Regional Brain Metabolism across the Alzheimer's Disease Continuum in Down Syndrome

IF 8.1 1区医学 Q1 CLINICAL NEUROLOGY

Annals of Neurology Pub Date : 2025-03-14 DOI:10.1002/ana.27226

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

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唐氏综合症患者阿尔茨海默病连续体的区域脑代谢

目的：探讨社会人口学变量、阿尔茨海默病（AD）临床分期和病理对唐氏综合征（DS）脑代谢的影响。方法：我们纳入了71名整倍体健康对照（HC）和105名来自唐氏阿尔茨海默病巴塞罗那神经影像学倡议的成年DS患者（67名无症状，12名前驱，26名痴呆）。参与者接受了[18F]氟脱氧葡萄糖正电子发射断层扫描、3磁共振成像和腰椎穿刺来测量脑脊液（CSF）生物标志物（淀粉样蛋白β肽42和40的比值、磷酸化tau 181和神经丝轻链[NfL]）。SPM12的体素分析检查了年龄、性别、智力残疾、阿尔茨海默氏症临床阶段和脑脊液生物标志物对脑代谢的影响。结果：HC患者脑代谢随年龄的增长而下降，主要发生在额叶。相比之下，随着年龄的增长，在DS中观察到更分散的代谢损失模式，主要是在颞顶叶区域。与无症状的DS参与者相比，前驱期的参与者表现出内侧顶叶代谢低下，随后在痴呆期扩展到其他颞顶叶和额叶区域。在无症状个体中，与HC相比，我们观察到广泛的低代谢，主要在内侧额叶和顶叶区域。所有脑脊液生物标志物都与疾病影响区域的低代谢密切相关，其中在内侧顶叶结构中观察到的NfL相关性最强。解释：随着年龄的增长，退行性痴呆的脑代谢下降反映了阿尔茨海默病的病理过程，并以与其他形式的AD相似的模式涉及颞顶区域。与核心AD生物标志物相比，低代谢与CSF NfL水平的关系更为密切。Ann neurol 2025。

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来源期刊

Annals of Neurology 医学-临床神经学

CiteScore

18.00

自引率

1.80%

发文量

270

审稿时长

3-8 weeks

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.