Dicks Ellen, Vermunt Lisa, van der Flier Wiesje M, Barkhof Frederik, Scheltens Philip, Tijms Betty M
Alzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, 1081 HV Amsterdam, The Netherlands.
Department of Radiology and Nuclear Medicine, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, 1081 HV Amsterdam, The Netherlands; Institutes of Neurology & Healthcare Engineering, UCL London, London WC1E, UK.
Brain Commun. 2020 Aug 20;2(2):fcaa177. doi: 10.1093/braincomms/fcaa177. eCollection 2020.
Biomarkers are needed to monitor disease progression in Alzheimer's disease. Grey matter network measures have such potential, as they are related to amyloid aggregation in cognitively unimpaired individuals and to future cognitive decline in predementia Alzheimer's disease. Here, we investigated how grey matter network measures evolve over time within individuals across the entire Alzheimer's disease cognitive continuum and whether such changes relate to concurrent decline in cognition. We included 190 cognitively unimpaired, amyloid normal (controls) and 523 individuals with abnormal amyloid across the cognitive continuum (preclinical, prodromal, Alzheimer's disease dementia) from the Alzheimer's Disease Neuroimaging Initiative and calculated single-subject grey matter network measures (median of five networks per individual over 2 years). We fitted linear mixed models to investigate how network measures changed over time and whether such changes were associated with concurrent changes in memory, language, attention/executive functioning and on the Mini-Mental State Examination. We further assessed whether associations were modified by baseline disease stage. We found that both cognitive functioning and network measures declined over time, with steeper rates of decline in more advanced disease stages. In all cognitive stages, decline in network measures was associated with concurrent decline on the Mini-Mental State Examination, with stronger effects for individuals closer to Alzheimer's disease dementia. Decline in network measures was associated with concurrent cognitive decline in different cognitive domains depending on disease stage: In controls, decline in networks was associated with decline in memory and language functioning; preclinical Alzheimer's disease showed associations of decline in networks with memory and attention/executive functioning; prodromal Alzheimer's disease showed associations of decline in networks with cognitive decline in all domains; Alzheimer's disease dementia showed associations of decline in networks with attention/executive functioning. Decline in grey matter network measures over time accelerated for more advanced disease stages and was related to concurrent cognitive decline across the entire Alzheimer's disease cognitive continuum. These associations were disease stage dependent for the different cognitive domains, which reflected the respective cognitive stage. Our findings therefore suggest that grey matter measures are helpful to track disease progression in Alzheimer's disease.
需要生物标志物来监测阿尔茨海默病的疾病进展。灰质网络测量具有这样的潜力，因为它们与认知未受损个体中的淀粉样蛋白聚集以及前驱性阿尔茨海默病未来的认知衰退有关。在此，我们研究了灰质网络测量在整个阿尔茨海默病认知连续体中的个体随时间如何演变，以及这种变化是否与同时发生的认知衰退相关。我们纳入了来自阿尔茨海默病神经影像倡议的190名认知未受损、淀粉样蛋白正常的个体（对照组）以及523名在认知连续体（临床前、前驱期、阿尔茨海默病痴呆）中淀粉样蛋白异常的个体，并计算了单受试者灰质网络测量值（每位个体在2年期间五个网络的中位数）。我们拟合线性混合模型来研究网络测量如何随时间变化，以及这种变化是否与记忆、语言、注意力/执行功能以及简易精神状态检查中的同时变化相关。我们进一步评估了关联是否因基线疾病阶段而改变。我们发现认知功能和网络测量均随时间下降，在疾病更晚期下降速度更快。在所有认知阶段，网络测量的下降与简易精神状态检查中的同时下降相关，对于更接近阿尔茨海默病痴呆的个体影响更强。网络测量的下降与不同认知领域的同时认知衰退相关，具体取决于疾病阶段：在对照组中，网络下降与记忆和语言功能下降相关；临床前阿尔茨海默病显示网络下降与记忆和注意力/执行功能下降相关；前驱期阿尔茨海默病显示网络下降与所有领域的认知衰退相关；阿尔茨海默病痴呆显示网络下降与注意力/执行功能下降相关。灰质网络测量随时间的下降在更晚期疾病阶段加速，并且与整个阿尔茨海默病认知连续体中的同时认知衰退相关。这些关联在不同认知领域中因疾病阶段而异，这反映了各自的认知阶段。因此，我们的研究结果表明灰质测量有助于追踪阿尔茨海默病的疾病进展。
