Deep brain stimulation of fornix in Alzheimer's disease: From basic research to clinical practice

Abstract

Alzheimer's disease (AD) is one of the most common progressive neurodegenerative diseases associated with the degradation of memory and cognitive ability. Current pharmacotherapies show little therapeutic effect in AD treatment and still cannot prevent the pathological progression of AD. Deep brain stimulation (DBS) has shown to enhance memory in morbid obese, epilepsy and traumatic brain injury patients, and cognition in Parkinson's disease (PD) patients deteriorates during DBS off. Some relevant animal studies and clinical trials have been carried out to discuss the DBS treatment for AD. Reviewing the fornix trials, no unified conclusion has been reached about the clinical benefits of DBS in AD, and the dementia ratings scale has not been effectively improved in the long term. However, some patients have presented promising results, such as improved glucose metabolism, increased connectivity in cognition‐related brain regions and even elevated cognitive function rating scale scores. The fornix plays an important regulatory role in memory, attention, and emotion through its complex fibre projection to cognition‐related structures, making it a promising target for DBS for AD treatment. Moreover, the current stereotaxic technique and various evaluation methods have provided references for the operator to select accurate stimulation points. Related adverse events and relatively higher costs in DBS have been emphasized. In this article, we summarize and update the research progression on fornix DBS in AD and seek to provide a reliable reference for subsequent experimental studies on DBS treatment of AD.

Microglia and Astrocytes in Alzheimer’s Disease: Significance and Summary of Recent Advances

“…Deep brain stimulation (DBS) has emerged as a potential method for improving cognitive function in AD through the modulation of neural circuits [ 291 ]. Compared to non-invasive neural modulation strategies, invasive DBS through implanted electrodes targets specific brain areas and provides real-time EEG-neurofeedback, resulting in better treatment effects [ 292 ]. Chronic fornix DBS treatment significantly reduced amyloid deposition in the hippocampus and cortex, decreased activation of astrocytes and microglia, and promoted neurogenesis [ 293 ].…”

“…Interestingly, the rats treated with DBS showed a decrease in the number of abnormally activated astrocytes and morphological changes, indicating that DBS contributes to restoring the balance of the nervous system [ 293 ]. Clinical trials also found that DBS targeting the fornix helps to regulate cognitive ability and stabilize or attenuate memory impairment in mild AD patients [ 292 , 293 ]. Unfortunately, current DBS therapy targeting the fornix for AD only improves episodic memory in a subset of patients [ 294 ].…”

Alzheimer’s Disease Treatment: The Search for a Breakthrough

“…DBS, specifically the fornix, is being investigated as a treatment for patients with mild AD. Results from randomized clinical trials have demonstrated an improvement in cognitive function among some patients and no benefit in others [ 209 ]. The fornix, a part of the Papez circuit, is the principal inflow and outflow tract of the hippocampus and middle temporal lobe.…”