Mnemonic strategy training modulates functional connectivity at rest in mild cognitive impairment: Results from a randomized controlled trial.

INTRODUCTION: Mnemonic strategy training (MST) has been shown to improve cognitive performance and increase brain activation in those with mild cognitive impairment (MCI). However, little is known regarding the effects of MST on functional connectivity (FC) at rest. The aim of the present study was to investigate the MST focused on face-name associations effect on resting-state FC in those with MCI. METHODS: Twenty-six amnestic MCI participants were randomized in MST (N = 14) and Education Program (active control; N = 12). Interventions occurred twice a week over two consecutive weeks (ie, four sessions). Resting-state functional magnetic resonance imaging was collected at pre- and post-intervention. Regions of interest (ROIs) were selected based on areas that previously showed task-related activation changes after MST. Changes were examined through ROI-to-ROI analysis and significant results were corrected for multiple comparisons. RESULTS: At post-intervention, only the MST group showed increased FC, whereas the control group showed decreased or no change in FC. After MST, there was an increased FC between the left middle temporal gyrus and right orbitofrontal cortex. In addition, a time-by-group interaction indicated that the MST group showed greater increased FC between the right inferior frontal gyrus and left brain regions, such as fusiform gyrus, temporal pole, and orbitofrontal cortex relative to controls. DISCUSSION: MST enhanced FC in regions that are functionally relevant for the training; however, not in all ROIs investigated. Our findings suggest that MST-induced changes are reflected in task-specific conditions, as previously reported, but also in general innate connectivity. Our results both enhance knowledge about the mechanisms underlying MST effects and may provide neurophysiological evidence of training transfer.

Training gains and transfer effects after mnemonic strategy training in mild cognitive impairment: A fMRI study.

Prior work has revealed that mnemonic strategy training (MST) can enhance memory for specific content and engages regions in the frontoparietal cognitive control network. Evidence of transfer to novel content is less clear. Here, we provide secondary analysis of functional magnetic resonance imaging (fMRI) data acquired during a randomized controlled trial that compared MST to an active education control condition in patients with amnestic mild cognitive impairment (a-MCI). In the trial, thirty participants with a-MCI were randomized to the education program (EP) or MST, where they learned to apply the technique to face-name associations during four intervening hour long training sessions. Participants underwent pre- and post-training fMRI scans, during which they encoded both the trained (i.e., those used during the four training sessions) and untrained ('novel') face-name associations. The primary cognitive outcome measures revealed significantly improved memory for both trained and novel stimuli - effects supporting near transfer of MST. Relative to pre-training, there were significant and highly similar increases in activation for both trained and novel stimuli, especially in regions associated with the frontoparietal cognitive control network bilaterally, but also in temporal areas related to social cognition and emotional processing. Critically, this pattern of activation was notably different from the EP group. Thus, the changes in activation were consistent with the strategies trained and, combined with the cognitively-based near transfer effects, suggest that MST focused on face-name association enhances performance by engaging cognitive control and social/emotional processing. Finally, our data indicated that our MST is a relevant and efficient intervention to a-MCI.

MoCA Test: normative and diagnostic accuracy data for seniors with heterogeneous educational levels in Brazil.

INTRODUCTION: The Montreal Cognitive Assessment (MoCA) has been described as a good tool to detect cognitive impairment. The ideal MoCA cutoff score is still under debate. The aim was to provide MoCA norms and accuracy data for seniors with a lower education level, including illiterates. METHODS: Data originated from an epidemiological study conducted in the municipality of Tremembe, Brazil. The Brazilian MoCA test was applied as part of the cognitive assessment in all participants. Of the 630 participants, 385 were classified as cognitively normal (CN) and were included in the normative data set, 110 individuals were diagnosed with dementia and 135 were classified as having cognitive impairment no dementia (CIND). RESULTS: The total scores varied significantly according to age and education among the three diagnostic groups: CN, CIND and dementia (p < 0.001). To distinguish participants with CN from dementia, the best MoCA cutoff was 15 points (sensitivity 90%, specificity 77%) and to differentiate those with CN from CIND, the MoCA cutoff was 19 points (sensitivity 84%, specificity 49%). Those scores varied according to education level. CONCLUSIONS: The MoCA test did not have a high accuracy for detecting CIND in the population with a low educational level. Nevertheless, this tool may be used to detect dementia, especially in individuals with more than five years of education, if a lower cutoff score is adopted.

MoCA Test: normative and diagnostic accuracy data for seniors with heterogeneous educational levels in Brazil / Teste MoCA: dados normativos e de acurácia diagnóstica para idosos com níveis educacionais heterogêneos no Brasil

ABSTRACT The Montreal Cognitive Assessment (MoCA) has been described as a good tool to detect cognitive impairment. The ideal MoCA cutoff score is still under debate. The aim was to provide MoCA norms and accuracy data for seniors with a lower education level, including illiterates. Methods: Data originated from an epidemiological study conducted in the municipality of Tremembe, Brazil. The Brazilian MoCA test was applied as part of the cognitive assessment in all participants. Of the 630 participants, 385 were classified as cognitively normal (CN) and were included in the normative data set, 110 individuals were diagnosed with dementia and 135 were classified as having cognitive impairment no dementia (CIND). Results: The total scores varied significantly according to age and education among the three diagnostic groups: CN, CIND and dementia (p < 0.001). To distinguish participants with CN from dementia, the best MoCA cutoff was 15 points (sensitivity 90%, specificity 77%) and to differentiate those with CN from CIND, the MoCA cutoff was 19 points (sensitivity 84%, specificity 49%). Those scores varied according to education level. Conclusions: The MoCA test did not have a high accuracy for detecting CIND in the population with a low educational level. Nevertheless, this tool may be used to detect dementia, especially in individuals with more than five years of education, if a lower cutoff score is adopted.

RESUMO O Montreal Cognitive Assessment (MoCA) foi descrito como uma boa ferramenta para detectar comprometimento cognitivo. A nota de corte ideal do MoCA ainda está em debate. O objetivo é fornecer normas do MoCA e dados de acurácia para idosos dentro de uma faixa educacional mais baixa, incluindo analfabetos. Métodos: Os dados foram provenientes do estudo epidemiológico realizado no município de Tremembé, Brasil. A versão brasileira do MoCA foi aplicada como parte da avaliação cognitiva em todos os participantes. Dos 630 participantes, 385 foram classificados como cognitivamente normais (CN) e foram incluídos no conjunto de dados normativos, 110 indivíduos foram diagnosticados com demência e 135 foram classificados como tendo comprometimento cognitivo sem demência (CCSD). Resultados: Os escores totais variaram significativamente de acordo com a idade e escolaridade entre os três grupos diagnósticos: CN, CCSD e demência (p < 0,001). Para distinguir CN de demência, a melhor nota de corte do MoCA foi de 15 pontos (sensibilidade 90%, especificidade 77%) e para diferenciar o grupo CN de CCSD, a nota de corte do MoCA foi de 19 pontos (sensibilidade 84%, especificidade 49%). Essas notas de corte variaram conforme o nível de escolaridade. Conclusões: O teste MoCA não teve alta acurácia para detectar CCSD nesta população de baixa escolaridade. No entanto, esta ferramenta poderia ser usada para detectar demência, especialmente em indivíduos com mais de 5 anos de escolaridade, se uma menor nota de corte fosse adotada.

Cognitive and Brain Activity Changes After Mnemonic Strategy Training in Amnestic Mild Cognitive Impairment: Evidence From a Randomized Controlled Trial.

Background: Mnemonic strategy training (MST) has been shown to improve cognitive performance in amnestic mild cognitive impairment (a-MCI), however, several questions remain unresolved. The goal of the present study was to replicate earlier pilot study findings using a randomized controlled design and to evaluate transfer effects and changes in brain activation. Methods: Thirty patients with a-MCI were randomized into MST or education program. At baseline, participants completed clinical and neuropsychological assessments as well as structural and functional magnetic resonance imaging (fMRI). Interventions were administered individually and comprised four sessions, over 2 weeks. MST taught patients to use a three-step process to learn and recall face-name associations. Post-treatment assessment included fMRI, a separate face-name association task, neuropsychological tests, and measures of metamemory. Behavioral (i.e., non-fMRI) measures were repeated after one and 3-months. Results: Participants in the MST condition showed greater improvement on measures of face-name memory, and increased associative strategy use; effects that were accompanied by increased fMRI activation in the left anterior temporal lobe. While all participants reported greater contentment with their everyday memory following intervention, only the MST group reported significant improvements in their memory abilities. There was no clear indication of far-transfer effects to other neuropsychological tests. Conclusion: Results demonstrate that patients with a-MCI not only show stimulus specific benefits of MST, but that they appear capable of transferring training to at least some other cognitive tasks. MST also facilitated the use of brain regions that are involved in face processing, episodic and semantic memory, and social cognition, which are consonant with the cognitive processes engaged by training.

Addenbrooke's cognitive examination-revised: normative and accuracy data for seniors with heterogeneous educational level in Brazil.

BACKGROUND: Several cognitive tools have been developed aiming to diagnose dementia. The cognitive battery Addenbrooke's Cognitive Examination - Revised (ACE-R) has been used to detect cognitive impairment; however, there are few studies including samples with low education. The aim of the study was to provide ACE-R norms for seniors within a lower education, including illiterates. An additional aim was to examine the accuracy of the ACE-R to detect dementia and cognitive impairment no dementia (CIND). METHODS: Data originated from an epidemiological study conducted in the municipality of Tremembé, Brazil. The Brazilian version of ACE-R was applied as part of the cognitive assessment in all participants. Of the 630 participants, 385 were classified as cognitively normal (CN) and were included in the normative data set, 110 individuals were diagnosed with dementia, and 135 were classified as having CIND. RESULTS: ACE-R norms were provided with the sample stratified into age and education bands. ACE-R total scores varied significantly according to age, education, and sex. To distinguish CN from dementia, a cut-off of 64 points was established (sensitivity 91%, specificity 76%) and to differentiate CN from CIND the best cut-off was 69 points (sensitivity 73%, specificity 65%). Cut-off scores varied according to the educational level. CONCLUSIONS: This study offers normative and accuracy parameters for seniors with lower education and it should expand the use of the ACE-R for this population segment.

GRN and MAPT Mutations in 2 Frontotemporal Dementia Research Centers in Brazil.

BACKGROUND: Mutations in GRN (progranulin) and MAPT (microtubule-associated protein tau) are among the most frequent causes of monogenic frontotemporal dementia (FTD), but data on the frequency of these mutations in regions such as Latin America are still lacking. OBJECTIVE: We aimed to investigate the frequencies of GRN and MAPT mutations in FTD cohorts from 2 Brazilian dementia research centers, the University of Sao Paulo and the Federal University of Minas Gerais medical schools. METHODS: We included 76 probands diagnosed with behavioral-variant FTD (n=55), semantic-variant Primary Progressive Aphasia (PPA) (n=11), or nonfluent-variant PPA (n=10). Twenty-five percent of the cohort had at least 1 relative affected with FTD. RESULTS: Mutations in GRN were identified in 7 probands, and in MAPT, in 2 probands. We identified 3 novel GRN mutations (p.Q130X, p.317Afs*12, and p.K259Afs*23) in patients diagnosed with nonfluent-variant PPA or behavioral-variant FTD. Plasma progranulin levels were measured and a cutoff value of 70 ng/mL was found, with 100% sensitivity and specificity to detect null GRN mutations. CONCLUSIONS: The frequency of GRN mutations was 9.6% and that of MAPT mutations was 7.1%. Among familial cases of FTD, the frequency of GRN mutations was 31.5% and that of MAPT mutations was 10.5%.

One of the most well-established age-related changes in neural activity disappears after controlling for visual acuity.

Numerous studies using a variety of imaging techniques have reported age-related differences in neural activity while subjects carry out cognitive tasks. Surprisingly little attention has been paid to the potential impact of age-associated changes in sensory acuity on these findings. Studies in the visual modality frequently report that their subjects had "normal or corrected- to-normal vision." However, in most cases, there is no indication that visual acuity was actually measured, and it is likely that the investigators relied largely on self-reported visual status of subjects, which is often inaccurate. We investigated whether differences in visual acuity influence one of the most commonly observed findings in the event-related potentials literature on cognitive aging, a reduction in posterior P3b amplitude, which is an index of cognitive decision-making/updating. Well-matched young (n=26) and old adults (n=29) participated in a visual oddball task. Measured visual acuity with corrective lenses was worse in old than young adults. Results demonstrated that the robust age-related decline in P3b amplitude to visual targets disappeared after controlling for visual acuity, but was unaffected by accounting for auditory acuity. Path analysis confirmed that the relationship between age and diminished P3b to visual targets was mediated by visual acuity, suggesting that conveyance of suboptimal sensory data due to peripheral, rather than central, deficits may undermine subsequent neural processing. We conclude that until the relationship between age-associated differences in visual acuity and neural activity during experimental tasks is clearly established, investigators should exercise caution attributing results to differences in cognitive processing.

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.

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

INTRODUCTION: Mild 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. METHODS: Ninety-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-ß, tau, and phosphorylated tau levels in the CSF. RESULTS: Both 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-ß relative to aMCI subjects. CONCLUSION: While 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-ß 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-ß 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.

Analysis of the posterior cingulate cortex with [18F]FDG-PET and Naa/mI in mild cognitive impairment and Alzheimer's disease: Correlations and differences between the two methods.

Reduction of regional brain glucose metabolism (rBGM) measured by [18F]FDG-PET in the posterior cingulate cortex (PCC) has been associated with a higher conversion rate from mild cognitive impairment (MCI) to Alzheimer's disease (AD). Magnetic Resonance Spectroscopy (MRS) is a potential biomarker that has disclosed Naa/mI reductions within the PCC in both MCI and AD. Studies investigating the relationships between the two modalities are scarce. OBJECTIVE: To evaluate differences and possible correlations between the findings of rBGM and NAA/mI in the PCC of individuals with AD, MCI and of cognitively normal volunteers. METHODS: Patients diagnosed with AD (N=32) or MCI (N=27) and cognitively normal older adults (CG, N=28), were submitted to [18F]FDG-PET and MRS to analyze the PCC. The two methods were compared and possible correlations between the modalities were investigated. RESULTS: The AD group exhibited rBGM reduction in the PCC when compared to the CG but not in the MCI group. MRS revealed lower NAA/mI values in the AD group compared to the CG but not in the MCI group. A positive correlation between rBGM and NAA/mI in the PCC was found. NAA/mI reduction in the PCC differentiated AD patients from control subjects with an area under the ROC curve of 0.70, while [18F]FDG-PET yielded a value of 0.93. CONCLUSION: rBGM and Naa/mI in the PCC were positively correlated in patients with MCI and AD. [18F]FDG-PET had greater accuracy than MRS for discriminating AD patients from controls.

Redução do metabolismo cerebral regional glicolítico (MRG) medido pela PET-18FDG no giro do cíngulo posterior (GCP) está relacionada a maior conversão para doença de Alzheimer (DA) em sujeitos com comprometimento cognitivo leve (CCL). Espectroscopia por ressonância magnética (MRS), um biomarcador promissor, demonstra redução de Naa/mI no GCP na DA. Raros estudos avaliam relações entre Naa/mI e MRG. OBJETIVO: Avaliar diferenças e possíveis correlações entre MRG com PET-18FDG e Naa/mI por MRS no GCP de sujeitos com DA, CCL e voluntários normais. MÉTODOS: Sujeitos com DA (N=32), CCL amnéstico (N=27) e voluntários idosos normais (GC, N=28), foram submetidos a PET-18FDG e análise de Naa/mI no GCP. A performance de ambos os métodos foi então comparada e verificou-se a existência de correlações entre os achados da PET e da MRS. RESULTADOS: Observou-se hipometabolismo glicolítico nos pacientes com DA no GCP em relação ao GC, porém não no CCL. A MRS demonstrou valores menores de Naa/mI no CP do grupo DA em relação ao GC, porém também sem diferenças entre CCL e GC. A área sob a curva ROC demonstrou valor de 0,70 para MRS e 0,93 para o MRG no GCP para diferenciar DA do GC. Houve correlação positiva entre o MRG e o Naa/mI no GCP. CONCLUSÃO: Os valores de metabolismo de glicose à PET e de Naa/mI à MRS no giro do cíngulo posterior apresentaram correlação positiva estatisticamente significante na presente amostra. Houve ainda superioridade da PET-18FDG para diferenciar DA do GC.

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 city's 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.

A depressão é um problema importante e crescente de saúde pública. É muito comum ser encontrada uma relação significativa entre depressão e a presença de distúrbios cognitivos nos estudos populacionais. OBJETIVO: Estabelecer a correlação entre a Escala Analógica Visual de Felicidade e a Escala Cornell de Depressão em Demência na população de 60 anos ou mais da cidade de Tremembé, estado de São Paulo, Brasil. MÉTODOS: Estudo epidemiológico no qual foram realizadas visitas domiciliares na cidade de Tremembé. A amostra foi aleatória, através do sorteio de 20% da população acima de 60 anos de cada setor censitário do município. Este estudo foi de fase única, tendo sido realizada anamnese, exames físico e neurológico, avaliação cognitiva e aplicação de escalas Cornell de Depressão em Demência e Escala Analógica de Felicidade para verificar a presença de sintomas depressivos. Foi adotado como critério da presença de sintomas depressivos, pontuação maior ou igual a 8 na escala de Cornell. RESULTADOS: Foram avaliadas 623 pessoas e destas 251 (40,3%) apresentaram sintomas depressivos significativos clinicamente na escala de Cornell, com associação significativa com gênero feminino (p<0,001) e com a baixa escolaridade (p=0,012). Cento e trinta e seis participantes (21,8%) apontaram para faces de infelicidade, com associação significativa com idade (p<0,001), com gênero feminino (p=0,020) e com baixo nível socioeconômico (p=0,012). Embora tenha havido significância estatística no teste de correlação, a correlação entre as duas escalas analisadas não foi alta (rho=0,47). CONCLUSÃO: A prevalência de sintomas depressivos foi elevada nesta amostra e a Escala Analógica de Felicidade e a Escala Cornell de Depressão em Demência não devem ser utilizadas como alternativas similares para avaliar a presença de sintomas depressivos, pelo menos em populações com baixa escolaridade.

Hemimedullary infarct with ipsilateral hemiplegia: a vertebral artery dissection syndrome?

BACKGROUND: Hemimedullary syndrome is very rare and combines the clinical features of lateral and medial medullary infarctions. In patients with hemimedullary syndrome, the presence of ipsilateral, rather than contralateral hemiplegia, is rare. OBJECTIVE: To describe a patient with an infarction in the right hemimedulla with an ipsilateral motor deficit due to dissection of the right vertebral artery (VA) and to assess whether the ipsilateral hemiplegia may be the result of a specific stroke mechanism. METHODS: We reviewed the reports of hemimedullary syndrome in the literature and compared the characteristics of patients with dissection of the VA with those with VA atherosclerotic disease. RESULTS: In our patient, magnetic resonance angiography showed dissection of the right VA to be the cause of the stroke. In a review of the literature (including our case), hemiplegia was ipsilateral to the infarction in four of the five patients with VA dissection, but contralateral in all six patients with atherosclerotic disease of the VA (p=0.01). In all five cases of VA dissection, the right hemimedulla was involved, while, in the six cases of atherosclerotic disease, the left side of the medulla oblongata was affected in five instances and the right side in one (p=0.01). CONCLUSION: Dissection of the VA may provoke a hemimedullary lesion at a lower level than atherosclerosis, thus affecting medullary-penetrating branches that irrigate the medulla immediately below the pyramidal decussation. Hemimedullary syndrome accompanied by ipsilateral motor deficit should raise suspicion of dissection of the VA.

The Syndrome of Irreversible Lithium-Effectuated Neurotoxicity (SILENT): one-year follow-up of a single case.

In this article, we report the case history of a 44-year-old female patient with bipolar disorder who developed the so-called Syndrome of Irreversible Lithium-Effectuated Neurotoxicity (SILENT). A detailed description of our patient's neurologic status is provided at baseline (i.e. during lithium intoxication) and after one year of follow-up, confirming the persistency of cerebellar signs and symptoms. Although rare, our report - which shows a severe and disabling form of SILENT - underscores the need to perform a strict control of the putative risk factors argued to be associated with the development of this syndrome. In our case, the presence of fever and the administration of multiple doses of antipsychotics may have contributed to the poor outcome exhibited by the patient.