle Hypertonie (AH) zurückgeführt [24]. Über die Konstruktion einer einfachen ätiopa-thogenetischen Reihe AH -Schlaganfall -vaskuläre Demenz (VD) ist die AH mit dem Syndrom Demenz verknüpft. Die Demenzinzidenz nach Schlaganfall wird in der Literatur mit 6-33% angegeben [52,59]. Für den Oberbegriff VD ist eine Reihe spezifischerer Unterteilungen vorgenommen worden. Román et al. unterscheiden eine zerebrale Makroangiopathie+Demenz mit Unterkategorien "multi-infarct" und "strategic-infarct dementia" von einer zerebralen Mikroangiopathie+Demenz mit Unterkategorien "subkortikal ischämisch" und "kortikal subkortikal". Weitere Kategorien sind "ischämisch hypoperfusive VD" und "hämorrhagische VD" [7]. Ein aktueller klinisch-pragmatisch orientierter Ansatz schlägt die Unterscheidung von 3 Typen vor: "post-stroke dementia", subkortikale VD und Alzheimer+VD [86]. Als verbindender Überbegriff dient der Terminus "vascular cognitive impairment" [30,59].Aber auch für die häufigere degenerative Demenz, die Alzheimer-Demenz (AD), wird die AH zunehmend als Risikofaktor diskutiert [0, 72, 75, 79]

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The relationship of hypertension in the elderly to AD, vascular dementia, and cognitive function

Abstract: Hypertension after age 65 years is not associated with AD and does not adversely affect memory, language, or general cognitive function. A history of hypertension may be an antecedent to VaD, particularly in the presence of heart disease or diabetes.

Cited by 279 publications

References 40 publications

Drug Repositioning Approaches for the Discovery of New Therapeutics for Alzheimer's Disease

Drug Repositioning Approaches for the Discovery of New Therapeutics for Alzheimer's Disease

Cognitive Impairment in the Aging Dialysis and Chronic Kidney Disease Populations: An Occult Burden

Arterielle Hypertonie und Demenz

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