Citations 2
Sex differences in neuromodulatory subcortical systems and their implications for Alzheimer's disease
Rae, Rosaria J., Alberhasky, Jessica Marie Hunter, Bangasser, Debra A. , Berteotti, Chiara, Bow, Hannah, Caldwell, Jessica Z. K., Carpi, Matteo , Ciampa, Claire J., Ehrenberg, Alexander J. , Fenlon, Haley A., Fitzhugh, Megan C. , Gallay, Clara , Hamilton, Derek A. , Hasan, Zia , Huarte, Oihane Uriarte , Jabeen, Shaista , Kolling, Louis John , Liguori, Claudio , Omoluabi, Tamunotonye, Pa, Judy, Pentkowski, Nathan S. , Pereira, Joana B., Ramos, Rhudovic R., Sargin, Derya , Seto, Mabel, Shaik, Shabana M. , Ucheagwu, Valentine , Kelberman, Michael A. , Grinberg, Lea Tenenholz, Satpati, Abhijit, Son, Gowoon, Rae, Rosaria Josephine, Baillet, Marion , Belloy, Michaël E. , Berry, Anne S. , Berteotti, Chiara , Bow, Hannah, Buckley, Rachel F. , Caldwell, Jessica K. , Clark, Benjamin J. , Conley, Alexander C. , Dahl, Martin J. , Donaldson, Zoe R. , Einstein, Gillian , Falgàs, Neus , Froemke, Robert C. , Grinberg, Lea T. , Jacobs, Heidi I.L. , Koops, Elouise A. , Lenzoni, Sabrina , Manca, Riccardo , Marcinkiewcz, Catherine Anne , Omoluabi, Tamunotonye, Oria, Rademene Sunday , Orsini, Caitlin A. , Ortega, Nancy Elizabeth , Pa, Judy , Pereira, Joana B. , Satpati, Abhijit , Sellés, María Clara , Seto, Mabel , Sindi, Shireen , Son, Gowoon , Egroo, Maxime Van , Yuan, Qi
Alzheimer's & Dementia | March 19, 2026 | Volume: 22 | Issue: 3 | Pages: No page available
Abstract Neuromodulatory subcortical systems (NSSs) are uniquely susceptible to dementia‐related pathology, leading to frequent molecular and behavioral impairments associated with altered function of these nuclei. Some of these systems display clear sex‐specific cytoarchitecture and signaling leading to distinct physiology and behavioral outputs in males and females, while other regions display nominal sex differences. However, the relevance of sex differences in modulating dysfunction of NSSs in Alzheimer's disease (AD) and related dementias is not well understood. This review is a joint effort by the Neuromodulatory Subcortical Systems and Sex and Gender Differences in Alzheimer's Disease Professional Interest Areas of the Alzheimer's Association. We review sex differences in NSSs, both in non‐disease states and in AD models and patients. We highlight the possible role of NSSs in driving sex‐specific AD susceptibility and potential footholds for sex‐based interventions targeting these systems. We conclude by outlining immediate and long‐term actions to address the intersection of NSSs, sex, and AD.
Presynaptic Dopaminergic Imaging Characterizes Patients with REM Sleep Behavior Disorder Due to Synucleinopathy
Arnaldi, Dario , Mattioli, Pietro , Raffa, Stefano, Pardini, Matteo , Massa, Federico , Iranzo, Álex , Perissinotti, Andrés , Gaig, Carles , Serradell, Mónica , Muñoz‐Lopetegi, Amaia , Mayà, Gerard , Liguori, Claudio , Fernandes, Mariana , Miyagawa, Toji , Lowe, Val J. , Puligheddu, Monica , Serra, Alessandra , Hu, Michele T., Klein, Johannes , Bes, Frédérik , Kunz, Dieter , Verbizier, Delphine de, Kulcsárová, Kristína , Giuliani, Alessandro , Pagani, Marco , Group, International REM Sleep Behavior Disorder Study, Liguori, Claudio , Miyamoto, Tomoyuki , Kunz, Dieter , Antelmi, Elena , Terzaghi, Michele , Massa, Federico , Maya, Gerard , Puligheddu, Monica , Kulcsarova, Kristina , Mattioli, Pietro , Arnaldi, Dario , Niñerola‐Baizán, Aida , Gaig, Carles , Placidi, Fabio , Chiaravalloti, Agostino , Šonka, Karel , Dušek, Petr , Zogala, David , Trnka, Jiří , Boeve, Bradley F. , Miyamoto, Tomoyuki , Miyamoto, Masayuki , Figorilli, Michela , Hu, Michele T., Cochen De Cock, Valérie , Plazzi, Giuseppe , Antelmi, Elena , Bossert, Irene , Martino, Alessio , Nobili, Flavio Mariano , Morbelli, Silvia , Group, International REM Sleep Behavior Disorder Study
Annals of Neurology | March 11, 2024 | Volume: 95 | Issue: 6 | Pages: 1178-1192
Objective To apply a machine learning analysis to clinical and presynaptic dopaminergic imaging data of patients with rapid eye movement (REM) sleep behavior disorder (RBD) to predict the development of Parkinson disease (PD) and dementia with Lewy bodies (DLB). Method s In this multicenter study of the International RBD study group, 173 patients (mean age 70.5 ± 6.3 years, 70.5% males) with polysomnography‐confirmed RBD who eventually phenoconverted to overt alpha‐synucleinopathy (RBD due to synucleinopathy) were enrolled, and underwent baseline presynaptic dopaminergic imaging and clinical assessment, including motor, cognitive, olfaction, and constipation evaluation. For comparison, 232 RBD non‐phenoconvertor patients (67.6 ± 7.1 years, 78.4% males) and 160 controls (68.2 ± 7.2 years, 53.1% males) were enrolled. Imaging and clinical features were analyzed by machine learning to determine predictors of phenoconversion. Results Machine learning analysis showed that clinical data alone poorly predicted phenoconversion. Presynaptic dopaminergic imaging significantly improved the prediction, especially in combination with clinical data, with 77% sensitivity and 85% specificity in differentiating RBD due to synucleinopathy from non phenoconverted RBD patients, and 85% sensitivity and 86% specificity in discriminating PD‐converters from DLB‐converters. Quantification of presynaptic dopaminergic imaging showed that an empirical z ‐score cutoff of −1.0 at the most affected hemisphere putamen characterized RBD due to synucleinopathy patients, while a cutoff of −1.0 at the most affected hemisphere putamen/caudate ratio characterized PD‐converters. Interpretation Clinical data alone poorly predicted phenoconversion in RBD due to synucleinopathy patients. Conversely, presynaptic dopaminergic imaging allows a good prediction of forthcoming phenoconversion diagnosis. This finding may be used in designing future disease‐modifying trials. ANN NEUROL 2024;95:1178–1192