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.

Biomarkers for dementia in Latin American countries: Gaps and opportunities.

Limited knowledge on dementia biomarkers in Latin American and Caribbean (LAC) countries remains a serious barrier. Here, we reported a survey to explore the ongoing work, needs, interests, potential barriers, and opportunities for future studies related to biomarkers. The results show that neuroimaging is the most used biomarker (73%), followed by genetic studies (40%), peripheral fluids biomarkers (31%), and cerebrospinal fluid biomarkers (29%). Regarding barriers in LAC, lack of funding appears to undermine the implementation of biomarkers in clinical or research settings, followed by insufficient infrastructure and training. The survey revealed that despite the above barriers, the region holds a great potential to advance dementia biomarkers research. Considering the unique contributions that LAC could make to this growing field, we highlight the urgent need to expand biomarker research. These insights allowed us to propose an action plan that addresses the recommendations for a biomarker framework recently proposed by regional experts.

Diagnostic accuracy of brief cognitive screening tools to diagnose vascular cognitive impairment in Peru.

INTRODUCTION: To evaluate the diagnostic accuracy of three brief cognitive screening (BCS) tools, Peruvian version of Addenbrooke's Cognitive Examination (ACE-Pe), of INECO Frontal Screening (IFS-Pe) and of the Mini-Mental State Examination (MMSE-Pe), for the diagnosis of vascular cognitive impairment (VCI) and its non-dementia stages (VCI-ND) and vascular dementia (VD) in patients with cerebral stroke in Lima-Peru. MATERIALS AND METHODS: A cohort analysis to evaluate the diagnostic accuracy of three BCS for VCI. RESULTS: Two hundred and four patients were evaluated: 61% Non-VCI, 30% VCI-ND and 9% VD. To discriminate patients with VCI from controls, the area under the curve (AUC) of ACE-Pe, IFS-Pe and MMs-Pe were 0.99 (95% confidence interval [CI] 0.98-0.99), 0.99 (95%CI 0.98-0.99) and 0.87 (95%CI 0.82-0.92), respectively. Of the three BCS, the IFS-Pe presented a larger AUC to discriminate VCI-ND from VD (AUC = 0.98 [95%CI 0.95-1]) compared to ACE-Pe (AUC = 0.84 [95%CI 0.74-0.95]) and MMSE-Pe (0.92 [95%CI 0.86-0.99]). The IFS-Pe presented a higher sensitivity (S), specificity (Sp), and positive (+LR) and negative likelihood ratios (-LR) (S = 96.72%, Sp = 89.47%, +LR = 9.1 and -LR = 0.03) than ACE-Pe (S = 96.72%, Sp = 63.16%, +LR = 2.62 and -LR = 0.05) and MMSE-Pe (S = 90.16%, Sp = 78.95%, +LR = 4.28 and -LR = 0.12). In the multiple regression analysis, the IFS-Pe was not affected by age, sex or years of schooling. CONCLUSION: The IFS-Pe has the best diagnostic accuracy for detecting VCI and discriminating between pre-dementia (VCI-ND) and dementia (VD) stages.

Knowledge of dementia and Alzheimer's disease among healthcare professionals in Peru.

BACKGROUND: Primary care physicians and other healthcare providers report feeling unprepared to treat persons with dementia (PWD), especially in developing countries OBJECTIVE: We aimed to assess the knowledge of dementia and Alzheimer's disease (AD) among health professionals in both primary and tertiary care in Peru. METHODS: We conducted an in-person and virtual survey of healthcare professionals trained in Peru throughout the year 2020. The survey was developed based on a previously published one and reviewed by an expert panel. We compared groups using a Chi-squared test. A Bonferroni corrected p-value of 0.008 was used for statistical significance. RESULTS: Out of 804 surveys, we excluded 56 due to incomplete data. A total of 41.6% of respondents were doctors and 21.8%, nurses. One fifth of participants did not recognize AD as a cause of dementia and over half considered "senile dementia" a valid clinical entity. Scores were higher among those with postgraduate training, multiple patients with dementia, or those who had practiced for over 10 years. CONCLUSION: There is a low level of knowledge of dementia and AD among health professionals in Peru, which worsens outside of Lima. Pernicious ideas, such as senile dementia, are still significantly present among respondents.

ANTECEDENTES: Los médicos de primer nivel de atención y otros profesionales de la salud no se consideran cómodos tratando pacientes con demencia, especialmente en países en vías de desarrollo. OBJETIVO: Buscamos evaluar el conocimiento sobre demencia y enfermedad de Alzheimer entre profesionales de la salud en centros de atención primaria y terciaria en Perú.: MéTODOS: Realizamos una encuesta virtual y presencial a trabajadores de la salud entrenados en Perú en el año 2020. La encuesta fue desarrollada con base en una previamente publicada y revisada por un panel de expertos. Comparamos los grupos por medio de una prueba de Chi-cuadrado. Un valor de p de 0.008, obtenido por una corrección de Bonferroni, fue usado para determinar la significancia estadística. RESULTADOS: De 804 encuestados, excluimos 56 debido a datos incompletos. En total, 41.6% de los encuestados eran médicos y 21.8%, enfermeras. Un quinto no reconocía a la enfermedad de Alzheimer como una causa de demencia, y más de la mitad consideraban a la "demencia senil" una entidad clínica válida. Los puntajes fueron mayores para aquellos con entrenamiento de posgrado, experiencia con pacientes con demencia, o más de 10 años de experiencia. CONCLUSIóN: Existe un bajo nivel de conocimiento sobre demencia y enfermedad de Alzheimer entre profesionales de la salud en Perú. Este es aún más bajo fuera de Lima. Ideas dañinas como la "demencia senil" aún están significativamente presentes entre los encuestados.

The Brain Health Diplomat's Toolkit: supporting brain health diplomacy leaders in Latin America and the Caribbean.

Maintaining and improving brain health, one of the most critical global challenges of this century, necessitates innovative, interdisciplinary, and collaborative strategies to address the growing challenges in Latin America and the Caribbean. This paper introduces Brain Health Diplomacy (BHD) as a pioneering approach to bridge disciplinary and geographic boundaries and mobilize resources to promote equitable brain health outcomes in the region. Our framework provides a toolkit for emerging brain health leaders, equipping them with essential concepts and practical resources to apply in their professional work and collaborations. By providing case studies, we highlight the importance of culturally sensitive, region-specific interventions to address unique needs of vulnerable populations. By encouraging dialogue, ideation, and cross-sector discussions, we aspire to develop new research, policy, and programmatic avenues. The novel BHD approach has the potential to revolutionize brain health across the region and beyond, ultimately contributing to a more equitable global cognitive health landscape.

A Functional Assessment Tool to Distinguish Controls From Alzheimer's Disease in Lima, Peru.

BACKGROUND: The Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) scale is a versatile functional assessment tool for patients with Alzheimer's disease (ad). We evaluated its performance in controls, Peruvians with MCI or AD. METHODS: A cross-sectional study of older adults attending a neurology institute in Lima (Peru) with mild cognitive impairment (MCI), ad or cognitively healthy. Test-retest reliability (intraclass correlation coefficient, ICC; internal consistency, Cronbach's alpha) and validity were assessed. RESULTS: We enrolled 276 individuals (ad: 113, MCI: 68, controls: 95) with no age, sex, educational level, and depressive symptom differences. Reliability was ideal (ICC: .996), and Cronbach's alpha was adequate (.937). The ADCS-ADL could not differentiate MCI from controls but did differentiate ad severity. The ADCS-ADL correlated highly with nearly all tools. CONCLUSIONS: The ADCS-ADL scale is reliable in a population with ad in Lima, Peru. Future work may validate a tool for Peruvians with lower educational levels.

Facilitators and Barriers to Dementia Assessment and Diagnosis: Perspectives From Dementia Experts Within a Global Health Context.

Objectives: Dementia poses one of the greatest global health challenges, affecting 50 million people worldwide. With 10 million new cases each year, dementia is a growing burden, particularly in low- and middle-income countries (LMIC). This study aimed to identify the facilitators and barriers to providing quality dementia assessment and care in LMICs from a global health perspective. Methods/Design: A qualitative semi-structured interview study with 20 dementia expert healthcare providers from 19 countries. To be included, providers had to: practice dementia assessment or care in LMICs where the population over age 60 is projected to more than double by 2050 and be recognized as a leading dementia expert in the region based on position, research publications, and/or policy leadership. Interviews were analyzed by a multidisciplinary team of researchers using thematic analysis. Results: Barriers to dementia assessment and care included stigma about dementia, poor patient engagement in and access to healthcare, inadequate linguistic and cultural validation, limited dementia capable workforce, competing healthcare system priorities, and insufficient health financing. Facilitators included the rise in dementia awareness campaigns, dementia training for general practitioners, availability of family support and family caregivers, and national and international collaborations including coordinated policy efforts and involvement in international research initiatives. Conclusions: Findings from this study provide insights for prioritizing dementia assessment and care capacity-building in LMICs as a global health priority and for tailored public health approaches to strengthen dementia assessment and care at the individual, community, national, and multi-national levels.

Thyroid Dysfunction, Vitamin B12, and Folic Acid Deficiencies Are Not Associated With Cognitive Impairment in Older Adults in Lima, Peru.

Background: Reversible etiologies of cognitive impairment are common and treatable, yet the majority of mild cognitive impairment (MCI) and dementia research in Latin America has focused on irreversible, neurodegenerative etiologies. Objective: We sought to determine if thyroid dysfunction and vitamin B12 and folate deficiencies are associated with cognitive disorders among older adults with memory complaints in Lima, Peru. Methods: This was a retrospective review of patients who presented for cognitive evaluations to a multidisciplinary neurology clinic in Lima, Peru from January 2014 to February 2020. We included individuals aged ≥60 years, native Spanish-speakers, with at least a primary school educational level and a complete clinical assessment. Patients had either subjective cognitive decline (SCD), MCI, or dementia. One-way ANOVA and multiple logistic regression analyses were performed. Results: We included 720 patients (330 SCD, 154 MCI, and 236 dementia); the dementia group was significantly older [mean age SCD 69.7 ± 4.1, dementia 72.4 ± 3.7 (p = 0.000)] and had lower folate levels than SCD patients. The MCI group had higher free T3 levels compared with SCD patients. Those with lower TSH had greater dementia risk (OR = 2.91, 95%CI: 1.15-6.86) but not MCI risk in unadjusted models. B12 deficiency or borderline B12 deficiency was present in 34% of the dementia group, yet no clear correlation was seen between neuropsychological test results and B12 levels in our study. There was no association between MCI or dementia and thyroid hormone, B12 nor folate levels in adjusted models. Conclusion: Our findings do not support an association between metabolic and endocrine disorders and cognitive impairment in older Peruvians from Lima despite a high prevalence of B12 deficiency. Future work may determine if cognitive decline is associated with metabolic or endocrine changes in Latin America.

Performance of the Rowland Universal Dementia Assessment Scale for the Detection of Mild Cognitive Impairment and Dementia in a Diverse Cohort of Illiterate Persons From Rural Communities in Peru.

Background: The accurate diagnosis of neurocognitive disorders in illiterate Peruvian populations is challenging, largely owing to scarcity of brief cognitive screening tools (BCST) validated in these diverse populations. The Peruvian version of the Rowland Universal Dementia Assessment Scale (RUDAS-PE) is a BCST that relies minimally on educational attainment and has shown good diagnostic accuracy in an urban illiterate population in Peru, yet its psychometric properties in illiterate populations in rural settings of the country have not been previously investigated. Objectives: To establish the diagnostic accuracy of the RUDAS-PE compared to expert clinical diagnosis using the Clinical Dementia Rating (CDR) Scale in healthy and cognitively impaired illiterate persons living in two culturally and geographically distinct rural communities of Peru. Methods: A cross-sectional, population-based study of residents ≥ 50 years of age living in the Peruvian rural communities of Santa Clotilde and Chuquibambilla. A total of 129 subjects (76 from Santa Clotilde and 53 from Chuquibambilla) were included in this study. Gold standard diagnostic neurocognitive evaluation was based on expert neurological history and examination and administration of the CDR. Receiver operating characteristics, areas under the curve (AUC), and logistic regression analyses were conducted to determine the performance of RUDAS-PE compared to expert gold standard diagnosis. Results: Compared to gold standard diagnosis, the RUDAS-PE was better at correctly discriminating between MCI and dementia than discriminating between MCI and controls in both sites (97.0% vs. 76.2% correct classification in Chuquibambilla; 90.0% vs. 64.7% in Santa Clotilde). In Chuquibambilla, the area under the curve (AUC) of the RUDAS to discriminate between dementia and MCI was 99.4% (optimal cutoff at <18), whereas between MCI and controls it was 82.8% (optimal cutoff at <22). In Santa Clotilde, the area under the curve (AUC) of the RUDAS to discriminate between dementia and MCI was 99.1% (optimal cutoff at <17), whereas between MCI and controls it was 75.5% (optimal cutoff at <21). Conclusions: The RUDAS-PE has acceptable psychometric properties and performed well in its ability to discriminate MCI and dementia in two cohorts of illiterate older adults from two distinct rural Peruvian communities.

Social Cognition and Behavioral Assessments Improve the Diagnosis of Behavioral Variant of Frontotemporal Dementia in Older Peruvians With Low Educational Levels.

Background: The behavioral variant of frontotemporal dementia (bvFTD), characterized by early behavioral abnormalities and late memory impairment, is a neurodegenerative disorder with a detrimental impact on patients and their caregivers. bvFTD is often difficult to distinguish from other neurodegenerative diseases, such as Alzheimer's disease (AD), using brief cognitive tests. Combining brief socio-cognitive and behavioral evaluations with standard cognitive testing could better discriminate bvFTD from AD patients. We sought to evaluate the diagnostic accuracy of brief socio-cognitive tests that may differentiate bvFTD and AD patients with low educational levels. Methods: A prospective study was performed on 51 individuals over the age of 50 with low educational levels, with bvFTD or AD diagnosed using published criteria, and who were receiving neurological care at a multidisciplinary neurology clinic in Lima, Peru, between July 2017 and December 2020. All patients had a comprehensive neurological evaluation, including a full neurocognitive battery and brief tests of cognition (Addenbrooke's Cognitive Examination version III, ACE-III), social cognition (Mini-social Cognition and Emotional Assessment, Mini-SEA), and behavioral assessments (Frontal Behavioral Inventory, FBI; Interpersonal Reactivity Index-Emphatic Concern, IRI-EC; IRI-Perspective Taking, IRI-PT; and Self-Monitoring Scale-revised version, r-SMS). Receiver operating characteristic (ROC) analysis to calculate the area under the curve (AUC) was performed to compare the brief screening tests individually and combined to the gold standard of bvFTD and AD diagnoses. Results: The AD group was significantly older than the bvFTD group (p < 0.001). An analysis of the discriminatory ability of the ACE-III to distinguish between patients with AD and bvFTD (AUC = 0.85) and the INECO Frontal Screening (IFS; AUC = 0.78) shows that the former has greater discriminatory ability. Social and behavioral cognition tasks were able to appropriately discriminate bvFTD from AD. The Mini-SEA had high sensitivity and high moderate specificity (83%) for discriminating bvFTD from AD, which increased when combined with the brief screening tests ACE-III and IFS. The FBI was ideal with high sensitivity (83%), as well as the IRI-EC and IRI-PT that also were adequate for distinguishing bvFTD from AD. Conclusions: Our study supports the integration of socio-behavioral measures to the standard global cognitive and social cognition measures utilized for screening for bvFTD in a population with low levels of education.

Global Perspectives on Brief Cognitive Assessments for Dementia Diagnosis.

BACKGROUND: Timely diagnosis of dementia is a global healthcare priority, particularly in low to middle income countries where rapid increases in older adult populations are expected. OBJECTIVE: To investigate global perspectives on the role of brief cognitive assessments (BCAs) in dementia diagnosis, strengths and limitations of existing measures, and future directions and needs. METHODS: This is a qualitative study of 18 dementia experts from different areas of the world. Participants were selected using purposeful sampling based on the following criteria: 1) practicing in countries with projected growth of older adult population of over 100%by 2050; 2) expertise in dementia diagnosis and treatment; 3) involvement in clinical practice and training; and 4) recognition as a national dementia expert based on leadership positions within healthcare system, research, and/or policy work. Participants were individually interviewed in their language of choice over secure videoconference sessions. Interviews were analyzed by a multidisciplinary team using theme identification approach. RESULTS: Four domains with subthemes emerged illustrating participants' perspectives: 1) strengths of BCAs; 2) limitations of BCAs; 3) needs related to the use of BCAs; and 4) characteristics of an ideal BCA. While most experts agreed that BCAs were important and useful for dementia diagnosis, the themes emphasized the need for development and validation of novel measures that are sensitive, psychometrically sound, and culturally appropriate. CONCLUSION: BCAs are important for guiding diagnosis and care for dementia patients. Findings provide a roadmap for novel BCA development to assist in diagnostic decision making for clinicians serving a rapidly growing and diverse dementia population.

The Multi-Partner Consortium to Expand Dementia Research in Latin America (ReDLat): Driving Multicentric Research and Implementation Science.

Dementia is becoming increasingly prevalent in Latin America, contrasting with stable or declining rates in North America and Europe. This scenario places unprecedented clinical, social, and economic burden upon patients, families, and health systems. The challenges prove particularly pressing for conditions with highly specific diagnostic and management demands, such as frontotemporal dementia. Here we introduce a research and networking initiative designed to tackle these ensuing hurdles, the Multi-partner consortium to expand dementia research in Latin America (ReDLat). First, we present ReDLat's regional research framework, aimed at identifying the unique genetic, social, and economic factors driving the presentation of frontotemporal dementia and Alzheimer's disease in Latin America relative to the US. We describe ongoing ReDLat studies in various fields and ongoing research extensions. Then, we introduce actions coordinated by ReDLat and the Latin America and Caribbean Consortium on Dementia (LAC-CD) to develop culturally appropriate diagnostic tools, regional visibility and capacity building, diplomatic coordination in local priority areas, and a knowledge-to-action framework toward a regional action plan. Together, these research and networking initiatives will help to establish strong cross-national bonds, support the implementation of regional dementia plans, enhance health systems' infrastructure, and increase translational research collaborations across the continent.

Validation of the RUDAS for the Identification of Dementia in Illiterate and Low-Educated Older Adults in Lima, Peru.

Objectives: To evaluate the performance of the Peruvian version of the Rowland Universal Dementia Assessment Scale (RUDAS-PE) in discriminating between controls and patients with mild cognitive impairment (MCI) and dementia in an illiterate population with low-levels of education. Methods: We compared the cognitive performance of 187 elderly subjects who were illiterate (controls n = 60; MCI n = 64; dementia n = 63). Neuropsychological measures included the RUDAS-PE, Mini-Mental State Examination (MMSE), INECO Frontal Screening (IFS), and Pfeffer Functional Activities Questionnaire (PFAQ). The results were compared to a neuropsychological evaluation (gold standard), including use of Clinical Dementia Rating (CDR) scores. Results: We found a Cronbach's alpha was 0.65; Spearman's correlation coefficient was 0.79 (p < 0.01). The area under the receiver operating characteristics curve for the RUDAS to discriminate dementia from MCI was 98.0% with an optimal cut-off <19 (sensitivity 95%, specificity 97%); whereas, to differentiate MCI and controls was 98.0% with an optimal cut-off <23 (sensitivity 89%, specificity 93%). Conclusions: Based on its excellent psychometric properties, we find the RUDAS-PE suitable to aid in the opportune detection of dementia in a geriatric illiterate population with low-levels of education.

The impact of SARS-CoV-2 in dementia across Latin America: A call for an urgent regional plan and coordinated response.

The SARS-CoV-2 global pandemic will disproportionately impact countries with weak economies and vulnerable populations including people with dementia. Latin American and Caribbean countries (LACs) are burdened with unstable economic development, fragile health systems, massive economic disparities, and a high prevalence of dementia. Here, we underscore the selective impact of SARS-CoV-2 on dementia among LACs, the specific strain on health systems devoted to dementia, and the subsequent effect of increasing inequalities among those with dementia in the region. Implementation of best practices for mitigation and containment faces particularly steep challenges in LACs. Based upon our consideration of these issues, we urgently call for a coordinated action plan, including the development of inexpensive mass testing and multilevel regional coordination for dementia care and related actions. Brain health diplomacy should lead to a shared and escalated response across the region, coordinating leadership, and triangulation between governments and international multilateral networks.