Jarbas S. Roriz-Filho

(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.

Stroke-Independent Association Between Metabolic Syndrome and Functional Dependence, Depression, and Low Quality of Life in Elderly Community-Dwelling Brazilian People

OBJECTIVES: Metabolic syndrome (Met.S) is a risk factor for stroke, dementia, and ischemic heart disease (IHD). It is unclear whether Met.S is an independent risk factor for functional dependence, depression, cognitive impairment, and low health‐related quality of life (HRQoL) in a population free of clinical stroke.

Correlation between Alzheimer's disease, pre-diabetes and diabetes mellitus evaluated by quantitative magnetic resonance imaging

regions. The diagnostic accuracy of conventional EEG in AD is around 80%. Statistical Pattern Recognition (SPR) is a statistical analysis that uses a database of information, in this case features from EEG registration, to identify individuals with aberrant pattern of brain waves. By using this method, the intention is to increase the diagnostic accuracy of EEG in AD. Methods: The participants were 300 patients diagnosed with AD at a Memory Clinic and 400 normal individuals evenly distributed in the age range of 50 90 years. SPR was used to identify the patients using more than 600 features of the EEG registration. A numeric index from 0-100 was established to describe the likelihood of AD in each case. Results: This method correctly identified AD patients when compared to the normal group with >90% accuracy. Furthermore, the AD-index correlated with the severity of the disease as evaluated by the MMSE. The method also correctly identified AD patients when compared to EEG in patients with vascular dementia (VD) with some overlap in patients with mixed VD and AD. Conclusions: By using SPR on features of EEG registration, this method is more sensitive in identifying patients with AD from normal individuals and from patients with VD than conventional EEG. The method is easy to use and is therefore more widely applicable than more specialized methods like MRI or SPECT/PET.

REASONS FOR THE HIGH COMPETITIVENESS IN ENTERING A GERIATRICS FELLOWSHIP IN BRAZIL: SOME COMPARISONS WITH THE UNITED STATES

dictors in the oldest-old. Cad Saude Publica 2003;19:799–807. 8. Xavier FM. Bereavement-related cognitive impairment in an oldest-old community-dwelling Brazilian sample. J Clin Exp Neuropsychol 2002;24:294–301. 9. Xavier FM, Ferraza MP, Argimon I et al. The DMS IV ‘minor depression’ disorder in the oldest-old: Prevalence rate, sleep patterns, memory function and quality of life in elderly people of Italian descent in southern Brazil. Int J Geriatr Psychiatry 2002;17:107–116. 10. Xavier FM, Ferraza MP, Trenti CM et al. Generalized anxiety disorder in a population aged 80 years and older [Portuguese]. Rev Saude Publica 2001; 35:294–302.

ON THE BRAZILIAN ELDERLY AMERINDIAN HERITAGE AND THE VERY OLD ITALIAN-BRAZILIAN LONGITUDINAL STUDY ON AGING

To the Editor: In a recent article entitled ‘‘Geriatrics in Brazil: A Big Country with Big Opportunities,’’ GarcezLeme et al. point out that ‘‘the ethnic distribution in Brazil includes 53.8% whites, 6.2% blacks, 39.1% mulattos, . . . and 0.2% Indians.’’ These data are based on the Brazilian census, which takes individuals’ own subjective impressions about their skin color, do not represent reality, and clearly underestimate the Brazilian elderly Amerindian heritage. Indeed, most Brazilians (including older people) are genetically mestizo, either white/black (mulattos), white/ Indian (Caboclo), orFmore commonlyFa mosaic of the three (Brazilian mestizo par excellence). The proportion of contribution of each of those three ethnicities to the makeup of the typical Brazilian elderly genetic pool is curiously racially democratic: approximately one-third of each group. Even what Garcez-Leme is considering to be a white person is on average a tri-hybrid mestizo with 39% European, 33% Amerindian, and 28% African genetic background. This is an important phenomenon not just for genetics but also to understand the typical Brazilian elderly cultural identity as being part of a new and universal civilization, instead of just being Europeans transplanted to the Americas. Moreover, Amerindians used to hold their older people in high esteem, and this influence can still be seen not just in Brazilian society, but in all of Latin America. Garcez-Leme et al. cited the Bambuı́ Aging Study but failed to refer to the ‘‘Very-old Italian-Brazilian Longitudinal Study on Aging’’ (Veranopólis Project), which was the first longitudinal study on aging in Brazil. This study was implemented originally by the ‘‘WHO Collaborating Research Center for Prevention of ChronicDegenerative Diseases Associated with Aging,’’ located at the Department of Geriatrics of the Catholic University of Porto Alegre. It consists of a very old cohort ( 80) of Italian Brazilians living in VeranópolisFin southern BrazilFand it was conceptualized by Dr. Elisabete Michelon, who noted that this population had the longest life expectancy in Brazil: greater than 80. Of the possible factors associated with longevity in this population is the almost universal moderate intake of red wine by its inhabitants, especially older people. This study has been contributing important knowledge to the field of the ‘‘oldest-old’’ in geriatrics, especially in the topics of cardiogeriatrics and geriatric psychiatry.