Basal forebrain atrophy along the Alzheimer's disease continuum in adults with Down syndrome
Mateus Rozalem Aranha, M. Florencia Iulita, Víctor Montal, Jordi Pegueroles, Alexandre Bejanin, Lídia Vaqué‐Alcázar, Michel J. Grothe, María Carmona‐Iragui, Laura Videla, Bessy Benejam, Javier Arranz, Concepción Padilla, Sílvia Valldeneu, Isabel Barroeta, Miren Altuna, Susana Fernández, Laia Ribas, Natalia Valle‐Tamayo, Daniel Alcolea, Sofía González‐Ortiz, Núria Bargalló, Henrik Zetterberg, Kaj Blennow, Rafael Blesa, Thomas Wısnıewskı, Jorge Busciglio, A. Claudio Cuello, Alberto Lleó, Juan Fortea
Abstract
BACKGROUND: Basal forebrain (BF) degeneration occurs in Down syndrome (DS)-associated Alzheimer's disease (AD). However, the dynamics of BF atrophy with age and disease progression, its impact on cognition, and its relationship with AD biomarkers have not been studied in DS. METHODS: We included 234 adults with DS (150 asymptomatic, 38 prodromal AD, and 46 AD dementia) and 147 euploid controls. BF volumes were extracted from T-weighted magnetic resonance images using a stereotactic atlas in SPM12. We assessed BF volume changes with age and along the clinical AD continuum and their relationship to cognitive performance, cerebrospinal fluid (CSF) and plasma amyloid/tau/neurodegeneration biomarkers, and hippocampal volume. RESULTS: In DS, BF volumes decreased with age and along the clinical AD continuum and significantly correlated with amyloid, tau, and neurofilament light chain changes in CSF and plasma, hippocampal volume, and cognitive performance. DISCUSSION: BF atrophy is a potentially valuable neuroimaging biomarker of AD-related cholinergic neurodegeneration in DS.