Kazuaki SHIMAMOTO, Katsuyuki ANDO, Toshiro FUJITA, Naoyuki HASEBE, Jitsuo HIGAKI, Masatsugu HORIUCHI, Yutaka IMAI, Tsutomu IMAIZUMI, Toshihiko ISHIMITSU, Masaaki ITO, Sadayoshi ITO, Hiroshi ITOH, Hiroshi IWAO, Hisashi KAI, Kazuomi KARIO, Naoki KASHIHARA, Yuhei KAWANO, Shokei KIM-MITSUYAMA, Genjiro KIMURA, Katsuhiko KOHARA, Issei KOMURO, Hiroo KUMAGAI, Hideo MATSUURA, Katsuyuki MIURA, Ryuichi MORISHITA, Mitsuhide NARUSE, Koichi NODE, Yusuke OHYA, Hiromi RAKUGI, Ikuo SAITO, Shigeyuki SAITOH, Kazuyuki SHIMADA, Tatsuo SHIMOSAWA, Hiromichi SUZUKI, Kouichi TAMURA, Norio TANAHASHI, Takuya TSUCHIHASHI, Makoto UCHIYAMA, Shinichiro UEDA, Satoshi UMEMURA, on behalf of The Japanese Society of Hypertension Committee for Guidelines for the Management of Hypertension

/pdf/the-japanese-society-of-hypertension-guidelines-for-the-39bqgfj2cl.pdf

The Japanese Society of Hypertension guidelines for the management of hypertension (JSH 2014)

Satoshi Umemura ● Hisatomi Arima ● Shuji Arima ● Kei Asayama ● Yasuaki Dohi ● Yoshitaka Hirooka ● Takeshi Horio ● Satoshi Hoshide ● Shunya Ikeda ● Toshihiko Ishimitsu ● Masaaki Ito ● Sadayoshi Ito ● Yoshio Iwashima ● Hisashi Kai ● Kei Kamide ● Yoshihiko Kanno ● Naoki Kashihara ● Yuhei Kawano ● Toru Kikuchi ● Kazuo Kitamura ● Takanari Kitazono ● Katsuhiko Kohara ● Masataka Kudo ● Hiroo Kumagai ● Kiyoshi Matsumura ● Hideo Matsuura ● Katsuyuki Miura ● Masashi Mukoyama ● Satoko Nakamura ● Takayoshi Ohkubo ● Yusuke Ohya ● Takafumi Okura ● Hiromi Rakugi ● Shigeyuki Saitoh ● Hirotaka Shibata ● Tatsuo Shimosawa ● Hiromichi Suzuki ● Shori Takahashi ● Kouichi Tamura ● Hirofumi Tomiyama ● Takuya Tsuchihashi ● Shinichiro Ueda ● Yoshinari Uehara ● Hidenori Urata ● Nobuhito Hirawa

The Japanese Society of Hypertension Guidelines for the Management of Hypertension (JSH 2019)

The genetic underpinnings of Alzheimer's disease (AD) remain largely elusive despite early successes in identifying three genes that cause early-onset familial AD (those that encode amyloid precursor protein (APP) and the presenilins (PSEN1 and PSEN2)), and one genetic risk factor for late-onset AD (the gene that encodes apolipoprotein E (APOE)) A large number of studies that aimed to help uncover the remaining disease-related loci have been published in recent decades, collectively proposing or refuting the involvement of over 500 different gene candidates Systematic meta-analyses of these studies currently highlight more than 20 loci that have modest but significant effects on AD risk This Review discusses the putative pathogenetic roles and common biochemical pathways of some of the most genetically and biologically compelling of these potential AD risk factors

Thirty years of Alzheimer's disease genetics: the implications of systematic meta-analyses

That the renin–angiotensin system (RAS) is involved in regulation of blood pressure, vasoconstriction, sodium intake and potassium excretion is well established. Studies in the last few years have however documented new roles for this molecule as a pro-inflammatory molecule and more recently as a possible pro-fibrotic agent that contributes to progressive deterioration of organ function in disease. Binding of Ang II to its receptors (in particular AT1) mediates intracellular free radical generation that contributes to tissue damage by promoting mitochondrial dysfunction. Blocking Ang II signalling protects against neurodegenerative processes and promotes longevity in rodents. Altogether these findings open the unanticipated perspective for exploring Ang II signalling in therapeutic interventions in inflammatory diseases and aging-related tissue injury. This review extends from the discovery of Ang II and its implications in renal and cardiovascular physiology to cover the roles of the system in inflammation, tissue injury, autoimmunity, oxidative stress and aging.

https://www.embopress.org/doi/pdf/10.1002/emmm.201000080

Angiotensin II revisited: new roles in inflammation, immunology and aging

Objective To investigate whether angiotensin receptor blockers protect against Alzheimer’s disease and dementia or reduce the progression of both diseases. Design Prospective cohort analysis. Setting Administrative database of the US Veteran Affairs, 2002-6. Population 819 491 predominantly male participants (98%) aged 65 or more with cardiovascular disease. Main outcome measures Time to incident Alzheimer’s disease or dementia in three cohorts (angiotensin receptor blockers, lisinopril, and other cardiovascular drugs, the “cardiovascular comparator”) over a four year period (fiscal years 2003-6) using Cox proportional hazard models with adjustments for age, diabetes, stroke, and cardiovascular disease. Disease progression was the time to admission to a nursing home or death among participants with pre-existing Alzheimer’s disease or dementia. Results Hazard rates for incident dementia in the angiotensin receptor blocker group were 0.76 (95% confidence interval 0.69 to 0.84) compared with the cardiovascular comparator and 0.81 (0.73 to 0.90) compared with the lisinopril group. Compared with the cardiovascular comparator, angiotensin receptor blockers in patients with pre-existing Alzheimer’s disease were associated with a significantly lower risk of admission to a nursing home (0.51, 0.36 to 0.72) and death (0.83, 0.71 to 0.97). Angiotensin receptor blockers exhibited a dose-response as well as additive effects in combination with angiotensin converting enzyme inhibitors. This combination compared with angiotensin converting enzyme inhibitors alone was associated with a reduced risk of incident dementia (0.54, 0.51 to 0.57) and admission to a nursing home (0.33, 0.22 to 0.49). Minor differences were shown in mean systolic and diastolic blood pressures between the groups. Similar results were observed for Alzheimer’s disease. Conclusions Angiotensin receptor blockers are associated with a significant reduction in the incidence and progression of Alzheimer’s disease and dementia compared with angiotensin converting enzyme inhibitors or other cardiovascular drugs in a predominantly male population.

https://www.bmj.com/content/bmj/340/bmj.b5465.full.pdf

Use of angiotensin receptor blockers and risk of dementia in a predominantly male population: prospective cohort analysis

There is evidence that certain components of the renin-angiotensin system (RAS) may have a crucial role in learning and memory processes.1,2⇓ Angiotensin-converting enzyme (ACE) is overexpressed in the hippocampus, frontal cortex, and caudate nucleus of patients with Alzheimer disease (AD).1 In an animal model with AD, brain-distributing ACE inhibitors are reported to rescue neuronal damage and improve behavior.2 Furthermore, we have shown that brain-penetrating ACE inhibitors can reduce the incidence of AD in elderly hypertensive patients.3 In the present study, we tested the hypothesis that treatment with brain-penetrating ACE inhibitors3 would slow the rate of cognitive decline in mild-to-moderate AD patients with hypertension.

We performed a randomized, prospective, parallel group trial with 1-year exposure to study medications. Participants were recruited from three long-term care facilities in Sendai, Japan. Patients eligible for this study had a diagnosis of mild to moderate AD,4,5⇓ were aged 65 years and older, had Mini-Mental State Examination (MMSE) scores within the range of 13 to 23, showed no evidence of stroke; insulin-dependent diabetes mellitus, or other endocrine disorders, or asthma or obstructive pulmonary disease, and had a blood pressure of higher than 140 mm Hg systolic or 90 mm Hg diastolic. The diagnosis of probable AD was made according to National Institute of Neurological and Communicative Disorders and Stroke–Alzheimer’s Disease and Related Disorders Association criteria with no clinical or laboratory evidence of a cause other than AD for dementia.5 Brain MRI was obtained in all participants within 3 months prior to the study enrollment to exclude patients with possible or probable vascular dementia and other neurodegenerative dementias. Patients …

T. Sato-Nakagawa

Papers

Effects of brain-penetrating ACE inhibitors on Alzheimer disease progression.