Neurología Cognitiva

Cortical asymmetry in autosomal dominant Alzheimer's disease progression

2026-05-07T13:04:56Z

Cortical asymmetry in autosomal dominant Alzheimer's disease progression Pérez-Millan, Agnès; Falgàs, Neus; Bosch, Beatriz; Borrego-Écija, Sergi; Antonell, Anna; Fernández-Villullas, Guadalupe; Esteller-Gauxax, Diana; Tort-Merino, Adrià; Bargalló, Núria; Balasa, Mircea; Lladó, Albert; Aguillon, David; Chrem Méndez, Patricio Alexis; Day, Gregory S.; Devenney, Emma; Huey, Edward D.; Ikeuchi, Takeshi; Jucker, Mathias; Kasuga, Kensaku; Dominantly Inherited Alzheimer Network (DIAN) The cortical asymmetry index evaluates the cortical thickness asymmetry between hemispheres. We investigated cortical asymmetry index in asymptomatic and symptomatic mutation carriers of autosomal dominant Alzheimer's disease to explore the brain asymmetry within the Alzheimer's disease continuum. Sixty baseline T1-weighted MRI scans were obtained from the Clinic Barcelona cohort. Baseline and longitudinal MRI data from 564 participants within the dominantly inherited Alzheimer network observational study were used as an independent, confirmatory cohort. Cerebrospinal fluid and plasma neurofilament light chain levels were included when available. Cortical thickness was calculated using Freesurfer and cortical asymmetry index was calculated via an open-source pipeline. Cross-sectional analyses examined cortical asymmetry index differences based on clinical classification and APOE ε4 status, adjusting for age, sex and estimated years from onset, while correlations were assessed with age, estimated years from onset, mini-mental state examination scores, and neurofilament light. Longitudinal cortical asymmetry index evolution was modelled using generalized additive models in the dominantly inherited Alzheimer network observational study cohort, incorporating age, sex, and the interaction between group and estimated years from onset. The cortical asymmetry index successfully distinguished asymptomatic mutation carrier and symptomatic mutation carriers from healthy controls in the Clinic Barcelona cohort and symptomatic mutation carriers from controls in dominantly inherited Alzheimer network observational study. Higher cortical asymmetry index in mutation carriers (asymptomatic mutation carrier and symptomatic mutation carriers combined) and in symptomatic mutation carriers were associated with higher plasma neurofilament light levels, a closer proximity to symptom onset, and lower mini-mental state examination in the Clinic Barcelona cohort. In the dominantly inherited Alzheimer network observational study cohort, mutation carriers exhibited increased cortical asymmetry index compared to controls and correlated with elevated neurofilament light (plasma and Cerebrospinal fluid), lower mini-mental state examination, and a closer proximity to symptom onset. APOE3/3 carriers showed greater asymmetry than other APOE genotypes and significant cortical asymmetry index differences between asymptomatic mutation carrier and symptomatic mutation carriers. Longitudinally, cortical asymmetry index increased over time significantly in symptomatic mutation carriers. These findings underscore brain asymmetry as a potential biomarker for early Alzheimer's disease progression in autosomal dominant Alzheimer's disease, with implications for detection and monitoring tracking disease-related neuroanatomical changes.

Executive Functions in Latin American Older Adults: Exploring the Concept Shifting Test and Its Relationship with the APOE Gene in a Cross‐Sectional Sample from the LatAm‐FINGERS Study

2026-03-10T11:49:30Z

Executive Functions in Latin American Older Adults: Exploring the Concept Shifting Test and Its Relationship with the APOE Gene in a Cross‐Sectional Sample from the LatAm‐FINGERS Study Melillo Cardoso, Davi; Vasconcelos Friedlander, Clarisse; Sanches Yassuda, Monica; Cruz de Souza, Leonardo; Crivelli, Lucía; Kimie Suemoto, Claudia; Martin, Maria Eugenia; Calandri, Ismael Luis; Acosta‐Baena, Natalia; Surace, Ezequiel Ignacio; Damian, Andrés; Da Graça Morais Martin, Maria; Vigil‐Martinez, Ana; Henrique Cançado, Gustavo; Salinas‐Contreras, Rosa Maria; Custodio, Belen; Cusicanqui, María Isabel; Delgado, Carolina; Sevlever, Gustavo Emilio; Allegri, Ricardo Francisco Background Latin America (LA) faces high vulnerability to dementia risk factors. Early detection of cognitive decline, particularly in executive functions (EF), is crucial. The Trail Making Test (TMT) has limitations, while the Concept Shifting Test (CST) offers potential advantages but lacks LA adaptation. This study examines CST's correlation with other EF tests and its relationship with APOE‐ε4 in older adults. Methods Cross‐sectional analysis of LatAm‐FINGERS baseline data, including TMT, CST, Stroop Test, and fluency tasks. APOE genotyping used PCR‐RFLP analysis. Jamovi software (v2.3) analyzed correlations (p < 0.05). Results Sample: 1,143 individuals from 11 LA countries. Mean age = 67.4 years (±4.7), education = 13.2 years (±3.5), 73.9% women, 57.3% mixed‐race. 21.4% carried APOE‐ε4 allele. Mean CST shifting score: 16.0 (±19.3). Significant correlations with age (𝜌=0.085; p = 0.009) and education (𝜌 = ‐0.201; p <0.001). No sex differences (p = 0.172). CST shifting score showed moderate correlation with TMT‐flexibility (𝜌=0.372; p <0.001), weak correlations with Stroop (𝜌=‐0.175; p <0.001), semantic (𝜌=‐0.133; p <0.001) and phonemic fluency (𝜌=‐0.184; p <0.001). No significant differences in CST shifting (p = 0.951) or TMT‐flexibility (p = 0.767) between APOE‐ε4 groups. Conclusions Weak correlations between CST shifting, Stroop‐flexibility, and fluency tasks suggest they assess different EF aspects. The moderate CST‐TMT correlation may indicate refined cognitive flexibility measurement in CST. While useful for EF assessment in LA, CST doesn't replace TMT. Diverse tools are crucial for early dementia detection. The lack of association between APOE‐ε4 and cognitive scores emphasizes the importance of assessment regardless of genetic risk.

Cognitive and neuroimaging trajectories in the behavioral variant of Alzheimer's disease

2026-03-05T15:56:12Z

Cognitive and neuroimaging trajectories in the behavioral variant of Alzheimer's disease Calandri, Ismael Luis; Phillips, Jeffrey S.; Tideman, Pontus; Singleton, Ellen Hanna; La Joie, Renaud; van der Flier, Wiesje M.; Jonkman, Laura E.; Hansson, Oskar; Rabinovici, Gil D.; Pijnenburg, Yolande A. L.; Ossenkoppele, Rik; Mastenbroek, Sophie E. Background The behavioral variant of Alzheimer's disease (bvAD) is a rare atypical presentationcharacterized by early and prominent behavioral changes, clinically akin to the behavioral variant of fronto‐temporal dementia (bvFTD). The natural history of bvAD is poorly understood. This study investigates the progression of bvAD in a multinational cohort, comparing bvAD with matched bvFTD and typical AD (tAD) groups. Method We analyzed 81 bvAD participants from four centers and matched them by age, sex, and education to bvFTD (n = 80), tAD (n = 81), and controls (n = 78). Participants completed longitudinal clinical assessments and underwent repeated structural MRI. We combined neurocognitive variables into domain‐specific composites. Furthermore, we extracted cortical thickness and volumetric MRI data using FreeSurfer andcomputed atemporal AD‐signature and a frontal region‐of‐interest. Linear mixed models were used to evaluate cognitive and neuroimaging trajectories. The model coefficients are presented as standardized (β), and the effect is assessed through estimated marginal means (EMM). Result Demographic features are shown in Table 1. Subjects with bvAD exhibited significant decline in executive function (β=‐0.62, 95%CI[‐1.02, ‐0.22], p = 0.03, EMM=‐0.19), memory (β=‐1.62, 95%CI[‐1.90, ‐1.33], p < 0.001, EMM=‐0.49), language (β=‐0.95, 95%CI[‐1.31, ‐0.59], p < 0.01, EMM=‐0.18), and visuospatial function (β=‐0.80, 95%CI[‐1.31, ‐0.28], p < 0.05) compared to controls. Compared to bvFTD, individuals with bvAD showed relatively greater memory (p = 0.005) and language (p = 0.04) preservation over time, while no significant differences were observed in visuospatial function (p = 0.65) or executive function (p = 0.4). In contrast, bvAD did not differ significantly from tAD in memory (p = 0.1), language (p = 0.6), visuospatial function (p = 0.99), or executive function. Individuals with bvAD exhibited significant decline in the AD‐signature (β=‐0.91, 95%CI[‐1.34, ‐0.48], EMM=‐0.49) and frontal ((β=‐0.66, 95%CI[‐1.16, ‐0.15], EMM=‐0.29) regions‐of‐interest compared to controls. Compared to tAD, no significant differences were found in both regions of interest (p = 0.61, p = 0.91). Compared to bvFTD, individuals with bvAD showed significantly greater atrophy in the AD‐signature regions (p = 0.02) and significantly less atrophy in frontal lobe (p = 0.03). Conclusion The progression of bvAD differs both cognitivelyand anatomically from bvFTD, while showing a progression pattern that is very similar to tAD. These results underscore the importance of investigating AD pathology in the context of cognitive‐behavioral decline.

CADASIL Argentine Registry: Study Design and Preliminary Data

2026-02-19T13:41:59Z

CADASIL Argentine Registry: Study Design and Preliminary Data Ardohain Cristalli, Carolina Agata; Rosales, Julieta Soledad; Gonzalez, Fabio; Selvaggi, Valentin; Alonso, Julián Martín; López, Juan Ignacio; Aguilar, Martín Santiago; Kauffman, Marcelo; Saks, Danit G.; Allegri, Ricardo Francisco; Sevlever, Gustavo Emilio; Chaves, Hernán; Cristalli, Diana Olga; Calandri, Ismael Luis Background: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), the most common hereditary small vessel disease, leads to early-onset stroke and vascular cognitive impairment (VCI). Despite its importance, data from Latin America remain scarce. The CADASIL Argentine registry (CADASILAr) was created to harmonize clinical data, promote international collaboration, and provide a reproducible, longitudinal framework to study disease progression and expand to neighboring countries. This study aims to present the cohort design and preliminary results from the cross-sectional phase. Method: CADASILAr was developed to document demographic, clinical, imaging, and genetic features of CADASIL patients and to explore factors associated with disease progression and cognitive decline in an Argentinian multisite cohort. The study includes two phases: (1) a cross-sectional phase (CADASILAR-C) and (2) a longitudinal phase (CADASILAR-Long), following adults aged ≥18 years with genetically confirmed or suspected CADASIL. Variables collected include demographics, symptom onset, clinical features, neuroimaging, genetic data, and vascular risk factors. The study also examines socio-economic disparities, integrates biobanks, and harmonizes data collection with international CADASIL and dementia registries. Longitudinal followups are planned annually over 5 years (Figure 1), with cognitive batteries aligned with international cohorts and a brain donation program to establish a CADASIL brain bank in Argentina. Result: Preliminary data from 90 patients (50% female) show a mean age of 43.8±11.9 years, with family history in 91.6% (Figure 2). The most common clinical presentations were cerebrovascular events (72.9%), cognitive impairment (56.7%), and migraine (69%). The most frequent comorbidities included hypertension (64%) and dyslipidemia (55%). Among 86 confirmed cases, 63 were diagnosed through genetic testing and 20 through skin biopsy. Genetic analysis identified cysteine-altering NOTCH3 mutations in all confirmed cases, predominantly affecting epidermal growth factor-like repeats (Figure 3). Of the 33 patients assessed with the MMSE, the median score was 28 (IQR: 22–29). Conclusion: CADASILAr is the first systematic effort to study this disease in Latin America and the twelfth global CADASIL registry. By integrating baseline and longitudinal data, it offers a robust platform to investigate genetic, neuroimaging, and cognitive outcomes while fostering international collaborations to advance research and understanding of CADASIL.