Event Abstract

"To be active or not to be sedentary": relationships between actigraphic measures of PA, response inhibition and BDNF serum levels in parkinson disease

  • 1 University of Poitiers, France
  • 2 UMR7295 Centre de recherches sur la cognition et l'apprentissage (CeRCA), France
  • 3 GIGA-Cyclotron Research Center In Vivo Imaging, University of Liege, Belgium
  • 4 GIGA Cardiovascular Sciences, University of Liège Hospital, Belgium

Introduction Parkinson’s Disease (PD) is a neurodegenerative pathology characterized by a progressive degeneration of nigrostriatal neurons and loss of dopaminergic transmission affecting around 3.3% of the elderly population and increasing with aging (Barbosa et al., 2006). It is characterized by motor impairment whose major clinical features are tremor, ridigity and bradykinesia, but cognitive deficits are also observed. A common point of the cognitive deficits in PD is the executive functions (EFs) decline (Higginson et al., 2003), which has been related to neurologic substrates mainly on the connections between prefrontal regions and sub-cortical structures (Dujardin et al., 2003). Executive dysfunction may occur at an early stage of PD (Stella et al., 2007) and underlies all characteristic manifestations of cognitive impairment in PD, particularly with advanced age and longer duration of the disease (Sammer et al., 2006). Meanwhile, compelling evidence shows that regular practice of physical activity (PA) improve EFs in healthy elderly people (Colcombe & Kramer, 2003), mostly for the response inhibition function (Boucard et al., 2012). Only two studies examined the link between PA and EFs in PD. A combined strength and aerobic training intervention leads to a selective benefit for frontal lobe based EFs compared to tasks mediated by the fronto-temporal and temporal lobe (Cruise et al., 2011). Tanaka and colleagues demonstrated an improvement on EFs in PD as a result of a multimodal training (Tanaka et al., 2009). PD patients exhibited a significant reduction in perseverative errors in the Wisconsin Card Sorting Test after the 3 months training program, contrary to PD patients of the control group who did not. However, it should be noted that these studies used tasks involving different EFs such as switching, inhibition response and updating of working memory functions (see Miyake et al., 2000), making difficult to disentangle the specific effect of PA on a single EF as response inhibition. While regular PA may slow the cognitive decline of PD, the mechanisms underlying this effect are not yet elucidated. According to the neurotrophical hypothesis, regular release of neurotrophic factors during moderate-to-vigorous PA, like the brain-derived neurotrophical factor (BDNF), may improve brain plasticity. Although BDNF is reduced in in the substantia nigra of PD patients (Howells et al., 2000), a higher BDNF expression is associated to a better performance in the Go/NoGo inhibition task (Beste et al., 2010), and higher BDNF serum levels are related to a less executive dysfunction (Costa et al., 2015). We may therefore expect a mediator role of BDNF serum between PA and response inhibition in PD. The aim of this study was to determine the associations between objectively-measured PA and cognitive performance assessed from an inhibition task in healthy and PD patients, and to test whether or not BDNF serum is a good mediator of these relationships. Methods Thirty-four older adults (19 men, 15 women) and 31 parkinsonian patients (21 men, 12 women) who varied in PA level were recruited for this study. All the included participants performed more than the critical score of 26 to the Mini-Mental State Examination (Hébert et al., 1992). Motor aspects were evaluated by the Unified Parkinson Disease Rating scales, i.e. the part II (motor experiences in free daily-living activities) and the part III (disease severity). We used a classical experimental paradigm to tap response inhibition, the Go/NoGo task, which requires executing manual response to Go stimuli, and withholding that response to NoGo stimuli. Participants performed the manual classical task, but also an original task with the feet as effector. PD patients realized the task with the most affected member. As both tasks did not induce enough false alarms, we kept mean RT as measure of response inhibition. Blood sampling for BDNF analysis were collected in the morning in sterile serum separator tubes. The samples were centrifuged at 3000 rpm for 10 min. Serum was then harvested, aliquoted, and stored at −20 °C until analysis. BDNF serum (BDNFs) was quantified using an enzyme-linked immunosorbent assay (R & D Systems) according to the manufacturer’s instructions. PA level was assessed from by the Actigraph Model GT3x. This small uniaxial piezoelectric accelerometer was worn superior to the iliac crest for 7 days, i.e. a typical week. Subsequently, data were downloaded using the manufacturer’s software and activity counts were delineated in intensity categories using the Sasaki et al. (2011) equation for the magnitude vector. We assessed for each participant the time spent (in minutes) above the 2690 count/min cut-point, which defines the boundary between light (<3 METs) and moderate-to-vigorous (>3 METs) activity. Sedentary behavior was also measured as the time in sedentary bouts (in minutes), i.e. the accumulated in bouts during at least 10 minutes in which the intensity is under the 100 count/min cut-point (< 1.5 METs). Total PA was assessed by daily steps number and by energy expenditure (METs-min/day), which was estimated from the 2-regression equation, established by Crouter et al. (2010). Results We assessed the extent to which each PA variable accounted for the variance of cognitive performance in both groups, using hierarchical regression analyses. For each group, hand RT and feet RT were separately entered as dependent variables. Age, education level and depression score of the HADS were considered as control variables and entered first as one block into the models (Block 1). Clinical parameters were also both entered in the block for the parkinsonian patients group (i.e. disease duration and UPDRS III score). This was followed by the main effect of each PA measure with separate analyses (Block 2). Mediation analysis was then conducted. Independent study variables (PA variables) have to be associated with the cognitive outcome and the potential mediator (BDNFs) to be included in the mediation analysis (Judd & Kenny, 1981). For the older adults group, sedentary behavior predicted both hand RT and feet RT (p < .05), but none of the other PA patterns explained both cognitive measures (ps > .05). BDNFs was not related to cognitive measures and PA measures (ps > .05), making useless the mediation analysis. For the PD patients group, energy expenditure and sedentary behavior predicted both hand RT and feet RT (ps < .05), but energy expenditure was the only predictor of BDNFs (p < .01), and BDNFs predicted both hand RT and feet RT (ps < .05). The effect of energy expenditure on cognitive performance was no longer significant after controlling for BDNFs (p > .05), revealing the mediator role of BDNFs. Discussion These results show differentiated effects of PA and sedentary behavior on response inhibition in healthy older adults and PD patients. As we expected, BDNF is a good mediator of the link between PA and cognition in PD. Concerning the older adults, we failed to show relationships between PA measures and response inhibition in older adults. This could be due to the age of the participants (65 ± 4.2). In a previous study, Boucard et al. (2012) revealed the PA-effect on inhibition for the participants aged between 71 and 81 years, but not in the participants aged between 60 and 70. In PD patients, there was an effect of total PA on cognitive performance, as well as for the hand task than for the feet task, which was mediated by BDNF serum. This in line with the neurotrophical hypothesis, which won evidence from animal studies. Indeed, regular physical activity up-regulates BDNF, particularly in the dentate gyrus of the hippocampus which is one of the two sites of neurogenesis (see Churchill et al., 2002). In older humans, the study of Erickson et al. (2011) revealed a positive association, after a six-months training PA program, between BDNF serum levels and hippocampal volume, itself significantly related to the mnesic performance. As for the relationship between regular PA and memory in aging, the link between PA and response inhibition in PD is biologically plausible. In hemiparkinsonian rats, Tajiri et al. (2010) showed a positive effect of PA on the cellular proliferation from the subventricular area to the striatum and showed that the increases of striatal BDNF levels are associated to this mechanism neurogenesis. Thus, there would be a mechanism by which PA could preserve the integrity of the network interconnecting the prefrontal cortex and the striatum, related to response inhibition. The negative link between sedentary level and a response inhibition, independently of the neutrophical effects of PA, is in agreement with current scientific research. For example, Katzmarzyk et al. (2010) revealed associations between levels of sitting and mortality risk in both physically inactive and active adults. Further research is required to better define the interactive effects between sedentary behavior and PA on cognition. This study is the first to show a positive relationship between PA, BDNF and cognition in PD. Although it is challenging to found treatment strategies aimed at neuroprotection in PD, regular practice of PA may be a good candidate to compensate neurocognitive decline. However, the cross sectional design precludes inferences about causality between PA and cognition in PD, and controlled trials are needed before a definite conclusion can be made.


COFUND Marie-Curie Actions GIGA-CRC


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Keywords: BDNF (brain derived neurotrophic factor), Parkinson ' s disease, executive functions (EF), Physical activty, sedentary behavior

Conference: Belgian Brain Congress 2018 — Belgian Brain Council, LIEGE, Belgium, 19 Oct - 19 Oct, 2018.

Presentation Type: e-posters


Citation: Boucard G, Collette F, Pincemail J and Garraux G (2019). "To be active or not to be sedentary": relationships between actigraphic measures of PA, response inhibition and BDNF serum levels in parkinson disease. Front. Neurosci. Conference Abstract: Belgian Brain Congress 2018 — Belgian Brain Council. doi: 10.3389/conf.fnins.2018.95.00052

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Received: 15 Aug 2018; Published Online: 17 Jan 2019.

* Correspondence: Dr. Geoffroy Boucard, University of Poitiers, Poitiers, France, geoffroy.boucard@univ-poitiers.fr