Marcia Lorena Fagundes Chaves

(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.

Neuropsychological Performance in DSM-IV ADHD Subtypes: An Exploratory Study with Untreated Adolescents

Objective: To explore neuropsychological performance in untreated Brazilian adolescents suffering from attention-deficit hyperactivity disorder (ADHD). Method: We assessed 30 untreated adolescents with ADHD and 60 healthy control subjects, aged 12 to 16 years, using a neuropsychological battery including the Wisconsin Card-Sorting Test (WCST), the Stroop Test (ST), the Digit Span, and the Word Span. Results: We found neuropsychological differences among the DSM-IV ADHD subtypes. Adolescents with the predominantly inattentive subtype (ADHD-I) performed more poorly than did control subjects on both the Digit Span and the ST. On both the Digit Span and the WCST, adolescents with the combined subtype (ADHD-C) presented significantly more impairments than did control subjects. Adolescents with the predominantly hyperactive-impulsive type (ADHD-HI) did not differ significantly from the control subjects in any measure assessed, but had a better performance than did those with ADHD-C on both the Digit Span and the WCST. In addition, adolescents with ADHD-HI performed better on the ST than did adolescents with ADHD-I. Conclusions: These findings suggest cognitive differences among ADHD subtypes, supporting the diagnostic distinction among them. Adolescents with ADHD-HI do not seem to have significant cognitive deficits.

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.

The Mini Mental State Examination : review of cutoff points adjusted for schooling in a large Southern Brazilian sample

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. Method Demographic 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. Results The 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%). Conclusions The cut-off values revealed by this analysis, and adjusted for level of schooling, can improve the clinical evaluation of cognitive deficits.

Benchmarking matching pursuit to find sleep spindles

The aim of this study is to evaluate performance of Matching Pursuit (MP) algorithm against visual analysis for automatic sleep spindle (SS) detection in a sample of sleep stages 2-4 and REM pertaining to nine healthy young subjects. MP-SS voltage, frequency and duration characteristics were investigated for the amplitude threshold (AT) that maximized yield between test sensitivity and specificity. Parameter distribution curves were also built for correctly detected (true positive) and false-positive events. For sleep stage 2, MP reached 80.6% sensitivity and specificity for an AT value of 58.8. For all stages together, 81.2% sensitivity and specificity were reached for an AT value of 46.6. Specificity curves were adequate for all stages; sensitivity was lower for S3+4. Sigma frequency range activity with atypical characteristics was detected within REM sleep. Prevalence indexes obtained with MP were much higher than visual prevalence indexes for all stages; similar voltage, frequency and duration distribution curves were obtained for true positive and false positive events. For this sample of young male healthy subjects, the free-ware MP algorithm showed satisfactory performance for SS detection in sleep stage 2 as reported earlier, acceptable performance in sleep stages 3+4, although with lowered sensitivity, and sigma frequency range activity within REM sleep that needs better understanding. Within NREM sleep, correspondence between the MP automatic and the visual method was supported.

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.

Quality of life associated to chronic pelvic pain is independent of endometriosis diagnosis-a cross-sectional survey

BackgroundPain is strongly related to poor quality of life. We performed a cross-sectional study in a universitary hospital to investigate quality of life in women suffering from chronic pelvic pain (CPP) due to endometriosis and others conditions.MethodsFifty-seven patients aged between 25 and 48 years-old submitted to laparoscopy because of CPP were evaluated for quality of life and depressive symptoms. Quality of life was accessed by a quality of life instrument [World Health Organization Quality of Life Assessment-Bref (WHOQOL-bref)]. Causes of pelvic pain were determined and severity of CPP was measured with a visual analogue scale. According to the intensity of pelvic pain score, patients were classified in two groups (group Low CPP < 25th percentile visual analogue scale and group High CPP > 25th percentile). Four dimensions on quality of life were measured (physical, psychological, social and environmental). We stratified the analysis of quality of life according CPP causes (presence or not of endometriosis in laparoscopy).ResultsPatients with higher pain scores presented lower quality of life status in psychological and environmental dimensions. We found a negative correlation between pain scores and psychological dimension of quality of life (r = -0.310, P = .02). Quality of life scores were similar between groups with and without endometriosis (physical 54.2 ± 12.8 and 51.1 ± 13.8, P = 0.504; psychological 56.2 ± 14.4 and 62.8 ± 12.4, P = 0.182; social 55.6 ± 18.2 and 62.1 ± 19.1, P = 0.325; environmental 59.2 ± 11.7 61.2 ± 10.8, P = 0.608; respectively)ConclusionsHigher pain scores are correlated to lower quality of life; however the fact of having endometriosis in addition to CPP does not have an additional impact upon the quality of life.

Mental health screening by self-report questionnaire among community adolescents in Southern Brazil

PURPOSE To evaluate the frequency of symptoms of depression, suicidal ideation, suicide behavior, and hopelessness among adolescents in southern Brazil. METHODS The Self-Report Questionnaire (SRQ) was administered to a random sample of 126 community youngsters to screen for mental problems, the Montgomery-Asberg Depression Rating scale for signs and symptoms of depression, an adapted version of DIS (Diagnostic Interview Schedule) for suicidal ideation and behavior, and the Backs Hopelessness scale (adapted version). Social class, cognitive performance, age, and sex were also analyzed. RESULTS Levels of symptoms of depression, suicidal ideation and behavior, and hopelessness were higher among those who were SRQ positive (8%). Female youngsters presented higher SRQ scores and on the Montgomery-Asberg scale. Cognitive performance was similar among all groups. Differences were not found according to social classes. The 15-17 year-old individuals (middle stage) presented higher hopelessness than the other stages of adolescence. CONCLUSIONS The present findings suggest that screening for mental health conditions by self-report questionnaires may be of value of identify groups at major risk for violent, self-destructive behavior among community adolescents.