A call for clinical trial globalization in Alzheimer's disease and related dementia.

BACKGROUND: The burden of Alzheimer's disease and related dementia (ADRD) is projected to disproportionally impact low-middle-income countries (LMICs). However, there is a systematic under-representation of LMICs in ADRD clinical trial platforms. METHODS: We aimed to determine the global distribution of ADRD clinical trials and identify existing barriers for conducting clinical trials in LMICs. Primary data sources to identify trial distribution in LMICs included ClinicalTrials.gov and the International Trials Registry Platform. An additional systematic review and expert consensus interviews were conducted to identify barriers for conducting clinical trials in LMICs. FINDINGS: Among 1237 disease-modifying therapies tested in ADRD clinical trials, only 11.6% have been or are conducted in emerging economies (upper-middle income [9.6%] and low-middle income [2.0%]). We identified several limitations for trial implementation including a lack of financial resources, low industry presence, regulatory obstacles, and operational barriers INTERPRETATION: Although LMICs bear the greatest burden of ADRD globally, substantial development of clinical trial platforms to address this inequity and health disparity is lacking.

Dissipating the fog: Cognitive trajectories and risk factors 1 year after COVID-19 hospitalization.

INTRODUCTION: Cognitive impairment is common after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, associations between post-hospital discharge risk factors and cognitive trajectories have not been explored. METHODS: A total of 1105 adults (mean age ± SD 64.9 ± 9.9 years, 44% women, 63% White) with severe coronavirus disease 2019 (COVID-19) were evaluated for cognitive function 1 year after hospital discharge. Scores from cognitive tests were harmonized, and clusters of cognitive impairment were defined using sequential analysis. RESULTS: Three groups of cognitive trajectories were observed during the follow-up: no cognitive impairment, initial short-term cognitive impairment, and long-term cognitive impairment. Predictors of cognitive decline after COVID-19 were older age (ß = -0.013, 95% CI = -0.023;-0.003), female sex (ß = -0.230, 95% CI = -0.413;-0.047), previous dementia diagnosis or substantial memory complaints (ß = -0.606, 95% CI = -0.877;-0.335), frailty before hospitalization (ß = -0.191, 95% CI = -0.264;-0.119), higher platelet count (ß = -0.101, 95% CI = -0.185;-0.018), and delirium (ß = -0.483, 95% CI = -0.724;-0.244). Post-discharge predictors included hospital readmissions and frailty. DISCUSSION: Cognitive impairment was common and the patterns of cognitive trajectories depended on sociodemographic, in-hospital, and post-hospitalization predictors. HIGHLIGHTS: Cognitive impairment after coronavirus disease 2019 (COVID-19) hospital discharge was associated with higher age, less education, delirium during hospitalization, a higher number of hospitalizations post discharge, and frailty before and after hospitalization. Frequent cognitive evaluations for 12-month post-COVID-19 hospitalization showed three possible cognitive trajectories: no cognitive impairment, initial short-term impairment, and long-term impairment. This study highlights the importance of frequent cognitive testing to determine patterns of COVID-19 cognitive impairment, given the high frequency of incident cognitive impairment 1 year after hospitalization.

Latin American Initiative for Lifestyle Intervention to Prevent Cognitive Decline (LatAm-FINGERS): Study design and harmonization.

INTRODUCTION: Latin American Initiative for Lifestyle Intervention to Prevent Cognitive Decline (LatAm-FINGERS) is the first non-pharmacological multicenter randomized clinical trial (RCT) to prevent cognitive impairment in Latin America (LA). Our aim is to present the study design and discuss the strategies used for multicultural harmonization. METHODS: This 1-year RCT (working on a 1-year extension) investigates the feasibility of a multi-domain lifestyle intervention in LA and the efficacy of the intervention, primarily on cognitive function. An external harmonization process was carried out to follow the FINGER model, and an internal harmonization was performed to ensure this study was feasible and comparable across the 12 participating LA countries. RESULTS: Currently, 1549 participants have been screened, and 815 randomized. Participants are ethnically diverse (56% are Nestizo) and have high cardiovascular risk (39% have metabolic syndrome). DISCUSSION: LatAm-FINGERS overcame a significant challenge to combine the region's diversity into a multi-domain risk reduction intervention feasible across LA while preserving the original FINGER design.

Two Immersive Virtual Reality Tasks for the Assessment of Spatial Orientation in Older Adults with and Without Cognitive Impairment: Concurrent Validity, Group Comparison, and Accuracy Results.

OBJECTIVE: Spatial disorientation is common in Alzheimer's disease (AD), Mild Cognitive Impairment (MCI), and preclinical individuals with AD biomarkers. However, traditional neuropsychological tests lack ecological validity for the assessment of spatial orientation and to date, there is still no gold standard. The current study aimed to determine the validity and accuracy of two virtual reality tasks for the assessment of spatial orientation. METHODS: We adapted two spatial orientation tasks to immersive virtual environments: a "survey to route" task in which participants had to transfer information from a map to their body position within a maze [Spatial Orientation in Immersive Virtual Environment Test (SOIVET) Maze], and an allocentric-type, route learning task, with well-established topographic landmarks (SOIVET Route). A total of 19 MCI patients and 29 cognitively healthy older adults aged 61-92 participated in this study. Regular neuropsychological assessments were used for correlation analysis and participant performances were compared between groups. Receiver Operating Characteristic (ROC) curve analysis was performed for accuracy. RESULTS: The SOIVET Maze correlated with measures of visuoperception, mental rotation, and planning, and was not related to age, educational level, or technology use profile. The SOIVET Route immediate correlated with measures of mental rotation, memory, and visuoconstruction, and was influenced only by education. Both tasks significantly differentiated MCI and control groups, and demonstrated moderate accuracy for the MCI diagnosis. CONCLUSION: Traditional neuropsychological assessment presents limitations and immersive environments allow for the reproduction of complex cognitive processes. The two immersive virtual reality tasks are valid tools for the assessment of spatial orientation and should be considered for cognitive assessments of older adults.

Hippocampal subregional volume changes in elders classified using positron emission tomography-based Alzheimer's biomarkers of ß-amyloid deposition and neurodegeneration.

Changes in hippocampal subfield volumes (HSV) along the Alzheimer's disease (AD) continuum have been scarcely investigated to date in elderly subjects classified based on the presence of ß-amyloid aggregation and signs of neurodegeneration. We classified patients (either sex) with mild dementia compatible with AD (n = 35) or amnestic mild cognitive impairment (n = 39), and cognitively unimpaired subjects (either sex; n = 26) using [11 C]PIB-PET to assess ß-amyloid aggregation (A+) and [18 F]FDG-PET to account for neurodegeneration ((N)+). Magnetic resonance imaging-based automated methods were used for HSV and white matter hyperintensity (WMH) measurements. Significant HSV reductions were found in A+(N)+ subjects in the presubiculum/subiculum complex and molecular layer, related to worse memory performance. In both the A+(N)+ and A+(N)- categories, subicular volumes were inversely correlated with the degree of Aß deposition. The A-(N)+ subgroup showed reduced HSV relative to the A-(N)- subgroup also in the subiculum/presubiculum. Combining all (N)- subjects, HSV were lower in subjects presenting significant cognitive decline irrespective of A+/A- classification (controlling for WMH load); these between-group differences were detected again in the presubiculum, but also involved the CA4 and granular layer. These findings demonstrate that differential HSV reductions are detectable both in (N)+ and (N)- categories along the AD continuum, and are directly related to the severity of cognitive deficits. HSV reductions are larger both in A+(N)+ and A+(N)- subjects in direct proportion to the degree of Aß deposition. The meaningful HSV reductions detected in the A-(N)+ subgroup highlights the strength of biomarker-based classifications outside of the classical AD continuum.

FDG-PET Patterns Predict Amyloid Deposition and Clinical Profile in Corticobasal Syndrome.

BACKGROUND: Corticobasal syndrome (CBS) is an atypical parkinsonian syndrome related to multiple underlying pathologies. OBJECTIVE: To investigate if individual brain [18 F]fluorodeoxyglucose-positron emission tomography (FDG-PET) patterns could distinguish CBS due to Alzheimer's disease (AD) from other pathologies based on [11 C]Pittsburgh Compound-B (PIB)-PET. METHODS: Forty-five patients with probable CBS were prospectively evaluated regarding cognitive and movement disorders profile. They underwent FDG-PET and were distributed into groups: likely related to AD (CBS FDG-AD) or likely non-AD (CBS FDG-nonAD) pathology. Thirty patients underwent PIB-PET on a hybrid PET-magnetic resonance imaging equipment to assess their amyloid status. FDG and PIB-PET images were classified individually based on visual and semi-quantitative analysis, blinded to each other. Quantitative group analyses were also performed. RESULTS: CBS FDG-AD group demonstrated worse cognitive performances, mostly concerning attention, memory, visuospatial domains, and displayed more myoclonus and hallucinations. The non-AD metabolic group presented more often limb dystonia, ocular motor dysfunction, motor perseveration, and dysarthria. All patients classified as CBS FDG-AD tested positive at PIB-PET compared to 3 of 20 in the non-AD group. The individual FDG-PET classification demonstrated 76.92% of sensitivity, 100% of specificity and positive predictive value and 88.5% of balanced accuracy to detect positive PIB-PET scans. Individuals with positive and negative PIB-PET showed hypometabolism in posterior temporoparietal areas and in thalamus and brainstem, respectively, mainly contralateral to most affected side, disclosing possible metabolic signatures of CBS variants. CONCLUSION: FDG-PET was useful to predict AD and non-AD CBS variants depicting their specific degeneration patterns, different clinical features, and brain amyloid deposition. © 2020 International Parkinson and Movement Disorder Society.

Deficits in short-term memory binding are detectable in individuals with brain amyloid deposition in the absence of overt neurodegeneration in the Alzheimer's disease continuum.

The short-term memory binding (STMB) test involves the ability to hold in memory the integration between surface features, such as shapes and colours. The STMB test has been used to detect Alzheimer's disease (AD) at different stages, from preclinical to dementia, showing promising results. The objective of the present study was to verify whether the STMB test could differentiate patients with distinct biomarker profiles in the AD continuum. The sample comprised 18 cognitively unimpaired (CU) participants, 30 mild cognitive impairment (MCI) and 23 AD patients. All participants underwent positron emission tomography (PET) with Pittsburgh compound-B labelled with carbon-11 ([11C]PIB) assessing amyloid beta (Aß) aggregation (A) and 18fluorine-fluorodeoxyglucose ([18F]FDG)-PET assessing neurodegeneration (N) (A-N- [n = 35]); A+N- [n = 11]; A+ N+ [n = 19]). Participants who were negative and positive for amyloid deposition were compared in the absence (A-N- vs. A+N-) of neurodegeneration. When compared with the RAVLT and SKT memory tests, the STMB was the only cognitive task that differentiated these groups, predicting the group outcome in logistic regression analyses. The STMB test showed to be sensitive to the signs of AD pathology and may represent a cognitive marker within the AD continuum.

Dementia in Latin America: Paving the way toward a regional action plan.

Across Latin American and Caribbean countries (LACs), the fight against dementia faces pressing challenges, such as heterogeneity, diversity, political instability, and socioeconomic disparities. These can be addressed more effectively in a collaborative setting that fosters open exchange of knowledge. In this work, the Latin American and Caribbean Consortium on Dementia (LAC-CD) proposes an agenda for integration to deliver a Knowledge to Action Framework (KtAF). First, we summarize evidence-based strategies (epidemiology, genetics, biomarkers, clinical trials, nonpharmacological interventions, networking, and translational research) and align them to current global strategies to translate regional knowledge into transformative actions. Then we characterize key sources of complexity (genetic isolates, admixture in populations, environmental factors, and barriers to effective interventions), map them to the above challenges, and provide the basic mosaics of knowledge toward a KtAF. Finally, we describe strategies supporting the knowledge creation stage that underpins the translational impact of KtAF.

Correction to: Brain PET amyloid and neurodegeneration biomarkers in the context of the 2018 NIA-AA research framework: an individual approach exploring clinical-biomarker mismatches and sociodemographic parameters.

In the last paragraph of the subsession "Recruitment of the study population and clinical Evaluation" (Material and methods session).

Brain PET amyloid and neurodegeneration biomarkers in the context of the 2018 NIA-AA research framework: an individual approach exploring clinical-biomarker mismatches and sociodemographic parameters.

PURPOSE: [18F]FDG-PET and [11C]PIB-PET are validated as neurodegeneration and amyloid biomarkers of Alzheimer's disease (AD). We used a PET staging system based on the 2018 NIA-AA research framework to compare the proportion of amyloid positivity (A+) and hypometabolism ((N)+) in cases of mild probable AD, amnestic mild cognitive impairment (aMCI), and healthy controls, incorporating an additional classification of abnormal [18F]FDG-PET patterns and investigating the co-occurrence of such with A+, exploring [18F]FDG-PET to generate hypotheses in cases presenting with clinical-biomarker "mismatches." METHODS: Elderly individuals (N = 108) clinically classified as controls (N = 27), aMCI (N = 43) or mild probable AD (N = 38) were included. Authors assessed their A(N) profiles and classified [18F]FDG-PET neurodegenerative patterns as typical or non-typical of AD, performing re-assessments of images whenever clinical classification was in disagreement with the PET staging (clinical-biomarker "mismatches"). We also investigated associations between "mismatches" and sociodemographic and educational characteristics. RESULTS: AD presented with higher rates of A+ and (N)+. There was also a higher proportion of A+ and (N)+ individuals in the aMCI group in comparison to controls, however without statistical significance regarding the A staging. There was a significant association between amyloid positivity and AD (N)+ hypometabolic patterns typical of AD. Non-AD (N)+ hypometabolism was seen in all A- (N)+ cases in the mild probable AD and control groups and [18F]FDG-PET patterns classified such individuals as "SNAP" and one as probable frontotemporal lobar degeneration. All A- (N)- cases in the probable AD group had less than 4 years of formal education and lower socioeconomic status (SES). CONCLUSION: The PET-based staging system unveiled significant A(N) differences between AD and the other groups, whereas aMCI and controls had different (N) staging, explaining the cognitive impairment in aMCI. [18F]FDG-PET could be used beyond simple (N) staging, since it provided alternative hypotheses to cases with clinical-biomarker "mismatches." An AD hypometabolic pattern correlated with amyloid positivity. Low education and SES were related to dementia in the absence of biomarker changes.

Profiles of cognitive impairment in the continuum from normal cognition to Alzheimer's clinical syndrome: Contributions of the short-term memory binding tests.

BACKGROUND: Short-term memory binding (STMB) tests assess conjunctive binding, in which participants should remember the integration of features, such as shapes (or objects) and colors, forming a unique representation in memory. In this study, we investigated two STMB paradigms: change detection (CD) and free recall (FR). OBJECTIVE: To investigate the cognitive profile in the CD and FR tasks of three diagnostic groups: cognitively unimpaired (CU), mild cognitive impairment (MCI), and Alzheimer's clinical syndrome (ACS). In addition, we aimed to calculate and compare the accuracy of the CD and FR tasks to identify MCI and ACS. METHODS: Participants were 24 CU, 24 MCI, and 37 ACS. The cognitive scores of the clinical groups were compared using analysis of variance (ANOVA) and receiver-operating characteristic (ROC) analyses were carried out to verify the accuracy of the STMB tasks. RESULTS: In the CD task, CU was different from MCI and ACS (CU > MCI = ACS), while in the FR task all groups were different (CU > MCI > ACS). The ROC analyses showed an area under the curve (AUC) of 0.855 comparing CU with MCI for the CD task and 0.975 for the FR. The AUC comparing CU and ACS was 0.924 for the CD and 0.973 for the FR task. The FR task showed better accuracy to identify MCI patients, and the same accuracy to detect ACS. CONCLUSION: The present findings indicate that impairments in CD and FR of bound representations are features of the cognitive profiles of MCI and ACS patients.

Using temporal orientation, category fluency, and word recall for detecting cognitive impairment: the 10-point cognitive screener (10-CS).

OBJECTIVES: A screening strategy composed of three-item temporal orientation and three-word recall has been increasingly used for detecting cognitive impairment. However, the intervening task administered between presentation and recall has varied. We evaluated six brief tasks that could be useful as intervening distractors and possibly provide incremental accuracy: serial subtraction, clock drawing, category fluency, letter fluency, timed visual detection, and digits backwards. METHODS: Older adults (n = 230) consecutively referred for suspected cognitive impairment underwent a comprehensive assessment for gold-standard diagnosis, of whom 56 (24%) presented cognitive impairment not dementia and 68 (30%) presented dementia. Among those with dementia, 87% presented very mild or mild stages (Clinical Dementia Rating 0.5 or 1). The incremental value of each candidate intervening task in a model already containing orientation and word recall was assessed. RESULTS: Category fluency (animal naming) presented the highest incremental value among the six candidate intervening tasks. Reclassification analyses revealed a net gain of 12% among cognitively impaired and 17% among normal participants. A four-point scaled score of the animal naming task was added to three-item temporal orientation and three-word recall to compose the 10-point Cognitive Screener. The education-adjusted 10-point Cognitive Screener outperformed the longer Mini-Mental State Examination for detecting both cognitive impairment (area under the curve 0.85 vs 0.77; p = 0.027) and dementia (area under the curve 0.90 vs 0.83; p = 0.015). CONCLUSIONS: Based on empirical data, we have developed a brief and easy-to-use screening strategy with higher accuracy and some practical advantages compared with commonly used tools.

Direct and indirect assessments of activities of daily living in behavioral variant frontotemporal dementia and Alzheimer disease.

BACKGROUND: There is limited information about the functional profile of behavioral variant frontotemporal dementia (bvFTD). OBJECTIVE: To compare direct and indirect assessments of activities of daily living (ADLs) in bvFTD and Alzheimer disease (AD) and their relationship with cognitive performance. METHODS: In all, 20 patients with bvFTD, 30 patients with AD, and 34 normal controls (NCs), matched for age, education, and severity of dementia, completed the Direct Assessment of Functional Performance (DAFS-BR) and usual cognitive measures. The Disability Assessment for Dementia (DAD) was completed by caregivers. RESULTS: In DAFS-BR, patients with bvFTD and AD had similar performance but lower than NCs. In DAD, there were no significant differences for effective performance, but patients with bvFTD had lower scores for initiation and planning/organization. Patients with bvFTD were less impaired than AD in cognition. CONCLUSION: Functional changes in bvFTD seem to be better documented by indirect measures.

Suggested instruments for General Practitioners in countries with low schooling to screen for cognitive impairment in the elderly.

BACKGROUND: General Practitioners (GPs) from underdeveloped countries apply cognitive impairment (CI) assessment tools translated and adapted to cultural setting from other idioms, mainly English. As schooling in elderly from underdeveloped countries tends to be relatively heterogeneous, it is necessary to establish normative and cut-off scores for these CI instruments that are based on studies conducted locally. Some CI screening instruments frequently used by Brazilian specialists in dementia were analyzed to determine which could be most useful to GPs in their working sets. METHOD: Two hundred forty-eight patients aged 65 years or older that had been assisted by GPs in a tertiary hospital in Brazil were evaluated. Based on the MMSE and/or Short-IQCODE scores, 52 probable cases were identified on the basis of clinical data, performances on the neuropsychological tests and questionnaires (Functional Assessment Questionnaire/FAQ, Category Verbal Fluency/CVF, Clock Drawing Test/CDT) and blood tests and brain CT. RESULTS: The combination of a functional questionnaire with a cognitive instrument had higher sensitivity and specificity than using the instruments alone. A FAQ cut-off of 3 in conjunction with a CDT cut-off of 6 proved optimal (93% sensitivity and 92.5% specificity). A higher specificity (93.5%) was attained using a combination of the FAQ (cut-off of 3) with the CVF (cut-off of 10). CONCLUSIONS: For low schooling elderly, the combination of the FAQ and CVF represented a very simple method of increasing the chances of correct screening. For those with higher schooling, the combination of the FAQ and CDT was more suitable.

Detecting limited health literacy in Brazil: development of a multidimensional screening tool.

Screening questions have been proposed as practical tools for detecting limited functional health literacy, but have achieved only moderate accuracy in previous studies. We hypothesized that a combination of screening questions and demographic characteristics could better predict a patient's functional health literacy. Three hundred and twenty-two hospital users from São Paulo, Brazil, were interviewed for demographic information and answered questions about literacy habits and perceived difficulties. The Short Test of Functional Health Literacy in Adults was used to classify individuals as having adequate or limited functional health literacy. Of the 322 participants, 102 (31.7%) presented limited functional health literacy. The final logistic model included six predictors. The three demographic variables were educational attainment, mother's educational attainment and major lifetime occupation (manual or non-manual). The three questions concerned 'frequency of use of computers', 'difficulty with writing that have precluded the individual from getting a better job' and 'difficulty reading the subtitles while watching a foreign movie'. A simple score was derived to constitute a practical tool we named the Multidimensional Screener of Functional Health Literacy (MSFHL). The sensitivity of the MSFHL in detecting limited functional health literacy was 81.4% and the specificity was 87.7%, with an area under receiver operating characteristic (ROC) curve of 0.93 (95% CI 0.89-0.95). The MSFHL was better than educational attainment in accurately classifying functional health literacy status (p = 0.0018). We have developed a screening tool based on three demographic characteristics and three simple questions which provides an accurate prediction of a patient's functional health literacy level.

Development of the Brazilian version of the Mini-Addenbrooke Cognitive Examination (M-ACE BR) to screen for cognitive impairment in older adults.

BACKGROUND: Age is the most important risk factor for develop dementia, and the recommendation is that older adults are cognitively tested to detect impairment in the initial stage for adequate treatment. The demand for the care of these older adults is great, drawing attention to the need for rapid tests, with good accuracy and simple application to identify cognitive impairment. OBJECTIVE: To develop and validate the Brazilian Mini-Addenbrooke Cognitive Examination (M-ACE BR) as a short screening test for cognitive impairment in older adults. METHODS: The M-ACE BR was developed using the Mokken scaling analysis in 352 participants (cognitively unimpaired [CU] = 232, cognitive impairment no dementia [CIND] = 82; and dementia = 38) and validated in an independent sample of 117 participants (CU = 25; CIND = 88; and dementia = 4). RESULTS: The Mokken scaling analysis derived 9 items (spatial orientation, anterograde memory, retrograde memory, delayed recall, recognition [name and address], letter verbal fluency, repetition of 4 words, naming of 10 items, and comprehension) with a maximum score of 51 points and an average duration time of 7 minutes. The cut-off score ≤ 43/51 for CIND had a sensitivity of 59.09% and a specificity of 80%. For a screening test in which sensitivity is prioritized for further investigation, we suggest using a cutoff of ≤ 47 (sensitivity 85.23% and specificity 24%), maintaining a good positive predictive value (79.8%). CONCLUSION: The M-ACE BR is a brief and adequate instrument to detect cognitive impairment in older Brazilian adults. However, screening for CIND and for different educational levels should be further explored.

ANTECEDENTES: A idade é o fator de risco mais importante para o desenvolvimento de demência, e a recomendação é que os idosos sejam testados cognitivamente para detectar comprometimento na fase inicial para o tratamento adequado. A demanda pelo atendimento desses idosos é grande, chamando atenção para a necessidade de testes rápidos, com boa acurácia e de simples aplicação para identificar o comprometimento cognitivo. OBJETIVO: Desenvolver e validar a versão brasileira do Mini-Addenbrooke's Cognitive Examination (M-ACE BR) como um teste rápido para rastreio de comprometimento cognitivo em idosos. MéTODOS: A M-ACE BR foi desenvolvida usando análise da escala de Mokken em 352 participantes (cognitivamente saudáveis [CS] = 232, comprometimento cognitivo sem demência [CCSD] = 82; e demência = 38) e validado em uma amostra independente de 117 participantes (CS = 25; CCSD = 88; e demência = 4). RESULTADOS: A análise de escala de Mokken derivou 9 itens (orientação espacial, memória anterógrada, memória retrógrada, evocação tardia, reconhecimento [nome e endereço], fluência verbal de letras, repetição de 4 palavras, nomeação de 10 itens e compreensão) com pontuação máxima de 51 pontos e tempo médio de duração de 7 minutos. O escore de corte ≤ 43/51 para CCSD teve sensibilidade de 59,09% e especificidade de 80%. Para um teste de rastreio, em que a sensibilidade é priorizada para investigação posterior, sugerimos utilizar um ponto de corte ≤ 47 (sensibilidade 85,23% e especificidade 24%), mantendo um bom valor preditivo positivo (79,8%). CONCLUSãO: A M-ACE BR é um instrumento breve e adequado para detectar comprometimento cognitivo em idosos brasileiros. No entanto, o rastreio para a identificação de CCSD e para diferentes níveis de escolaridade deve ser melhor explorado.

COVID-19 and Cognitive and Mental Health During Post-Infection Phase: A Study Among Middle-Aged and Older Indigenous Adults From Brazilian Amazons.

OBJECTIVES: To examine the rate of self-reported coronavirus disease-2019 (COVID-19) and its association with mental and cognitive health during the post-infection phase among middle-aged and older indigenous adults. METHODS: A cross-sectional study was conducted, including 141 individuals ≥50 and over from an urban indigenous community in Amazonas, Brazil. COVID-19 was deduced from self-reported infections. Cognitive function was evaluated using the Mini-Mental State Exam, Brief Cognitive Screening Battery (BCSB), and language fluency tests. Meanwhile, mental health was assessed through validated scales examining happiness, stress, and depression symptoms. The association between the rate of COVID-19 and cognitive and mental well-being was analyzed using logistic and linear regressions, adjusted for covariates. RESULTS: From March 2020 to February 2022, 65.2% of the urban indigenous group tested positive for COVID-19. Lower functional capacity decreased the odds of contracting COVID-19 (p = .03). Adjusted linear regression models showed that COVID-19 was associated with higher BCSB learning (p = .017) and delayed recall (p = .028). Women, higher age, lower functional capacity, and hospitalization were associated with worse cognitive performance (p < .05). No impact of mental health indicators on past COVID-19 infection was noted. DISCUSSION: COVID-19 was prevalent among urban Indigenous Brazilians. Unexpectedly, it was linked to enhanced learning and memory, not mental health issues. Cognitive performance was lower for men, older individuals, those with less functional ability, and hospitalized patients, indicating that participant characteristics and disease severity affect the COVID-19 and cognition relationship. Longitudinal studies across diverse Indigenous communities are necessary to understand COVID-19's impact on their cognitive and mental health.

Feasibility, safety, and adherence of a remote physical and cognitive exercise protocol for older women.

BACKGROUND: Population aging and the consequences of social distancing after the COVID-19 pandemic make it relevant to investigate the feasibility of remote interventions and their potential effects on averting functional decline. OBJECTIVE: (1) To investigate the feasibility, safety, and adherence of a remote protocol involving physical and cognitive exercises for older women with normal cognition; (2) to examine its effects on cognitive and well-being variables. METHODS: Twenty-nine women (age ≥ 60 years old) were randomized into experimental group (EG; n = 15) and control group (CG; n = 14). The EG performed a 40-minute session of cognitive and physical exercises, and CG performed a 20-minute stretching session. Both groups performed 20 sessions via videoconference and 20 on YouTube twice a week. The Mini-Mental State Examination, Verbal Fluency Test, Digit Span (direct an inverse order), Geriatric Depression Scale (GDS), and Well-being Index (WHO-5) were applied in pre- and post-interventions by phone. RESULTS: Overall adherence was 82.25% in EG and 74.29% in CG. The occurrence of adverse events (mild muscle pain) was 33.3% in EG and 21.4% in CG. The EG improved verbal fluency and attention (p ≤ 0.05); both groups had improved depressive symptoms. CONCLUSION: The present study met the pre-established criteria for feasibility, safety, and adherence to the remote exercise protocol among older women. The results suggest that a combined protocol has more significant potential to improve cognitive function. Both interventions were beneficial in improving the subjective perception of well-being.

ANTECEDENTES: O envelhecimento populacional e as consequências do isolamento social após a pandemia de COVID-19 tornaram relevante investigar a viabilidade, segurança e aderência de intervenções remotas e potenciais efeitos para prevenir declínios funcionais. OBJETIVO: (1) Investigar a viabilidade, segurança e aderência de um protocolo remoto de exercícios físicos e cognitivos; (2) investigar os possíveis efeitos sobre variáveis de cognição e de bem-estar. MéTODOS: Vinte e nove mulheres foram randomicamente divididas em grupo experimental (GE; n = 15) e grupo controle (GC; n = 14). O GE realizou sessões de 40 minutos de exercícios físicos e cognitivos e o GC, 20 minutos de alongamentos. Totalizaram 20 sessões por videoconferência e 20 pelo YouTube, duas vezes por semana. O Teste de Fluência Verbal, o Teste de Dígitos (ordem direta e inversa), a Escala de Depressão Geriátrica (GDS) e o Índice de Bem-Estar (WHO-5) foram aplicados no pré e pós-intervenção, por telefone e formulário digital. RESULTADOS: A aderência geral média foi de 82,25% no GE e 74,29% no GC. A ocorrência de eventos adversos (dores musculares leves) foi de 33,3% no GE e 21,4% no GC. O GE teve melhora em fluência verbal e atenção (p ≤ 0.05) e ambos os grupos tiveram melhora significativa nos sintomas depressivos. CONCLUSãO: O presente estudo atendeu aos critérios preestabelecidos para a viabilidade, segurança e aderência do programa oferecido entre idosas. Os resultados sugerem que o protocolo combinado tenha maior potencial de aprimorar funções cognitivas. Ambas as intervenções foram benéficas para a percepção subjetiva de bem-estar.

Culturally adapted cognitive assessment tool for Indigenous communities in Brazil: Content, construct, and criterion validity.

INTRODUCTION: Initial dementia prevalence estimates have revealed a significant burden of the disease in Indigenous communities in Amazonas, Brazil. However, the need for culturally adapted cognitive tools poses a critical challenge when assessing cognitive performance in these communities. This study addressed this issue by culturally adapting and providing validity indicators for the Brazilian Indigenous Cognitive Assessment (BRICA) tool in Manaus, Brazil's urban multiethnic Indigenous community. METHODS: Using a three-stage process and a stakeholder-engaged approach, the BRICA tool was culturally adapted in an urban multiethnic Indigenous community from Manaus, Brazil. The content validity index (CVI) examined inter-rater concordance between experts, while criterion and concurrent validity were performed using diagnostic consensus criteria in 141 Indigenous participants aged ≥ 50 years. RESULTS: Findings showed evidence of content validity in terms of equivalence aspects (scale CVI [S-CVI] 0.93) and relevance ratings (S-CVI 0.85) between expert panels. The identified cut-off score of ≤ 33/39 on the BRICA demonstrated a sensitivity of 94.4%, specificity of 99.2%, positive predictive value of 94.4%, and negative predictive value of 99.2% for dementia diagnosis. DISCUSSION: Using a stakeholder-engaged approach, we culturally adapted the BRICA tool for a Brazilian urban multiethnic Indigenous community. This comprehensive adaptation process resulted in favorable indicators of content, construct, and criteria validity for the BRICA tool. By addressing the existing bias in cognitive assessment within Indigenous communities, the BRICA tool represents a noteworthy breakthrough. Its implementation exhibits potential for improving the early detection and management of dementia among Indigenous groups. Highlights: Culturally sensitive tools are essential to assess cognition in Indigenous populations.An expert panel and stakeholders' perspectives were incorporated to design the Brazilian Indigenous Cognitive Assessment (BRICA) tool.A cognitive screening tool was adapted and validated using a stakeholder approach.BRICA is the first culturally sensitive cognitive tool for urban Brazilian Indigenous individuals.

Bearded capuchin monkeys as a model for Alzheimer's disease.

The absence of a natural animal model is one of the main challenges in Alzheimer's disease research. Despite the challenges of using nonhuman primates in studies, these animals can bridge mouse models and humans, as nonhuman primates are phylogenetically closer to humans and can spontaneously develop AD-type pathology. The capuchin monkey, a New World primate, has recently attracted attention due to its skill in creating and using instruments. We analyzed one capuchin brain using structural 7 T MRI and performed a neuropathological evaluation of three animals. Alzheimer-type pathology was found in the two of the capuchins. Widespread ß-amyloid pathology was observed, mainly in focal deposits with variable morphology and a high density of mature plaques. Notably, plaque-associated dystrophic neurites associated with disruption of axonal transport and early cytoskeletal alteration were frequently found. Unlike in other species of New World monkeys, cerebral arterial angiopathy was not the predominant form of ß-amyloid pathology. Additionally, abnormal aggregates of hyperphosphorylated tau, resembling neurofibrillary pathology, were observed in the temporal and frontal cortex. Astrocyte hypertrophy surrounding plaques was found, suggesting a neuroinflammatory response. These findings indicate that aged capuchin monkeys can spontaneously develop Alzheimer-type pathology, indicating that they may be an advantageous animal model for research in Alzheimer's disease.