Received: 2 September 2020 Accepted: 11 September 2020 Published online: 19 November 2020 DOI: 10.1002/trc2.12092 POLICY FORUM The impact of SARS-CoV-2 in dementia across Latin America: A call for an urgent regional plan and coordinated response Agustin Ibanez1,2,3,4,5 Hernando Santamaria-Garcia6 Alejandra Guerrero Barragan1,7 Alexander Kornhuber1 Alyne Mendonca Marques Ton8 Andrea Slachevsky9,10,11,12 Antonio Lucio Teixeira13,14 Beatriz Marcela Mar Meza1 Cecilia M. Serrano15 Carlos Cano6 Carolina Arias Gonzalez16 Christian Gonzalez-Billault10 Christopher Butler17,18,19 Julian Bustin20 Claudia Duran-Aniotz4,10,21 Daisy Acosta22 Diana L. Matallana6 Diego Acosta-Alvear16 Dominic Trépel23 Elisa De Paula França Resende1,13,24 Fabricio Ferreira de Oliveira27 Francisco Ibanez28 Fernanda G. De Felice24,25 Gorka Navarrete4 Ioannis Tarnanas29,30 Irene B. Meier29,30 Jerusa Smid31 Jorge Llibre-Guerra1,32 Juan J. Llibre-Rodriguez33 Laís Fajersztajn1,34 Leonel Tadao Takada26 Lissette Duque35 Maira Okada de Oliveira1,26,36 Maria Aparecida Camargos Bicalho37 María Isabel Behrens11,38,39 Maritza Pintado-Caipa1,40 Mario Parra41 Maxwell Z. Wilson16 Myriam De La Cruz Puebla1,42 Nilton Custodio40 Rodrigo Santibanez19,43 Rodrigo Bernardo Serafim45 Ronnielly Melo Tavares44,45 Stefanie Danielle Piña Escudero1 Tomas Leon Rodriguez9 Walter Dawson1,46,47 Bruce L. Miller1 Kenneth S. Kosik16 1 Global Brain Health Institute (GBHI), University of California San Francisco (UCSF), San Francisco, California, USA 2 Cognitive Neuroscience Center (CNC), Universidad de San Andrés, Buenos Aires, Argentina 3 National Scientific and Technical Research Council (CONICET), Buenos Aires, Argentina 4 Center for Social and Cognitive Neuroscience (CSCN), Universidad Adolfo Ibanez, School of Psychology, Adolfo Ibañez University, Santiago, Chile 5 Universidad Autónoma del Caribe, Barranquilla, Colombia 6 Pontificia Universidad Javeriana, Bogotá, Departamentos de Psiquiatría, Instituto de Envejecimiento, Centro de Memoria y Cognición Intellectus, Hospital Universitario San Ignacio, Bogotá, Colombia 7 Servicio de Neurología, Subred de Servicios de Salud Suroccidente, Bogotá, Colombia 8 Laboratory of Translational Physiology and Pharmacology, Pharmaceutical Sciences Graduate Program, Vila Velha University, Vila Velha, Espírito Santo, Brazil 9 Memory and Neuropsychiatric Clinic (CMYN), Neurology Department, Del Salvador Hospital and University of Chile Faculty of Medicine, Santiago, Chile 10 Geroscience Center for Brain Health and Metabolism (GERO), Faculty of Medicine, University of Chile, Santiago, Chile 11 Neuropsychology and Clinical Neuroscience Laboratory (LANNEC), Physiopathology Department - ICBM, Neuroscience and East Neuroscience Departments, Faculty of Medicine, University of Chile, Santiago, Chile 12 Department of Neurology and Psychiatry, Clínica Alemana-Universidad del Desa, Concepción, Chile This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. © 2020 The Authors. Alzheimer’s & Dementia: Translational Research & Clinical Interventions published by Wiley Periodicals, Inc. on behalf of Alzheimer’s Association. Alzheimer’s Dement. 2020;6:e12092. wileyonlinelibrary.com/journal/trc2 1 of 13 https://doi.org/10.1002/trc2.12092 2 of 13 IBANEZ ET AL . 13 Instituto de Ensino e Pesquisa, Santa Casa BH, Belo Horizonte, Brazil 14 UT Health, Houston, Texas, USA 15 Cognitive Neurology, Department of Neurology, César Milstein Hospital, ALMA (Asociación de Lucha contra el Mal de Alzheimer y alteraciones semejantes de la República Argentina), Research Ethics Committee, Ministry of Health of Buenos Aires, Buenos Aires, Argentina 16 Neuroscience Research Institute and Department of Molecular Cellular and Developmental Biology, University of California Santa Barbara, Santa Barbara, California, USA 17 Department of Brain Sciences, Imperial College, London, UK 18 Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK 19 Department of Neurology, Pontificia Universidad Católica de Chile, Santiago, Chile 20 Instituto de Neurología Cognitiva, INCYT, Buenos Aires, Argentina 21 Biomedical Neuroscience Institute, Faculty of Medicine, University of Chile, Santiago, Chile 22 Universidad Nacional Pedro Henriquez Ureña (UNPHU), Internal Medicine Department, Geriatric Section, Santo Domingo, Dominican Republic 23 Global Brain Health Institute, Trinity College Dublin, Dublin, Ireland 24 Federal University of Rio de Janeiro, Rio de Janeiro, Brazil 25 Queen’s University, Kingston, Ontario, Canada 26 Hospital das Clinicas, University of Sao Paulo Medical School, Sao Paulo, Brazil 27 Department of Neurology and Neurosurgery, Escola Paulista de Medicina, Federal University of São Paulo - UNIFESP, São Paulo, Brazil 28 FCEFyN, Universidad Nacional de San Juan, San Juan, Argentina 29 Altoida Inc., Houston, Texas, USA 30 Swiss National Task Force for Dementia, Geneva, Switzerland 31 Department of Neurology, University of Sao Paulo; Institute of Infectious Diseases Emilio Ribas, São Paulo, Brazil 32 Department of Neurology, Washington University School of Medicine, St Louis, USA 33 Finlay-Albarrán Medicine Faculty, Universidad de Ciencias Médicas, La Havana, Cuba 34 Department of Pathology, Laboratory of Experimental Air Pollution, University of São Paulo School of Medicine, Sao Paulo, Brazil 35 Cognitive Disorders Unit, Neuromedicenter, National Commission in Bioethics, Quito, Ecuador 36 Hospital Santa Marcelina, Sao Paulo, Brazil 37 Federal University of Minas Gerais, Belo Horizonte, Brazil 38 FCEFyN, Universidad Nacional de San Juan, San Juan, Argentina 39 Departamento de Neurología and Neurocirugía Hospital Clínico, Departamento de Neurociencias, Centro de Investigación Clínica Avanzada (CICA) Facultad de Medicina, Hospital Clínico, Universidad de Chile, Santiago, Chile 40 Unit Cognitive Impairment and Dementia Prevention, Cognitive Neurology Center, Peruvian Institute of Neurosciences, Lima, Peru 41 University of Strathclyde, Glasgow, UK 42 Vall d’Hebron Research Institute (VHIR), Autonome University of Barcelona, Barcelona, Spain 43 Neurology Service, Complejo Asistencial Dr. Sótero del Río, Santiago, Chile 44 Federal University of Rio de Janeiro, Rio de Janeiro, Brazil 45 Behavioral Neurology Clinic, Santa Casa de Belo Horizonte, MG, Brazil 46 Department of Neurology, School of Medicine, Oregon Health and Science University, Portland, Oregon, USA 47 Institute on Aging, College of Urban and Public Affairs, Portland State University, Portland, Oregon, USA Correspondence Agustin Ibanez, Global Brain Health Institute Abstract (GBHI), University of California San Francisco, US; & Universidad de San Andrés, Buenos The SARS-CoV-2 global pandemic will disproportionately impact countries with weak Aires, USA. economies and vulnerable populations including people with dementia. Latin American E-mail: agustin.ibanez@gbhi.org and Caribbean countries (LACs) are burdened with unstable economic development, Authors Alejandra Guerrero Barragan, Alexan- fragile health systems, massive economic disparities, and a high prevalence of demen- der Kornhuber, Alyne Mendonca Marques tia. Here, we underscore the selective impact of SARS-CoV-2 on dementia among Ton, Andrea Slachevsky, Antonio Lucio Teix- eira, Beatriz Marcela Mar Meza, Cecilia M LACs, the specific strain on health systems devoted to dementia, and the subsequent Serrano, Carlos Cano, Carolina Arias Gonza- effect of increasing inequalities among those with dementia in the region. Imple- lez, Christian Gonzalez-Billault, Christopher mentation of best practices for mitigation and containment faces particularly steep IBANEZ ET AL . 3 of 13 Butler, Julian Bustin, Claudia Duran-Aniotz, Daisy Acosta, Diana L Matallana, Diego Acosta- challenges in LACs. Based upon our consideration of these issues, we urgently call for Alvear, Dominic Trépel, Elisa De Paula França Resende, Fabricio Ferreira de Oliveira; Fran- a coordinated action plan, including the development of inexpensive mass testing and cisco Ibanez, Fernanda G. De Felice, Gorka multilevel regional coordination for dementia care and related actions. Brain health Navarrete, Ioannis Tarnanas, Irene B. Meier, Jerusa Smid, Jorge Llibre- Guerra, Juan J diplomacy should lead to a shared and escalated response across the region, coordinat- Llibre-Rodriguez, Laís Fajersztajn, Leonel ing leadership, and triangulation between governments and international multilateral Tadao Takada, Lissette Duque, Maira Okada de Oliveira, Maria Aparecida Camargos Bicalho, networks. María Isabel Behrens, Maritza Pintado-Caipa, Mario Parra, Maxwell Z. Wilson, Myriam De KEYWORDS La Cruz Puebla, Nilton Custodio, Rodrigo San- coronavirus, dementia, health system, Latin American and Caribbean countries, SARS-CoV-2 tibanez, Rodrigo Bernardo Serafim, Ronnielly Melo Tavares, Stefanie Danielle Piña Escudero, Tomas Leon Rodriguez, Walter Dawson are listed alphabetically. Funding information National Institutes of Health, National Institutes of Aging, Grant/Award Number: R01 AG057234; Alzheimer’s Association, Grant/Award Numbers: GBHI ALZ UK-20- 639295, SG-20-725707 1 WHY LATIN AMERICA REQUIRES A America and Caribbean countries (LACs) now face an extremely chal- REGIONAL STRATEGY lenging situation. LACs remains a hot spot of the disease, and avail- able data show similar upward slopes of deaths in LACs similar to those The brunt of the SARS-CoV-2 pandemic is hitting the aged and par- in North America, Europe, or Asia (Figure 1). LACs have a reproduc- ticularly those who are disadvantaged.1 Often neglected is the dev- tion number (R) greater than one8 meaning that the number of cases astating impact of COVID-19 for individuals with dementia and for is growing exponentially. In addition, there is a fundamental lack of their caregivers.2,3 Across the world, while every age group is sus- preparedness to deal with the pandemic.9 We have recently raised ceptible to SARS-CoV-2 infection, older adults suffer a much higher awareness of the critical influence in LACs’ dementia patients.2 Beyond mortality with the disease. As health systems become overwhelmed, awareness, the situation requires an adequate response across the access to dementia programs is becoming even more restricted. Imple- region that can coordinate our approaches for the dementia popula- menting physical distancing in people with dementia is difficult.3 The tion. Here, collaborators from LACs and beyond first explore these combination of reduced work and quarantine can greatly disrupt fam- specific regional impacts and then urgently call for a collaborative ily dynamics. Dementia-associated comorbidities such as hyperten- response to anticipate the upcoming challenges. sion, diabetes, cardiovascular disease, and cerebrovascular disease all impact SARS-CoV-2 severity.4 Central nervous system deficits such as smell and taste impairments and even hallucinations have been 2 THE PANDEMIC THREATENS THE COLLAPSE observed in association with COVID-195,6 and rates of delirium are OF HEALTH SYSTEMS ACROSS LACs high in elders in intensive care units (ICU), particularly for those on a ventilator. Inflammatory responses elicited by infection may trig- Health care in the region was already precarious before the pandemic ger long-term mechanisms of neurodegeneration.7 For example, a still with a per capita expenditure of $949 a year,10 (only one quarter of poorly understood condition linked with the 1918 flu pandemic is the average rate for countries of the Organization for Economic Co- post-encephalitic Parkinsonism, with degeneration of the substantia operation and Development [OECD]). Further, in LACs expenditures nigra and the presence of neurofibrillary tangles but without senile are highly dependent on self-payment (LACs’ average = 34% of total plaques. The long-term consequences of COVID-19 remain completely health spending, OECD average = 21%). Universal health needs are unknown, although our centers are beginning to see post-COVID uncovered by insurance services, with unequal distribution between patients with cognitive complaints. rural/urban areas and public/private services. About 30% of the LACs’ Clearly, the coronavirus compromises dementia patients;3 how- population lacks regular access to health services and the number of ever, the impact is not equally distributed across the population. Here hospital beds is small (2.7 per 1000 inhabitants, with a very small por- we describe that patients, families, and health professionals in Latin tion of intensive care beds,10 compared to the OECD average of 4.7). 4 of 13 IBANEZ ET AL . Heterogeneity and fragmentation characterize the health systems specialized for dementia across LACs, with few available mechanisms RESEARCH IN CONTEXT for coordination among governmental and private providers. Countries 1. Systematic review: The authors reviewed the literature with stronger public health systems can develop specific responses. using traditional sources (eg, PubMed). The unique criti- Mexico implemented an epidemiological surveillance system that cal situation for dementia patients in Latin America and receives feedback from medical centers, and Chile has recently devel- the Caribbean countries (LACs) in the coronavirus era oped pilot care centers in primary and specialized care centers in the is reviewed. Other imperative calls for awareness of public sector enabling remote care during the outbreak, even when COVID-19’s impact on dementia have been raised at a coverage is limited.11 Cuba has also bet on its primary care system to global level, as well as the unique influence of pandemic proactively detect coronavirus cases in the population through general on LACs’ health. However, no previous work has proposed screening questionnaires and contact tracing.12 In Uruguay, to date, a coordinated response to the LACs’ selective impact on the coronavirus has been well controlled. By contrast, most of the other dementia patients yet. countries do not have specific resources for the pandemic, and have 2. Interpretation: We review the current situation of important barriers to care, particularly in rural areas and among poorer dementia patients across LACs under the pandemic. Then urban populations. According to the Pan-American Health Organiza- we present recommendations for a coordinated action tion (PAHO),13 the LACs will fail to provide basic responses to the pan- plan. Collaborators from LACs and beyond first explore demic including (1) widespread and massive testing with active iso- these specific regional impacts and then urgently call lation, (2) intensive and intermediate care units, (3) ventilators and for a collaborative response to anticipate the upcoming supplementary oxygen by nasal cannula, (4) access to pharmacological challenges. treatments, and (5) guaranteed protection for health workers. On the 3. Future directions: We propose specific actions and a horizon, we are also concerned about future access to a vaccine once regional brain health diplomacy framework to coordinate one becomes available. urgent responses for the dementia population. By 2050, the prevalence of dementia across LACs will increase four-fold, and patients from LACs suffer reduced social and health- care access.14 The pandemic is already impacting these people (see Box 1 for testimonies from across the region) and most countries are not ready to provide the necessary support to deliver social and Limited telemedicine capabilities, as well as restricted access to the residential care. The large drop in consultation rate in hospitals15 Internet in the region create additional complications for dementia involves a significant deficit of care for non–coronavirus-related care. Although telemedicine cannot replace face-to-face care, it is an diseases, such as dementia. A regional lack of sufficient numbers extremely important tool in pandemic times,22 in particular to sup- of ventilators will raise painful moral dilemmas for decision making port the care of dementia patients.23 However, many LAC hospitals regarding patients with dementia. Most public clinics have cancelled do not provide virtual consultation or medical prescription with a dig- patients’ appointments to make room to attend the pandemic, so there ital signature.24 As reported by some of the co-authors of this report are few physicians to receive those dementia patients needing medical working in hospitals, in specific areas of Argentina, Brazil, Colom- attention. bia, Ecuador, Dominican Republic, and Peru, many patients cannot be The LACs’ high prevalence of noncommunicable diseases16 across reached by telephone or e-mail. In Brazil, most dementia consultations vulnerable dementia patients will worsen COVID-19 health com- in the public health system are in person, with neither telemedicine plications. Conditions such as hypertension, cardiovascular disease, nor remote consultation. Approximately 40% of hospitals are unable to and chronic obstructive pulmonary disease all increase mortality provide remote consultations.25 Web pages, videos, and free demen- attributed to COVID-19.17 Cardiovascular diseases (CVD) are a rec- tia helplines are underused by relatives of dementia patients. Barriers ognized risk factor for dementia in LACs.18 Almost half of COVID- include geographic and economic conditions at remote and rural sites 19 patients who have been hospitalized show scan abnormalities that and impoverished urban areas. resemble the early stages of heart failure.19 The impact that such The imbalance in access to health systems24 is more severe interactive effects will have on LACs’ vulnerable older populations is when considering family dynamics. Formal long-term care (LTC) facil- unknown. Assisted living facilities and nursing homes have often been ities are insufficient in the region,26 and deficient for vulnerable sites with very high rates of infection.20 Specific co-morbidities in LACs populations. such as the dengue epidemic that has affected >3 million individu- Dementia patients often remain with their families even at the als and caused more than 1500 deaths, mainly in the socioeconomi- final stages of the disease, providing indirect care. The extended cally deprived population, has an unknown interaction with COVID-19. families in LACs with frequent social gatherings that ordinarily cre- About 500 million people in LACs are at risk of contracting dengue. ate a protective emotional environment for patients, will become Overlapping infections and co-occurrence of both diseases increase dangerous, resulting in further strain due to physical isolation.27 the severity of patients,21 especially in those suffering from dementia Family caregivers are facing paradoxical challenges regarding care and related comorbidities. and the contagious risk of patient contact. Amidst the pandemic IBANEZ ET AL . 5 of 13 F I G U R E 1 Patterns of COVID-19 death toll by regions and countries. A, Temporal dynamics of accumulated deaths. The accumulated deaths for all the countries and regions are shown per day. The slope represents growth rate. A dashed line of 30% growth in each region helps to visualize the similar growth rate across countries and regions. A gray headset in the top panels of Europe, Latin America, and North America also helps to identify the time gap in comparison to the start of the COVID-19 outbreak in China. Latin American and Caribben countries (LACs) are in the early days compared to other regions, although their growth is in line with Europe or North America. B, Exponential growth of confirmed daily deaths by countries and regions. Rate of change shown as new deaths (per week average) divided by total deaths. In this panel, the new deaths in the past week are plotted against the total confirmed deaths to date. When plotted in this way, exponential growth is represented as a straight line that slopes upward. Diagonal slopes indicate exponential growth rate. The rate of change in LACs is exponential. Plots provide a line for each country, plus a bold line for the regional smooth conditional mean (Loess method). Both panels show how the epidemic started relatively late in LACs. Despite this, global trajectories of the region suggest similar exponential growth. Data retrieved from Johns Hopkins CSSE (https://github.com/CSSEGISandData/COVID-19) through https://covid19api.com/ on July 20, 2020. The code for the creation of these plots can be found in https://github.com/gorkang/2020-coronavirus-LATAM. A daily updated interactive website to explore the data can be found in https://gorkang.shinyapps.io/2020-coronavirus-LATAM/ and the incumbent social distancing, caregivers will experience 3 SARS-CoV-2 AMPLIFIES THE INHERENT increased burnout syndrome, and dementia patients may face INEQUALITIES IN DEMENTIA CARE IN LACs additional mental health risks and mistreatment.28 Social isolation will contribute to already prevalent neuropsychiatric symptoms in According to the World Bank, Latin America is the most unequal elders, such as depression, distress, loneliness, anxiety, and sedentary region in the world. LACs host 8 of the 20 most unequal countries in behavior. the world, and three quarters of the LAC countries are low or lower- Finally, health professionals themselves, including neurologists and middle income. The LAC economic projection for 2020 was initially mental health workers, are among the vulnerable and their incapac- pessimistic, and the COVID-19 outbreak has now escalated these ity reduces the health delivery workforce. Adequate protective equip- problems. Weak institutional structures for intervention, fractured ment and medical support for health-care workers is scant across multinational cooperation, teetering health systems, low economic LAC.25 Health-care workers suffered an enormous toll in mortality, growth, poverty, inequality, and unemployment are all precipitating an and simultaneously weaken the health-care systems in LAC. In Brazil, unprecedented moment in the region’s history. LACs’ poverty is per- LTC facilities have shown one of the highest rates of nurses’ deaths,9 vasive (≈185 million needy individuals, 68 million in extreme poverty), and in Mexico, one fifth of health workers have died.29 Assisted liv- creating unstable and informal jobs (>50% of the regional population ing facilities and LTC facilities have often been sites with very high of workers) and restricting access to sanitation systems and essential rates of infection20 and are facing critical supply and staff shortages services (water and sewerage). These overcrowded populations are in LAC.9 These factors not only increase the burden upon health pro- forced by SARS-CoV-2 to a double tragedy: should they break the fessionals, but also the shortage of health-care responses to dementia quarantine to search for resources and increase the risk of contagion patients. for dementia patients or observe the quarantine and fall more deeply 6 of 13 IBANEZ ET AL . BOX 1—Voices About Coronavirus from Latin American Countries We selected particular testimonies across Latin American and Caribbean countries highlighting different dimensions of the coronavirus outbreak and the impact on dementia patients and families. Pictures showing four histories and testimonies from Peru: Enrique (top left), Juana (top right), Enedina (bottom left) and Rosita (bottom right). See below. Argentina This country has developed an early, preventive, and compulsory social isolation quarantine, but contagion in overcrowded vulnerable neighborhoods may still challenge the health system. María Berude, a member of the Argentinean network of physicians said in an open letter: “We are people who have courage, but we are also afraid of dying. . . . We have uncertainty and anxiety, because we are human beings. . . . Neither gods, nor heroes, nor murderers, nor mercenaries. Simply medical doctors.” Brazil The coronavirus in the largest country in the region has increased exponentially. Jerusa Smid (co-author) summarized the private/public gap: “I work in a privileged private hospital, they are prepared to amplify the ICU beds from 43 to 280. I also work in a public hospital which is now out of rooms.” Leonel Takada (co-author) said he was “told to reschedule [dementia patients’] appointments to after June . . . we couldn’t reach some of them by telephone and we don’t have their email addresses. This puts them into risk of not obtaining prescriptions.” Chile In 2019, the Chilean health system incorporated dementia care; however, the pandemic has suspended its implementation. For Andrea Slachevsky (co-author) “most of dementia patients are taken care by family members at home. Therefore, COVID-19 is imposing a hard burden on these families”. Claudia Duran (co-author) and basic scientist said: “I had to sacrifice most of my transgenic mice to decrease the load of work of veterinarians and technicians. . . . Concerning laboratory experiments, all of them are stopped.” Colombia In Colombia the response to pandemic encompasses a reduction of care for dementia patients. Alejandra Guerrero (co-author) said that “in public hospitals the government has implemented actions that impact in patients with dementia, including preventing people above 70 years old from going out, stopping their outpatient consults and leaving them without their prescriptions. Vulnerable populations do not have internet access for telemedicine or even phone consultation.” IBANEZ ET AL . 7 of 13 Cuba Rather than opting for mitigation, Cuba is a regional exception and has also bet on its primary care system and added a containment plan (prevention and control). For Juan J. Llibre (co-author), “Medical students, and health workers were mobilized nationwide for door-to- door surveys to identify vulnerable people including people living with dementia and check for symptoms, and roll out a testing program according to WHO standards. Furthermore, contact tracing and early contact isolation procedures have been imposed on all confirmed cases.” Dominican Republic For Daisy Acosta (co-author) “The Dominican Alzheimer’s Association is cooperating with the department of mental health. Initially, we knew about the virus but nobody took seriously the protective measures announced. The curfew has been violated by thousands of citi- zens. As a consequence they have been taken to jail to force them to observe the rules.” Ecuador For Myriam de la Cruz (co-author), the pandemic “increases social isolation and diminishes public attention to dementia patients, even reducing food availability for elders.” A resident of Guayaquil (Carol Neira) commented “Many deceased people and their bodies were not removed, people do not respect the curfew, and hospitals have not enough capacity for so many infected.” For Lissette Duque (co- author) “COVID-19 will place our country’s economy in a critical situation. This will probably hit not only the unemployment, but also the capacity of the public health system to support vulnerable people.” For Gabriel Trueba (University San Francisco Quito) “there are reports in some indigenous communities, specifically Shushufindi-Cuyabeno, presenting with pneumonia; however, nobody has tested them due to difficulties reaching them.” Mexico The country also struggles with great disparities of a fragmented health care system. For Stefanie Piña (co-author) ,“If a person with dementia requires treatment for COVID-19, the hospital lacks capacity to prevent hospital-related adverse outcomes. At nursing homes and in the community, primary and secondary prevention measures are demanding extra effort from caregivers. This is leading to com- promised safety for the dyad and to severe caregiver burnout that may end in patient mistreatment.” Peru The pictures above illustrates the people’s vulnerabilities and the unpreparedness of the health system. Top left: Enrique (64 years old, Trujillo) suffers from diabetes mellitus but cannot get medication since two months ago. He is a shoemaker working with a small mobile stall, and after months of quarantine, he has to go out to work. Top right: Juana (64 years old, Trujillo) is a merchant diagnosed with coro- navirus 3 months ago, which led to her needing supplemental oxygen and intravenous medications. Given the collapse of the hospitals, she was treated at home by her daughter. She said the thought might lose her life, unable to perform simple activities (such as walking and eating) without great efforts. Now she is recovering. Bottom left: Enedina (65 years old, Lima) lives with her youngest son who lost his job due to the pandemic restrictions. They live in a precarious room, without electricity, water, or drainage. Bottom right: On the other side of Lima, 83-year-old Mrs. Rosita lives with her family in a wealthy district. Her daughter has noted typical dementia symptoms, which exacerbated since the quarantine. She doesn’t understand the isolation, needs constant monitoring, and urgently requires a neurological evaluation, but there are no services available due to the pandemic. Photos and testimonies from Peru documented by Alexander Kornhuber and Maritza Pintado Caipa. Individuals and relatives portrayed in the photos have provided written consent for reproduction. into poverty. Inequalities amplify the hardships of a pandemic.9 For tion for educated middle-class workers, but it is out of reach for the vulnerable populations, quarantine is often an unreachable luxury as most vulnerable. they have to work to survive. Dementia is compromised by intersectional inequalities, including Social containment measures can have a devastating impact on socioeconomic factors30 and modifiable risk-related social determi- LACs’ households. Informal workers represent a significant share of the nants of health (SDH).31 These factors are stronger determinants LACs’ workforce. Most have no access to social protection, and almost of dementia prevalence than race or cultural identifiers,30 are more no savings to carry them through the pandemic.2 Informal employees accentuated in LACs,31,32 and will be violently worsened by COVID- are the first to lose their jobs, while self-employed workers such as 19. Vulnerable and ethnic minorities suffering with dementia often street sellers and small service providers are left with no source of receive inadequate care (access to diagnostic testing and medica- income as streets became empty. Working from home may be a solu- tions, and near absence of 24-hour care)33 and now will be exposed 8 of 13 IBANEZ ET AL . BOX 2—Recommendations for Latin American and Caribbean Countries (LACs) A. General recommendations - Coordination and integration of isolated actions to support dementia patients (prevention actions, test development, epidemiologic measures, awareness of dementia risk, recommendations for dissemination). B. Specific recommendations Testing dementia populations - Dementia patient inclusion in priority lists allowing widespread point-of-service testing will permit contact tracing and containment for those who test positive. - Massive testing in LACs for priority populations including people living with dementia with allow innovative solutions (scalable technologies with low-cost instrumentation, non-specialized training, and available reagent supply chain). Boosting regional coordination to actively engage in global response - Coordination between available standards (i.e., Organization for Economic Co-operation and Development Policy Response to COVID-19, G20’s large-scale coordination) and regional non-governmental organizations (NGOs). - Networking between interregional agencies and multicentric research and interventions. - Action-to-knowledge framework to prioritize most vulnerable dementia patients. - Developing essential care required for dementia patients in different contexts considering the vast heterogeneity across LACs. C. Brain health diplomacy actions - Brain health diplomacy must build international partnerships to improve dementia care at micro- (individual), meso- (community), and macro- (national and transnational) levels. - Multiregional NGOs focused on dementia (Alzheimer’s Association, Alzheimer’s Disease International, the Global Brain Health Institute), in partnership with local institutions must coordinate a leadership action plan. to new constraints. With the anticipated poverty increase, most SDH mechanisms, as well as transition to tailored levels of telemedicine will worsen. Coronavirus-related burnout syndrome, mental health and serve as a model for cooperation throughout LACs (see Box 2 for risks, and patient mistreatment28 will be accentuated by new eco- the actionable recommendations proposed in this paper). We assess nomic inequalities. Among the more vulnerable, for example, Venezue- two main actions requiring urgent response: testing and regional lan refugees (with 8000% increase) have no guaranteed access to coordination. These actions are critical to avoid a long delay in the health and social services.34 Similarly, the pandemic is already spread- required actions toward public policy changes for dementia in LACs.14 ing across the LACs’ rural indigenous communities,35 which includes 42 million people in the region who are typically exposed to large inequalities.36 Indigenous peoples suffer from early onset dementia 4.1 Toward massive testing to assess dementia and elevated mortality rate, with greater vulnerability to cognitive populations disorders.37 In Brazil, the coronavirus-related indigenous death toll rate is double that of the general population.36 These people are them- Strategies adopted elsewhere in the world as “flatten the curve” cer- selves invisible in most the health statistics. But dementia patients tainly apply to LACs and dementia populations, but the challenges of from these vulnerable populations are even less visible36 during the implementation of quarantine and social isolation are far greater. Along pandemic. with these measures we need widespread point-of-service testing, con- tact tracing, and containment for those who test positive. How to implement a program of mitigation followed by containment is an enor- 4 AN URGENT CALL FOR A COLLABORATIVE mous challenge and even greater challenge for elders especially those ACTION PLAN with dementia across LACs. In particular, the combination of socioeco- nomic constraints and patient conditions will make general quarantine The rise of SARS-CoV-2 pandemic creates an uncharted scenario that unsustainable for the region in the long term. Therefore, we need reli- will undoubtedly impact LACs’ long-term responses to dementia, even able, massive, and efficient testing. Moreover, testing programs need to in the post-pandemic era. A LACs taskforce on dementia may help to consider LTC facilities as a priority sector. articulate prevention actions, implement inexpensive SARS-CoV-2 test Any global action plan requires massive testing.38,39 Given the development, improve epidemiologic measures, increase awareness of current limited testing capacity, the current diagnosis strategies are atypical SARS-Cov-2 in people with dementia, identify best practices mainly restricted to priority lists (hospitalized patients and health care, in underserved populations, offer information about dissemination aging, and underlying conditions, among others),40 thereby reducing IBANEZ ET AL . 9 of 13 F I G U R E 2 Cas13-based methods and detection of SARS-CoV-2 RNA using Cas13-based, Rugged, Equitable, Scalable Testing (CREST). A, Overview of Cas13-based detection methods and CREST modifications: (i–iii) Standard sample collection, RNA extraction, and reverse transcription. (iv) Amplification using cost-effective Taq polymerase and portable thermocyclers instead of isothermal reactions. (v) Transcription and Cas13 activation are followed by visualization with blue LED (∼495 nm) and orange filter. B, Detection of SARS-CoV-2 RNA using CREST. The miniPCR mini16 thermocycler and P51 molecular fluorescence visualizer used in this study. Both are portable, can be operated with batteries, and have minimal footprint. C, Fluorescence visualization of N1, N2, and N3 synthetic targets using P51 visualizer. Reproduced with authorization from Rauch et al.41 the availability of massive testing among dementia patients. Testing Polymerase Chain Reaction (RTqPCR) with a throat or nasal swab. for dementia patients will help the entire population because they Unfortunately, RTqPCR is limited, especially in underserved regions represent a significant number of patients with severe complications due to expensive reagents, a constricted supply chain, specialized requiring intensive health support. The percentage of dementia instrumentation, and trained personnel. In comparison, CRISPR-based patients being infected appears to be high. According to the World detection allows scalable, non-specialized performance and a more Health Organization (WHO), COVID-19 mortality data in people with available reagent supply chain. Several of the authors (MZW, KSK, DA- dementia is elevated, with most of COVID-19 deaths coming from LTC A, CA) have developed such a test called CREST (Cas13-based, Rugged, (two thirds of people in LTC have dementia); and is estimated that 75% Equitable, Scalable Testing41 ). CREST pairs commonplace and reliable of all COVID-19 care home deaths are people with dementia. biochemical methods (PCR) with low-cost instrumentation, without Massive testing in LACs for priority populations including dementia sacrificing detection sensitivity (Figure 2). CREST uses fluorescence needs innovative actions. A variety of testing approaches exist. These visualizers for a quick binary interpretation of results, and provides include direct testing for the viral genome which in the cases of SARS- a scalable sample collection (laboratory-made viral transport media, Cov2 is an RNA, testing for the viral protein called the antigen and 3D-printed swabs) that is highly sensitive and requires minimal infras- testing for immune response to the virus, which involves detection of tructure. Results can be provided with Bluetooth-enabled thermocy- the antibodies. These tests provide different types of information. For clers that run using mobile device applications, combined with simple example, detection of the viral genome indicates active infection even light-emitting diode (LED) visualizers, and uploaded with a smart- if the person is asymptomatic and detection of antibodies indicates a phone camera. CREST can provide a point-of-care solution to increase history of infection. Most of the current emphasis is on testing for the COVID-19 surveillance and diagnostic testing. The same group has presence of the viral genome sequences using Reverse Transcription- also reported a field-deployable RNA-extraction procedure called 10 of 13 IBANEZ ET AL . PEARL.42 Use of the test in Ecuador is currently under way. Similarly, future pandemic scenarios.46 The OECD Policy Response to COVID a laboratory in Brazil has developed a SARS-CoV-2 detection method pointed to the complex, nested, interconnected systems needed to in saliva, using RT-LAMP (loop mediated isothermal amplification),43 deliver solutions.47 The G20 countries have called for large-scale coor- which is also scalable and relatively inexpensive. Researchers from dination and science- based global response to overcome the pan- Havana’s Immunoassay Center (CIE) designed a diagnostic test that demic. Solidarity is a key component for action. Clinical trials and uses the enzyme linked immunosorbent assay (ELISA) technique, which subsidies must be coordinated and based on knowledge and solution identifies small particles and germs that cause disease, and is based on sharing.48 The European Parliament has requested that EU-funded ultramicroanalytic (SUMA) technology. Argentina is also developing medical technologies should be made available, accessible, and afford- potential massive testing kits, including CRISPR-based detection able. The SOLIDARITY trial (ISRCTN83971151) is a large global study approaches.44 In the future, these affordable and non-technically (45 countries to date) to provide estimations of safety and efficacy demanding tests may be combined via machine learning with clinical of treatments that will allow stressed hospitals to participate. Small symptoms, exposure history, and clinical imaging (chest tomography) and non-coordinated trials are considered unethical under the current to improve diagnosis.45 However, alternative testing strategies are not circumstances.48 Networking has become crucial for developing global without limitations, in particular test sensitivity involving both false advances. Different interregional agencies (Horizon 2020, the National positive and false negative rates. Similar limitations of local technology Institutes of Health, US Department of Defense) have facilitated mul- availability call for additional cooperation, pondering the procedures ticentric research and interventions. Overburdened global health sys- with less time to obtain test results. Human recourses (delivered tems can be supported by free and open source scientific and medical by health-care systems and dementia-related non-governmental hardware (FOSH).49 FOSH works through a united global community organizations [NGOs]) are critical for providing local logistics for test and constitutes a key strategy highlighted in the 2019 Novel Coron- administration. avirus Global Research and Innovation Forum. Similarly, collaborative The current testing capacity for coronavirus across LACs is lim- responses such as the High Performance Computing Consortium, or ited, and an established infrastructure for diagnostic and laboratory the Coronavirus Census Collective (an open-access platform that helps testing is not available in several hospitals and related institutions in to predict the location of future outbreaks by combining surveys, diag- the region.9 Affordable and simple massive testing approaches like nostic results, and geospatial data) are just some examples50 of global CREST would allow the tracking of people with cognitive impairment networking. Consistent scientific evidence needs to be verified, com- and dementia patients who are exposed to higher risks. Early identi- posed, and evaluated with large-scale efforts.51 Any delay in joining fication of dementia patients with SARS-CoV-2 will reduce costs and global actions will worsen the consequences of the pandemic. mortality considerably. More tailored solutions are requested for Latin America. The Once testing of dementia patients is widely available, the next step combination of health, political, and economic emergency triggered is following up with the positive cases. To achieve this, international by the coronavirus make the regional networks best placed to assess cooperation is critically need. For instance, the WHO-Alzheimer’s needs and lead planning, especially in low and middle income countries Association International Cohort Study of Chronic Sequeale of (LMIC)52 and LACs.53 Regional coordination should also establish SARS-CoV-2 (CNS-SARS-CoV-2) has established a global consortium the priorities for the most vulnerable and orchestrate compensatory to longitudinally assess individuals and characterize neurological and actions for patient suffering. LAC scientists, advocates, and health neuropsychiatric sequalae. As this consortium includes dementia policymakers need to be included as equal partners in the global plans. patients, and several LACs are part of the initiative, the outcomes This will allow the efficient distribution of global resources, as is the of this project will be relevant for the region. In particular, the CNS- case of support from the Asia-PAHO collaboration for the general SARS-CoV-2 initiative will provide a clearer picture of the role of population of Latin America.9 Strategies for developing essential viral infections on cognitive decline and dementia risk, and their care required for dementia patients in different contexts should be impact in symptom development (eg, loss of smell/taste, seizures, identified at regional bases. As Latin America became a hot spot stroke, delirium, etc.). The study of genetic and social determinants of of the pandemic, the role of its regional initiatives connected with health risks and their interaction with SARS-CoV-2 may also provide global responses becomes critical.54 These actions, preliminary and relevant pathways to understand the impact on the most vulnerable imperfect, will require coordinated efforts to evolve toward more dementia patients in the region, as well as other long-term unexplored equitable solutions.52 consequences of coronavirus–induced cognitive decline and dementia. 4.3 Acknowledging the challenges of 4.2 Boosting regional coordination to actively non-homogeneous scenarios across LACs engage in global responses One important step to deliver an efficient regional action plan con- The COVID-19 pandemic has become a brain health catastrophe, and sists in identifying and incorporating the large heterogeneity across global actions coordinating economic, health, scientific, and technolog- the region. Latin America is a very heterogeneous region, with ical actions are required to rebuild living standards and to anticipate socioeconomic and cultural contrasts, as well as different political, IBANEZ ET AL . 11 of 13 health, and diplomacy structures. Homogenizing a vast region with The Latin American and Caribbean consortium on dementia widespread diversity will not work. LACs are not uniform, and some (LAC-CD), has developed a regional action plan for a coordinated cities with stronger health organization and resources to face demen- and multilevel response to fight dementia.56 This plan includes a tia needs (such as Havana, Medellin, Montevideo, Buenos Aires) can knowledge-to action-framework (KtAF) to deliver coordinative pro- respond better than others (such as Guayaquil, Manaus, Lima, Iquitos). grams involving hundreds of local institutions and carry out additional Even within the same country, this scenario has been highlighted in triangulation with regional NGOs. The LAC-CD coordinative plan must Guayaquil, Ecuador where health services were so overwhelmed that urgently consider additional challenges imposed by the pandemic,2 they were unable to clear the numerous bodies from the street. This sit- connecting both local initiatives and global dementia strategies (as has uation contrasts with SARS-CoV-2 cases and mortality in Quito, where been recently done in dementia care and prevention). case numbers have been more comparable to other regions. These local differences may be explained by the acceptance of physical distancing and the use of masks in the community; however, it would be useful to 5 THE ROLE OF NGOs AND BRAIN HEALTH survey for local viral strains that may be associated with phenotypic dif- DIPLOMACY FOR DEMENTIA IN LACs ferences. Importantly, regional assessments must be conducted down to the level of municipalities and even more locally to guide remedia- Regional cooperation and shared experience for dementia can- tion toward the areas of greatest need. In Peru, Lima is suffering one not be ignored in this time of crisis. In other regions, coordinated of the most severe impacts of COVID-19, but Cuzco, a very crowded plans improved the adequate responses to SARS-CoV-2 in aging tourist destination at high altitude, has had few deaths.9 Similar differ- populations.57 Brain health diplomacy58,59 can help build international ences are also observed between countries in available resources, with partnerships to improve dementia outcomes for LACs at micro- (indi- Guatemala and Haiti having less than 200 ventilators between them,24 vidual), meso- (community), and macro- (national and transnational) but Argentina having more than 10,000. levels. Large-scale diplomatic action may include efforts to coordinate Given this heterogeneity, not all initiatives will work well in dif- lessons learned across other countries; share protocols; and establish ferent settings. The response to the pandemic is influenced by local, multi-national agreements for research, advocacy, clinical care, and regional, national, and global policies and political decisions. Early public health. By increasing coordination across countries, disciplines, containment measures in Germany lowered COVID-19 incidence and and sectors already working on coronavirus and dementia in the region mortality, but these strategies might not be feasible or could have can bring novel solutions to current challenges. Brain health diplomacy unintended consequences in Latin America. Similar positive results should be led by multiregional NGOs focused on dementia such as the in some countries within LACs should be extrapolated to others with Alzheimer’s Association (AA), Alzheimer’s Disease International (ADI), caution. Cuba, Argentina, and Costa Rica had better management of or the Global Brain Health Institute (GBHI), in strong partnership with this unique situation by developing strict enforcement of social dis- local institutions on the ground that can coordinate a leadership action tancing and lockdown. In the Caribbean, specific actions for dementia plan supported by multilateral networking. include special focus on LTC, developing 24/7 help-lines, assessing mental health disorders in elders, and providing caregiving training ACKNOWLEDGMENTS and strategies to cope with loneliness.55 Although many of these The authors thank the Alzheimer’s Association (AA), the Global Brain strategies can be potentially extrapolated to other countries in the Health Institute (GBHI-UCSF), the Tau Consortium, the National region, they seem to work better for containment when the numbers Institutes of Health/National Institute on Aging, and the Inter- are small, but less well for mitigation. Moreover, specific links among American Development Bank (IDB). Authors also thanks the grant scientists, health workers, non-governmental organizations, and GBHI ALZ UK-20-639295, and the MULTI-PARTNER CONSORTIUM government should be carefully considered in each case when imple- TO EXPAND DEMENTIA RESEARCH IN LATIN AMERICA (ReDLat, menting regional strategies to deal with the full manifestation of the supported by National Institutes of Health, National Institutes of coronavirus. Aging [R01 AG057234], Alzheimer’s Association [SG-20-725707], Tau Beyond these acknowledged differences, common problems Consortium, and the Global Brain Health Institute). The contents of triggered by the pandemic impacting dementia patients require a coor- this publication are solely the responsibility of the authors and do not dinated response supporting aggressive governmental investment. represent the official views of these institutions. Importantly, the planet is globally connected and a highly infectious disease in one place will not remain there despite the radical solution AUTHOR CONTRIBUTIONS of sealing off an entire country. Responses can be sustainable only if Agustin Ibanez and Kenneth S. Kosik designed the proposal. Agustin control measures are implemented nationally, regionally, and globally. Ibanez, Hernando Santamaria-Garcia, and Kenneth S. Kosik provided PAHO has estimated that an additional ≈$100,000,000 is required the first complete draft and searched the literature. All authors con- to support a basic response in the region to face the short-term tributed to the draft. Gorka Navarrete prepared Figure 1. Kenneth effects of the crises. Beyond monetary efforts, urgent calls for orga- S. Kosik and Bruce L. Miller provided revisions. All authors partici- nizational coalitions are required for LMIC1 and dementia patients pated in discussing the content of the paper, contributed to editing, and in LACs.53 approved the final version of the article. 12 of 13 IBANEZ ET AL . CONFLICTS OF INTEREST 10. OECD/The World Bank (2020), Health at a Glance: Latin America and Agustin Ibanez is partially supported by grants from CON- the Caribbean 2020, OECD Publishing, Paris, https://doi.org/10.1787/ 6089164f-en. ICET, FONCyT-PICT 2017-1818, FONCyT-PICT 2017 1820, 11. Thumala D, Kennedy BK, Calvo E, et al. Aging and health policies in ANID/FONDAP/15150012, INECO Foundation, the Interamerican chile: new agendas for research. Health Syst Reform. 2017;3(4):253- Development Bank (IDB), GBHI ALZ UK-20-639295, and the MULTI- 260. PARTNER CONSORTIUM TO EXPAND DEMENTIA RESEARCH 12. Llibre-Guerra JJ, Jiménez-Velázquez IZ, Llibre-Rodriguez JJ, Acosta D. The impact of COVID-19 on Mental Health in the Hispanic Caribbean IN LATIN AMERICA (ReDLat, supported by National Institutes of Region. Int Psychogeriatr. 2020:1-9. Health, National Institutes of Aging [R01 AG057234], Alzheimer’s 13. Pan American Health Organization (PAHO). Time is of the Association [SG-20-725707], Tau Consortium, and Global Brain Health essence – countries of the Americas must act now to slow the Institute). Fabricio Ferreira de Oliveira has contributed by way of spread of COVID-19. https://www.paho.org/hq/index.php?option= com_content&view=article&id=15762:time-is-of-the-essence- a grant from FAPESP - The State of São Paulo Research Founda- countries-of-the-americas-must-act-now-to-slow-the-spread-of- tion (grant #2015/10109-5). Alzheimer’s Society Canada and the covid-19&Itemid=1926&lang=en Weston Brain Institute (to FGF), National Institute for Translational 14. Parra MA, Baez S, Allegri R, et al. Dementia in Latin America: assess- Neuroscience (INNT/Brazil) (to FGF), the Brazilian funding agencies ing the present and envisioning the future. Neurology. 2018;90(5):222- Conselho Nacional de Desenvolvimento Científico e Tecnológico 231. 15. Wong LE, Hawkins HE, Langness S, Murrell KL, Iris P, Sammann A. (CNPq) and Fundação de Amparo à Pesquisa do Estado do Rio de Where Are All the Patients? Addressing COVID-19 Fear to Encourage Janeiro (FAPERJ) (to FGF). Elisa De Paula França Resende received Sick Patients to Seek Emergency Care. NEJM Catalyst non-issue content. funding from the Alzheimer’s Association. Alzheimer’s Association 2020;1(3). https://doi.org/10.1056/CAT.20.0193 Research Grant 2018-AARG-591107 and REDI170583 (CDA). María 16. Miranda JJ, Barrientos-Gutierrez T, Corvalan C, et al. Understanding the rise of cardiometabolic diseases in low- and middle-income coun- Isabel Behrens is supported by grants from FONDECYT (Fondo de tries. Nat Med. 2019;25(11):1667-1679. Desarrollo Científico y Tecnológico) Grant 1190958, FONDEF (Fondo 17. Chen T, Wu D, Chen H, et al. Clinical characteristics of 113 deceased de Fomento al Desarrollo Científico y Tecnológico Grant ID19I10302, patients with coronavirus disease 2019: retrospective study. BMJ. and URedes URC-036/17. Andrea Slachevsky is partially supported by 2020;368:m1091. 18. Nitrini R, Barbosa MT, Dozzi Brucki SM, Yassuda MS, Caramelli P. Cur- grants from ANID/FONDAP/15150012, ANID / Fondecyt/ 1141279. rent trends and challenges on dementia management and research in Kenneth S. Kosik has support from the Alzheimer’s Association Latin America. J Glob Health. 2020;10(1):010362. and Tau Consortium. The contents of this publication are solely 19. Cosyns B, Lochy S, Luchian ML, et al. The role of cardiovascular imaging the responsibility of the authors and do not represent the official for myocardial injury in hospitalized COVID-19 patients. 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