Neurología

Cortical asymmetry in autosomal dominant Alzheimer's disease progression

2025-12-19T00:00:00Z

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

2025-12-26T00:00:00Z

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

2025-12-26T00:00:00Z

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.

Chorea and Levodopa-Induced Dyskinesia in Corticobasal Syndrome: Two Case Reports with Pathological Insights and Literature Review

2025-05-11T00:00:00Z

Chorea and Levodopa-Induced Dyskinesia in Corticobasal Syndrome: Two Case Reports with Pathological Insights and Literature Review Medina Escobar, Alex; Rossi, Malco Damián; Richer, Maxime; Gautreau, Sylvia; Lang, Anthony E. Background: Corticobasal syndrome (CBS) is a rare, clinically heterogeneous form of atypical Parkinsonism. Hyperkinetic movements, aside from myoclonus and dystonia, have rarely been reported in CBS. Cases: We present two patients with CBS, one with pathologically confirmed corticobasal degeneration (CBD) and generalized chorea, and another with probable CBS and Levodopa-induced dyskinesia (LID). Case 1 exhibited late-onset generalized chorea, which was preceded by several years of dystonia, rigidity and apraxia affecting the right upper limb. Case 2 presented with dystonia, cortical sensory loss, and apraxia in the left upper limb, while LID affected the face and the right side of the body. Literature review: A systematic review of published cases of chorea or levodopa-induced dyskinesia (LID) in CBS was performed. The literature search was executed in PubMed from its inception for cases of chorea or LID associated with CBS. Twelve patients were identified across eight studies. Only five cases of pathologically confirmed CBD with chorea were found; chorea developed after 4 years of disease progression. Conclusions: Chorea and LID are rare but may represent late manifestations of CBS. The exact mechanisms are unclear; they may relate to variability in anatomical involvement, particularly relative sparing of the GPi. Greater understanding of topographical disease progression may improve diagnostic precision and phenotypic classification in CBS and related tauopathies.