José Enrique Arriola-Infante MD, Alejandra O. Morcillo-Nieto MSc, Sara E. Zsadanyi MSc, María Franquesa-Mullerat Msc, Lídia Vaqué-Alcázar PhD, Mateus Rozalem-Aranha MD, PhD, Javier Arranz MD, Íñigo Rodríguez-Baz MD, PhD, Lucia Maure-Blesa MD, Laura Videla PhD, Isabel Barroeta MD, PhD, Laura Del Hoyo Soriano PhD, Bessy Benejam PhD, Susana Fernández MD, Aida Sanjuan-Hernández BSc, Sandra Giménez MD, PhD, Daniel Alcolea MD, PhD, Olivia Belbin PhD, Albert Flotats MD, PhD, Valle Camacho MD, PhD, Alberto Lleó MD, PhD, María Carmona-Iragui MD, PhD, Juan Fortea MD, PhD, Alexandre Bejanin PhD
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引用次数: 0
Abstract
Objective
The goal was to examine the effect of sociodemographic variables, Alzheimer's disease (AD) clinical stages and pathology on brain metabolism in Down syndrome (DS).
Methods
We included 71 euploid healthy controls (HC) and 105 adults with DS (67 asymptomatic, 12 prodromal, and 26 with dementia) from the Down-Alzheimer Barcelona Neuroimaging Initiative. Participants underwent [18F]fluorodeoxyglucose positron emission tomography, 3 Tmagnetic resonance imaging, and lumbar puncture to measure cerebrospinal fluid (CSF) biomarkers (ratio beween amyloid β peptide 42 and 40, phosphorylated tau 181, and neurofilament light chain [NfL]). Voxel-wise analyses in SPM12 examined the effects of age, sex, intellectual disability, Alzheimer's clinical stage, and CSF biomarkers on brain metabolism.
Results
In HC, brain metabolism decreased with age primarily in the frontal lobe. By contrast, a more distributed pattern of metabolic loss was observed in DS with age, predominating in temporoparietal regions. Compared to asymptomatic DS participants, those at the prodromal stage exhibited medial parietal hypometabolism, which later extended to other temporoparietal and frontal regions at the dementia stage. In asymptomatic individuals, we observed a widespread hypometabolism compared to HC, mainly in medial frontal and parietal regions. All CSF biomarkers were closely associated with hypometabolism in regions affected by the disease, with the strongest association observed for NfL in medial parietal structures.
Interpretation
The brain metabolic decline in DS with age reflects Alzheimer's pathological processes and involves temporoparietal regions in a similar pattern to that found in other forms of AD. Hypometabolism is more tightly related to CSF NfL levels than to core AD biomarkers. ANN NEUROL 2025;98:163–173
期刊介绍:
Annals of Neurology publishes original articles with potential for high impact in understanding the pathogenesis, clinical and laboratory features, diagnosis, treatment, outcomes and science underlying diseases of the human nervous system. Articles should ideally be of broad interest to the academic neurological community rather than solely to subspecialists in a particular field. Studies involving experimental model system, including those in cell and organ cultures and animals, of direct translational relevance to the understanding of neurological disease are also encouraged.