From the German Center for Neurodegenerative Diseases (DZNE) (M.S., S.W., L.K., I.F., F.B., K.F., O.K., N.R.-K., A. Schneider, A. Spottke, I.R.V., F.J., M.W.), Bonn; Department of Neurodegenerative Diseases and Geriatric Psychiatry (M.S., S.W., L.K., I.F., K.F., A. Schneider, M.W.), University of Bonn Medical Center, Germany; German Center for Neurodegenerative Diseases (DZNE) (S.A., O.P., J.P., E.J.S.), Berlin; Department of Psychiatry and Psychotherapy (S.A., J.P., E.J.S.), Campus Charité Mitte, Charité-Universitätsmedizin Berlin, Germany; Department of Psychiatry and Psychotherapy (C.B., N.H., B.H.S., J.W.), University Medical Center Goettingen, University of Goettingen, Germany; German Center for Neurodegenerative Diseases (DZNE) (K.B., M.E., R.P.), Munich; Institute for Stroke and Dementia Research (ISD) (K.B., M.E., D.J.), University Hospital, LMU Munich; Department of Psychiatry and Psychotherapy (L.B., R.P., B.-S.R.), University Hospital, LMU Munich, Germany; German Center for Neurodegenerative Diseases (DZNE) (M.B., W.G., E.I.I., E.D.), Magdeburg; Department of Psychiatry and Psychotherapy (T.G., D. Gref, O.P., L.P.), Campus Benjamin Franklin, Charité-Universitätsmedizin Berlin, Germany; German Center for Neurodegenerative Diseases (DZNE) (D. Goerss, I.K., S.T.), Rostock; Department of Psychosomatic Medicine (D. Goerss, I.K., S.T.), Rostock University Medical Center, Germany; Luxembourg Center for Systems Biomedicine (LCSB) (M.T.H.), University of Luxembourg, Esch-sur-Alzette; German Center for Neurodegenerative Diseases (DZNE) (P.H., C.L., M.H.M., C.S.), Tübingen; Institute for Cognitive Neurology and Dementia Research (IKND) (E.I.I., E.D.), Otto-von-Guericke University, Magdeburg, Germany; Department for Psychiatry and Psychotherapy (E.I.I.), University Clinic Magdeburg, Germany; Section for Dementia Research (C.L.), Hertie Institute for Clinical Brain Research and Department of Psychiatry and Psychotherapy, University of Tübingen, Germany; Department of Psychiatry and Psychotherapy (M.H.M.), University of Tübingen, Germany; Munich Cluster for Systems Neurology (SyNergy) (R.P.), Germany; Ageing Epidemiology Research Unit (AGE) (R.P.), School of Public Health, Imperial College London, United Kingdom; Department of Psychiatry and Psychotherapy (J.P.), School of Medicine, Technical University of Munich, Germany; University of Edinburgh and UK DRI (J.P.), United Kingdom; Department of Neuroradiology (B.-S.R.), University Hospital, LMU Munich, Germany; Sheffield Institute for Translational Neuroscience (SITraN) (B.-S.R.), University of Sheffield, United Kingdom; Department of Psychiatry (A.R., F.J.), Medical Faculty, University of Cologne, Germany; German Center for Neurodegenerative Diseases (DZNE) (B.H.S., J.W.), Goettingen; Department of Neurology (A. Spottke), University of Bonn Medical Center, Germany; Neurosciences and Signaling Group (J.W.), Institute of Biomedicine (iBiMED), Department of Medical Sciences, University of Aveiro, Portugal; and Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD) (F.J.), University of Cologne, Germany.
Neurology. 2023 Nov 21;101(21):e2185-e2196. doi: 10.1212/WNL.0000000000207844. Epub 2023 Oct 11.
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 study. We defined MNPD as a performance of at least 0.5SD below the mean on a demographically adjusted total score derived from the 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-tau) total tau and Aβ42/p-tau levels, longitudinal cognitive composite trajectories, and risk of clinical progression to incident MCI (follow-up ± : 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.
为了确定主观认知衰退（SCD）患者的轻度神经认知缺陷（MNPD）与脑脊液阿尔茨海默病（AD）生物标志物、认知衰退和向轻度认知障碍（MCI）临床进展的相关性。
本研究纳入了来自观察性研究的具有临床 SCD 和 SCD 无认知衰退且健康对照（HC）参与者，这些参与者基线时具有脑脊液和/或纵向认知数据。我们将 MNPD 定义为在经过人口统计学调整的神经心理评估工具总分数中，表现至少低于平均水平 0.5 个标准差。我们比较了有 MNPD 和无 MNPD 的 SCD 患者与脑脊液 Aβ42/Aβ40、磷酸化 tau（p-tau）总 tau 和 Aβ42/p-tau 水平、纵向认知综合轨迹以及向新发 MCI （随访 ±：40.6 ± 23.7 个月）的临床进展风险。此外，我们还在无 MNPD 的 SCD 和 HC 参与者中探讨了组间差异。
在我们的样本中（N = 672，平均年龄：70.7 ± 5.9 岁，50%为女性），有 MNPD 的 SCD 患者（n = 55，占 SCD 组的 12.5%）显示出明显更多的异常 CSF 生物标志物水平、认知衰退增加以及向新发 MCI 进展的风险更高（HR：4.07，95%CI 2.46-6.74），与无 MNPD 的 SCD 患者（n = 384）相比。MNPD 对 SCD 在 3 年内进展为 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）。无 MNPD 的 SCD 患者与无 MNPD 的 HC 参与者（n = 215）相比，认知衰退增加且新发 MCI 的风险更高（HR：4.09，95%CI 2.07-8.09），而这些组之间的 AD 生物标志物水平无显著差异。
我们的研究结果表明，在因 SCD 而寻求医疗咨询的认知正常患者中，MNPD 是与 AD 相关临床进展的危险因素。因此，MNPD 的评估可能对个体临床预测和临床试验中的 AD 风险分层有用。然而，即使在没有 MNPD 的情况下，SCD 仍然是未来认知衰退的一个危险因素。
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