Ferraro Pilar M, Filippi Laura, Ponzano Marta, Signori Alessio, Orso Beatrice, Massa Federico, Arnaldi Dario, Caneva Stefano, Argenti Lucia, Losa Mattia, Lombardo Lorenzo, Mattioli Pietro, Costagli Mauro, Gualco Lorenzo, Pulze Martina, Plantone Domenico, Brugnolo Andrea, Girtler Nicola, Diociasi Andrea, Garbarino Sara, Villani Flavio, Sormani Maria Pia, Uccelli Antonio, Roccatagliata Luca, Pardini Matteo
IRCCS Ospedale Policlinico San Martino, Genoa, Italy.
Department of Health Sciences (DISSAL), University of Genoa, Genoa, Italy.
J Alzheimers Dis. 2025 Jan;103(1):243-255. doi: 10.1177/13872877241299843. Epub 2024 Nov 25.
Magnetic resonance imaging (MRI) has recently enabled to identify four distinct Alzheimer's disease (AD) subtypes: hippocampal sparing (HpSp), typical AD (tAD), limbic predominant (Lp), and minimal atrophy (MinAtr). To date, however, the natural history of these subtypes, especially regarding the presence of subjects switching to other MRI patterns and their clinical and biological differences, remains poorly understood.
To investigate the clinical and biological underpinnings of longitudinal atrophy pattern progression in AD.
251 AD patients (16 with significant memory concern, 66 with early mild cognitive impairment (MCI), 125 with late MCI, and 44 with AD dementia) from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database were assigned to their baseline MRI atrophy subtype using Freesurfer-derived cortical:hippocampal volumes ratio. Switching to other MRI patterns was investigated on longitudinal scans, and patients were accordingly classified as "" and "". Logistic regression models were applied to identify predictors of switching to other MRI patterns.
40% of Lp, 26% of HpSp, and 35% of MinAtr cases switched to other MRI patterns, with tAD representing the destination subtype of all switching HpSp and Lp, and the majority of MinAtr. At baseline significant clinical, cognitive and biomarkers differences were observed across the four subtypes. Only clinical and cognitive variables, however, were significantly associated with switch to other MRI patterns.
Our results suggest convergent directions of disease progression across atypical and typical AD forms, at least in a subset of AD subjects, and highlight the importance of deep-phenotyping approaches to understand AD heterogeneity.
磁共振成像（MRI）最近已能够识别出四种不同的阿尔茨海默病（AD）亚型：海马保留型（HpSp）、典型AD（tAD）、边缘叶为主型（Lp）和轻度萎缩型（MinAtr）。然而，迄今为止，这些亚型的自然病程，尤其是关于出现转换为其他MRI模式的受试者情况及其临床和生物学差异，仍知之甚少。
研究AD纵向萎缩模式进展的临床和生物学基础。
来自阿尔茨海默病神经影像倡议（ADNI）数据库的251例AD患者（16例有明显记忆问题，66例有早期轻度认知障碍（MCI），125例有晚期MCI，44例有AD痴呆）使用基于Freesurfer得出的皮质：海马体积比被分配到其基线MRI萎缩亚型。在纵向扫描中研究转换为其他MRI模式的情况，并据此将患者分类为“”和“”。应用逻辑回归模型来识别转换为其他MRI模式的预测因素。
40%的Lp、26%的HpSp和35%的MinAtr病例转换为其他MRI模式，tAD是所有转换的HpSp和Lp以及大多数MinAtr的目标亚型。在基线时，观察到四种亚型之间存在显著的临床、认知和生物标志物差异。然而，只有临床和认知变量与转换为其他MRI模式显著相关。
我们的结果表明，至少在一部分AD受试者中，非典型和典型AD形式存在疾病进展的趋同方向，并强调了深度表型分析方法对于理解AD异质性的重要性。
