Figure Dissection 1

Overview:

This experiment shows the connections between IGF-1 in the brain, cognitive function, and volume of the hippocampus in healthy older adult humans. This experiment provides data on the effect of exercise in the human model. While this experiment was conducted with healthy older adult participants the findings can provide insight on how exercise has neuroprotective properties in the hippocampus that could link the benefit of exercise on Alzheimer's Disease (AD) prevention. An increase in IGF-1 could lead to an increase in neural plasticity and the prevention of the neurodegeneration involved in AD.

Background Information:

IGF-1:

Animal models have shown that peripheral growth factors play a central role in mediating the downstream effects of exercise on hippocampal plasticity and memory benefits. This experiment focuses on insulin-like growth factor-I (IGF-1) that are up-regulated after exercise. The mechanism of this up-regulation is not discussed within this paper. IGF-1 is a growth factor that modulates synaptic plasticity, synaptic density, neurotransmission, and adult neurogenesis. An increase in IGF-1 could lead to an increase in neural plasticity and the prevention of neurodegeneration involved in Alzhimers. Animal models have demonstrated that exercise prevents and protects from brain damage through increased uptake of circulating IGF-1 by the brain (Carro et al., 2001). Increased levels of IGF-1 is associated with the mediation of inducing hippocampal BDNF levels that are discussed in Figure Dissection 2. IGF-1 is considered one of the key factors in the effect of exercise on learning and memory. For additional information on the role of IGF-1 in the body please watch the video linked on the left. (Maass et al., 2016)

Verbal Learning and Memory Test

This experiment assessed episodic memory by the verbal learning and memory test (VLMT). The VLMT assesses learning of words through five learning trials, free recall tests directly after interference and 30 min later (late recall), and a final recognition test. The VLMT asses early recall, late recall, and recognition memory. In the data presented I focused on the results of late recall from the VLMT. The image below shows the VLMT in an infographic.(Maass et al., 2016)

Image created with Canva.

Experimental approach:

The experimenters tested changes in IGF-1 levels in comparision to VLMT scores and hippocampal volume. They conducted a controlled 3-month intervention trial, in which 40 sedentary healthy older adults were either training on a treadmill (experimental, n=21) or performing progressive-muscle relaxation/stretching exercise (control, n=19). Prior to treatment, all participants had a comprehensive cardiological examination, neuropsychological assessment, and MRI session. All participants were pseudo randomly assigned to one group. After intervention blood samples were collected to analyze the change in IGF-1 and patients underwent VLMT for early and late recall data.

(Maass et al., 2016)

Data:

Figure 1: Voxel-based regressions of changes in IGF-1 in the hippocampus.

Subregion-specific volume changes were derived by manual segmentation on the high-resolution 7 T MRI data. Warm colors(red) indicate high positive correlations between IGF-1 and hippocampal GM volume and cold (dark blue) colors indicate low correlation coefficients. (Maass et al., 2016)

Figure 1 Analysis:

Figure 1A is a high-resolution 7 T MRI data of the effect of IGF-1 change on hippocampal volume change. This imaging shows that there is a positive correlation between hippocampal volume and IGF-1 changes, particularly in the hippocampal head volume. This relationship is further analyzed in Figure 2. Figure 1B provides a threshold level of hippocampal volume. Figure 2B is essential for the analysis of the 7 T MRI data because it allows the baseline for the experimenter to analyze the changes in hippocampal volume. This suggests that the increased IGF-1 levels due to exercise had a preventative and protective effect on the hippocampus in regards to neurodegeneration associated with Alzheimer's. In Alzheimer's disease, a typical marker is a decrease in hippocampal volume. Therefore, if the hippocampal volume is potentially increasing in response to elevated IGF-1 levels this suggests that exercise has a specific neuroprotective mechanism against the decrease in hippocampal volume commonly seen in Alzheimer's. (Maass et al., 2016)

Figure 2. Relationship of Changes in IGF-1 Levels, Hippocampal Volume and Verbal Recall.

Changes in IGF-1 over a 3-month period were positively correlated with changes in hippocampal volume (head and whole hippocampus) measured by manual segmentation on the 7 T high-resolution T1-images and changes in late recall performance in the VLMT. Plots display partial residuals after controlling for age, gender, and ΔT from pre to post-intervention. Volumes refer to the bilateral hippocampus. Asterisks highlight significant correlations (**p<.01). VLMT: Verbal Learning and Memory Test. (Maass et al., 2016)

Figure 2 Analysis:

Figure 2 shows a positive correlation between increased IGF-1 levels and an increase in the hippocampal head volume in the left graph. See figure 1 analysis for more information on this correlation in terms of Alzhiemers prevention.

The graph on the right in figure 2 shows a weak positive correlation between an increase in IGF-1 levels and a VLMT late recall response. VLMT is used to measure the cognitive function of the study participants as outlined in the background information above. A hallmark of Alzhiemers is loss of cognitive function and recall. This study demonstrates that a 3-month period of endurance exercise in healthy older adults elicited improved VLMT late recall responses with a possible correlation to the endurance exercise condition. Therefore, if exercise improves VLMT late recall responses it is a preventative method against the neurodegeneration seen in Alzhiemers.

Conclusion:

This experiment overall demonstrates that exercise induces elevated levels of IGF-1 that are correlated with volume changes in the hippocampus possibly demonstrating a neural protective advantage and some cognitive advantages shown by the VLMT late recall response. This experiment illustrates the beneficial effects of exercise in the hippocampus in a human model. This data answers my research question of “what are the effects of exercise on the brain, particularly the hippocampus in older adults?”. While this data examines healthy older adults, the information can be used to predict the effect of exercise on the hippocampus and cognition in the prevention of the neurodegeneration observed in AD. Therefore, if exercise increases both hippocampal volume and cognitive function it might delay the onset of AD symptoms because there will be more hippocampal volume. Thus, more neurodegeneration of the enlarged hippocampus would have to occur for the onset of AD symptoms. This data shows a positive effect of exercise on IGF-I, hippocampal volume, or cognitive function but does not propose a mechanistic pathway for these observed results. The next experiment presented will define a potential pathway of exercise to neural plasticity and cognitive function changes by examining the pathway of BDNF.

References:

Cotman, C. W., Berchtold, N. C., & Christie, L. A. (2007). Exercise builds brain health: key roles of growth factor cascades and inflammation. Trends in neurosciences, 30(9), 464–472. https://doi.org/10.1016/j.tins.2007.06.011

Maass, A., Düzel, S., Brigadski, T., Goerke, M., Becke, A., Sobieray, U., Neumann, K., Lövdén, M., Lindenberger, U., Bäckman, L., Braun-Dullaeus, R., Ahrens, D., Heinze, H. J., Müller, N. G., Lessmann, V., Sendtner, M., & Düzel, E. (2016). Relationships of peripheral IGF-1, VEGF and BDNF levels to exercise-related changes in memory, hippocampal perfusion and volumes in older adults. NeuroImage, 131, 142–154. https://doi.org/10.1016/j.neuroimage.2015.10.084

Growth factor IGF-1 increases risk for several cancers • healthcare-in-europe.com

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