Matheus Roriz-Cruz

(Pre)diabetes, brain aging, and cognition.

Cognitive dysfunction and dementia have recently been proven to be common (and underrecognized) complications of diabetes mellitus (DM). In fact, several studies have evidenced that phenotypes associated with obesity and/or alterations on insulin homeostasis are at increased risk for developing cognitive decline and dementia, including not only vascular dementia, but also Alzheimers disease (AD). These phenotypes include prediabetes, diabetes, and the metabolic syndrome. Both types 1 and 2 diabetes are also important risk factors for decreased performance in several neuropsychological functions. Chronic hyperglycemia and hyperinsulinemia primarily stimulates the formation of Advanced Glucose Endproducts (AGEs), which leads to an overproduction of Reactive Oxygen Species (ROS). Protein glycation and increased oxidative stress are the two main mechanisms involved in biological aging, both being also probably related to the etiopathogeny of AD. AD patients were found to have lower than normal cerebrospinal fluid levels of insulin. Besides its traditional glucoregulatory importance, insulin has significant neurothrophic properties in the brain. How can clinical hyperinsulinism be a risk factor for AD whereas lab experiments evidence insulin to be an important neurothrophic factor? These two apparent paradoxal findings may be reconciliated by evoking the concept of insulin resistance. Whereas insulin is clearly neurothrophic at moderate concentrations, too much insulin in the brain may be associated with reduced amyloid-beta (Abeta) clearance due to competition for their common and main depurative mechanism - the Insulin-Degrading Enzyme (IDE). Since IDE is much more selective for insulin than for Abeta, brain hyperinsulinism may deprive Abeta of its main clearance mechanism. Hyperglycemia and hyperinsulinemia seems to accelerate brain aging also by inducing tau hyperphosphorylation and amyloid oligomerization, as well as by leading to widespread brain microangiopathy. In fact, diabetes subjects are more prone to develop extense and earlier-than-usual leukoaraiosis (White Matter High-Intensity Lesions - WMHL). WMHL are usually present at different degrees in brain scans of elderly people. People with more advanced WMHL are at increased risk for executive dysfunction, cognitive impairment and dementia. Clinical phenotypes associated with insulin resistance possibly represent true clinical models for brain and systemic aging.

Diferenciais socioeconômicos e de saúde entre duas comunidades de idosos longevos

OBJETIVO: Identificar diferencias demograficas y socioeconomicas relacionadas con el estado de salud de ancianos mas viejos residentes en dos ciudades de diferentes regiones de Brasil. METODOS: Estudio epidemiologico transversal y comparativo de ancianos mas viejos (>80 anos) residentes en Ribeirao Preto (RP - Sureste de Brasil) y Caxias do Sul (Sur), con muestra probabilistica de 117 sujetos en CS y 155 en RP, realizados entre 2007 y 2008. El instrumento de colecta incluyo datos demograficos y socioeconomicos mini-examen del estado mental, Medida de Independencia Funcional, numero de comorbilidades autoreferidas y Escala de Depresion Geriatrica. RESULTADOS: La edad promedio fue similar, con predominancia de mujeres (~70%) y viudos (~60%) en ambos municipios. La escolaridad promedio no difirio estadisticamente, pero la renta promedio del anciano fue mayor en RP que en CS (p=0,05). RP presento mayor concentracion de individuos en los extremos de escolaridad y renta que CS. El escore promedio del mini-examen del estado mental fue similar entre los dos grupos y mayor para individuos del sexo masculino, con edad entre 80 y 84 anos, casados y con mayor escolaridad. Se observo mejor desempeno funcional entre ancianos de 80 a 84 anos en ambos municipios, entre los de mayor escolaridad en RP; y entre los de sexo masculino y los casados en CS. Ancianos de CS presentaron mayor numero de comorbilidades que los de RP (p<0,001). Ancianos del sexo masculino, casados, y con mayor renta presentaron menos sintomas depresivos en ambos grupos; y los de RP presentaron mayor escores en la Escala de Depresion Geriatrica que los de CS (p<0,001). CONCLUSIONES: Aunque los ancianos de CS presenten menor desigualdad socioeconomica y menos sintomas depresivos, poseen tambien mayor numero promedio de comorbilidades y menor nivel de independencia funcional, al compararlos con los de RP.OBJECTIVEnTo identify demographic and socioeconomic differentials associated with the health status of oldest-old individuals living in two cities of different Brazilian regions.nnnMETHODSnA comparative and cross-sectional epidemiological study was conducted with the oldest-old (> 80 years), living in the cities of Ribeirão Preto (RP, Southeastern Brazil) and Caxias do Sul (CS, Southern). The probabilistic sample included 117 individuals in CS and 155 in RP, and data were collected between 2007 and 2008. The instrument included demographic and socioeconomic data, Mini-Mental State Examination, Functional Independence Measure, number of self-reported comorbidities and Geriatric Depression Scale.nnnRESULTSnMean age was similar, with predominance of women (~70%) and widowed individuals (~60%) in both cities. Mean level of education did no differ statistically, although mean income was higher in RP than in CS (p = 0.05). RP showed a higher concentration of individuals in the extreme levels of education and income than that of CS. Mean score of the Mini-Mental State Examination was similar in both groups and higher among men, individuals aged between 80 and 84 years, married and with a higher level of education. Better functional performance was observed in elderly individuals aged between 80 and 84 years in both cities, in those with higher level of education in RP; and in males and married individuals in CS. Elderly individuals in CS showed higher number of comorbidities than those in RP (p < 0.001). Male elderly individuals, married and with -higher income level showed fewer depressive symptoms in both groups; and those in RP showed higher Geriatric Depression Scale score than the others in CS (p < 0.001).nnnCONCLUSIONSnAlthough the oldest old in CS showed lower socioeconomic inequality and fewer depressive symptoms, they also had a higher mean number of comorbidities and lower level of functional independence, when compared to those in RP.

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.

Tendências dos estudos com idosos mais velhos na comunidade : uma revisão sistemática (inter)nacional

The purpose of this study was to identify and analyze the tendencies and types of studies published in Brazil and abroad, involving elders aged>80 years, living in the community. A systematic review of national literature was performed using the LILACS and SciELO databases, and PUBMED and EMBASE for international literature, covering publications of the last two decades. Twelve national and 162 international references were selected. Biological sciences were the prevalent area both at the national (50%) and international (74.1%) levels. All national studies were observational, 91.7% of which were cross-sectional. Of the international studies, 93.3% were observational, 48.1% of which were cross-sectional and 37.6% were cohort studies. The United States were the country responsible for 41.4% of all international publications. Brazil and China were the only developing countries with international publications. Despite the significant number of international scientific publications as of 2005, this fact has not been observed at the national level.The purpose of this study was to identify and analyze the tendencies and types of studies published in Brazil and abroad, involving elders aged >80 years, living in the community. A systematic review of national literature was performed using the LILACS and SciELO databases, and PUBMED and EMBASE for international literature, covering publications of the last two decades. Twelve national and 162 international references were selected. Biological sciences were the prevalent area both at the national (50%) and international (74.1%) levels. All national studies were observational, 91.7% of which were cross-sectional. Of the international studies, 93.3% were observational, 48.1% of which were cross-sectional and 37.6% were cohort studies. The United States were the country responsible for 41.4% of all international publications. Brazil and China were the only developing countries with international publications. Despite the significant number of international scientific publications as of 2005, this fact has not been observed at the national level.

[Tendencies of studies addressing the eldest individuals of aged population in the community: a (inter)national systematic review].

The purpose of this study was to identify and analyze the tendencies and types of studies published in Brazil and abroad, involving elders aged>80 years, living in the community. A systematic review of national literature was performed using the LILACS and SciELO databases, and PUBMED and EMBASE for international literature, covering publications of the last two decades. Twelve national and 162 international references were selected. Biological sciences were the prevalent area both at the national (50%) and international (74.1%) levels. All national studies were observational, 91.7% of which were cross-sectional. Of the international studies, 93.3% were observational, 48.1% of which were cross-sectional and 37.6% were cohort studies. The United States were the country responsible for 41.4% of all international publications. Brazil and China were the only developing countries with international publications. Despite the significant number of international scientific publications as of 2005, this fact has not been observed at the national level.The purpose of this study was to identify and analyze the tendencies and types of studies published in Brazil and abroad, involving elders aged >80 years, living in the community. A systematic review of national literature was performed using the LILACS and SciELO databases, and PUBMED and EMBASE for international literature, covering publications of the last two decades. Twelve national and 162 international references were selected. Biological sciences were the prevalent area both at the national (50%) and international (74.1%) levels. All national studies were observational, 91.7% of which were cross-sectional. Of the international studies, 93.3% were observational, 48.1% of which were cross-sectional and 37.6% were cohort studies. The United States were the country responsible for 41.4% of all international publications. Brazil and China were the only developing countries with international publications. Despite the significant number of international scientific publications as of 2005, this fact has not been observed at the national level.

Socioeconomic and health differentials between two community-dwelling oldest-old groups

OBJETIVO: Identificar diferencias demograficas y socioeconomicas relacionadas con el estado de salud de ancianos mas viejos residentes en dos ciudades de diferentes regiones de Brasil. METODOS: Estudio epidemiologico transversal y comparativo de ancianos mas viejos (>80 anos) residentes en Ribeirao Preto (RP - Sureste de Brasil) y Caxias do Sul (Sur), con muestra probabilistica de 117 sujetos en CS y 155 en RP, realizados entre 2007 y 2008. El instrumento de colecta incluyo datos demograficos y socioeconomicos mini-examen del estado mental, Medida de Independencia Funcional, numero de comorbilidades autoreferidas y Escala de Depresion Geriatrica. RESULTADOS: La edad promedio fue similar, con predominancia de mujeres (~70%) y viudos (~60%) en ambos municipios. La escolaridad promedio no difirio estadisticamente, pero la renta promedio del anciano fue mayor en RP que en CS (p=0,05). RP presento mayor concentracion de individuos en los extremos de escolaridad y renta que CS. El escore promedio del mini-examen del estado mental fue similar entre los dos grupos y mayor para individuos del sexo masculino, con edad entre 80 y 84 anos, casados y con mayor escolaridad. Se observo mejor desempeno funcional entre ancianos de 80 a 84 anos en ambos municipios, entre los de mayor escolaridad en RP; y entre los de sexo masculino y los casados en CS. Ancianos de CS presentaron mayor numero de comorbilidades que los de RP (p<0,001). Ancianos del sexo masculino, casados, y con mayor renta presentaron menos sintomas depresivos en ambos grupos; y los de RP presentaron mayor escores en la Escala de Depresion Geriatrica que los de CS (p<0,001). CONCLUSIONES: Aunque los ancianos de CS presenten menor desigualdad socioeconomica y menos sintomas depresivos, poseen tambien mayor numero promedio de comorbilidades y menor nivel de independencia funcional, al compararlos con los de RP.OBJECTIVEnTo identify demographic and socioeconomic differentials associated with the health status of oldest-old individuals living in two cities of different Brazilian regions.nnnMETHODSnA comparative and cross-sectional epidemiological study was conducted with the oldest-old (> 80 years), living in the cities of Ribeirão Preto (RP, Southeastern Brazil) and Caxias do Sul (CS, Southern). The probabilistic sample included 117 individuals in CS and 155 in RP, and data were collected between 2007 and 2008. The instrument included demographic and socioeconomic data, Mini-Mental State Examination, Functional Independence Measure, number of self-reported comorbidities and Geriatric Depression Scale.nnnRESULTSnMean age was similar, with predominance of women (~70%) and widowed individuals (~60%) in both cities. Mean level of education did no differ statistically, although mean income was higher in RP than in CS (p = 0.05). RP showed a higher concentration of individuals in the extreme levels of education and income than that of CS. Mean score of the Mini-Mental State Examination was similar in both groups and higher among men, individuals aged between 80 and 84 years, married and with a higher level of education. Better functional performance was observed in elderly individuals aged between 80 and 84 years in both cities, in those with higher level of education in RP; and in males and married individuals in CS. Elderly individuals in CS showed higher number of comorbidities than those in RP (p < 0.001). Male elderly individuals, married and with -higher income level showed fewer depressive symptoms in both groups; and those in RP showed higher Geriatric Depression Scale score than the others in CS (p < 0.001).nnnCONCLUSIONSnAlthough the oldest old in CS showed lower socioeconomic inequality and fewer depressive symptoms, they also had a higher mean number of comorbidities and lower level of functional independence, when compared to those in RP.

LOWER MORTALITY FROM H1N1 INFLUENZA IN OLDER ARGENTINEANS: MEN MORE AFFECTED

ically require more-frequent daily dosing to avoid large peak-to-trough concentration variation. Conversely, drugs with long elimination half-lives generally require lessfrequent dosing because plasma concentration variations between doses are smaller. The pharmacokinetic comparison of memantine 20 mg one daily and 10 mg twice daily demonstrates that peak-totrough fluctuations with once-daily dosing regimens is similar to twice-daily dosing. Therefore, it is expected that the efficacy and adverse effect profile would be comparable between these dosing schemes. Recent clinical studies in which the safety and tolerability of once-daily dosing has been shown to be comparable with that of twice daily dosing support the results of the analysis. Recent clinical trials also suggest that an extended-release once-daily formulation is well tolerated and effective for the treatment of moderate to severe Alzheimer’s disease. Based on the current pharmacokinetic analysis, a single conventionalrelease 20-mg dose (two 10-mg tablets) may offer the same daily convenience as a single extended-release formulation and with similar tolerability as 10 mg taken twice daily.

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.

Acculturation, Obesity, and Hypertension Among Female Brazilian Indians

To the Editor:nnThe Amazon is the largest native forest in the word. There, many isolated and relatively unacculturated Amerindian populations still strive to keep their cultures untouched. In a series of reports from 1989 to 1992, one of us (Carvalho) and colleagues of the Intersalt Study have evidenced that both obesity and hypertension were entirely absent among an uncivilized Amazon tribe named Yanomamo.1–5 Moreover, blood pressure did not increase with age, and both salt and alcohol were unknown among this ethnic group.nnPresently, there are ≈460 000 Indians in Brazil living in 225 villages and speaking 180 languages. They correspond to 0.26% of the Brazilian population and live in preserved areas that represent ≈15% of the country’s territory.6 Approximately 175 000 Brazilian …

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.