Ana Luiza Camozzato

(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.

Relationship between depressive mood and chronotype in healthy subjects.

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.

Serum levels of S100B and NSE proteins in Alzheimer's disease patients

BackgroundAlzheimers 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 Alzheimers 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.

Incidence of Mild Cognitive Impairment and Alzheimer Disease in Southern Brazil

The objective of the study was to evaluate incident cases of Alzheimer disease (AD) and mild cognitive impairment (MCI) in an elderly community cohort in a major city of southern Brazil and to determine the variables associated with the development of cognitive dysfunction. Data were drawn from a cohort to investigate healthy aging among community elderly (N = 345) and were derived from the follow-up for a maximum of 8 years. Sociodemographic, psychiatric and medical information, the Mini-Mental State Examination (MMSE), and the Clinical Dementia Rating scale were obtained in each assessment. The Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition; DSM-IV), NINCDS-ADRDA (National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer’s Disease and related Disorders Association), and the Mayo Clinic criteria were applied to ascertain diagnoses of AD and MCI. The incidence rate per 1000 persons-year for MCI was 13.2 (95% confidence interval [CI] 7.79-20.91) and for AD was 14.8 (95% CI 9.04-22.94). Cognitive dysfunction was associated with education (odds ratio [OR] = 0.86; confidence limit [CL] 0.76-0.97 95%) and baseline MMSE (OR = 0.81; CL 0.70-0.94 95%). The AD incidence in this sample was higher than those reported in a previous Brazilian study. The study filled the epidemiological gap in the evaluation of MCI in Brazil.

Predictors of Normal and Successful Aging Among Urban-Dwelling Elderly Brazilians

The association of successful aging with demographic, socioeconomic, and medical characteristics in healthy community-dwelling Brazilian individuals aged 60 years and older (N = 345) was investigated. Participants were classified as successful (n = 214, 62%) or normal (n = 131, 38%) agers. Successful agers participated in significantly more leisure activities (34%) than did normal agers (21%). Multivariate logistic regression analysis revealed that the number of living children was a risk factor, whereas confidants and family income were protective factors for successful aging.

Brain-derived neurotrophic factor serum levels and hippocampal volume in mild cognitive impairment and dementia due to Alzheimer disease

Background/Aims: Hippocampal atrophy is a recognized biomarker of Alzheimer disease (AD) pathology. Serum brain-derived neurotrophic factor (BDNF) reduction has been associated with neurodegeneration. We aimed to evaluate BDNF serum levels and hippocampal volume in clinical AD (dementia and mild cognitive impairment [MCI]). Methods: Participants were 10 patients with MCI and 13 with dementia due to AD as well as 10 healthy controls. BDNF serum levels were determined by ELISA and volumetric measures with NeuroQuant®. Results: MCI and dementia patients presented lower BDNF serum levels than healthy participants; dementia patients presented a smaller hippocampal volume than MCI patients and healthy participants. Discussion: The findings support that the decrease in BDNF might start before the establishment of neuronal injury expressed by the hippocampal reduction.

Estimation of the risk of conversion of mild cognitive impairment of Alzheimer type to Alzheimer's disease in a south Brazilian population-based elderly cohort: the PALA study

BACKGROUND Higher mild cognitive impairment (MCI) prognostic variability has been related to sample characteristics (community-based or specialized clinic) and to diverse operationalization criteria. The aim of the study was to evaluate the trajectory of MCI of Alzheimer type in a population-based elderly cohort in Southern Brazil. We also estimated the risk for the development of probable Alzheimers disease (AD) in comparison with healthy subjects. METHODS Data were derived from a population-based cohort (the PALA study). MCI outcomes were sub-classified into three categories: conversion, stabilization, and reconversion. The risk of progression to dementia was compared between MCI and normal participants. The analysis was based on 21 MCI subjects and 220 cognitively intact participants (N = 241). RESULTS Of the 21 MCI subjects, 38% developed dementia, 24% remained stable and 38% improved. The MCI annual conversion rate to AD was 8.5%. MCI was associated with significantly higher risk of conversion to AD (HR = 49.83, p = 0.004), after adjustment for age, education, sex and Mini-Mental State Examination score. CONCLUSIONS Independent of the heterogeneity of the outcomes, MCI of the Alzheimer type participants showed significantly higher risk of developing probable AD, demonstrating the impact of the use of these MCI criteria that emphasize long-term episodic memory impairment.

Predictors of the progression of dementia severity in Brazilian patients with Alzheimer's disease and vascular dementia

Introduction. This study evaluates the progression of dementia and identifies prognostic risk factors for dementia. Methods. A group of 80 Brazilian community residents with dementia (34 with Alzheimers disease and 46 with vascular dementia) was assessed over the course of 2 years. Data were analyzed with Cox regression survival analysis. Results. The data showed that education predicted cognitive decline (HR = 1.2; P < .05) when analyzed without controlling for vascular risk factors. After the inclusion of vascular risk factors, education (HR = 1.32; P < .05) and hypertension were predictive for cognitive decline (HR = 38; P < .05), and Alzheimers disease diagnosis was borderline predictive (P = .055). Conclusion. Vascular risk factors interacted with the diagnosis of vascular dementia. Education was a strong predictor of decline.

Neuropsychiatric symptoms as the main determinant of caregiver burden in Alzheimer's disease

Caregiver burden is common in Alzheimer’s disease (AD), decreasing the quality of life among caregivers and patients. Projections of aging and aging-related diseases such as AD in developing countries justify additional data about this issue because people living in these countries have shown similarly high levels of caregiver strain as in the developed world. Objective The aim of this study was to analyze the association of AD caregivers’ burden with patients’ neuropsychiatric symptoms (NPS), cognitive status, severity of dementia, functional capacity, caregiver sociodemographic characteristics, and the characteristics of care provided by caregivers. Methods A cross-sectional study was conducted in a sample of 39 consecutive AD patients and their primary caregivers. NPS were evaluated using the Neuropsychiatric Inventory (NPI). Severity of dementia was assessed with the Clinical Dementia Rating (CDR) scale. Functional capacity was assessed using the Katz and Lawton scales. The burden level was rated using the Burden Interview (BI). Sociodemographic characteristics of caregivers and the characteristics of care provided by them were evaluated. The Mann-Whitney U-test, Kruskal-Wallis test and Spearman’s rho coefficient were performed. Results The BI had a moderate correlation with NPI intensity (rho=0.563), p<001. Female caregivers reported a greater level of burden (p=0.031) than male caregivers. The other variables were not significantly associated to caregiver burden. Conclusion NPS were the main determinant of burden in primary caregivers of AD patients. This result underscores the need for prevention and treatment of these symptoms. Sex also had an effect on caregiver burden, but the small male sample in this study precludes the generalization of this finding.

Validation of a telephone screening test for Alzheimer's disease

ABSTRACT Financial constraints, mobility issues, medical conditions, crime in local areas can make cognitive assessment difficult for elders and telephone interviews can be a good alternative. This study was carried out to evaluate the reliability, validity and clinical utility of a Brazilian telephone version of the Mini Mental State Examination (Braztel-MMSE) in a community sample of healthy elderly participants and AD patients. The MMSE and the Braztel-MMSE were applied to 66 AD patients and 67 healthy elderly participants. The test–retest reliability was strong and significant (r = .92, p = .01), and the correlation between the Braztel-MMSE and the MMSE were significant (p = .01) and strong (r = .92). The general screening ability of the Braztel-MMSE was high (AUC = 0.982; CI95% = 0.964–1.001). This telephone version can therefore be used as a screening measure for dementia in older adults that need neuropsychological screening and cannot present for an evaluation.