Jiskoot Lize C, Russell Lucy L, Peakman Georgia, Convery Rhian S, Greaves Caroline V, Bocchetta Martina, Poos Jackie M, Seelaar Harro, Giannini Lucia A A, van Swieten John C, van Minkelen Rick, Pijnenburg Yolande A L, Rowe James B, Borroni Barbara, Galimberti Daniela, Masellis Mario, Tartaglia Carmela, Finger Elizabeth, Butler Chris R, Graff Caroline, Laforce Robert, Sanchez-Valle Raquel, de Mendonça Alexandre, Moreno Fermin, Synofzik Matthis, Vandenberghe Rik, Ducharme Simon, le Ber Isabelle, Levin Johannes, Otto Markus, Pasquier Florence, Santana Isabel, Cash David M, Thomas David, Rohrer Jonathan D
Department of Neurology, Erasmus Medical Center, Rotterdam, the Netherlands; Dementia Research Centre, University College London, London, UK.
Dementia Research Centre, University College London, London, UK.
J Neurol Sci. 2023 Mar 15;446:120590. doi: 10.1016/j.jns.2023.120590. Epub 2023 Feb 16.
Sensitive cognitive markers are still needed for frontotemporal dementia (FTD). The Benson Complex Figure Test (BCFT) is an interesting candidate test, as it assesses visuospatial, visual memory, and executive abilities, allowing the detection of multiple mechanisms of cognitive impairment. To investigate differences in BCFT Copy, Recall and Recognition in presymptomatic and symptomatic FTD mutation carriers, and to explore its cognitive and neuroimaging correlates.
We included cross-sectional data from 332 presymptomatic and 136 symptomatic mutation carriers (GRN, MAPT or C9orf72 mutations), and 290 controls in the GENFI consortium. We examined gene-specific differences between mutation carriers (stratified by CDR® NACC-FTLD score) and controls using Quade's / Pearson Χ tests. We investigated associations with neuropsychological test scores and grey matter volume using partial correlations and multiple regression models respectively.
No significant differences were found between groups at CDR® NACC-FTLD 0-0.5. Symptomatic GRN and C9orf72 mutation carriers had lower Copy scores at CDR® NACC-FTLD ≥2. All three groups had lower Recall scores at CDR® NACC-FTLD ≥2, with MAPT mutation carriers starting at CDR® NACC-FTLD ≥1. All three groups had lower Recognition scores at CDR® NACC FTLD ≥2. Performance correlated with tests for visuoconstruction, memory, and executive function. Copy scores correlated with frontal-subcortical grey matter atrophy, while Recall scores correlated with temporal lobe atrophy.
In the symptomatic stage, the BCFT identifies differential mechanisms of cognitive impairment depending on the genetic mutation, corroborated by gene-specific cognitive and neuroimaging correlates. Our findings suggest that impaired performance on the BCFT occurs relatively late in the genetic FTD disease process. Therefore its potential as cognitive biomarker for upcoming clinical trials in presymptomatic to early-stage FTD is most likely limited.
额颞叶痴呆（FTD）仍需要敏感的认知标志物。本森复杂图形测验（BCFT）是一个有趣的候选测验，因为它评估视觉空间、视觉记忆和执行能力，能够检测认知障碍的多种机制。研究有症状和无症状FTD突变携带者在BCFT临摹、回忆和再认方面的差异，并探讨其认知和神经影像学相关性。
我们纳入了GENFI联盟中332名无症状和136名有症状突变携带者（GRN、MAPT或C9orf72突变）以及290名对照的横断面数据。我们使用Quade检验/Pearson Χ检验检查突变携带者（按CDR® NACC-FTLD评分分层）与对照之间的基因特异性差异。我们分别使用偏相关和多元回归模型研究与神经心理测验分数和灰质体积的关联。
在CDR® NACC-FTLD 0-0.5时，各组之间未发现显著差异。有症状的GRN和C9orf72突变携带者在CDR® NACC-FTLD≥2时临摹分数较低。所有三组在CDR® NACC-FTLD≥2时回忆分数均较低，MAPT突变携带者在CDR® NACC-FTLD≥1时就开始出现。所有三组在CDR® NACC FTLD≥2时再认分数均较低。表现与视觉构建、记忆和执行功能测验相关。临摹分数与额-皮质下灰质萎缩相关，而回忆分数与颞叶萎缩相关。
在有症状阶段，BCFT根据基因突变确定认知障碍的不同机制，基因特异性认知和神经影像学相关性证实了这一点。我们的研究结果表明，BCFT表现受损在遗传性FTD疾病过程中出现相对较晚。因此，其作为症状前至早期FTD即将开展的临床试验的认知生物标志物的潜力很可能有限。
