Exciting networks: multi-modal mapping and modulating network breakdown in early Alzheimers disease
Human Cognitive and Systems Neuroscience
Final Report Abstract
Alzheimer’s disease is the most common form of dementia, characterized by memory problems in the first stage. The cause of this disease is related to the accumulation of toxic proteins in the brain. These toxic proteins affect the communication between brain cells, which leads to memory problems. In the current project, the researchers set out to investigate whether communication between specific regions that are early affected in the disease (hippocampus and retrosplenial cortex) are related to memory deficits. In addition, they aimed to modulate the communication between these regions by using non-invasive brain stimulation methods with the goal to delay or improve memory performance. First, the researchers investigated 25 clinically normal persons, 27 patients with subjective memory complaints and 24 patients with very mild Alzheimer’s disease using magnetic resonance imaging and tests assessing cognitive functions. We found higher communication between specific regions in the brain and this higher level of communication was associated with worse memory performance. The retrosplenial cortex, a region hidden in the middle part of the brain, was crucial to enable the communication between these regions. In the next step, we tested a memory task that can be used in the scanner and that measures activity in the hippocampus and retrosplenial cortex. We observed that this task was sensitive to specific changes in the hippocampus from middle age. Autopsy studies have indicated that brains of middle-aged individuals already harbor a significant amount of toxic proteins. This suggests that our task may be sensitive to the earliest Alzheimer’s disease related brain changes, though studies also visualizing these proteins will be necessary to confirm this hypotheses. Finally, based on the previous findings we designed a study to stimulate the communication between the hippocampus and retrosplenial cortex while performing our memory task in healthy older individuals and patients with very mild Alzheimer’s disease. All participants received sham or real stimulation during 5 consecutive days. In the first part, using a novel method that administers stimulation with random amplitude and frequencies, we found no difference in memory performance between the 18 healthy older individuals in the stimulated group and the18 healthy older individuals in the sham group. In our second part, we used the established direct current stimulation method, applying a low consistent current on the brain. Because in this study, stimulation and functional magnetic resonance imaging were performed simultaneously, more stringent exclusion criteria had to be applied. Therefore, we were not able to recruit many people. So far, we have been able to include 11 clinically normal and 3 patients with mild Alzheimer’s disease. The first preliminary results in the clinically normal individuals show no effect of stimulation on memory performance, but there is a trend for the more complex condition. Given these encouraging results, we received additional intramural scan funds from Maastricht University that will enable us to include more participants and further explore the effects of stimulation on memory and brain changes. Given the disappointing results of several clinical trials focused on removal of amyloid-beta, one of the toxic proteins, the results of this study have the potential to lead to new developments in non-pharmacological treatments for Alzheimer’s disease. On the short-term, further investigations can assess whether the memory task in this project could be a valuable marker for early detection of Alzheimer’s disease.
Publications
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(2016) Aberrant functional connectivity differentiates retrosplenial cortex from posterior cingulate cortex in prodromal Alzheimer’s disease. Neurobiology of Aging, 44, 114-26
Dillen K.N.H., Jacobs H.I.L., Kukolja J., von Reutern B., Richter N., Onur Ö.A., Dronse J., Langen K.-J. & Fink G.R.
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(2017) Functional disintegration of the default mode network in prodromal Alzheimer's disease. Journal Of Alzheimer's Disease , 59(1), 169-187
Dillen K.N.H., Jacobs H.I.L., Kukolja J., Richter N., von Reutern B., Onur Ö.A., Langen K.-J. & Fink G.R.
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(2018). On the extraction and analysis of graphs from resting-state fMRI to support a correct and robust diagnostic tool for Alzheimer's disease. Frontiers in Neuroscience, 12, 528
Bachmann C, Jacobs HIL, Porta Mana P, Dillen K, Richter N, von Reutern B, Dronse J, Onur OA, Langen KJ, Fink GR, Kukolja J, Morrison A
