From the Division of Clinical Geriatrics (O.V., K.P., L.-O.W., E.W.), Department of Neurobiology, Care Sciences and Society, Karolinska Institute, Stockholm; Department of Diagnostic Radiology (P.S., D.v.W.), Lund University; Imaging and Function (D.v.W.), Skåne University Health Care, Lund; Clinical Memory Research Unit (S.P., E.S., O.H.), Department of Clinical Sciences, Malmö, Lund University; Memory Clinic (E.S., O.H.), Skåne University Hospital, Malmö, Sweden; and Department of Neuroimaging (E.W.), Centre for Neuroimaging Sciences, Institute of Psychiatry, Psychology and Neuroscience, King's College London, UK.
Neurology. 2019 Jan 29;92(5):e395-e405. doi: 10.1212/WNL.0000000000006852. Epub 2019 Jan 4.
To investigate the association between longitudinal changes in proton magnetic resonance spectroscopy (MRS) metabolites and amyloid pathology in individuals without dementia, and to explore the relationship between MRS and cognitive decline.
In this longitudinal multiple time point study (a subset of the Swedish BioFINDER), we included cognitively healthy participants, individuals with subjective cognitive decline, and individuals with mild cognitive impairment. MRS was acquired serially in 294 participants (670 individual spectra) from the posterior cingulate/precuneus. Using mixed-effects models, we assessed the association between MRS and baseline β-amyloid (Aβ), and between MRS and the longitudinal Mini-Mental State Examination, accounting for , age, and sex.
While baseline MRS metabolites were similar in Aβ positive (Aβ+) and negative (Aβ-) individuals, in the Aβ+ group, the estimated rate of change was +1.9%/y for myo-inositol (mI)/creatine (Cr) and -2.0%/y for -acetylaspartate (NAA)/mI. In the Aβ- group, mI/Cr and NAA/mI yearly change was -0.05% and +1.2%; however, this was not significant across time points. The mild cognitive impairment Aβ+ group showed the steepest MRS changes, with an estimated rate of +2.93%/y ( = 0.07) for mI/Cr and -3.55%/y ( < 0.01) for NAA/mI. Furthermore, in the entire cohort, we found that Aβ+ individuals with low baseline NAA/mI had a significantly higher rate of cognitive decline than Aβ+ individuals with high baseline NAA/mI.
We demonstrate that the longitudinal change in mI/Cr and NAA/mI is associated with underlying amyloid pathology. MRS may be a useful noninvasive marker of Aβ-related processes over time. In addition, we show that in Aβ+ individuals, baseline NAA/mI may predict the rate of future cognitive decline.
研究无痴呆个体质子磁共振波谱（MRS）代谢物的纵向变化与淀粉样蛋白病理学之间的关系，并探讨 MRS 与认知能力下降之间的关系。
在这项纵向多时间点研究（瑞典生物发现者研究的一个子集）中，我们纳入了认知正常的参与者、有主观认知下降的个体和有轻度认知障碍的个体。从后扣带回/楔前叶采集了 294 名参与者（670 个个体谱）的 MRS 数据。使用混合效应模型，我们评估了 MRS 与基线β-淀粉样蛋白（Aβ）之间的关系，以及 MRS 与纵向简易精神状态检查（MMSE）之间的关系，同时考虑了年龄和性别。
虽然基线 MRS 代谢物在 Aβ 阳性（Aβ+）和阴性（Aβ-）个体中相似，但在 Aβ+组中，肌醇（mI）/肌酸（Cr）的估计变化率为 +1.9%/年，而乙酰天门冬氨酸（NAA）/mI 的变化率为-2.0%/年。在 Aβ-组中，mI/Cr 和 NAA/mI 的年变化率分别为-0.05%和+1.2%；然而，这在各时间点均无统计学意义。轻度认知障碍 Aβ+组显示出最陡峭的 MRS 变化，mI/Cr 的估计变化率为 +2.93%/年（ = 0.07），NAA/mI 的变化率为-3.55%/年（<0.01）。此外，在整个队列中，我们发现基线 NAA/mI 水平较低的 Aβ+个体的认知衰退速度明显高于基线 NAA/mI 水平较高的 Aβ+个体。
我们证明了 mI/Cr 和 NAA/mI 的纵向变化与潜在的淀粉样蛋白病理学有关。MRS 可能是一种随时间推移评估 Aβ 相关过程的有用的非侵入性标志物。此外，我们表明在 Aβ+个体中，基线 NAA/mI 可能预测未来认知衰退的速度。
