Maira Okada de Oliveira

Effects of Aerobic Training on Cognition and Brain Glucose Metabolism in Subjects with Mild Cognitive Impairment

BACKGROUND Aerobic training (AT) is a promising intervention for mild cognitive impairment (MCI). OBJECTIVE To evaluate the effects of AT on cognition and regional brain glucose metabolism (rBGM) in MCI patients. METHODS Subjects performed a twice-a-week, moderate intensity, AT program for 24 weeks. Assessment with ADAS-cog, a comprehensive neuropsychological battery, and evaluation of rBGM with positron emission tomography with 18F-fluorodeoxyglucose ([18F]FDG-PET) were performed before and after the intervention. Aerobic capacity was compared using the maximal oxygen consumption VO2max (mL/Kg/min). [18F]FDG-PET data were analyzed on a voxel-by-voxel basis with SPM8 software. RESULTS Forty subjects were included, with a mean (M) age of 70.3 (5.4) years and an initial Mini-Mental State Exam score of 27.4 (1.7). Comparisons using paired t-tests revealed improvements in the ADAS-cog (M difference: -2.7 (3.7), p <  0.001) and VO2max scores (M difference: 1.8 (2.0) mL/kg/min, p <  0.001). Brain metabolic analysis revealed a bilateral decrease in the rBGM of the dorsal anterior cingulate cortex, pFWE = 0.04. This rBGM decrease was negatively correlated with improvement in a visuospatial function/attentional test (rho =-0.31, p = 0.04). Several other brain areas also showed increases or decreases in rBGM. Of note, there was an increase in the retrosplenial cortex, an important node of the default mode network, that was negatively correlated with the metabolic decrease in the dorsal anterior cingulate cortex (r =-0.51, p = 0.001). CONCLUSION AT improved cognition and changed rBGM in areas related to cognition in subjects with MCI.

Brain metabolism and cerebrospinal fluid biomarkers profile of non-amnestic mild cognitive impairment in comparison to amnestic mild cognitive impairment and normal older subjects

IntroductionMild cognitive impairment (MCI) is classically considered a transitional stage between normal aging and dementia. Non-amnestic MCI (naMCI) patients, however, typically demonstrate cognitive deficits other than memory decline. Furthermore, as a group, naMCI have a lower rate of an eventual dementia diagnosis as compared to amnestic subtypes of MCI (aMCI). Unfortunately, studies investigating biomarker profiles of naMCI are scarce. The study objective was to investigate the regional brain glucose metabolism (rBGM) with [18F]FDG-PET and cerebrospinal fluid (CSF) biomarkers in subjects with naMCI as compared to a control group (CG) and aMCI subjects.MethodsNinety-five patients were included in three different groups: naMCI (N = 32), aMCI (N = 33) and CG (N = 30). Patients underwent brain MRI and [18F]FDG-PET. A subsample (naMCI = 26, aMCI = 28) also had an assessment of amyloid-β, tau, and phosphorylated tau levels in the CSF.ResultsBoth MCI groups had lower rBGM in relation to the CG in the precuneus. Subjects with naMCI showed decreased right prefrontal metabolism as well as higher levels of CSF amyloid-β relative to aMCI subjects.ConclusionWhile amnestic MCI subjects showed a biomarker profile classically related to MCI due to Alzheimer’s disease, naMCI patients illustrated a decrease in both prefrontal hypometabolism and higher CSF amyloid-β levels relative to the aMCI group. These biomarker findings indicate that naMCI is probably a heterogeneous group with similar precuneus hypometabolism compared to aMCI, but additional frontal hypometabolism and less amyloid-β deposition in the brain. Clinical follow-up and reappraisal of biomarkers of the naMCI group is needed to determine the outcome and probable etiological diagnosis.

Vocabulary Is an Appropriate Measure of Premorbid Intelligence in a Sample with Heterogeneous Educational Level in Brazil

Crystallized intelligence refers to ones knowledge base and can be measured by vocabulary tests. Fluid intelligence is related to nonverbal aspects of intelligence, depends very little on previously acquired knowledge, and can be measured by tests such as Block Design (BD) and Raven Colored Matrices (RCM). Premorbid intelligence quotient (IQ) refers to ones intellectual ability level previous to the onset of disorders like mild cognitive impairment (MCI) and Alzheimers disease (AD) and it is important to estimate disease severity. The objective was to compare performance in tests that measure crystallized and fluid intelligence in healthy subjects and patients with amnestic MCI (aMCI) and AD. One hundred forty-four participants (aMCI (n = 38), AD (n = 45), and healthy controls (n = 61)) were submitted to neuropsychological tests (WAIS-III vocabulary, BD, and RCM). There were significant among groups, except for vocabulary, indicating a relative stability of crystallized intelligence in the continuum from normal to pathological cognitive decline. Vocabulary seems to be stable during the progression of the disease and useful as a measure of premorbid intelligence, that is, to estimate previous function in relation to the level of education and, as a collateral measure of cognition in people with low education.

Voxel-based morphometry findings in Alzheimer's disease: neuropsychiatric symptoms and disability correlations - preliminary results

INTRODUCTION: The role of structural brain changes and their correlations with neuropsychiatric symptoms and disability in Alzheimers disease are still poorly understood. OBJECTIVE: To establish whether structural changes in grey matter volume in patients with mild Alzheimers disease are associated with neuropsychiatric symptoms and disability. METHODS: Nineteen Alzheimers disease patients (9 females; total mean age  = 75.2 y old ±4.7; total mean education level  = 8.5 y ±4.9) underwent a magnetic resonance imaging (MRI) examination and voxel-based morphometry analysis. T1-weighted images were spatially normalized and segmented. Grey matter images were smoothed and analyzed using a multiple regression design. The results were corrected for multiple comparisons. The Neuropsychiatric Inventory was used to evaluate the neuropsychiatric symptoms, and the Functional Activities Questionnaire and Disability Assessment for Dementia were used for functional evaluation. RESULTS: A significant negative correlation was found between the bilateral middle frontal gyri, left inferior temporal gyrus, right orbitofrontal gyrus, and Neuropsychiatric Inventory scores. A negative correlation was found between bilateral middle temporal gyri, left hippocampus, bilateral fusiform gyri, and the Functional Activities Questionnaire. There was a positive correlation between the right amygdala, bilateral fusiform gyri, right anterior insula, left inferior and middle temporal gyri, right superior temporal gyrus, and Disability Assessment for Dementia scores. CONCLUSIONS: The results suggest that the neuropsychiatric symptoms observed in Alzheimers disease patients could be mainly due to frontal structural abnormalities, whereas disability could be associated with reductions in temporal structures.

The thickness of posterior cortical areas is related to executive dysfunction in Alzheimer's disease

OBJECTIVE: To establish whether alterations of brain structures in Alzheimers disease are associated with executive dysfunction. METHODS: Nineteen patients with Alzheimers disease and 22 older control subjects underwent a comprehensive evaluation. The clock drawing test, digit span test, executive motor function test, Behavioral Assessment of the Dysexecutive Syndrome battery (Rule Shift Cards test), and Stroop test were used to evaluate executive dysfunction. A multiparametric approach using the FreeSurfer image analysis suite provided a description of volumetric and geometric features of the gray matter structures. RESULTS: The cortical thickness maps showed a negative correlation between the Behavioral Assessment of the Dysexecutive Syndrome battery (Rule Shift Cards test) and the right middle frontal gyrus; a positive correlation between the executive motor function test and the left superior parietal gyrus, left middle temporal gyrus, bilateral supramarginal gyri, right middle frontal gyrus, and right precuneus; a negative correlation between the Stroop test (part III) and the right superior parietal gyrus; and a negative correlation between the Stroop test (part III) and the right middle temporal gyrus. CONCLUSION: Executive dysfunction in Alzheimers disease is correlated with alterations not only in the frontal areas but also within many temporal and parietal regions.

Prevalence of Cognitive Impairment Without Dementia and Dementia in Tremembé, Brazil.

Background:The prevalence of cognitive impairment is insufficiently determined in developing countries. The aim of this study was to ascertain the prevalence of cognitive impairment without dementia and dementia in community-dwelling elderly in Brazil. Methods:This was a single-phase cross-sectional survey of the elderly (aged 60 years and above) living in the municipality of Tremembé, Brazil. Twenty percent of the households with elderly persons were randomly selected from urban and rural areas, to obtain a homogenous representation of all socioeconomic and cultural levels. Results:We assessed 630 individuals [mean age, 71.3 y (±7.99); mean years of education, 4.9 (±4.54)] and found prevalence rates of 17.5% (95% confidence interval, 14.6-20.6) for dementia and 19.5% (95% confidence interval, 16.6-22.8) for cognitive impairment without dementia. These prevalence rates were influenced by age (P<0.001) and by educational level (P<0.001). There was no significant sex difference among diagnostic groups (P=0.166). The prevalence of dementia was higher in relatively younger individuals (below 70 y) when compared with other studies. Besides, dementia was associated with low socioeconomic status, stroke, previous psychiatric disorder, alcoholism, and epilepsy. Conclusions:The prevalence of dementia in this study was higher than in other studies, particularly among younger elderly.

A Score Based on Screening Tests to Differentiate Mild Cognitive Impairment from Subjective Memory Complaints

It is not easy to differentiate patients with mild cognitive impairment (MCI) from subjective memory complainers (SMC). Assessments with screening cognitive tools are essential, particularly in primary care where most patients are seen. The objective of this study was to evaluate the diagnostic accuracy of screening cognitive tests and to propose a score derived from screening tests. Elderly subjects with memory complaints were evaluated using the Mini Mental State Examination (MMSE) and the Brief Cognitive Battery (BCB). We added two delayed recalls in the MMSE (a delayed recall and a late-delayed recall, LDR), and also a phonemic fluency test of letter P fluency (LPF). A score was created based on these tests. The diagnoses were made on the basis of clinical consensus and neuropsychological testing. Receiver operating characteristic curve analyses were used to determine area under the curve (AUC), the sensitivity and specificity for each test separately and for the final proposed score. MMSE, LDR, LPF and delayed recall of BCB scores reach statistically significant differences between groups (P=0.000, 0.03, 0.001 and 0.01, respectively). Sensitivity, specificity and AUC were MMSE: 64%, 79% and 0.75 (cut off <29); LDR: 56%, 62% and 0.62 (cut off <3); LPF: 71%, 71% and 0.71 (cut off <14); delayed recall of BCB: 56%, 82% and 0.68 (cut off <9). The proposed score reached a sensitivity of 88% and 76% and specificity of 62% and 75% for cut off over 1 and over 2, respectively. AUC were 0.81. In conclusion, a score created from screening tests is capable of discriminating MCI from SMC with moderate to good accurancy.

S-TOFHLA in mild Alzheimer's disease and Mild Cognitive Impairment patients as a measure of functional literacy Preliminary study

The greatest difficulty in diagnosing cognitive loss in our population is the diversity of its education which has a broad spectrum ranging from illiteracy, functional illiteracy and different degrees of literacy, even in those with the same level of schooling. Objectives To verify whether there is impairment on the S-TOFHLA among individuals with AD and MCI compared with healthy controls, and to compare performance on the S-TOFHLA performance with neuropsychological tests and the scores achieved on the Raven’s Colored Matrices and Vocabulary and Block Design (WAIS-III) as a measure of estimated intellectual level. Methods 59 subjects: controls (n=23; age 70.96±8.31y; schooling 10.2±5.87y; 6 men), MCI patients (n=11; age 74.18±8.12y; schooling 7.55±4.32y; 5 men) and AD patients (n=25; age 76.16±4.96y; schooling 7.32±4.78y; 10 men) were submitted to neuropsychological assessment, S-TOFHLA and functional evaluation. Results Differences on BD, Raven and Estimated IQ were found between controls and MCI patients as well as controls and AD patients. On the S-TOFHLA, differences were found between MCI and AD patients, controls and AD patients, but not between control and MCI groups. S-TOFHLA performance correlated strongly with schooling and all neuropsychological tests, except Clock Drawing. Conclusions The S-TOFHLA seems to be a useful measure for determining the level of literacy in MCI patients, but not in AD patients. S-TOFHLA performance was more closely associated with neuropsychological test scores than were years of education and seems to be a good predictor of level of literacy. The Vocabulary subtest proved to be uninfluenced by the disease process in early stages and preserved in both MCI and AD patients, showing that semantic memory and crystallized intelligence are preserved.

Clinical Implications of the National Institute of Neurological Disorders and Stroke Criteria for Diagnosing Psychosis in Parkinson’s Disease

The effect of psychotic symptoms in Parkinsons disease (PD) is variable among patients, and different methods to assess psychosis may yield conflicting results. A sample of 102 patients with a diagnosis of idiopathic PD underwent neurological, psychiatric, and neuropsychological assessment. Participants were divided into three groups: those who met DSM criteria for psychotic disorder, those who had psychotic symptoms but did not meet DSM criteria, and those without any psychotic symptoms. The first group had significantly worse sleep and worse cognitive and psychopathological symptoms compared with the other two groups. Results suggested that patients meeting DSM criteria for psychotic disorder comprise a separate clinical category.

Comparison of performance on neuropsychological tests in amnestic Mild Cognitive Impairment and Alzheimer's disease patients

Mild Cognitive Impairment (MCI) can be an intermediate state between normality and dementia in some patients. An early diagnosis, through neuropsychological assessment, could identify individuals at risk of developing dementia. Objective To verify differences in performance on neuropsychological tests among controls, amnestic MCI (aMCI) and Alzheimer’s disease (AD) patients. Methods Sixty-eight AD patients (mean age 73.77±7.24; mean schooling 9.04±4.83; 40 women and 28 men), 34 aMCI patients (mean age 74.44±7.05; mean schooling 12.35±4.01; 20 women) and 60 controls (mean age 68.90±7.48; mean schooling 10.72±4.74; 42 women) were submitted to a neuropsychological assessment composed of tasks assessing executive functions, language, constructive abilities, reasoning and memory. Results There were statistically significant differences in performance across all tests among control, aMCI and AD groups, and also between only controls and AD patients. On comparing control and aMCI groups, we found statistically significant differences in memory tasks, except for immediate recall of Visual Reproduction. There were also statistically significant differences between aMCI and AD groups on tasks of constructive and visuoperceptual abilities, attention, language and memory, except for delayed recall of Visual Reproduction. Conclusions Neuropsychological assessment was able to discriminate aMCI from AD patients in almost all tests except for delayed recall of Visual Reproduction, visual organization (Hooper) and executive functions (WCST); and discriminate controls from AD patients in all tests, and controls from aMCI patients in all memory tests except for immediate recall of Visual Reproduction.