Centre for Neurodegenerative Disorders, University of Brescia, Brescia, Italy.
PLoS One. 2013 Sep 9;8(9):e74762. doi: 10.1371/journal.pone.0074762. eCollection 2013.
Consistent with the cognitive reserve hypothesis, higher education and occupation attainments may help persons with neurodegenerative dementias to better withstand neuropathology before developing cognitive impairment. We tested here the cognitive reserve hypothesis in patients with frontotemporal dementia (FTD), with or without pathogenetic granulin mutations (GRN+ and GRN-), and in presymptomatic GRN mutation carriers (aGRN+).
Education and occupation attainments were assessed and combined to define Reserve Index (RI) in 32 FTD patients, i.e. 12 GRN+ and 20 GRN-, and in 17 aGRN+. Changes in functional connectivity were estimated by resting state fMRI, focusing on the salience network (SN), executive network (EN) and bilateral frontoparietal networks (FPNs). Cognitive status was measured by FTD-modified Clinical Dementia Rating Scale.
In FTD patients higher level of premorbid cognitive reserve was associated with reduced connectivity within the SN and the EN. EN was more involved in FTD patients without GRN mutations, while SN was more affected in GRN pathology. In aGRN+, cognitive reserve was associated with reduced SN.
This study suggests that cognitive reserve modulates functional connectivity in patients with FTD, even in monogenic disease. In GRN inherited FTD, cognitive reserve mechanisms operate even in presymptomatic to clinical stages.
与认知储备假说一致，较高的教育和职业成就可能有助于神经退行性痴呆患者在出现认知障碍之前更好地承受神经病理学变化。我们在这里测试了认知储备假说在额颞叶痴呆（FTD）患者中的作用，这些患者包括有或没有致病颗粒蛋白基因突变（GRN+和 GRN-），以及无症状 GRN 基因突变携带者（aGRN+）。
评估了教育和职业成就，并将其结合起来定义了 32 名 FTD 患者（即 12 名 GRN+和 20 名 GRN-）和 17 名 aGRN+的储备指数（RI）。通过静息态 fMRI 估计功能连接的变化，重点关注突显网络（SN）、执行网络（EN）和双侧额顶网络（FPNs）。认知状态通过 FTD 改良临床痴呆评定量表进行测量。
在 FTD 患者中，较高的认知储备水平与 SN 和 EN 内的连接减少有关。在没有 GRN 突变的 FTD 患者中，EN 更易受累，而 SN 在 GRN 病变中更易受累。在 aGRN+中，认知储备与 SN 减少有关。
这项研究表明，认知储备调节 FTD 患者的功能连接，即使在单基因疾病中也是如此。在遗传性 GRN FTD 中，认知储备机制甚至在无症状到临床阶段都在起作用。
