Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Alzheimer Centre Limburg, Maastricht University, Maastricht, The Netherlands.
Neurochemistry Laboratory and Biobank, Department of Clinical Chemistry, Neuroscience Campus Amsterdam, VU University Medical Centre Amsterdam, The Netherlands.
J Alzheimers Dis. 2017;60(3):1025-1034. doi: 10.3233/JAD-170564.
Impaired olfactory function is an early characteristic of Alzheimer's disease (AD), but it remains unclear if odor identification also relates to early markers of AD in cerebrospinal fluid (CSF).
To investigate the association between odor identification and amyloid-β 1-42 (Aβ42) and total tau (t-tau) concentrations in CSF. In addition, to examine the relation between odor identification and cognitive function at baseline and at follow-up, and whether these associations are moderated by CSF Aβ42 and t-tau and apolipoprotein E (APOE) genotype.
We included 160 individuals (40 with normal cognition, 45 with mild cognitive impairment (MCI), 42 with AD-type dementia, and 26 individuals with non-AD dementia) from the EDAR study. Individuals were recruited from six memory clinics across Europe. Odor identification was tested with the brief University of Pennsylvania Smell Identification Test. CSF Aβ42 and t-tau were assessed with INNO-BIA AlzBio3 Luminex assay. Neuropsychological assessment included tests for verbal memory, verbal fluency, attention, executive function, and visuoconstruction. Follow-up was performed within 3 years after baseline.
Lower odor identification scores correlated with increased CSF t-tau concentrations and with lower scores on all cognitive measures at baseline independent of diagnostic group. Lower odor identification scores predicted decline on the MMSE in the total group, and decline on wordlist learning and delayed recall in APOE ɛ4 carriers and in individuals with abnormal Aβ42.
Odor identification impairment may be an indicator of neuronal injury rather than amyloid pathology.
嗅觉功能障碍是阿尔茨海默病(AD)的早期特征,但目前尚不清楚气味识别是否与脑脊液(CSF)中 AD 的早期标志物有关。
探讨气味识别与 CSF 中β淀粉样蛋白 1-42(Aβ42)和总 tau(t-tau)浓度之间的关系。此外,还研究了气味识别与基线和随访时认知功能的关系,以及这些关联是否受 CSF Aβ42 和 t-tau 以及载脂蛋白 E(APOE)基因型的调节。
我们纳入了来自 EDAR 研究的 160 名个体(40 名认知正常、45 名轻度认知障碍(MCI)、42 名 AD 型痴呆和 26 名非 AD 痴呆患者)。这些患者来自欧洲的 6 家记忆诊所招募而来。使用简短的宾夕法尼亚大学嗅觉识别测试(brief University of Pennsylvania Smell Identification Test)测试气味识别。使用 INNO-BIA AlzBio3 Luminex 测定法检测 CSF Aβ42 和 t-tau。神经心理学评估包括语言记忆、语言流畅性、注意力、执行功能和视空间构建的测试。随访在基线后 3 年内进行。
较低的气味识别得分与 CSF t-tau 浓度的升高以及所有认知测试的基线得分降低相关,与诊断组无关。较低的气味识别得分预测了总人群中 MMSE 的下降,以及 APOE ɛ4 携带者和 Aβ42 异常个体的词汇学习和延迟回忆的下降。
嗅觉识别障碍可能是神经元损伤的指标,而不是淀粉样蛋白病理。