Image_1_Effects of age and sex on outcomes of the Q-Motor speeded finger tapping and grasping and lifting tests-findings from the population-based BiDirect Study.pdf

BackgroundQ-Motor is a suite of motor tests originally designed to assess motor symptoms in Huntington's disease. Among others, Q-Motor encompasses a finger tapping task and a grasping and lifting task. To date, there are no systematic investigations regarding effects of variables which may affect the performance in specific Q-Motor tests per se, and normative Q-Motor data based on a large population-based sample are not yet available.ObjectiveWe investigated effects of age and sex on five selected Q-Motor outcomes representing the two core Q-Motor tasks speeded finger tapping and grasping and lifting in a community sample of middle-aged to elderly adults. Furthermore, we explored effects of the potentially mediating variables educational attainment, alcohol consumption, smoking status, and depressive symptoms. Moreover, we explored inter-examiner variability. Finally, we compared the findings to findings for the Purdue Pegboard test.MethodsBased on a sample of 726 community-dwelling adults and using multiple (Gaussian) regression analysis, we modeled the motor outcomes using age, sex, years in full-time education, depressive symptoms in the past seven days, alcohol consumption in the past seven days, and smoking status as explanatory variables.ResultsWith regard to the Q-Motor tests, we found that more advanced age was associated with reduced tapping speed, male sex was associated with increased tapping speed and less irregularity, female sex was associated with less involuntary movement, more years of education were associated with increased tapping speed and less involuntary movement, never smoking was associated with less involuntary movement compared to current smoking, and more alcohol consumed was associated with more involuntary movement.ConclusionThe present results show specific effects of age and sex on Q-Motor finger tapping and grasping and lifting performance. In addition, besides effects of education, there also were specific effects of smoking status and alcohol consumption. Importantly, the present study provides normative Q-Motor data based on a large population-based sample. Overall, the results are in favor of the feasibility and validity of Q-Motor finger tapping and grasping and lifting for large observational studies. Due to their low task-complexity and lack of placebo effects, Q-Motor tests may generate additional value in particular with regard to clinical conditions such as Huntington's or Parkinson's disease.</p

Correlation of digitomotography measures with clinical data.

<p>Data are calculated with simple regression, and presented with the coefficient of determination (r²).</p><p>* <i>p</i> < 0.05.</p><p>BDI, Becks Depression Inventory; CoV, coefficient of variation; DEV mean, mean tap deviation from the predefined 1.55 Hertz cueing tone; Delta TMT, Trail Making Test part B minus part A, a measure of cognitive flexibility and working memory [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0123914#pone.0123914.ref018" target="_blank">18</a>]; DEV SD, variability of tap deviation from the predefined 1.55 Hertz cueing tone; IPI, interpeak interval; MMSE, Mini-Mental State Examination; SD, standard deviation; TF, tap force; UPDRS III, Motor part of the Unified Parkinson’s Disease Rating Scale.</p><p>Correlation of digitomotography measures with clinical data.</p

Q-Motor digitomotography device and position of the hand for the index finger tapping assessment.

<p>The hand with palm down is placed on a fixed support surface on a table, with the index finger located above the force transducer surface before the tapping experiments are started.</p

Demographics and clinical characteristics.

<p>Data are presented with median (range) and frequency. Statistical comparisons were performed with the Kruskal-Wallis / Wilcoxon rank sum test, and the Pearson / Fisher’s Exact test, with analyses between single cohorts using Bonferroni correction (controls versus early PD, controls versus mid-stage PD, early PD versus mid-stage PD, <i>p</i> < 0.05/3 = 0.017).</p><p>° Compared to controls</p><p>* Compared to early Parkinson’s disease (PD).</p><p>BDI, Becks Depression Inventory; MMSE, Mini-Mental State Examination; UPDRS III, Motor part of the Unified Parkinson’s Disease Rating Scale.</p><p>Demographics and clinical characteristics.</p

Behavioral testing of minipigs transgenic for the Huntington gene—A three-year observational study

<div><p>Background</p><p>Large animal models of Huntington’s disease (HD) may increase the reliability of translating preclinical findings to humans. Long live expectancy offers opportunities particularly for disease modifying approaches, but also challenges. The transgenic (tg) HD minipig model assessed in this study exhibits a high genetic homology with humans, similar body weight, and comparable brain structures. To test long-term safety, tolerability, and efficacy of novel therapeutic approaches in this model reliable assessments applicable longitudinally for several years are warranted for all phenotypical domains relevant in HD.</p><p>Objective</p><p>To investigate whether the tests proposed assessing motor, cognitive and behavioral domains can be applied repetitively over a 3-year period in minipigs with acceptable variability or learning effects and whether tgHD minipigs reveal changes in these domains compared to wildtype (wt) minipigs suggesting the development of an HD phenotype.</p><p>Methods</p><p>A cohort of 14 tgHD and 18 wt minipigs was followed for three years. Tests applied every six months included a tongue coordination and hurdle test for the motor domain, a color discrimination test for cognition, and a dominance test for assessing behavior. Statistical analyses were performed using repeated ANOVA for longitudinal group comparisons and Wilcoxon-tests for intra-visit differences between tgHD and wt minipigs.</p><p>Results</p><p>All tests applied demonstrated feasibility, acceptable variance and good consistency during the three-year period. No significant differences between tgHD and wt minipigs were detected suggesting lack of a phenotype before the age of four years.</p><p>Conclusions</p><p>The assessment battery presented offers measures in all domains relevant for HD and can be applied in long-term phenotyping studies with tgHD minipigs. The observation of this cohort should be continued to explore the timeline of phenotype development and provide information for future interventional studies.</p></div

Setup of behavioral tests.

<p>(A) In the tongue coordination test, pigs had to enter the walkway and approach the tongue board (TB). The ability to recover the rewards (cornflakes) from holes with continuously increasing depth from left to right was assessed. (B) The hurdle test aimed to assess gait coordination under challenge compared to normal walking. (C) The discrimination test was designed to evaluate the cognitive domain. Minipigs had to explore all boxes and were supposed to learn and remember that only the blue box could be opened. (D) The dominance test was applied to assess behavior. Two animals entered the setup from opposite sides and the animal pushing the opponent backwards was considered dominant. Calculation of an index after exposure of each animal to all group mates was used to determine hierarchy within groups (modified from [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0185970#pone.0185970.ref027" target="_blank">27</a>]).</p

Arrangement of stables.

<p>Arrangement of the stables (each~12m²) in the ZTE showing all six groups with their individual distribution of genotypes (tg = transgenic, wt = wildtype). The assessment area is located in the middle of the stables and hosts the variable setups outlined in Figs <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0185970#pone.0185970.g002" target="_blank">2</a> and <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0185970#pone.0185970.g003" target="_blank">3</a>.</p

Discrimination test—Reversal learning.

<p>Results of the yellow box reversal learning Discrimination test for each visit v1 –v6 (means of six runs, compared between tgHD and wt minipigs). (A) “Initiation and exploration time” needed to enter the walkway and open the correct (yellow) box. Figs (B) and (C) show the number of attempts to open the red or the blue box before opening the correct box. Measures in Figs A-C show a significant decrease in time and number of attempts during the course of the study. (D) Negative correlation between age and “initiation and exploration time” (***). [* = p≤0.05, ** = p≤0.01, *** = p≤0.001]</p

Dominance test.

<p>Results of the Dominance test. The figures shows the Clutton-Brock-Index (CBI) [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0185970#pone.0185970.ref027" target="_blank">27</a>]. (A) Mean CBI compared between tgHD and wt minipigs at each visit (v1-v6). (B), (C) and (D) sample CBIs of individual pigs in groups 1, 4 and 6 (v1-v6).</p

Hurdle test.

<p>Results of the Hurdle test (means of six runs, compared between tgHD and wt minipigs per visit). (A) “Initiation time”, i.e. time the pigs need to enter the walkway. (B) “Run time”, i.e. time to complete the walk and arrive in startbox B.</p