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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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Gaps in clinical research in frontotemporal dementia: A call for diversity and disparities–focused research
(2023)
Sanne Franzen
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Karen Nuytemans
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Renelle Bourdage
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Paulo Caramelli
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Ratnavalli Ellajosyula
<jats:title>Abstract</jats:title><jats:p>Frontotemporal dementia (FTD) is one of the leading causes of dementia before age 65 and often manifests as abnormal behavior (in behavioral variant FTD) or language impairment (in primary progressive aphasia). FTD's exact clinical presentation varies by culture, language, education, social norms, and other socioeconomic factors; current research and clinical practice, however, is mainly based on studies conducted in North America and Western Europe. Changes in diagnostic criteria and procedures as well as new or adapted cognitive tests are likely needed to take into consideration global diversity. This perspective paper by two professional interest areas of the Alzheimer's Association International Society to Advance Alzheimer's Research and Treatment examines how increasing global diversity impacts the clinical presentation, screening, assessment, and diagnosis of FTD and its treatment and care. It subsequently provides recommendations to address immediate needs to advance global FTD research and clinical practice.</jats:p>
27Scopus© Citations 12
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Moral Emotions and Their Brain Structural Correlates Across Neurodegenerative Disorders
(2023)
Sandra Baez
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Catalina Trujillo-Llano
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Leonardo Cruz de Souza
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Patricia Lillo
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Gonzalo Forno
<jats:p>Background: Although social cognition is compromised in patients with neurodegenerative disorders such as behavioral variant frontotemporal dementia (bvFTD) and Alzheimer’s disease (AD), research on moral emotions and their neural correlates in these populations is scarce. No previous study has explored the utility of moral emotions, compared to and in combination with classical general cognitive state tools, to discriminate bvFTD from AD patients. Objective: To examine self-conscious (guilt and embarrassment) and other-oriented (pity and indignation) moral emotions, their subjective experience, and their structural brain underpinnings in bvFTD (n = 31) and AD (n = 30) patients, compared to healthy controls (n = 37). We also explored the potential utility of moral emotions measures to discriminate bvFTD from AD. Methods: We used a modified version of the Moral Sentiment Task measuring the participants’ accuracy scores and their emotional subjective experiences. Results: bvFTD patients exhibited greater impairments in self-conscious and other-oriented moral emotions as compared with AD patients and healthy controls. Moral emotions combined with general cognitive state tools emerged as useful measures to discriminate bvFTD from AD patients. In bvFTD patients, lower moral emotions scores were associated with lower gray matter volumes in caudate nucleus and inferior and middle temporal gyri. In AD, these scores were associated with lower gray matter volumes in superior and middle frontal gyri, middle temporal gyrus, inferior parietal lobule and supramarginal gyrus. Conclusion: These findings contribute to a better understanding of moral emotion deficits across neurodegenerative disorders, highlighting the potential benefits of integrating this domain into the clinical assessment.</jats:p>
24Scopus© Citations 3
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Biomarkers for dementia in Latin American countries: Gaps and opportunities
(2022)
Mario A. Parra
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ORELLANA VILLENA, VIVIANA PAULINA
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Tomas Leon
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Cabello G. Victoria
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Rodrigo Gomez
1Scopus© Citations 32 2
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Does culture shape our understanding of others’ thoughts and emotions? An investigation across 12 countries.
(2022)
François Quesque
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Antoine Coutrot
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Sharon Cox
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Leonardo Cruz de Souza
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Sandra Baez
24Scopus© Citations 35
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Multidimensional Clinical Assessment in Frontotemporal Dementia and Its Spectrum in Latin America and the Caribbean: A Narrative Review and a Glance at Future Challenges
(2022)
Fernando Henríquez
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Victoria Cabello
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Sandra Baez
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Leonardo Cruz de Souza
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Patricia Lillo
<jats:p>Frontotemporal dementia (FTD) is the third most common form of dementia across all age groups and is a leading cause of early-onset dementia. The Frontotemporal dementia (FTD) includes a spectrum of diseases that are classified according to their clinical presentation and patterns of neurodegeneration. There are two main types of FTD: behavioral FTD variant (bvFTD), characterized by a deterioration in social function, behavior, and personality; and primary progressive aphasias (PPA), characterized by a deficit in language skills. There are other types of FTD-related disorders that present motor impairment and/or parkinsonism, including FTD with motor neuron disease (FTD-MND), progressive supranuclear palsy (PSP), and corticobasal syndrome (CBS). The FTD and its associated disorders present great clinical heterogeneity. The diagnosis of FTD is based on the identification through clinical assessments of a specific clinical phenotype of impairments in different domains, complemented by an evaluation through instruments, i.e., tests and questionnaires, validated for the population under study, thus, achieving timely detection and treatment. While the prevalence of dementia in Latin America and the Caribbean (LAC) is increasing rapidly, there is still a lack of standardized instruments and consensus for FTD diagnosis. In this context, it is important to review the published tests and questionnaires adapted and/or validated in LAC for the assessment of cognition, behavior, functionality, and gait in FTD and its spectrum. Therefore, our paper has three main goals. First, to present a narrative review of the main tests and questionnaires published in LAC for the assessment of FTD and its spectrum in six dimensions: (i) Cognitive screening; (ii) Neuropsychological assessment divided by cognitive domain; (iii) Gait assessment; (iv) Behavioral and neuropsychiatric symptoms; (v) Functional assessment; and (vi) Global Rating Scale. Second, to propose a multidimensional clinical assessment of FTD in LAC identifying the main gaps. Lastly, it is proposed to create a LAC consortium that will discuss strategies to address the current challenges in the field.</jats:p>
1 4Scopus© Citations 18
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Inside minds, beneath diseases: social cognition in amyotrophic lateral sclerosis-frontotemporal spectrum disorder
(2020)
Patricia Lillo
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Paulo Caramelli
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Gada Musa
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Teresa Parrao
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Ricardo Hughes
<jats:sec><jats:title>Objective</jats:title><jats:p>To compare social cognition performance between patients with amyotrophic lateral sclerosis (ALS) and those patients with behavioural variant frontotemporal dementia (bvFTD).</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>We included 21 participants with ALS, 20 with bvFTD and 21 healthy controls who underwent a comprehensive cognitive battery, including the short version of the Social Cognition and Emotional Assessment (Mini-SEA), which comprises the <jats:italic>faux pas</jats:italic> test and Facial Emotion Recognition Test (FERT); Mini-Mental State Examination; Frontal Assessment Battery; lexical fluency (F-A-S), category fluency (animals/minute), digit span (direct and backwards) tests and the Hayling test. A post hoc analysis was conducted with the patients with ALS divided into two subgroups: patients without cognitive impairment (ALScn; n=13) and patients with cognitive impairment (ALSci; n=8).</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>No significant difference was noted between participant groups in terms of the age, sex and education. ALS-total group and patients with bvFTD had similar disease durations. Patients with ALSci performed poorly when compared with controls with regard to the FERT (p<0.001), the <jats:italic>faux pas</jats:italic> (p<0.004) and the Mini-SEA (p<0.002) total scores. Moreover, patients with bvFTD performed poorly in comparison with controls in executive and social cognition tests. The performance of patients with ALSci was similar to that of patients with bvFTD, while the performance of patients with ALScn was similar to that of controls.</jats:p></jats:sec><jats:sec><jats:title>Discussion</jats:title><jats:p>Our findings support a cognitive continuum between ALS and bvFTD and shed light on the cognitive heterogeneity of ALS, expanding its possible neuropsychological profiles.</jats:p></jats:sec>
8Scopus© Citations 9

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