Siguier Perrine Laury Marie, Planton Mélanie, Pages Bérengère, Gérard Fleur, Rafiq Marie, Wolfrum Marie, Archambault Ombeline, Damour Anise, Guidolin Valentine, Pefferkorn Pauline, Danet Lola, Virchien Laurine, Magnin Eloi, Richard-Mornas Aurélie, Sauvée Mathilde, Thomas-Antérion Catherine, Mouton Servane, Jucla Mélanie, Pariente Jérémie
ToNIC, Toulouse NeuroImaging Center, UMR 1214, Université de Toulouse, INSERM, Paul Sabatier University (UT3), Pavillon BAUDOT, TOULOUSE Cedex 3, France.
Laboratoire de Neuropsycholinguistique, EA4156, Université de Toulouse, Jean Jaurès University (UT2), Toulouse Cedex 9, France.
Eur J Neurol. 2025 Aug;32(8):e70322. doi: 10.1111/ene.70322.
Neurodevelopmental disorders (NDDs) may influence the course of Alzheimer's disease (AD) and frontotemporal dementia (FTD). However, prior studies have focused on specific pairs of NDDs and variants of AD/FTD. Adopting a dimensional approach to NDDs and considering the heterogeneity of AD/FTD, we investigated the association between a neurodevelopmental vulnerability (DV) and the clinical presentation and age at onset of AD/FTD.
We prospectively and consecutively recruited 84 AD/FTD participants and 41 matched controls. AD/FTD participants were classified into typical (amnestic AD, behavioral FTD) and atypical (primary progressive aphasia, frontal and posterior variants of AD, right temporal variant of FTD, amnestic FTD) presentations. Participants underwent a neuropsychological assessment and answered a novel questionnaire on NDDs symptoms. Using k-means clustering based on the questionnaire, participants were assigned to a DV+ (with neurodevelopmental vulnerability) or a DV- (without) cluster. This data-driven approach enabled an unbiased classification of individuals with a DV, beyond traditional diagnostic labels.
DV frequencies did not differ between the AD/FTD (18%) and control (15%) χ = 0.205; p = 0.651); and between typical (21%) and atypical (11%) subgroups (Fisher's test, p = 0.184). However, in DV+ patients, symptom onset occurred 8.0 years earlier than in DV- patients (95% CI [-14, -3.0]; p = 0.005), with a median onset age of 58 years (IQR: 15).
A DV could favor early-onset AD/FTD, but may not affect susceptibility to typical and atypical variants of AD/FTD. The underlying neurophysiological processes involved require future investigation, with implications for precision medicine and individualized treatment strategies.
RnIPH 2023-71 and Research Ethics Committee file No. 2023_765.
神经发育障碍（NDDs）可能会影响阿尔茨海默病（AD）和额颞叶痴呆（FTD）的病程。然而，先前的研究主要集中在特定的NDDs对以及AD/FTD的变体上。我们采用维度方法研究NDDs，并考虑到AD/FTD的异质性，调查了神经发育易损性（DV）与AD/FTD的临床表现及发病年龄之间的关联。
我们前瞻性且连续招募了84名AD/FTD参与者和41名匹配的对照者。AD/FTD参与者被分为典型（遗忘型AD、行为型FTD）和非典型（原发性进行性失语、AD的额叶和后叶变体、FTD的右颞叶变体、遗忘型FTD）表现类型。参与者接受了神经心理学评估，并回答了一份关于NDDs症状的新问卷。基于该问卷，使用k均值聚类将参与者分为DV+（有神经发育易损性）或DV-（无神经发育易损性）组。这种数据驱动的方法能够对有DV的个体进行无偏分类，超越了传统的诊断标签。
AD/FTD组（18%）和对照组（15%）的DV频率无差异（χ = 0.205；p = 0.651）；典型（21%）和非典型（11%）亚组之间也无差异（Fisher检验，p = 0.184）。然而，在DV+患者中，症状发作比DV-患者早8.0年（95%CI[-14，-3.0]；p = 0.005），中位发病年龄为58岁（IQR：15）。
DV可能有利于早发型AD/FTD，但可能不影响对AD/FTD典型和非典型变体的易感性。其中涉及的潜在神经生理过程需要未来进一步研究，这对精准医学和个体化治疗策略具有重要意义。
RnIPH 2023 - 71和研究伦理委员会文件编号2023_765。
