Department of Neurology and Neurosurgery, Escola Paulista de Medicina, Federal University of São Paulo (UNIFESP), Rua Botucatu 740, Vila Clementino, São Paulo, SP, 04023-900, Brazil.
Department of Biophysics, Escola Paulista de Medicina, Federal University of São Paulo (UNIFESP), São Paulo, SP, Brazil.
Aging Clin Exp Res. 2023 Aug;35(8):1741-1752. doi: 10.1007/s40520-023-02452-5. Epub 2023 Jun 2.
To explore associations of cerebrospinal fluid biomarkers of neurodegeneration and amyloidosis with caregiver burden, cognition and functionality in dementia with Lewy bodies (DLB) paired with late-onset Alzheimer's disease (AD) and healthy older people.
Consecutive outpatients with DLB were matched with outpatients with AD according to sex, cognitive scores and dementia stage, and with cognitively healthy controls according to age and sex to investigate associations of cerebrospinal fluid amyloid-β (Aβ,Aβ,Aβ), tau, phospho-tau Thr, ubiquitin, α-synuclein and neurofilament light with caregiver burden, functionality, reverse digit span, a clock drawing test, Mini-Mental State Examination (MMSE) and Severe MMSE, adjusted for sex, age, education, dementia duration and APOE-ε4 alleles.
Overall, 27 patients with DLB (78.98 ± 9.0 years-old; eleven APOE-ε4 +) were paired with 27 patients with AD (81.50 ± 5.8 years-old; twelve APOE-ε4 +) and 27 controls (78.98 ± 8.7 years-old; four APOE-ε4 +); two-thirds were women. In AD, Aβ/Aβ and Aβ were lower, while tau/Aβ and phospho-tau Thr/Aβ were higher; α-synuclein/Aβ was lower in DLB and higher in AD. The following corrected associations remained significant: in DLB, instrumental functionality was inversely associated with tau/phospho-tau Thr and tau/Aβ, and reverse digit span associated with α-synuclein; in AD, instrumental functionality was inversely associated with neurofilament light, clock drawing test scores inversely associated with phospho-tau Thr/Aβ and α-synuclein/Aβ, and Severe MMSE inversely associated with tau/Aβ and tau/phospho-tau Thr.
Cerebrospinal fluid phospho-tau Thr in DLB was similar to AD, but not Aβ. In associations with test scores, biomarker ratios were superior to isolated biomarkers, while worse functionality was associated with axonal degeneration only in AD.
探讨与神经退行性变和淀粉样变性相关的脑脊液生物标志物与路易体痴呆（DLB）患者的照料者负担、认知和功能之间的关系，这些患者与晚发性阿尔茨海默病（AD）和健康老年人相匹配。
连续入组 DLB 门诊患者，根据性别、认知评分和痴呆阶段与 AD 门诊患者相匹配，并根据年龄和性别与认知健康对照相匹配，以调查脑脊液 Aβ（Aβ）、tau、磷酸化 tau Thr、泛素、α-synuclein 和神经丝轻链与照料者负担、功能、倒数数字广度、时钟绘制测试、简易精神状态检查（MMSE）和严重 MMSE 之间的关系，这些因素调整了性别、年龄、教育、痴呆持续时间和 APOE-ε4 等位基因。
总体而言，27 例 DLB 患者（78.98±9.0 岁；11 例 APOE-ε4+）与 27 例 AD 患者（81.50±5.8 岁；12 例 APOE-ε4+）和 27 例对照（78.98±8.7 岁；4 例 APOE-ε4+）相匹配；三分之二为女性。在 AD 中，Aβ/Aβ 和 Aβ 降低，而 tau/Aβ 和磷酸化 tau Thr/Aβ 升高；α-synuclein/Aβ 在 DLB 中降低，在 AD 中升高。以下校正后的关联仍然显著：在 DLB 中，工具性功能与 tau/phospho-tau Thr 和 tau/Aβ 呈负相关，倒数数字广度与 α-synuclein 呈正相关；在 AD 中，工具性功能与神经丝轻链呈负相关，时钟绘制测试评分与 phospho-tau Thr/Aβ 和 α-synuclein/Aβ 呈负相关，严重 MMSE 与 tau/Aβ 和 tau/phospho-tau Thr 呈负相关。
DLB 中的脑脊液磷酸化 tau Thr 与 AD 相似，但与 Aβ 不同。在与测试评分的关联中，生物标志物比值优于单独的生物标志物，而较差的功能仅与 AD 中的轴突变性相关。
