The number of the elderly with dementia is increasing as the number aging people is increasing. The increase of dementia has been social problem, because the most majority cause of bedridden in the elderly is dementia replaced by cerebrovascular disease. Hypertension is associated with increased risk for dementia both in Alzheimer’s disease and vascular dementia. However, interventional studies failed to establish the relationship between blood pressure lowering and dementia. Antihypertensive treatment with renin-angiotensin-aldosterone system (RAAS) blocker may be an additional strategy for preventing dementia because systemic or local RAAS activation exacerbate neurovascular damage through enhancement of oxidative stress. Especially aldosterone, the most downstream component of RAAS, plays a pivotal role on progression of dementia. Thus, mineralocorticoid receptor blockade might be beneficial for preventing dementia.

Translational research (TR) refers to a series of research processes from basic research in academia to the application of new drugs and medical technologies in clinical practice. Compared to conventional basic research, in which the goal is the publication of papers, TR involves a long period of research and many hurdles, including many failures. Therefore, perseverance is required to overcome these hurdles. In addition, it is difficult for a researcher to complete a project alone; thus, it is necessary to appeal to and work closely with many collaborators. It is also important to have a mission to help others through research. In this paper, I outline the points for successful TR, including those from basic research to non-clinical studies, related to obtaining intellectual property rights, and regarding industry-academia collaborations.

Cardiovascular diseases (CVDs) have become a major health problem, because of the associated high morbidity and mortality among patients. Gut microbiota have been recently implicated as a novel endocrine organ that play critical roles in regulating the host cardiometabolic function through producing bioactive metabolites. This review investigated the evidence from several clinical and experimental studies indicating an association between gut microbiota and atherosclerotic CVDs. We mainly focused on the anti-atherogenic gram-negative bacteria, Bacteroides vulgatus and dorei, and their producing lipopolysaccharide. Further, we would pay attention to gut microbiota-derived deleterious metabolites, trimethylamine N-oxide, and described the present status of its related research. We believe some of the methods to change the gut microbiota or reduce the deleterious metabolites could be clinically applied to prevent CVDs in the near future.

Vascular dementia (VaD) is the second most common causative disease of dementia, after Alzheimer’s disease (AD). Regarding the diagnosis of VaD, the presence of cerebrovascular impairments such as cerebral infarction and intracranial hemorrhage is confirmed by brain imaging and then followed by the temporal causality that cognitive dysfunction develops. As VaD has a wide range of pathologies and clinical symptoms, its diagnosis and the development of therapeutics specific to VaD could be difficult. The challenge is in searching for biomarkers that reflect the pathological conditions, prognosis, and severity of VaD and the detailed stratification of patients. Breakdown of the blood-brain barrier and extracellular matrix, along with axonal disorders, demyelinating disorders, and gliosis, plays a significant role in the pathogenesis of cerebrovascular impairment. Increased cerebrospinal fluid (CSF)/serum albumin quotient, decreased matrix metalloproteinase-2 index, and increased neurofilament light have been reported as biomarkers of these disorders. Measuring CSF amyloid-β 42 (Aβ42), tau, and phosphorylated tau (p-tau) as biomarkers of AD has proved useful, but the significance of these markers in VaD has not been investigated in detail. The complications of VaD and AD are common, so determining which is closer to the core of the pathological conditions is often difficult. Biomarkers specific to VaD are expected to be useful for the differential diagnosis and prognosis prediction of dementia.

Hypertension (HTN) is known to be associated with cognitive decline and dementia. It causes cerebral vascular damage, which leads to pathological changes not only in vascular dementia but also in Alzheimer’s disease. Epidemiological evidence also suggests that HTN in midlife is probably a risk factor for dementia. Conversely, blood pressure variability or hypotension may also be associated with cerebral damage and cognitive decline. Blood pressure must be controlled for dementia prevention. We discuss the relationship between blood pressure dysregulation and cognitive decline and dementia with respect to current evidence and clinical research.

Alzheimer’s disease (AD) is a progressive neurological disease that leads to dementia and ultimately death due to cognitive decline caused by the loss of neurons in the brain. It has been reported that type 2 diabetes increases the risk of developing AD dementia, although the molecular mechanism linking type 2 diabetes and AD is unknown. The high incidence of AD in patients with type 2 diabetes may be explained by the effect of diabetes on tau pathology, one of the cardinal neuropathological features of the AD brain. Clinical studies using biofluid biomarkers report that tau in cerebrospinal fluid is increased by diabetic conditions; however, studies using post-mortem brain and positron emission tomography imaging provided controversial results regarding the effect of type 2 diabetes on tau pathology. In animal models, the effects of type 2 diabetes on tau have been extensively examined at the molecular level. The effect of type 2 diabetes increases phosphorylated tau in the brain via multiple intracellular signaling pathways. Therefore, tau phosphorylation may underlie the pathological interplay between diabetes and AD. A better understanding of the molecular mechanisms linking these two diseases may provide novel insights into diagnostic and therapeutic developments for AD.

A 59-year-old man, who began to suffer from ulcerative colitis at the age of 58, developed gradual cognitive decline and was referred to our clinic when he was 60 years old. Cerebrospinal fluid analysis revealed a decrease in the Aβ42 and Aβ42/Aβ40 ratio. He showed mild bilateral medial temporal lobar atrophy and decreased blood flow in the bilateral temporal lobe and posterior cingulate gyrus. A genetic test revealed that the APOE ε4 was homozygous but no mutations were found in APP, PSEN1, or PSEN2 genes. Therefore, he was diagnosed with Alzheimer’s disease. Systemic inflammation of ulcerative colitis may have accelerated Alzheimer’s disease in the present case.