Universidad del Desarrollo

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Gaps in biomedical research in frontotemporal dementia: A call for diversity and disparities focused research
(2024)
Karen Nuytemans
;
Sanne Franzen
;
Iris J. Broce
;
Paulo Caramelli
;
Ratnavalli Ellajosyula
<jats:title>Abstract</jats:title><jats:p>Frontotemporal dementia (FTD) is one of the leading causes of young‐onset dementia before age 65, typically manifesting as abnormal behavior (in behavioral variant FTD) or language impairment (in primary progressive aphasia). Although FTD affects all populations across the globe, knowledge regarding the pathophysiology and genetics derives primarily from studies conducted in North America and Western Europe. Globally, biomedical research for FTD is hindered by variable access to diagnosis, discussed in this group's earlier article, and by reduced access to expertise, funding, and infrastructure. This perspective paper was produced by two professional interest areas of the Alzheimer's Association International Society to Advance Alzheimer's Research and Treatment (ISTAART) and discusses the field's current status on the cross‐cultural aspects of basic and translational research in FTD (including that focused on epidemiology, genetics, biomarkers, and treatment). It subsequently provides a summary of gaps and needs to address the disparities and advance global FTD biomedical research.</jats:p>
Scopus© Citations 4
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Neural basis of speech and grammar symptoms in non-fluent variant primary progressive aphasia spectrum
(2023)
Diego L Lorca-Puls
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GAJARDO VIDAL, ANDREA ELIZABETH
;
Maria Luisa Mandelli
;
Ignacio Illán-Gala
;
Zoe Ezzes
The non-fluent/agrammatic variant of primary progressive aphasia (nfvPPA) is a neurodegenerative syndrome primarily defined by the presence of apraxia of speech (AoS) and/or expressive agrammatism. In addition, many patients exhibit dysarthria and/or receptive agrammatism. This leads to substantial phenotypic variation within the speech-language domain across individuals and time, in terms of both the specific combination of symptoms as well as their severity. How to resolve such phenotypic heterogeneity in nfvPPA is a matter of debate. ‘Splitting’ views propose separate clinical entities: ‘primary progressive apraxia of speech’ when AoS occurs in the absence of expressive agrammatism, ‘progressive agrammatic aphasia’ (PAA) in the opposite case, and ‘AOS + PAA’ when mixed motor speech and language symptoms are clearly present. While therapeutic interventions typically vary depending on the predominant symptom (e.g. AoS versus expressive agrammatism), the existence of behavioural, anatomical and pathological overlap across these phenotypes argues against drawing such clear-cut boundaries. In the current study, we contribute to this debate by mapping behaviour to brain in a large, prospective cohort of well characterized patients with nfvPPA (n = 104). We sought to advance scientific understanding of nfvPPA and the neural basis of speech-language by uncovering where in the brain the degree of MRI-based atrophy is associated with inter-patient variability in the presence and severity of AoS, dysarthria, expressive agrammatism or receptive agrammatism.</jats:p> <jats:p>Our cross-sectional examination of brain-behaviour relationships revealed three main observations. First, we found that the neural correlates of AoS and expressive agrammatism in nfvPPA lie side by side in the left posterior inferior frontal lobe, explaining their behavioural dissociation/association in previous reports. Second, we identified a ‘left-right’ and ‘ventral-dorsal’ neuroanatomical distinction between AoS versus dysarthria, highlighting (i) that dysarthria, but not AoS, is significantly influenced by tissue loss in right-hemisphere motor-speech regions; and (ii) that, within the left hemisphere, dysarthria and AoS map onto dorsally versus ventrally located motor-speech regions, respectively. Third, we confirmed that, within the large-scale grammar network, left frontal tissue loss is preferentially involved in expressive agrammatism and left temporal tissue loss in receptive agrammatism.</jats:p> <jats:p>Our findings thus contribute to define the function and location of the epicentres within the large-scale neural networks vulnerable to neurodegenerative changes in nfvPPA. We propose that nfvPPA be redefined as an umbrella term subsuming a spectrum of speech and/or language phenotypes that are closely linked by the underlying neuroanatomy and neuropathology.
10Scopus© Citations 19
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Assessing processing speed and its neural correlates in the three variants of primary progressive aphasia with a non-verbal tablet-based task
(2024)
GAJARDO VIDAL, ANDREA ELIZABETH
;
Maxime Montembeault
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Diego L. Lorca-Puls
;
Abigail E. Licata
;
Rian Bogley
Scopus© Citations 4 1
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Gaps in clinical research in frontotemporal dementia: A call for diversity and disparities–focused research
(2023)
Sanne Franzen
;
Karen Nuytemans
;
Renelle Bourdage
;
Paulo Caramelli
;
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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