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Alzheimer Disease as a Clinical-Biological Construct—An International Working Group Recommendation
(2024)
Bruno Dubois
;
Nicolas Villain
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Lon Schneider
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Nick Fox
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Noll Campbell
<jats:sec id="ab-nsc240001-1"><jats:title>Importance</jats:title><jats:p>Since 2018, a movement has emerged to define Alzheimer disease (AD) as a purely biological entity based on biomarker findings. The recent revision of the Alzheimer’s Association (AA) criteria for AD furthers this direction. However, concerns about a purely biological definition of AD being applied clinically, the understanding of AD by society at large, and the translation of blood-based biomarkers into clinical practice prompt these International Working Group (IWG) updated recommendations.</jats:p></jats:sec><jats:sec id="ab-nsc240001-2"><jats:title>Objective</jats:title><jats:p>To consider the revised AA criteria and to offer an alternative definitional view of AD as a clinical-biological construct for clinical use. The recommendations of the 2021 IWG diagnostic criteria are updated for further elaborating at-risk and presymptomatic states.</jats:p></jats:sec><jats:sec id="ab-nsc240001-3"><jats:title>Evidence Review</jats:title><jats:p>PubMed was searched for articles published between July 1, 2020, and March 1, 2024, using the terms “biomarker” OR “amyloid” OR “tau” OR “neurodegeneration” OR “preclinical” OR “CSF” OR “PET” OR “plasma” AND “Alzheimer’s disease.” The references of relevant articles were also searched.</jats:p></jats:sec><jats:sec id="ab-nsc240001-4"><jats:title>Findings</jats:title><jats:p>In the new AA diagnostic criteria, AD can be defined clinically as encompassing cognitively normal people having a core 1 AD biomarker. However, recent literature shows that the majority of biomarker-positive cognitively normal individuals will not become symptomatic along a proximate timeline. In the clinical setting, disclosing a diagnosis of AD to cognitively normal people with only core 1 AD biomarkers represents the most problematic implication of a purely biological definition of the disease.</jats:p></jats:sec><jats:sec id="ab-nsc240001-5"><jats:title>Conclusions and Relevance</jats:title><jats:p>The ultimate aim of the field was to foster effective AD treatments, including preventing symptoms and dementia. The approach of diagnosing AD without a clinical and biological construct would be unwarranted and potentially concerning without a clear knowledge of when or whether symptoms will ever develop. It is recommended that those who are amyloid-positive only and, more generally, most biomarker-positive cognitively normal individuals, should not be labeled as having AD. Rather, they should be considered as being at risk for AD. The expansion of presymptomatic AD is viewed as a better diagnostic construct for those with a specific pattern of biomarkers, indicating that they are proximate to the expression of symptoms in the near future.</jats:p></jats:sec>
Scopus© Citations 73 2
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Systematic Review: Genetic, Neuroimaging, and Fluids Biomarkers for Frontotemporal Dementia Across Latin America Countries
(2021)
Claudia Duran-Aniotz
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Paulina Orellana
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Tomas Leon Rodriguez
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Victoria Cabello
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Fernando Henriquez
<jats:p>Frontotemporal dementia (FTD) includes a group of clinically, genetically, and pathologically heterogeneous neurodegenerative disorders, affecting the fronto-insular-temporal regions of the brain. Clinically, FTD is characterized by progressive deficits in behavior, executive function, and language and its diagnosis relies mainly on the clinical expertise of the physician/consensus group and the use of neuropsychological tests and/or structural/functional neuroimaging, depending on local availability. The modest correlation between clinical findings and FTD neuropathology makes the diagnosis difficult using clinical criteria and often leads to underdiagnosis or misdiagnosis, primarily due to lack of recognition or awareness of FTD as a disease and symptom overlap with psychiatric disorders. Despite advances in understanding the underlying neuropathology of FTD, accurate and sensitive diagnosis for this disease is still lacking. One of the major challenges is to improve diagnosis in FTD patients as early as possible. In this context, biomarkers have emerged as useful methods to provide and/or complement clinical diagnosis for this complex syndrome, although more evidence is needed to incorporate most of them into clinical practice. However, most biomarker studies have been performed using North American or European populations, with little representation of the Latin American and the Caribbean (LAC) region. In the LAC region, there are additional challenges, particularly the lack of awareness and knowledge about FTD, even in specialists. Also, LAC genetic heritage and cultures are complex, and both likely influence clinical presentations and may modify baseline biomarker levels. Even more, due to diagnostic delay, the clinical presentation might be further complicated by both neurological and psychiatric comorbidity, such as vascular brain damage, substance abuse, mood disorders, among others. This systematic review provides a brief update and an overview of the current knowledge on genetic, neuroimaging, and fluid biomarkers for FTD in LAC countries. Our review highlights the need for extensive research on biomarkers in FTD in LAC to contribute to a more comprehensive understanding of the disease and its associated biomarkers. Dementia research is certainly reduced in the LAC region, highlighting an urgent need for harmonized, innovative, and cross-regional studies with a global perspective across multiple areas of dementia knowledge.</jats:p>
1 2Scopus© Citations 23
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The Multi-Partner Consortium to Expand Dementia Research in Latin America (ReDLat): Driving Multicentric Research and Implementation Science
(2021)
Agustin Ibanez
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Jennifer S. Yokoyama
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Katherine L. Possin
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Diana Matallana
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Francisco Lopera
<jats:p>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.</jats:p>
Scopus© Citations 53 9
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Dementia in Latin America: Paving the way toward a regional action plan
(2020)
Mario Alfredo Parra
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Sandra Baez
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Lucas Sedeño
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Cecilia Gonzalez Campo
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Hernando Santamaría‐García
2Scopus© Citations 115
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The power of knowledge about dementia in Latin America across health professionals working on aging
(2020)
Agustin Ibanez
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Daniel Flichtentrei
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Eugenia Hesse
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Martin Dottori
;
Ailin Tomio
21Scopus© Citations 20

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