Neurología Cognitiva.pósters

Can the Cognitive Function Index identify cognitive impairment in Latin America?

2025-12-25T00:00:00Z

Can the Cognitive Function Index identify cognitive impairment in Latin America? Sanchez Yossuda, Monica; Crivelli, Lucía; Calandri, Ismael Luis; Kimie Soto, Claudia; Sevlever, Gustavo Emilio; Salinas-Contreras, Rosa María; Caramelli, Paulo; Dozzi Brucki, Sonia Maria; Cançado, Gustavo Henrique; Vigil-Martínez, Ana; Martin, María Eugenia; Surace, Ezequiel Ignacio; Martin, Maria Da Graça Morais; Damian, Andrés; Custodio, Belén; Corvalan, Nicolás; Fernandez Slezak, Diego; Velilla, Lina Marcela; Lima Carreira, Luzia; Studart Neto, Adalberto; Allegri, Ricardo Francisco Background: The Cognitive Function Index (CFI) was developed to identify individuals with Subjective Cognitive Decline (SCD), which is defined by the self‐perception of cognitive impairment, not detected in neuropsychological tests. Limited research has been done with this tool in Latin America (LA). We aimed to investigate the association between CFI and global cognition and to investigate whether CFI scores can identify participants with cognitive performance below 1.0 standard deviation (SD) of the sample mean. Method: The LatAm‐FINGERS study is a dementia prevention feasibility study in 12 LA countries. For the present analysis, 815 participants with complete cognitive data (604 women, 74.1%; 436 mestizo 53.5%; mean age=67.5, SD=4.8; mean education = 13.0, SD=3.6; mean GDS=2.7, SD=2.8) were included. The CFI is a 14‐item self‐report measure of cognitive change; higher scores indicate higher concerns. CFI total score was normalized into a z‐score, as some questions were not applicable to all participants and total score differed among them. Cognition was assessed with the Preclinical Alzheimer Cognitive Composite (PACC‐5) ‐ Mini‐Mental State Examination; Logical Memory Delayed Recall; Free and Cued Selective Reminding Test; Digit Symbol Substitution Test; and Animal Category Fluency. Participants were classified into those with PACC‐5 at or above 1 SD from the mean (n = 764) and those below (n = 51). Bivariate and partial correlations (controlling for sex, age, education and GDS score) were used to assess the association b tween the CFI and PACC‐5 scores. Receiver operating characteristic (ROC) analyses were used to assess CFI accuracy to identify participants with PACC‐5 scores below 1 SD. Result: CFI and PACC‐5 scores were negatively associated with each other (r = ‐0.27; p <0.001; partial r = ‐0.12; p <0.001). ROC analyses indicated an area under the curve (AUC) of 0.71 (sensitivity=0.64; specificity=0.70) with an optimal threshold of 0.36 (Youden Index=0.35) as a suggested cutoff score for the normalized CFI score. Conclusion: The CFI may be added to cognitive screening protocols to identify individuals who may need further assessment. Integrating the CFI into screening strategies in LA could play a pivotal role in reducing cognitive health disparities and advancing tailored dementia prevention initiatives that address the region's specific sociocultural and healthcare challenges.

Characterization of individuals fulfilling clinical criteria for limbic-predominant age-related TDP43 encephalopathy (LATE) in a tertiary memory clinic

2026-01-07T00:00:00Z

Characterization of individuals fulfilling clinical criteria for limbic-predominant age-related TDP43 encephalopathy (LATE) in a tertiary memory clinic Groot, Colin; Calandri, Ismael Luis; Bader, Ilse; Bocancea, Diana I.; de Bruin, Hannah; Carrigan, Maria; Kamps, Suzie; de Koning, Lotte A.; Mastenbroek, Sophie E.; Rikken, Roos M.; van Tol, Bastiaan G. J.; Vermeiren, Marie R.; Wesseling, Alex; Xia, Ye; Teunissen, Charlotte E.; van de Giessen, Elsmarieke; Barkhof, Frederik; Jonkman, Laura E.; van der Lee, Sven J.; de Boer, Casper Background Limbic-predominant age-related TDP-43 encephalopathy (LATE) clinically mimics and often co-occurs with Alzheimer's disease (AD). Expert consensus criteria have been proposed for the LATE clinical diagnosis, integrating clinical and radiological features, and AD biomarkers. Here, we applied the newly proposed criteria in a tertiary memory clinic population. Method We included participants from the Amsterdam Dementia Cohort aged >50 years who received a diagnosis of MCI or dementia between 1997-2024. Following the LATE consensus criteria scheme (Figure 1), we categorized participants as “Probable LATE”, “Possible LATE” or “Possible LATE-AD” (i.e. LATE clinical and radiological profile with AD biomarker profile). Participants not fulfilling criteria for LATE but fulfilling NIA-AA criteria for AD were categorized as AD. We compared the LATE groups with AD on cognitive decline (N = 1046, N Mean time=2.7[1.8] years) and atrophy (N = 208, Mean time=2.1[1.6]) using linear-mixed effects models, and on mortality rates using Cox proportional hazard models. Result Of the 3367 individuals, 1920 were classified into one of the four groups. Fifty-one (1.5%) were classified as Probable LATE, 102 (3.0%) as Possible LATE, 122 (3.6%) as Possible LATE-AD, and 1645 (48.8%) as AD (Table 1). Compared to AD, Probable LATE showed an attenuated cognitive decline (b[SE] for MMSE=0.12[0.05], p = 0.02) and lower mortality rates (HR[95% CI]=0.75[0.58-0.95], p = 0.02), while individuals with Possible LATE-AD had faster cognitive decline (b for MMSE=-0.12[0.05], p = 0.01) and higher mortality rates (HR=1.55[1.25-1.92], p <0.001, Figure 2). Compared to AD, Probable LATE had, at baseline, lower hippocampal volumes (b=-0.83[0.27], p <0.01), and higher inferior-temporal to hippocampal volume ratios (b=0.81[0.27], p <0.01). Furthermore, in Probable LATE, atrophy in a whole-brain region-of-interest was slower compared to AD (b=0.14[0.08], p = 0.04). Possible LATE-AD had, at baseline, thinner whole-brain cortex (b=-0.69[0.30], p = 0.02), lower hippocampal volumes (b=-1.54[0.31], p <0.01), and higher inferior-temporal to hippocampal volume ratios (b=1.73[0.30], p <0.01) than AD, but there was no difference in atrophy rates between Possible LATE-AD and the other groups (Figure 3). Conclusion In a tertiary memory clinic population, the newly proposed clinical LATE criteria reveal clinical and atrophy trajectories that are distinct from AD, especially for Probable LATE and Possible LATE-AD. Differential clinical and biological disease trajectories highlight the relevance of the LATE classification for diagnostic and prognostic purposes

Bridging Science and Care: 14 Years of Genetic and Biomarker Research in Neurodegenerative Diseases at an Argentine Memory Clinic

2025-12-24T00:00:00Z

Bridging Science and Care: 14 Years of Genetic and Biomarker Research in Neurodegenerative Diseases at an Argentine Memory Clinic Surace, Ezequiel Ignacio; Romorini, Leonardo; Marazita, Mariela Claudia; Clas, Giulia Solange; Massazza, Victoria; Alvarez, María Florencia; Avendaño, Daniel; Itzcovich, Tatiana; Martinetto, Horacio Understanding the biological and genetic landscape of neurodegenerative diseases in diverse populations deepens our insight into complex pathophysiological mechanisms. Our laboratory, established 14 years ago in Buenos Aires, Argentina, serves as a regional hub for Latin America, focusing on familial and sporadic cases of Alzheimer's disease (AD), frontotemporal dementia (FTD), and amyotrophic lateral sclerosis (ALS). We were among the first in the region to incorporate cerebrospinal fluid AD biomarker analysis into clinical diagnostics. Our research includes genetic counseling, the study of novel genetic variants, and the development of patient-derived cell models using induced pluripotent stem cell technology. In this talk, we will discuss the challenges of staying at the forefront of technological advancements and underscore the importance of international collaboration in advancing both local and global knowledge.

Functional validation of the PSEN1 R358P and PSEN1 T119I variants in Alzheimer's Disease: an in vitro study

2025-12-23T00:00:00Z

Functional validation of the PSEN1 R358P and PSEN1 T119I variants in Alzheimer's Disease: an in vitro study García Chialva, Diego; Cifarelli, Diego; Isaja, Luciana; Apecetche, Manuela; Martínes Ojeda, Laura; Itzcovich, Tatiana; Chrem Méndez, Patricio Alexis; Sevlever, Gustavo Emilio; Scassa, Maria; Surace, Ezequiel Ignacio; Romorini, Leonardo Background Alzheimer's disease (AD) is a neurodegenerative disorder and the leading cause of dementia worldwide. It is characterized by progressive neuronal degeneration and the accumulation of beta‐amyloid plaques (Aβ) and neurofibrillary tangles (NFT) in the brain. AD manifests in sporadic AD (sAD) and familial AD (fAD). fAD is associated with inherited genetic mutations affecting amyloid precursor protein (APP) processing, involving genes such as APP, PSEN1, and PSEN2. Method The identification of two novel PSEN1 variants, p.T119I and p.R358P in early‐onset AD patients at FLENI provided a unique opportunity to study their possible implications in fAD. Notably, the patient harboring the PSEN1 R358P variant also carried a novel SORL1 variant (Gly1536Asp). Noteworthy, genetic variants in SORL1 are now considered a major AD risk factor. To evaluate the role of these two novel PSEN1 variants in APP processing, we developed a cellular model using PSEN1 Knock‐Out (KO) HEK293T cells created through CRISPR/Cas9 technology. We assessed the Aβ 42 /Aβ 40 ratio (AD biomarker) in the supernatant of PSEN1 KO‐cells transfected with expression vectors coding for APP and either wild‐type PSEN1, the novel PSEN1 variants or PSEN1 A246E (a known pathogenic mutation). Result We observed a significant (p <0.05) increase in the Aβ 42 /Aβ 40 ratio in HEK293T cells transfected with PSEN1 A246E or PSEN1 R358P plasmids and a slight trend towards an increase in cells transfected with PSEN1 T119I vector. In the case of PSEN1 R358P‐transfected cells, the increase in the Aβ 42 /Aβ 40 ratio observed was primarily due to the decrease in Aβ 40 levels in the supernatant. Conclusion These findings suggest a potential pathogenic role for the PSEN1 R358P variant in fAD, independent of the co‐occurring SORL1 mutation.