A modified Camel and Cactus Test detects presymptomatic semantic impairment in genetic frontotemporal dementia within the GENFI cohort
Creators: name: Moore, Katrina
name: Convery, Rhian
name: Bocchetta, Martina
name: Neason, Mollie
name: Cash, David M.
name: Greaves, Caroline
name: Russell, Lucy L.
name: Clarke, Mica T. M.
name: Peakman, Georgia
name: van Swieten, John
name: Jiskoot, Lize
name: Moreno, Fermin
name: Barandiaran, Myriam
name: Sanchez-Valle, Raquel
name: Borroni, Barbara
name: Laforce, Robert
name: Doré, Marie-Claire
name: Masellis, Mario
name: Tartaglia, Maria Carmela
name: Graff, Caroline
name: Galimberti, Daniela
name: Rowe, James B.
name: Finger, Elizabeth
name: Synofzik, Matthis
name: Karnath, Hans-Otto
name: Vandenberghe, Rik
name: de Mendonça, Alexandre
name: Maruta, Carolina
name: Tagliavini, Fabrizio
name: Santana, Isabel
name: Ducharme, Simon
name: Butler, Chris
name: Gerhard, Alex
name: Levin, Johannes
name: Danek, Adrian
name: Otto, Markus
name: Warren, Jason D
name: Rohrer, Jonathan D.
Publisher: name: Taylor & Francis
Year: 2020
Subjects: subject: Cell Biology
subject: Genetics
subject: FOS: Biological sciences
subject: Neuroscience
subject: Physiology
subject: 69999 Biological Sciences not elsewhere classified
subject: Cancer
subject: Science Policy
subject: 111714 Mental Health
subject: FOS: Health sciences

description: Impaired semantic knowledge is a characteristic feature of some forms of frontotemporal dementia (FTD), particularly the sporadic disorder semantic dementia. Less is known about semantic cognition in the genetic forms of FTD caused by mutations in the genes <i>MAPT</i>, <i>C9orf72</i>, and <i>GRN</i>. We developed a modified version of the Camel and Cactus Test (mCCT) to investigate the presence of semantic difficulties in a large genetic FTD cohort from the Genetic FTD Initiative (GENFI) study. Six-hundred-forty-four participants were tested with the mCCT including 67 <i>MAPT</i> mutation carriers (15 symptomatic, and 52 in the presymptomatic period), 165 <i>GRN</i> mutation carriers (33 symptomatic, 132 presymptomatic), and 164 <i>C9orf72</i> mutation carriers (56 symptomatic, 108 presymptomatic) and 248 mutation-negative members of FTD families who acted as a control group. The presymptomatic mutation carriers were further split into those early and late in the presymptomatic period (more than vs. within 10 years of expected symptom onset). Groups were compared using a linear regression model, adjusting for age and education, with bootstrapping. Performance on the mCCT had a weak negative correlation with age (rho = −0.20) and a weak positive correlation with education (rho = 0.13), with an overall abnormal score (below the 5th percentile of the control population) being below 27 out of a total of 32. All three of the symptomatic mutation groups scored significantly lower than controls: <i>MAPT</i> mean 22.3 (standard deviation 8.0), <i>GRN</i> 24.4 (7.2), <i>C9orf72</i> 23.6 (6.5) and controls 30.2 (1.6). However, in the presymptomatic groups, only the late <i>MAPT</i> and late <i>C9orf72</i> mutation groups scored lower than controls (28.8 (2.2) and 28.9 (2.5) respectively). Performance on the mCCT correlated strongly with temporal lobe volume in the symptomatic <i>MAPT</i> mutation group (rho &gt; 0.80). In the <i>C9orf72</i> group, mCCT score correlated with both bilateral temporal lobe volume (rho &gt; 0.31) and bilateral frontal lobe volume (rho &gt; 0.29), whilst in the <i>GRN</i> group mCCT score correlated only with left frontal lobe volume (rho = 0.48). This study provides evidence for presymptomatic impaired semantic knowledge in genetic FTD. The different neuroanatomical associations of the mCCT score may represent distinct cognitive processes causing deficits in different groups: loss of core semantic knowledge associated with temporal lobe atrophy (particularly in the <i>MAPT</i> group), and impaired executive control of semantic information associated with frontal lobe atrophy. Further studies will be helpful to address the longitudinal change in mCCT performance and the exact time at which presymptomatic impairment occurs.