Single-value scores reflecting the deviation from (FADE score) or similarity with (SAME score) prototypical novelty-related and memory-related functional magnetic resonance imaging (fMRI) activation patterns in young adults have been proposed as imaging biomarkers of healthy neurocognitive aging. Here, we tested the utility of these scores as potential diagnostic and prognostic markers in Alzheimer’s disease (AD) and risk states like mild cognitive impairment (MCI) or subjective cognitive decline (SCD). To this end, we analyzed subsequent memory fMRI data from individuals with SCD, MCI, and AD dementia as well as healthy controls (HC) and first-degree relatives of AD dementia patients (AD-rel) who participated in the multi-center DELCODE study (N = 468). Based on the individual participants’ whole-brain fMRI novelty and subsequent memory responses, we calculated the FADE and SAME scores and assessed their association with AD risk stage, neuropsychological test scores, CSF amyloid positivity, and ApoE genotype. Memory-based FADE and SAME scores showed a considerably larger deviation from a reference sample of young adults in the MCI and AD dementia groups compared to HC, SCD and AD-rel. In addition, novelty-based scores significantly differed between the MCI and AD dementia groups. Across the entire sample, single-value scores correlated with neuropsychological test performance. The novelty-based SAME score further differed between Aβ-positive and Aβ-negative individuals in SCD and AD-rel, and between ApoE ε4 carriers and non-carriers in AD-rel. Hence, FADE and SAME scores are associated with both cognitive performance and individual risk factors for AD. Their potential utility as diagnostic and prognostic biomarkers warrants further exploration, particularly in individuals with SCD and healthy relatives of AD dementia patients.

中文翻译：

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单值大脑活动评分反映了阿尔茨海默病连续体的严重程度和风险

反映年轻人典型新颖性相关和记忆相关功能磁共振成像（fMRI）激活模式的偏差（FADE评分）或相似性的单值评分已被提议作为健康神经认知衰老的成像生物标志物。在这里，我们测试了这些评分作为阿尔茨海默病 (AD) 和轻度认知障碍 (MCI) 或主观认知衰退 (SCD) 等风险状态的潜在诊断和预后标志物的实用性。为此，我们分析了参加多中心 DELCODE 的 SCD、MCI 和 AD 痴呆患者以及健康对照 (HC) 和 AD 痴呆患者的一级亲属 (AD-rel) 的后续记忆 fMRI 数据研究（N = 468）。根据个体参与者的全脑功能磁共振成像新颖性和随后的记忆反应，我们计算了 FADE 和 SAME 评分，并评估了它们与 AD 风险阶段、神经心理学测试评分、脑脊液淀粉样蛋白阳性和 ApoE 基因型的关联。与 HC、SCD 和 AD-rel 相比，基于记忆的 FADE 和 SAME 评分显示，MCI 和 AD 痴呆组中的年轻人与参考样本的偏差相当大。此外，MCI 和 AD 痴呆组之间基于新颖性的评分存在显着差异。在整个样本中，单值分数与神经心理学测试表现相关。基于新颖性的 SAME 评分在 SCD 和 AD-rel 中的 Aβ 阳性和 Aβ 阴性个体之间以及 AD-rel 中 ApoE ε4 携带者和非携带者之间也存在差异。因此，FADE 和 SAME 分数与 AD 的认知表现和个体风险因素相关。它们作为诊断和预后生物标志物的潜在用途值得进一步探索，特别是在 SCD 患者和 AD 痴呆患者的健康亲属中。