To determine the relevance of minor neuropsychological deficits (MNPD) in patients with subjective cognitive decline (SCD) with regard to CSF levels of Alzheimer disease (AD) biomarkers, cognitive decline, and clinical progression to mild cognitive impairment (MCI).

This study included patients with clinical SCD and SCD-free, healthy control (HC) participants with available baseline CSF and/or longitudinal cognitive data from the observational DZNE Longitudinal Cognitive Impairment and Dementia study. We defined MNPD as a performance of at least 0.5SD below the mean on a demographically adjusted total score derived from the Consortium to Establish a Registry for Alzheimer's Disease neuropsychological assessment battery. We compared SCD patients with MNPD and those without MNPD with regard to CSF amyloid-β (Aβ)42/Aβ40, phosphorylated tau (p-tau₁₈₁)_, total tau and Aβ42/p-tau₁₈₁ levels, longitudinal cognitive composite trajectories, and risk of clinical progression to incident MCI (follow-up M ± SD: 40.6 ± 23.7 months). In addition, we explored group differences between SCD and HC in those without MNPD.

In our sample (N = 672, mean age: 70.7 ± 5.9 years, 50% female), SCD patients with MNPD (n = 55, 12.5% of SCD group) showed significantly more abnormal CSF biomarker levels, increased cognitive decline, and a higher risk of progression to incident MCI (HR: 4.07, 95% CI 2.46–6.74) compared with SCD patients without MNPD (n = 384). MNPD had a positive predictive value of 57.0% (95% CI 38.5–75.4) and a negative predictive value of 86.0% (95% CI 81.9–90.1) for the progression of SCD to MCI within 3 years. SCD patients without MNPD showed increased cognitive decline and a higher risk of incident MCI compared with HC participants without MNPD (n = 215; HR: 4.09, 95% CI 2.07–8.09), while AD biomarker levels did not differ significantly between these groups.

Our results suggest that MNPD are a risk factor for AD-related clinical progression in cognitively normal patients seeking medical counseling because of SCD. As such, the assessment of MNPD could be useful for individual clinical prediction and for AD risk stratification in clinical trials. However, SCD remains a risk factor for future cognitive decline even in the absence of MNPD.

旨在确定主观认知衰退 (SCD) 患者的轻微神经心理缺陷 (MNPD) 与阿尔茨海默病 (AD) 生物标志物脑脊液水平、认知衰退和轻度认知障碍 (MCI) 临床进展的相关性。

这项研究包括患有临床 SCD 的患者和无 SCD 的健康对照 (HC) 参与者，这些参与者具有来自观察性DZNE 纵向认知障碍和痴呆研究的可用基线 CSF 和/或纵向认知数据。我们将 MNPD 定义为，根据建立阿尔茨海默氏病神经心理学评估组注册表的联盟得出的人口统计调整总分，其表现至少低于平均值 0.5SD 。我们比较了患有 MNPD 的 SCD 患者和不患有 MNPD 的患者的脑脊液淀粉样蛋白-β (Aβ)42/Aβ40、磷酸化 tau (p-tau 181 )、总 tau_和Aβ42 _/ p-tau ₁₈₁水平、纵向认知复合轨迹以及临床进展至 MCI 事件的风险（随访M ± SD：40.6 ± 23.7 个月）。此外，我们还探讨了无 MNPD 患者中 SCD 和 HC 之间的组间差异。

在我们的样本中（N = 672，平均年龄：70.7 ± 5.9 岁，50% 女性），患有 MNPD 的 SCD 患者（n = 55，SCD 组的 12.5%）表现出明显更异常的 CSF 生物标志物水平、认知能力下降加剧以及认知能力下降。与无 MNPD 的 SCD 患者 (n = 384) 相比，进展为 MCI 的风险更高（HR：4.07，95% CI 2.46–6.74）。MNPD 对于 3 年内 SCD 进展为 MCI 的阳性预测值为 57.0%（95% CI 38.5-75.4），阴性预测值为 86.0%（95% CI 81.9-90.1）。与没有 MNPD 的 HC 参与者相比，没有 MNPD 的 SCD 患者认知能力下降加剧，发生 MCI 的风险更高（n = 215；HR：4.09，95% CI 2.07–8.09），而 AD 生物标志物水平在这些组之间没有显着差异。

我们的结果表明，对于因 SCD 寻求医疗咨询的认知正常患者，MNPD 是 AD 相关临床进展的危险因素。因此，MNPD 的评估可用于个体临床预测和临床试验中的 AD 风险分层。然而，即使没有 MNPD，SCD 仍然是未来认知能力下降的危险因素。