Repositorio Institucional FLENI

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

Regional effects of gantenerumab on neuroimaging biomarkers in the DIAN-TU-001 trial

2025-07-01T00:00:00Z

Regional effects of gantenerumab on neuroimaging biomarkers in the DIAN-TU-001 trial McCullough, Austin; Chen, Charles D.; Gordon, Brian A.; Joseph-Mathurin, Nelly; Jack Jr, Clifford R; Koeppe, Robert; Hornbeck, Russ; Koudelis, Deborah; McKay, Nicole S.; Hobbs, Diana A.; Flores, Shaney; Keefe, Sarah J.; Aggarwal, Neelum T.; Allegri, Ricardo Francisco; Berman, Sarah B.; Bird, Thomas; Black, Sandra E.; Brooks, William S.; Chhatwal, Jasmeer P.; Day, Gregory S.; DIAN‐TU Study Team Introduction: Monoclonal anti-amyloid therapies are now accessible, but how these treatments influence changes within the brain is still not clear. We investigated overall and regional change in amyloid removal, glucose metabolism, and atrophy in trial participants with dominantly inherited Alzheimer's disease (DIAD). Methods: In the DIAN-TU-001 trial, 92 carriers received gantenerumab or placebo and underwent serial neuroimaging assessments including [11C]-Pittsburgh compound-B (PiB) positron emission tomography (PET), [18F]-fluoro-2-deoxyglucose (FDG) PET, and magnetic resonance imaging (MRI). Results: Gantenerumab significantly reduced PiB-PET uptake overall and in most regions and showed no changes in FDG-PET or MRI measures. Drug effects were associated with baseline PiB-PET uptake, and the largest effects occurred in medial regions. Discussion: Treated DIAD participants, and especially those with higher amyloid burden, showed a decrease in PiB-PET uptake, which was more pronounced in the basal ganglia and medial frontal structures. These results may inform patient response and future drug trial design. Highlights: Gantenerumab unevenly decreased Aβ burden as measured by PiB-PET across brain regions. The strongest decrease in PiB-PET uptake was in basal ganglia and medial frontal structures. Variable drug effect on Aβ was partly due to the amount of burden present before treatment. There was no regional effect on FDG-PET metabolism or MRI volumetrics after 4 years.

Advances in migraine prevention

2026-03-01T00:00:00Z

Advances in migraine prevention Martinelli, Daniele; De Icco, Roberto; Al-Khazali, Haidar M.; Ashina, Sait; Diener, Hans-Christoph; Dodd-Glover, Freda; Goicochea, María Teresa; Jenkins, Bronwyn; MaassenVanDenBrink, Antoinette; Lee, Mi Ji; Özge, Aynur; Prieto Peres, Mario Fernando; Pozo Rosich, Patricia; Puledda, Francesca; Sacco, Simona; Schwedt, Todd J.; Terwindt, Gisela M.; Tassorelli, Cristina Migraine imposes a heavy burden on patients and societies. Preventive treatments aimed at reducing the occurrence of migraine attacks and their intensity have been largely underused, leaving a multitude of people with migraine to rely exclusively on acute treatments, which, when used in excess, might even worsen the clinical situation. Large, randomised trials have established the tolerability and efficacy of calcitonin gene-related peptide (CGRP)-targeting drugs, a new class of migraine-specific treatment. The increased adherence to longer treatment cycles with migraine-specific preventive drugs, such as CGRP-targeting therapies, compared with non-migraine specific treatments has the potential to improve control of the disease. These migraine-specific drugs also provide benefits to individuals with migraine who previously did not benefit from non-specific migraine preventive medications. Increased reliance on preventive treatment with migraine-specific options is progressively optimising the management of migraine for mounting numbers of patients disabled by the disease, thereby improving disease control and their quality of life.

Systematic review of movement disorders mislabeled as functional : when incongruence misleads

2026-04-08T00:00:00Z

Systematic review of movement disorders mislabeled as functional : when incongruence misleads Marín-Medina, Daniel S.; Miño Zambrano, Joselyn; Espay, Alberto J.; Merello, Marcelo Background: Misdiagnosis of functional movement disorders (FMD) remains a concern for clinicians. We sought to review the phenomenology and clinical features associated with FMD misdiagnosis. Methods: We conducted a systematic review of case reports, case series, and observational studies of adults diagnosed with FMD and subsequently reclassified as having another neurological or medical condition. PubMed was searched from inception to September 13, 2025, focusing on reported features of inconsistency, incongruence with known diseases, and low-validity features. Isolated (iMD) and mixed (mMD) movement disorders were analyzed separately. Results: Forty-two included studies comprised 150 patients, of which 73 cases underwent detailed analysis. Gait disturbance (35%) and dystonia (27.5%) were the most common iMD phenomenologies (n = 40), while jerks and rigidity (24%) were the most common mMD phenomenology (n = 33). Incongruence with known diseases (50.7%), psychological factors (34.2%), and symptom variability (31.5%) were the main factors associated with misdiagnosis. Application of incongruence alone was associated with the highest rate of FMD misdiagnosis, similar to that of applying neither incongruence nor inconsistency (49% in both cases). Conversely, reliance on inconsistency alone was least associated with an FMD misdiagnosis (13.7%). Misdiagnoses of iMD were more likely in the absence of documented inconsistency (OR 3.94, 95% CI 1.32-12.82). Conclusions: FMD misdiagnoses, particularly of gait disorders and dystonia, were most commonly associated with the application of incongruence as diagnostic criterion. The lowest rate of FMD misdiagnosis was associated with ascertaining at least two positive neurological signs of inconsistency.