Katsumi Yuta, Touroutoglou Alexandra, Brickhouse Michael, Eloyan Ani, Eckbo Ryan, Zaitsev Alexander, La Joie Renaud, Lagarde Julien, Schonhaut Daniel, Thangarajah Maryanne, Taurone Alexander, Vemuri Prashanthi, Jack Clifford R, Dage Jeffrey L, Nudelman Kelly N H, Foroud Tatiana, Hammers Dustin B, Ghetti Bernardino, Murray Melissa E, Newell Kathy L, Polsinelli Angelina J, Aisen Paul, Reman Rema, Beckett Laurel, Kramer Joel H, Atri Alireza, Day Gregory S, Duara Ranjan, Graff-Radford Neill R, Grant Ian M, Honig Lawrence S, Johnson Erik C B, Jones David T, Masdeu Joseph C, Mendez Mario F, Musiek Erik, Onyike Chiadi U, Riddle Meghan, Rogalski Emily, Salloway Stephen, Sha Sharon, Turner R Scott, Wingo Thomas S, Wolk David A, Womack Kyle, Carrillo Maria C, Rabinovici Gil D, Apostolova Liana G, Dickerson Bradford C
Frontotemporal Disorders Unit and Massachusetts Alzheimer's Disease Research Center, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Department of Biostatistics, Center for Statistical Sciences, Brown University, Providence, Rhode Island, USA.
Alzheimers Dement. 2025 Feb;21(2):e14489. doi: 10.1002/alz.14489. Epub 2025 Feb 19.
Early-onset and late-onset Alzheimer's disease (EOAD and LOAD, respectively) have distinct clinical manifestations, with prior work based on small samples suggesting unique patterns of neurodegeneration. The current study performed a head-to-head comparison of cortical atrophy in EOAD and LOAD, using two large and well-characterized cohorts (LEADS and ADNI).
We analyzed brain structural magnetic resonance imaging (MRI) data acquired from 377 sporadic EOAD patients and 317 sporadicLOAD patients who were amyloid positive and had mild cognitive impairment (MCI) or mild dementia (i.e., early-stage AD), along with cognitively unimpaired participants.
After controlling for the level of cognitive impairment, we found a double dissociation between AD clinical phenotype and localization/magnitude of atrophy, characterized by predominant neocortical involvement in EOAD and more focal anterior medial temporal involvement in LOAD.
Our findings point to the clinical utility of MRI-based biomarkers of atrophy in differentiating between EOAD and LOAD, which may be useful for diagnosis, prognostication, and treatment.
Early-onset Alzheimer's disease (EOAD) and late-onset AD (LOAD) patients showed distinct and overlapping cortical atrophy patterns. EOAD patients showed prominent atrophy in widespread neocortical regions. LOAD patients showed prominent atrophy in the anterior medial temporal lobe. Regional atrophy was correlated with the severity of global cognitive impairment. Results were comparable when the sample was stratified for mild cognitive impairment (MCI) and dementia.
早发型和晚发型阿尔茨海默病（分别为EOAD和LOAD）具有不同的临床表现，先前基于小样本的研究表明存在独特的神经退行性变模式。本研究使用两个大型且特征明确的队列（LEADS和ADNI），对EOAD和LOAD的皮质萎缩进行了直接比较。
我们分析了从377例散发性EOAD患者和317例散发性LOAD患者获取的脑结构磁共振成像（MRI）数据，这些患者淀粉样蛋白呈阳性，有轻度认知障碍（MCI）或轻度痴呆（即早期AD），以及认知未受损的参与者。
在控制认知障碍水平后，我们发现AD临床表型与萎缩的定位/程度之间存在双重分离，其特征为EOAD主要累及新皮质，而LOAD更多累及前内侧颞叶。
我们的研究结果指出基于MRI的萎缩生物标志物在区分EOAD和LOAD方面的临床效用，这可能对诊断、预后和治疗有用。
早发型阿尔茨海默病（EOAD）和晚发型AD（LOAD）患者表现出不同且重叠的皮质萎缩模式。EOAD患者在广泛的新皮质区域出现明显萎缩。LOAD患者在前内侧颞叶出现明显萎缩。区域萎缩与整体认知障碍的严重程度相关。当样本按轻度认知障碍（MCI）和痴呆分层时，结果具有可比性。
