Department of Radiology and Nuclear Medicine, Amsterdam UMC - location VUmc, Amsterdam, The Netherlands.
Amsterdam Neuroscience, Brain Imaging, Amsterdam, The Netherlands.
Alzheimers Res Ther. 2023 Nov 27;15(1):207. doi: 10.1186/s13195-023-01351-1.
Previous studies demonstrated increases in diagnostic confidence and change in patient management after amyloid-PET. However, studies investigating longitudinal outcomes over an extended period of time are limited. Therefore, we aimed to investigate clinical outcomes up to 9 years after amyloid-PET to support the clinical validity of the imaging technique.
We analyzed longitudinal data from 200 patients (M = 61.8, 45.5% female, M = 23.3) suspected of early-onset dementia that underwent [F]flutemetamol-PET. Baseline amyloid status was determined through visual read (VR). Information on mortality was available with a mean follow-up of 6.7 years (range = 1.1-9.3). In a subset of 108 patients, longitudinal cognitive scores and clinical etiological diagnosis (eDx) at least 1 year after amyloid-PET acquisition were available (M = 3.06 years, range = 1.00-7.02). VR - and VR + patients were compared on mortality rates with Cox Hazard's model, prevalence of stable eDx using chi-square test, and longitudinal cognition with linear mixed models. Neuropathological data was available for 4 patients (mean delay = 3.59 ± 1.82 years, range = 1.2-6.3).
At baseline, 184 (92.0%) patients were considered to have dementia. The majority of VR + patients had a primary etiological diagnosis of AD (122/128, 95.3%), while the VR - group consisted mostly of non-AD etiologies, most commonly frontotemporal lobar degeneration (30/72, 40.2%). Overall mortality rate was 48.5% and did not differ between VR - and VR + patients. eDx at follow-up was consistent with baseline diagnosis for 92/108 (85.2%) patients, with most changes observed in VR - cases (VR - = 14/35, 40% vs VR + = 2/73, 2.7%, χ = 26.03, p < 0.001), who at no time received an AD diagnosis. VR + patients declined faster than VR - patients based on MMSE (β = - 1.17, p = 0.004), episodic memory (β = - 0.78, p = 0.003), fluency (β = - 1.44, p < 0.001), and attention scores (β = 16.76, p = 0.03). Amyloid-PET assessment was in line with post-mortem confirmation in all cases; two cases were VR + and showed widespread AD pathology, while the other two cases were VR - and showed limited amyloid pathology.
In a symptomatic population, we observed that amyloid-status did not impact mortality rates, but is predictive of cognitive functioning over time across several domains. Also, we show particular validity for a negative amyloid-PET assessment, as these patients did not receive an AD diagnosis at follow-up.
先前的研究表明，淀粉样蛋白-PET 后诊断信心增加和患者管理改变。然而，研究调查延长时间内的纵向结果的研究有限。因此，我们旨在研究淀粉样蛋白-PET 后长达 9 年的临床结果，以支持该成像技术的临床有效性。
我们分析了 200 名疑似早发性痴呆的患者（M=61.8，45.5%为女性，M=23.3）的纵向数据，这些患者接受了[F]flutemetamol-PET 检查。基线淀粉样蛋白状态通过视觉读片（VR）确定。平均随访 6.7 年后获得了死亡率信息（范围 1.1-9.3）。在 108 名患者的亚组中，获得了至少在淀粉样蛋白-PET 采集后 1 年的纵向认知评分和临床病因诊断（eDx）（M=3.06，范围 1.00-7.02）。使用 Cox 危害模型比较 VR+和 VR-患者的死亡率，使用卡方检验比较稳定的 eDx 的患病率，使用线性混合模型比较纵向认知。4 名患者（平均延迟 3.59±1.82 年，范围 1.2-6.3）有神经病理学数据。
基线时，184 名（92.0%）患者被认为患有痴呆症。大多数 VR+患者的主要病因诊断为 AD（122/128，95.3%），而 VR-组主要为非 AD 病因，最常见的是额颞叶变性（30/72，40.2%）。总体死亡率为 48.5%，VR-和 VR+患者之间无差异。随访时的 eDx 与基线诊断一致的有 108 名患者中的 92 名（85.2%），最明显的变化发生在 VR-病例中（VR-=14/35，40%与 VR+=2/73，2.7%，χ2=26.03，p<0.001），这些患者从未被诊断为 AD。基于 MMSE（β=−1.17，p=0.004）、情景记忆（β=−0.78，p=0.003）、流畅性（β=−1.44，p<0.001）和注意力评分（β=16.76，p=0.03），VR+患者的下降速度快于 VR-患者。淀粉样蛋白-PET 评估与死后证实完全一致；两例为 VR+，显示广泛的 AD 病理学，而另外两例为 VR-，显示有限的淀粉样蛋白病理学。
在有症状的人群中，我们观察到淀粉样蛋白状态并不影响死亡率，但可预测多个领域的认知功能随时间的变化。此外，我们还展示了阴性淀粉样蛋白-PET 评估的特殊有效性，因为这些患者在随访中未被诊断为 AD。
