Unidad de Trastornos del Movimiento, Servicio de Neurología y Neurofisiología Clínica, Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, 41013 Sevilla, Spain.
Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), 28029 Madrid, Spain.
Brain. 2023 Nov 2;146(11):4520-4531. doi: 10.1093/brain/awad194.
A clinical diagnosis of Alzheimer's disease dementia (ADD) encompasses considerable pathological and clinical heterogeneity. While Alzheimer's disease patients typically show a characteristic temporo-parietal pattern of glucose hypometabolism on 18F-fluorodeoxyglucose (FDG)-PET imaging, previous studies have identified a subset of patients showing a distinct posterior-occipital hypometabolism pattern associated with Lewy body pathology. Here, we aimed to improve the understanding of the clinical relevance of these posterior-occipital FDG-PET patterns in patients with Alzheimer's disease-like amnestic presentations. Our study included 1214 patients with clinical diagnoses of ADD (n = 305) or amnestic mild cognitive impairment (aMCI, n = 909) from the Alzheimer's Disease Neuroimaging Initiative, who had FDG-PET scans available. Individual FDG-PET scans were classified as being suggestive of Alzheimer's (AD-like) or Lewy body (LB-like) pathology by using a logistic regression classifier trained on a separate set of patients with autopsy-confirmed Alzheimer's disease or Lewy body pathology. AD- and LB-like subgroups were compared on amyloid-β and tau-PET, domain-specific cognitive profiles (memory versus executive function performance), as well as the presence of hallucinations and their evolution over follow-up (≈6 years for aMCI, ≈3 years for ADD). Around 12% of the aMCI and ADD patients were classified as LB-like. For both aMCI and ADD patients, the LB-like group showed significantly lower regional tau-PET burden than the AD-like subgroup, but amyloid-β load was only significantly lower in the aMCI LB-like subgroup. LB- and AD-like subgroups did not significantly differ in global cognition (aMCI: d = 0.15, P = 0.16; ADD: d = 0.02, P = 0.90), but LB-like patients exhibited a more dysexecutive cognitive profile relative to the memory deficit (aMCI: d = 0.35, P = 0.01; ADD: d = 0.85 P < 0.001), and had a significantly higher risk of developing hallucinations over follow-up [aMCI: hazard ratio = 1.8, 95% confidence interval = (1.29, 3.04), P = 0.02; ADD: hazard ratio = 2.2, 95% confidence interval = (1.53, 4.06) P = 0.01]. In summary, a sizeable group of clinically diagnosed ADD and aMCI patients exhibit posterior-occipital FDG-PET patterns typically associated with Lewy body pathology, and these also show less abnormal Alzheimer's disease biomarkers as well as specific clinical features typically associated with dementia with Lewy bodies.
临床诊断为阿尔茨海默病痴呆症（ADD）包括相当大的病理和临床异质性。虽然阿尔茨海默病患者通常在 18F-氟脱氧葡萄糖（FDG）-正电子发射断层扫描（PET）成像上表现出特征性的颞顶叶葡萄糖代谢低下，但先前的研究已经确定了一部分患者表现出与路易体病理学相关的独特的后枕叶代谢低下模式。在这里，我们旨在提高对阿尔茨海默病样遗忘表现患者中这些后枕叶 FDG-PET 模式的临床相关性的理解。我们的研究包括来自阿尔茨海默病神经影像学倡议的 1214 名临床诊断为 ADD（n=305）或遗忘型轻度认知障碍（aMCI，n=909）的患者，他们有 FDG-PET 扫描可供使用。使用基于尸检证实的阿尔茨海默病或路易体病理学的患者的独立 FDG-PET 扫描通过使用逻辑回归分类器进行分类，这些扫描被分类为提示阿尔茨海默病（AD 样）或路易体（LB 样）病理学。AD 和 LB 样亚组在淀粉样蛋白-β和 tau-PET、特定于域的认知特征（记忆与执行功能表现）以及幻觉的存在及其随时间的演变（aMCI 约 6 年，ADD 约 3 年）方面进行了比较。约 12%的 aMCI 和 ADD 患者被归类为 LB 样。对于 aMCI 和 ADD 患者，LB 样组的区域 tau-PET 负担明显低于 AD 样亚组，但仅在 aMCI LB 样亚组中淀粉样蛋白-β负荷明显降低。LB 和 AD 样亚组在全球认知方面没有显著差异（aMCI：d=0.15，P=0.16；ADD：d=0.02，P=0.90），但 LB 样患者的认知表现比记忆缺陷更失调（aMCI：d=0.35，P=0.01；ADD：d=0.85，P<0.001），并且在随访期间出现幻觉的风险显著增加[aMCI：风险比=1.8，95%置信区间=（1.29，3.04），P=0.02；ADD：风险比=2.2，95%置信区间=（1.53，4.06），P=0.01]。总之，相当一部分临床诊断为 ADD 和 aMCI 的患者表现出与路易体病理学相关的后枕叶 FDG-PET 模式，这些患者也表现出较少的异常阿尔茨海默病生物标志物以及与路易体痴呆症相关的特定临床特征。
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