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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.

Prospective memory in Alzheimer's disease and Mild Cognitive Impairment

Prospective memory (PM) is defined as remembering to carry out intended actions at an appropriate point in the future, and can be categorized into three types of situation: time-, event-, and activity-based tasks. PM involves brain structures such as frontal and medial temporal cortices. The aim of this study was to review the currently available literature on PM in Alzheimer’s disease and Mild Cognitive Impairment patients. We performed a search on Pubmed, Medline, ScieLO, LILACS and the Cochrane Library electronic databases from January 1990 to December 2010. The key terms used were: prospective memory, memory for intentions, delayed memory and memory for future actions, separately and also combined with the search terms dementia, Alzheimer’s disease and Mild Cognitive Impairment. Both patient groups showed significant impairment in PM. Further studies are needed to verify the accuracy of PM tasks as an early marker of mild cognitive impairment, and initial dementia.

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.

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.

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.

Prevalence of depressive symptoms among elderly in the city of Tremembé, Brazil: Preliminary findings of an epidemiological study

Depression is a heterogeneous mental disease classified as a set of disorders, which manifest with a certain duration, frequency and intensity. The prevalence of depression in the elderly ranges from 0.5 to 16%. OBJECTIVE To establish, in an epidemiological study, the prevalence of significant depressive symptoms in the population aged 60 years or older. METHODS Results of a cross-sectional epidemiological study, involving home visits, being carried out in the city of Tremembé, Brazil, were reported. The sample was randomly selected by drawing 20% of the population over 60 years from each of the citys census sectors. In this single-phase study, the assessment included clinical history, physical and neurological examination, cognitive evaluation, the Cornell scale and the Patient Health Questionnaire for psychiatric symptoms. Scores greater than or equal to 8 on the Cornell scale were taken to indicate the presence of depressive symptoms. RESULTS A total of 455 elders were assessed, and of these 169 (37.1%) had clinically significant depressive symptoms (CSDS). Depression prevalence was higher among women (p<0.001) and individuals with lower education (p=0.033). The Chi-square test for trends showed a significant relationship where lower socioeconomic status was associated with greater likelihood of depressive symptoms (p=0.005). CONCLUSION The prevalence of depressive symptoms was high in this sample of the population-based study and was associated with female gender, low educational level and socioeconomic status. The assessment of the entire population sample must be completed.

Paraneoplastic limbic encephalitis with prominent neuropsychiatric apathy

The spectrum of paraneoplastic neurologic syndromes has increased with the description of encephalitis associated with antibodies against cell surface and synaptic proteins. Subacute cognitive impairment, movement disorders, late onset epilepsy and neuropsychiatric syndromes were recently linked to paraneoplastic encephalitis. Despite that, probably some syndromes and antibodies are yet to be reported. Herein we reported the clinical and neuroimaging pictures of a patient with late onset medial temporal lobe epilepsy, subtle cognitive impairment, psychosis and severe apathy diagnosed with antibody-negative paraneoplastic encephalitis due to colonic adenocarcinoma. The apathy markedly improved after removal of the tumor, without concomitant immunotherapy (steroids, intravenous immunoglobulins, immunosuppressants, plasmapheresis, etc.). Our report highlights the importance of a full clinical and neurologic investigation in cases of atypical neuropsychiatric presentations, particularly in the elderly and with the concomitance of epilepsy and cognitive decline. Even chronic presentations must be considered. Neuroimaging is an important tool to demonstrate structural and functional brain dysfunction in these cases. Colonic adenocarcinoma should be searched for in cases in which a typical tumor related to paraneoplastic neurologic syndromes is not found.

Performance of the Visual Analogue Scale of Happiness and of the Cornell Scale for Depression in Dementia in the Tremembé Epidemiological Study, Brazil

Depression is a major growing public health problem. Many population studies have found a significant relationship between depression and the presence of cognitive disorders. Objective To establish the correlation between the Visual Analogue Scale of Happiness and the Cornell Scale for Depression in Dementia in the population aged 60 years or over in the city of Tremembé, state of São Paulo, Brazil. Methods An epidemiological survey involving home visits was carried out in the city of Tremembé. The sample was randomly selected by drawing 20% of the population aged 60 years or older from each of the citys census sectors. In this single-phase study, the assessment included clinical history, physical and neurological examination, cognitive evaluation, and application of both the Cornell Scale and the Analogue Scale of Happiness for psychiatric symptoms. The presence of depressive symptoms was defined as scores greater than or equal to 8 points on the Cornell Scale. Results A total of 623 subjects were evaluated and of these 251 (40.3%) had clinically significant depressive symptoms on the Cornell Scale, with a significant association with female gender (p<0.001) and with lower education (p=0.012). One hundred and thirty-six participants (21.8%) chose the unhappiness faces, with a significant association with age (p<0.001), female gender (p=0.020) and low socioeconomic status (p=0.012). Although there was a statistically significant association on the correlation test, the correlation was not high (rho=0.47). Conclusion The prevalence of depressive symptoms was high in this sample and the Visual Analogue Scale of Happiness and Cornell Scale for Depression in Dementia should not be used as similar alternatives for evaluating the presence of depressive symptoms, at least in populations with low educational level.

Differences in biomarker profiles of people with amnestic and nonamnestic mild cognitive impairment

opportunities to characterize and evaluate AD. However, the correspondence between ADAD and the far more prevalent sporadic AD (sAD) requires elucidation. Methods: We analyzed functional connectivity in multiple brain networks in a cross-sectional cohort of ADAD (N1⁄487) and sAD (N1⁄4507) participants using resting state functional connectivity magnetic resonance imaging (rs-fcMRI). For both types of AD, we quantified rs-fcMRI changes in five resting state networks (RSNs) with respect to progressing clinical dementia rating (CDR) using general linear mixed models with factors CDR, AD type, and CDR€ı,’€ıVAD type interaction. In the ADAD group, we investigated rs-fcMRI changes with respect to years from expected onset of symptoms. We also related rs-fcMRI differences to genetic mutation type (presenilin 1, presenilin 2, amyloid precursor protein). Results: rs-fcMRI decreases with advancing clinical status were similar for both forms of AD in multiple RSNs. However, it is possible that ADAD causes more rapid loss with respect to CDR than sAD in certain RSNs. Within ADAD participants, functional connectivity in multiple RSNs was lower in individuals closer to their expected age of onset of symptoms. Within cognitively normal ADAD participants (N1⁄433), mutation-specific effects may occur in particular RSNs. Conclusions: rsfcMRI can elucidate specific AD subtypes and may help evaluate future therapeutic interventions.