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 Alzheimer's 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.

Conduction along peripheral and central pain pathways is normal in patients with Parkinson disease with or without primary central pain. However, apart from signs of hyperalgesia, our patients exhibited lack of habituation of sympathetic sudomotor responses to repetitive pain stimuli, suggesting an abnormal control of the effects of pain inputs on autonomic centers. Abnormalities were attenuated by l-dopa, suggesting that the dysfunction may occur in dopamine-dependent centers regulating both autonomic function and inhibitory modulation of pain inputs.

The increase in life expectancy can influence the prevalence of dementias in the population. Instruments that evaluate cognitive functions such as the Mini Mental State Examination (MMSE) are necessary for the investigation of dementia. The supposition that patient score on the MMSE can be influenced by academic level points to the need for establishing cut-off values that take into account educational level. The aim of this study was to review MMSE cut-off values adjusted for schooling in a large southern Brazilian sample.MethodDemographic data and MMSE scores of 968 subjects, of which 162 were dementia patients and 806 healthy participants, were analyzed. The sample was grouped according to education. The cut-off values were established by ROC Curve analysis.ResultsThe total sample mean age was 70.6±7.3 years, and the mean years of education was 7.2±5.3. The cut-off score of 23 points (sensitivity=86%, specificity=83%) was observed as the optimal level to detect dementia on the MMSE instrument for the overall sample. Regarding level of schooling, the cut-off values were: 21 for the illiterate group (sensitivity=93%, specificity=82%), 22 for the low education group (sensitivity=87%, specificity=82%), 23 for the middle education group (sensitivity=86%, specificity=87%) and 24 for the high education group (sensitivity=81%, specificity=87%).ConclusionsThe cut-off values revealed by this analysis, and adjusted for level of schooling, can improve the clinical evaluation of cognitive deficits.

Aim:The endogenous circadian clock generates daily variations of physiological and behavior functions such as the endogenous interindividual component (morningness/eveningness preferences). Also, mood disorders are associated with a breakdown in the organization of ultradian rhythm. Therefore, the purpose of the present study was to assessed the association between chronotype and the level of depressive symptoms in a healthy sample population. Furthermore, the components of the depression scale that best discriminate the chronotypes were determined. Methods: This cross-sectional study involved 200volunteers, aged 18-99 years, 118 women and 82 men. The instruments were the Montgomery-Äsberg Depression Rating Scale (MADRS), the Morningness/ Eveningness Questionnaire, the Self-Reporting Questionnaire-20, and the future self-perception questionnaire.Results: Logistic regression showed that subjects with the eveningness chronotype had a higher chance of reporting more severe depressive symptoms compared to morning-and intermediate-chronotypes, with an odds ratio (OR) of 2.83 and 5.01, respectively. Other independent cofactors associated with a higher level of depressive symptoms were female gender (OR, 3.36), minor psychiatric disorders (OR, 3.70) and low future self-perception (OR, 3.11). Younger age, however, was associated with a lower level of depressive symptoms (OR, 0.97). The questions in the MADRS that presented higher discriminate coefficients among chronotypes were those related to sadness, inner tension, sleep reduction and pessimism. Conclusion:Identification of an association between evening typology and depressive symptoms in healthy samples may be useful in further investigation of circadian typology and the course of depressive disease.

This NPI version was found to be a reliable instrument for the evaluation of neuropsychiatric symptoms and caregiver distress due to dementia in AD. The profile of behavioral disturbances was similar to that observed in other countries. Severity of dementia may have biased some caregivers' answers.

Across Latin American and Caribbean countries (LACs), the fight against dementia faces pressing challenges, such as heterogeneity, diversity, political instability, and socioeconomic disparities. These can be addressed more effectively in a collaborative setting that fosters open exchange of knowledge. In this work, the Latin American and Caribbean Consortium on Dementia (LAC‐CD) proposes an agenda for integration to deliver a Knowledge to Action Framework (KtAF). First, we summarize evidence‐based strategies (epidemiology, genetics, biomarkers, clinical trials, nonpharmacological interventions, networking, and translational research) and align them to current global strategies to translate regional knowledge into transformative actions. Then we characterize key sources of complexity (genetic isolates, admixture in populations, environmental factors, and barriers to effective interventions), map them to the above challenges, and provide the basic mosaics of knowledge toward a KtAF. Finally, we describe strategies supporting the knowledge creation stage that underpins the translational impact of KtAF.

A battery of neuropsychological tests was examined to establish its value in differentiating mild dementia from depression. The battery was applied to 84 subjects: 31 dementia patients of several etiologies, 31 patients with major depression and 22 volunteers whose age and educational level was similar to that of the patients. The battery consisted of tests for immediate, recent and remote memory, the Mini Mental State examination, a screening test for language disorders, and tests measuring abstraction, calculation, judgement, praxic and gnosic functions. The results showed significant differences among the three groups in all memory tests. Deficits of abstraction, calculation, praxis and language functions were strongly associated with dementia. The epidemiological analysis of efficiency increment, with determination of sensitivity and specifity, showed a highly significant enhancement of efficiency for diagnostic purposes when the results of the tests were combined. These findings suggest that the entire battery of neuropsychological tests should be applied, and their results compared using the efficiency increment procedure, in order to establish a firm differential diagnosis between dementia and depression, and/or to detect the former when it is at a mild early stage.

BackgroundAlzheimer's disease is the most common dementia in the elderly, and the potential of peripheral biochemical markers as complementary tools in the neuropsychiatric evaluation of these patients has claimed further attention.MethodsWe evaluated serum levels of S100B and neuron-specific enolase (NSE) in 54 mild, moderate and severe Alzheimer's disease (AD) patients and in 66 community-dwelling elderly. AD patients met the probable NINCDS-ADRDA criteria. Severity of dementia was ascertained by the Clinical Dementia Rating (CDR) scale, cognitive function by the Mini Mental State Examination (MMSE), and neuroimage findings with magnetic resonance imaging. Serum was obtained from all individuals and frozen at -70°C until analysis.ResultsBy comparing both groups, serum S100B levels were lower in AD group, while serum NSE levels were the same both groups. In AD patients, S100B levels were positively correlated with CDR scores (rho = 0.269; p = 0.049) and negatively correlated with MMSE scores (rho = -0.33; P = 0.048). NSE levels decreased in AD patients with higher levels of brain atrophy.ConclusionsThe findings suggest that serum levels of S100B may be a marker for brain functional condition and serum NSE levels may be a marker for morphological status in AD.