中国神经再生研究(英文版) ›› 2021, Vol. 16 ›› Issue (5): 910-915.doi: 10.4103/1673-5374.297082

• 原著:退行性病与再生 • 上一篇    下一篇

前颗粒蛋白基因突变额颞叶痴呆患者的神经心理学特征:巢式病例对照研究

  

  • 出版日期:2021-05-15 发布日期:2020-12-29
  • 基金资助:

    葡萄牙科学技术基金会(FCT)支持

Neuropsychological features of progranulin-associated frontotemporal dementia: a nested case-control study

Marisa Lima1, 4, Miguel Tábuas-Pereira1, 2, *, Diana Duro1, 2, 4, João Durães1, Daniela Vieira1, Inês Baldeiras2, 3, Maria Rosário Almeida3, Isabel Santana1, 2, 3#br#   

  1. 1 Neurology Department, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal;  2 University of Coimbra, Faculty of Medicine, Coimbra, Portugal;  3 University of Coimbra, Center for Neuroscience and Cell Biology, Coimbra, Portugal;  4 University of Coimbra, Center for Research in Neuropsychology and Cognitive Behavioral Intervention (CINEICC), Faculty of Psychology and Educational Sciences, Coimbra, Portugal
  • Online:2021-05-15 Published:2020-12-29
  • Contact: Miguel Tábuas-Pereira, MD, miguelatcp@gmail.com.
  • Supported by:
    ML was supported by Portuguese Foundation for Science and Technology (FCT), No. SFRH/BD/144001/2019.

摘要:

散发性与遗传性行为变异型额颞叶痴呆(bvFTD)之间神经心理学(NP)特征区别仍无共识。此次巢式病例对照研究纳入18例来源于15个不同家族的前颗粒蛋白基因突变的额颞叶痴呆患者,并纳入疾病分期、年龄和教育程度与之匹配的18例散发性变异型额颞叶痴呆和18例阿尔茨海默病患者,所有患者均完成简易智力状态检查量表、蒙特利尔认知评估和全面的神经心理学评估。通过非参数检验Kruskal-Wallis检验评估组间神经心理学指标差异。前颗粒蛋白基因突变的额颞叶痴呆患者的词汇分类过程表现和视觉建构能力比散发性行为变异型额颞叶痴呆患者差。与阿尔茨海默病患者相比,前颗粒蛋白基因突变的额颞叶痴呆患者在记忆任务中表现更好,散发性行为变异型额颞叶痴呆患者在记忆和视觉空间技能方面更差。由此认为,前颗粒蛋白基因突变的额颞叶痴呆患者在视觉建构能力和情景语言记忆方面的表现是其较为显著的神经心理学特征。

https://orcid.org/0000-0002-3988-614X (Miguel Tábuas-Pereira)

Abstract: The distinction between sporadic and genetic behavioural-variant frontotemporal dementia (bvFTD) regarding some neuropsychological (NP) features remains challenging. Specifically, progranulin (GRN)-associated bvFTD frequently presents with early episodic memory impairment and some degree of parietal dysfunction which are supporters of Alzheimer’s disease (AD) diagnosis. In this context, we aimed to characterize the NP profile of GRN-bvFTD as compared to sporadic-bvFTD and AD in patients with mild dementia (Mini-Mental State Examination score ≥ 17 and Clinical Dementia Rating Scale score ≤ 1. We identified 21 patients at Centro Hospitalar e Universitário de Coimbra, Portugal with GRN mutations belonging to fifteen different families. As our focus was bvFTD variants, FTD-related aphasic forms (3 patients) were excluded. The remaining 18 GRN-bvFTD were further matched with 18 sporadic-bvFTD and 18 AD patients according to disease staging, age and education. All patients completed the Mini-Mental State Examination, Montreal Cognitive Assessment (MoCA) and a comprehensive NP assessment battery. Results were converted into z-scores. Differences between groups in individual NP measures and NP domains were assessed through non-parametric tests (Kruskal-Wallis test analysis) and eta squared (ŋ2) was calculated as a measure of effect size. Group comparisons show that GRN patients have worse performances on verbal retrieval processes (P = 0.039, ŋ2 = 0.110) and visuoconstructive abilities (P = 0.039, ŋ2 = 0.190) than sporadic bvFTD forms. When compared to AD, GRN patients present a higher impairment in frontal (P = 0.001, ŋ2 = 0.211) and parietal (P = 0.041, ŋ2 = 0.129) measures and a better performance in memory tasks (P = 0.020, ŋ2 = 0.120). Sporadic-bvFTD forms are worse than AD in frontal measures (P = 0.032, ŋ2 = 0.200), being better in both memory (P = 0.010, ŋ2 = 0.131) and visuospatial skills (P = 0.023, ŋ2 = 0.231). Considering these results, we conclude that GRN-bvFTD patients present a NP profile that associates the typical patterns of FTD and AD deficits. This is particularly expressive in visuoconstructive abilities, which was the more discriminative feature between groups, followed by episodic verbal memory. This study was approved by the Institutional Ethics Committee of Centro Hospitalar e Universitário de Coimbra, Portugal (CE-029/2019) on June 24, 2019.

Key words: Alzheimer’s disease, behavioral variant frontotemporal dementia, cognitive profile, frontotemporal dementia, genetics, memory, neuropsychology, progranulin, visuoconstructive ability