Department of Neurology, Nottingham University Hospitals NHS Trust, Nottingham, UK.
Mental Health and Clinical Neurosciences Academic Unit, University of Nottingham, Nottingham, UK.
J Alzheimers Dis. 2022;87(2):771-780. doi: 10.3233/JAD-215650.
The differentiation of a preclinical or prodromal Alzheimer's disease (AD) is challenging particularly in patients with early onset Alzheimer's or related dementias (EOARD). We report our experience on diagnostic lumbar puncture to diagnose EOARD at a tertiary neurocognitive referral center in Nottingham, England from March 2018 to October 2020.
To assess amyloid-β42 (Aβ42), total tau, and Thr181-phosphorylated tau (p-tau) measurements in the cerebrospinal fluid (CSF) in patients with mild cognitive impairment (MCI) and in relation to their follow-up cognitive performance.
Thirty participants aged 32-68 years old (mean 59 years; 57% female) were included. Clinical diagnosis was based on clinical presentation, neurocognitive profile, neuroradiological features (MRI, FDG-PET CT) and CSF Aβ42, total tau, and p-tau measurements.
Patients with MCI who progressed to AD (prodromal AD) had significantly higher CSF total (797.63 pg/ml) and p-tau (82.31 pg/ml), and lower Aβ42 levels (398.94 pg/ml) in comparison to their counterparts with stable MCI (total tau 303.67 pg/ml, p-tau 43.56 pg/ml, Aβ42 873.44 pg/ml) (p < 0.01 for CSF total and p-tau measures and p < 0.0001 for CSF Aβ42 measures). None of the CSF biomarkers correlated with any of the cognitive performance measures. Principal component analysis confirmed that the clinical diagnosis of MCI secondary to AD, namely prodromal AD (as per NIA-AA criteria) in younger adults, was associated with decreased CSF Aβ42.
In early onset AD, low levels of CSF Aβ42 appear to be more sensitive than total and p-tau measures in differentiating AD MCI from other forms of dementia. Further work on larger samples of EOARD in clinical practice will address the cost effectiveness of making an earlier diagnosis.
在临床前期或前驱期阿尔茨海默病（AD）的鉴别诊断极具挑战性，尤其是在早发性 AD 或相关痴呆（EOARD）患者中。我们报告了在英国诺丁汉的一家神经认知转诊中心，自 2018 年 3 月至 2020 年 10 月期间，对疑似 EOARD 患者进行腰椎穿刺以诊断该病的经验。
评估脑脊液（CSF）中淀粉样蛋白β42（Aβ42）、总 tau 和 Thr181 磷酸化 tau（p-tau）在轻度认知障碍（MCI）患者中的检测结果，并评估其与认知随访表现的关系。
纳入 30 名年龄 32-68 岁（平均 59 岁；57%为女性）的参与者。临床诊断基于临床表现、神经认知特征、神经影像学特征（MRI、FDG-PET CT）和 CSF Aβ42、总 tau 和 p-tau 检测结果。
与认知稳定的 MCI 患者相比，进展为 AD（前驱 AD）的 MCI 患者的 CSF 总 tau（797.63 pg/ml）和 p-tau（82.31 pg/ml）水平显著更高，而 Aβ42 水平更低（398.94 pg/ml）（CSF 总 tau 和 p-tau 水平的差异具有统计学意义，p 值均＜0.01，而 CSF Aβ42 水平的差异具有显著统计学意义，p 值＜0.0001）。CSF 生物标志物均与任何认知表现测量结果均无相关性。主成分分析证实，AD 所致 MCI 的临床诊断（即 NIA-AA 标准下的前驱 AD）在年轻患者中与 CSF Aβ42 降低相关。
在早发性 AD 中，CSF Aβ42 水平降低可能比总 tau 和 p-tau 检测更敏感，可用于区分 AD-MCI 与其他类型的痴呆。在临床实践中，进一步对更大样本量的 EOARD 进行研究，将解决早期诊断的成本效益问题。
