Maria Aparecida Camargos Bicalho

Clinical Applicability and Cutoff Values for an Unstructured Neuropsychological Assessment Protocol for Older Adults with Low Formal Education

Background and Objectives The neuropsychological exam plays a central role in the assessment of elderly patients with cognitive complaints. It is particularly relevant to differentiate patients with mild dementia from those subjects with mild cognitive impairment. Formal education is a critical factor in neuropsychological performance; however, there are few studies that evaluated the psychometric properties, especially criterion related validity, neuropsychological tests for patients with low formal education. The present study aims to investigate the validity of an unstructured neuropsychological assessment protocol for this population and develop cutoff values for clinical use. Methods and Results A protocol composed by the Rey-Auditory Verbal Learning Test, Frontal Assessment Battery, Category and Letter Fluency, Stick Design Test, Clock Drawing Test, Digit Span, Token Test and TN-LIN was administered to 274 older adults (96 normal aging, 85 mild cognitive impairment and 93 mild Alzheimer`s disease) with predominantly low formal education. Factor analysis showed a four factor structure related to Executive Functions, Language/Semantic Memory, Episodic Memory and Visuospatial Abilities, accounting for 65% of explained variance. Most of the tests showed a good sensitivity and specificity to differentiate the diagnostic groups. The neuropsychological protocol showed a significant ecological validity as 3 of the cognitive factors explained 31% of the variance on Instrumental Activities of Daily Living. Conclusion The study presents evidence of the construct, criteria and ecological validity for this protocol. The neuropsychological tests and the proposed cutoff values might be used for the clinical assessment of older adults with low formal education.

Association of polymorphisms of the tryptophan hydroxylase 2 gene with risk for bipolar disorder or suicidal behavior

Bipolar disorder (BD) is a severe psychiatric illness characterized by the occurrence of elevated mood alternating with depressive episodes, having a estimated lifetime prevalence of 0.4-1.6% using DSM-IV criteria. Disturbances of the central serotonergic system has been associated with the pathophysiology of affective disorders and suicidal behavior. Tryptophan hydroxylase 2 (TPH2) which is a rate limiting enzyme in the serotonin synthesis is considered an important candidate gene associated with psychiatric disorders. Our sample consisted of 527 subjects (303 diagnosed with bipolar disorder and 224 healthy controls) which were genotyped for eight tagSNPs (rs4448731, rs4565946, rs11179000, rs7955501, rs10506645, rs4760820, rs1487275 and rs10879357) covering the whole gene of the human TPH2. Statistical analyses were performed using UNPHASED version 3.0.12 and Haploview((R)). Single markers, genotype and haplotype association analysis did not show significant genetic association with bipolar disorder or suicidal behavior. Our findings do not support the association between diagnosis of BD or suicidal behavior and TPH2 polymorphisms.

Genotyping of the G1463A (Arg441His) TPH2 polymorphism in a geriatric population of patients with major depression

Genotyping of the G1463A (Arg441His) TPH2 polymorphism in a geriatric population of patients with major depression

Doenças crônicas, cognição, declínio funcional e Índice de Charlson em idosos com demência

OBJECTIVEnTo assess the association between chronic degenerative diseases and functional decline, cognition, and mortality prediction.nnnMETHODSnA cross-sectional study was conducted in a geriatrics service in Belo Horizonte, Brazil, involving 424 patients subdivided into two groups: control and dementia. The study analyzed socio-demographic and environmental data, chronic degenerative diseases, the Charlson index, and data on functional and cognitive dementia.nnnRESULTSnAfter a univariate analysis, there was a greater frequency of cerebrovascular accident (CVA), urinary incontinence, constipation, and sleep disorder in the dementia group, while the multivariate analysis showed a greater number of environmental factors and sleep disorder. Regarding the Mini Mental State Examination (MMSE), patients with chronic obstructive pulmonary disease (COPD), CVA, and heart failure presented lower scores. There was a greater score in the dementia group with regarding the Charlson index.nnnCONCLUSIONnThese comorbidities were associated with the functional decline in elderly people with dementia.

Sociodemographic characteristics, clinical factors, and genetic polymorphisms associated with Alzheimer's disease

Alzheimers disease (AD) has a multifactorial etiology involving an interaction of genetic and environmental factors. The Apolipoprotein E ε4 (ApoE ε4) is the single most important genetic risk factor for sporadic AD. Our aim was to study the association between sociodemographic, clinical data and gene polymorphisms in patients with sporadic AD in a heterogeneous genomic Brazilian population with low educational levels.

Association Between Tryptophan Hydroxylase-2 Gene and Late-Onset Depression

OBJECTIVEnThe aim of this study was to examine the association between polymorphisms (SNP) in the tryptophan hydroxylase-2 (TPH2) gene and late-onset depression (LOD) in the Brazilian population.nnnMETHODSnWe genotyped 8 tag SNPs in the TPH2 gene in 84 outpatients with LOD and 79 individuals belonging to the comparison group to investigate an association between the TPH2 gene and LOD.nnnRESULTSnOur findings suggested an association between tag SNP rs4565946 heterozygous C/T (p = 0.034; χ2 = 6.7; df = 2) and decreased risk of LOD. The tag SNP rs11179000 ancestral homozygous A/A (p = 0.025; χ2 = 7.3; df = 2) and increase risk of LOD and allelic association of ancestral allele A and increase risk of LOD was demonstrated (p = 0.005; χ2 = 7.8; df = 1).nnnCONCLUSIONnWe found the statistically significant association between two tag SNPs and LOD. Our results support the hypothesis that the TPH2 gene is associated with LOD.

Catechol-O-Methyltransferase GeneticVariant Associated with the Risk of Alzheimer’s Disease in a Brazilian Population

The aim of the present study was to examinethe association between polymorphism in thecatechol-O-methyltransferase(COMT) gene and Alzheimer’s disease (AD) in a Brazilianpopulation. The case-control method was used to study the association between AD and geneticvariants of COMT. Six tag single-nucleotide polymorphisms(SNPs) in the COMT gene were genotyped by RT-PCR. Ourfindings showed that the 6 tag SNPs analyzed in this study were not associated with AD at the alleleand genotype levels in comparison with the control group. No statistical difference was foundbetween groups with and without behavioral and psychological symptoms of dementia (BPSD). Ourresults do not support the hypothesis that the polymorphisms of theCOMT gene may be associated with susceptibility to AD withand without BPSD.

Genetic variant of AKT1 and AKTIP associated with late-onset depression in a Brazilian population

Examine the association between polymorphisms in the AKT1 and AKTIP genes and late‐onset depression (LOD). Major depressive disorder is one of the most prevalent neuropsychiatric diseases. LOD is a disorder that starts after 65u2009years old. AKT1 is a downstream enzyme that has been implicated in the pathogenesis of neurotransmitter‐related disorders, such as depression. The identification of a novel AKT1‐binding protein (AKTIP) was pointed as an important new target. AKTIP binds directly to AKT1, enhancing the phosphorylation of regulatory sites, and this modulation are affected by AKT1 activation. The association of AKT1 and AKTIP polymorphisms with depressive symptoms was not investigated in LOD.

The GAB2 and BDNF polymorphisms and the risk for late-onset Alzheimer's disease in an elderly Brazilian sample

BACKGROUNDnEvidences suggest that GAB2 and BDNF genes may be associated with Alzheimers disease (AD). We aimed to investigate the GAB2 rs2373115 and BDNF rs6265 polymorphisms and the risk of AD in a Brazilian sample.nnnMETHODSn269 AD patients and 114 controls were genotyped with Real-time PCR. Multifactor dimensionality reduction (MDR) was employed to explore the effects of gene-gene interactions.nnnRESULTSnGAB2 and BDNF were not associated with AD in our sample. Nevertheless BDNF Val allele (rs6265) presented a synergic association with the APOE ε4 allele. A multiple logistic regression demonstrated that the APOE ε4 allele and years of education were the best predictors for AD. In ε4 non-carriers sex, education and hypertension were independently correlated with AD, while in ε4 carriers we did not observe any association. The findings were further confirmed by bootstrapping method.nnnCONCLUSIONSnOur data suggest that the interaction of BDNF and APOE has significant effect on AD. Moreover in absence of ε4, female sex, low level of education and hypertension are independently associated with AD. Interventions aimed to prevent AD should focus on these factors and also taking into account the APOE alleles.

Verbal learning on depressive pseudodementia: accentuate impairment of free recall, moderate on learning processes, and spared short-term and recognition memory

OBJECTIVEnDepressive pseudodementia (DPD) is a clinical condition characterized by depressive symptoms followed by cognitive and functional impairment characteristics of dementia. Memory complaints are one of the most related cognitive symptoms in DPD. The present study aims to assess the verbal learning profile of elderly patients with DPD.nnnMETHODSnNinety-six older adults (34 DPD and 62 controls) were assessed by neuropsychological tests including the Rey auditory-verbal learning test (RAVLT). A multivariate general linear model was used to assess group differences and controlled for demographic factors.nnnRESULTSnModerate or large effects were found on all RAVLT components, except for short-term and recognition memory.nnnCONCLUSIONnDPD impairs verbal memory, with large effect size on free recall and moderate effect size on the learning. Short-term storage and recognition memory are useful in clinical contexts when the differential diagnosis is required.