Liara Rizzi

Global Epidemiology of Dementia: Alzheimer's and Vascular Types

The prevalence of dementia varies substantially worldwide. This is partially attributed to the lack of methodological uniformity among studies, including diagnostic criteria and different mean population ages. However, even after considering these potential sources of bias, differences in age-adjusted dementia prevalence still exist among regions of the world. In Latin America, the prevalence of dementia is higher than expected for its level of population aging. This phenomenon occurs due to the combination of low average educational attainment and high vascular risk profile. Among developed countries, Japan seems to have the lowest prevalence of dementia. Studies that evaluated the immigration effect of the Japanese and blacks to USA evidenced that acculturation increases the relative proportion of AD cases compared to VaD. In the Middle East and Africa, the number of dementia cases will be expressive by 2040. In general, low educational background and other socioeconomic factors have been associated with high risk of obesity, sedentarism, diabetes, hypertension, dyslipidemia, and metabolic syndrome, all of which also raise the risk of VaD and AD. Regulating these factors is critical to generate the commitment to make dementia a public health priority.

Mechanisms of Brain Aging Regulation by Insulin: Implications for Neurodegeneration in Late-Onset Alzheimer's Disease

Insulin and IGF seem to be important players in modulating brain aging. Neurons share more similarities with islet cells than any other human cell type. Insulin and insulin receptors are diffusely found in the brain, especially so in the hippocampus. Caloric restriction decreases insulin resistance, and it is the only proven mechanism to expand lifespan. Conversely, insulin resistance increases with age, obesity, and sedentarism, all of which have been shown to be risk factors for late-onset Alzheimers disease (AD). Hyperphagia and obesity potentiate the production of oxidative reactive species (ROS), and chronic hyperglycemia accelerates the formation of advanced glucose end products (AGEs) in (pre)diabetes—both mechanisms favoring a neurodegenerative milieu. Prolonged high cerebral insulin concentrations cause microvascular endothelium proliferation, chronic hypoperfusion, and energy deficit, triggering β-amyloid oligomerization and tau hyperphosphorylation. Insulin-degrading enzyme (IDE) seems to be the main mechanism in clearing β-amyloid from the brain. Hyperinsulinemic states may deviate IDE utilization towards insulin processing, decreasing β-amyloid degradation.

C-reactive protein and cognition are unrelated to leukoaraiosis.

Elevated serum levels of C-reactive protein (CRP) have been associated with leukoaraiosis in elderly brain. However, several studies indicate that leukoaraiosis is associated with an increased risk of cognitive impairment. It is unknown how the effect of CRP on cognition is mediated by leukoaraiosis. The purpose of this study is to assess the relationship between serum levels of CRP, the presence of leukoaraiosis, and cognitive impairment in a population of coronary patients over 50 years old. CRP levels explained 7.18% (P: 0.002) of the variance of the MMSE. The adjustment for the presence of leukoaraiosis little changed this variance (5.98%, P: 0.005), indicating that only a small portion of the CRP influence on cognition was mediated via leukoaraiosis. Patients with CRP levels ≥5.0 had 2.9 (95% CI: 1.26–6.44) times more chance to present cognitive impairment (P: 0.012). We found that elevated serum levels of CRP were associated with increased risk of cognitive impairment in elderly and it was not mediated by presence of leukoaraiosis.

Inverse Relationship Between Depressive Symptoms and Arterial Blood Pressure in Community-Dwelling Oldest-Old Brazilians

Conflict of Interest: This study was supported by the Organization for Healthcare Research in the Netherlands. The editor in chief has reviewed the conflict of interest checklist provided by the authors and has determined that the authors have no financial or any other kind of personal conflicts with this paper. Author Contributions: Ellen Smulders: Study design, data analysis, interpretation of data, preparation of letter. Yvonne Schoon: Study concept and design, acquisition of subjects and data, interpretation of data, preparation of data. Marcel Olde Rikkert: Study concept and design, preparation of letter. Vivian Weerdesteyn: Study design, interpretation of data, preparation of letter. Sponsor’s Role: None.

Cerebrospinal fluid inflammatory markers in amnestic mild cognitive impairment

Inflammatory processes might play a significant role at the pathophysiology of Alzheimers disease (AD). Neuroinflammation is characterized by activation of microglia and the release of inflammatory cytokines, such as interleukin (IL)‐1β, IL‐6 and tumor necrosis factor‐α. Although, it is unknown what the real contribution of these inflammatory markers in the development of AD is. The purpose of the present study was to assess the possible relationship between inflammatory markers in the cerebrospinal fluid (CSF) of amnestic mild cognitive impairment patients (aMCI), aged 60 years or older, and compare with aged healthy controls.

Sirtuin 1 and Alzheimer's disease: An up-to-date review

Sirtuins are NAD+-dependent enzymes that regulate a large number of cellular pathways and are related to aging and age-associated diseases. In recent years, the role of sirtuins in Alzheimers disease (AD) has become increasingly apparent. Growing evidence demonstrates that sirtuin 1 (SIRT1) regulates many processes that go amiss in AD, such as: APP processing, neuroinflammation, neurodegeneration, and mitochondrial dysfunction. Here we review how SIRT1 affects AD and cognition, the main mechanisms in which SIRT1 is related to AD pathology, and its importance for the prevention and possible diagnosis of AD.

CSF Aβ1–42, but not p-Tau181, differentiates aMCI from SCI

AIM Individuals with amnestic mild cognitive impairment (aMCI) are at a high risk to develop Alzheimers disease (AD). We compared CSF levels of biomarkers of amyloidosis (Aβ1-42) and neurodegeneration (p-Tau181) in individuals with aMCI and with subjective cognitive impairment (SCI) in order to ascertain diagnostic accuracy and predict the odds ratio associated with aMCI. METHODS We collected CSF of individuals clinically diagnosed with aMCI (33) and SCI (12) of a memory clinic of Southern Brazil. Levels of Aβ1-42 and p-Tau181 were measured by immunoenzymatic assay. Participants also underwent neuropsychological testing including the verbal memory test subscore of the Consortium to Establish a Registry for Alzheimers Disease (VM-CERAD). RESULTS CSF concentration of Aβ1-42 was significantly lower (p: .007) and p-Tau181/Aβ1-42 ratio higher (p: .014) in aMCI individuals than in SCI. However, isolate p-Tau181 levels were not associated with aMCI (p: .166). There was a statistically significant association between Aβ1-42 and p-Tau181 (R2: 0.177; β: -4.43; p: .017). ROC AUC of CSF Aβ1-42 was 0.768 and of the p-Tau181/Aβ1-42 ratio equals 0.742. Individuals with Aβ1-42 < 823 pg/mL levels were 6.0 times more likely to be diagnosed with aMCI (p: .019), with a 68.9% accuracy. Those with p-Tau181/Aβ1-42 ratio > 0.071 were at 4.6 increased odds to have aMCI (p: .043), with a 64.5% accuracy. VM-CERAD was significantly lower in aMCI than among SCI (p: .041). CONCLUSION CSF Aβ1-42, but not p-Tau181, level was significantly associated with aMCI.

Research reportCSF Aβ1–42, but not p-Tau181, differentiates aMCI from SCI

AIM Individuals with amnestic mild cognitive impairment (aMCI) are at a high risk to develop Alzheimers disease (AD). We compared CSF levels of biomarkers of amyloidosis (Aβ1-42) and neurodegeneration (p-Tau181) in individuals with aMCI and with subjective cognitive impairment (SCI) in order to ascertain diagnostic accuracy and predict the odds ratio associated with aMCI. METHODS We collected CSF of individuals clinically diagnosed with aMCI (33) and SCI (12) of a memory clinic of Southern Brazil. Levels of Aβ1-42 and p-Tau181 were measured by immunoenzymatic assay. Participants also underwent neuropsychological testing including the verbal memory test subscore of the Consortium to Establish a Registry for Alzheimers Disease (VM-CERAD). RESULTS CSF concentration of Aβ1-42 was significantly lower (p: .007) and p-Tau181/Aβ1-42 ratio higher (p: .014) in aMCI individuals than in SCI. However, isolate p-Tau181 levels were not associated with aMCI (p: .166). There was a statistically significant association between Aβ1-42 and p-Tau181 (R2: 0.177; β: -4.43; p: .017). ROC AUC of CSF Aβ1-42 was 0.768 and of the p-Tau181/Aβ1-42 ratio equals 0.742. Individuals with Aβ1-42 < 823 pg/mL levels were 6.0 times more likely to be diagnosed with aMCI (p: .019), with a 68.9% accuracy. Those with p-Tau181/Aβ1-42 ratio > 0.071 were at 4.6 increased odds to have aMCI (p: .043), with a 64.5% accuracy. VM-CERAD was significantly lower in aMCI than among SCI (p: .041). CONCLUSION CSF Aβ1-42, but not p-Tau181, level was significantly associated with aMCI.

Haemodialysis improves uraemic patients’ cognition: a pilot study

Uraemia is a state of elevated plasma urea well related to a low cognitive profile. Although renal transplantation has been proved to improve cognition in these patients, little is known about how haemodialysis act on this scenario. Here we aimed to conduct a pilot study to fathom the presence and magnitude of a possible benefit of haemodialysis in cognition. Our main instrument was the Montreal Cognitive Assessment (MoCA) test, a tool designed to allow for a sensitive score for cognitive impairment. Although preliminary, our data were significant (p=0.012) to suggest that haemodialysis might be an important tool for cognitive improvement of end-stage kidney disease patients, tough not sufficient for a full cognitive recovery. Correspondence to: Rodrigo T Starosta, School of Medicine, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil, Tel: +555181724749; E-mail: rodrigo.starosta@ufrgs.br