Deep brain stimulation for Alzheimer's Disease: An update

Abstract

Background:Dementia is among the leading causes of severe and long-term disability worldwide, decreasing the quality of life of individuals and families. Moreover, it induces an enormous economic burden on societies. The most prevalent cause of dementia is Alzheimer's disease (AD). Because current treatment options for AD are limited, deep brain stimulation (DBS) has been considered.Methods:The aim of this review is to survey the current understanding regarding the effects of DBS in AD and possibly shed light on the mechanisms of DBS in AD. We searched PubMed and Cochrane for various studies in English literature describing DBS in patients with AD and relevant preclinical studies. All related studies published from December 2013 to March 2017 were included in this review.Results:Our understanding of the neural circuitry underlying learning and memory in both rodent models and human patients has grown over the past years and provided potential therapeutic targets for DBS such as the fornix and the nucleus basalis of Meynert. Clinical results indicate that DBS is most beneficial for patients who are in the early stages of AD. Potential mechanisms of action of DBS in AD comprise long-term structural plasticity, including hippocampal enlargement as well as enhanced neurotransmitter release.Conclusion:It is still premature to conclude that DBS can be used in the treatment of AD, and the field will wait for the results of ongoing and future clinical trials.

The effect of fornix deep brain stimulation in brain diseases

“…The circuit of Papez is considered one of the major pathways of the limbic system and is primarily involved in emotional expression, neurovegetative function, and memory [ 3 ]. While DBS applied to limbic targets has been evaluated for patients with treatment-resistant depression [ 4 – 6 ] and obsessive–compulsive disorder [ 7 ], recently studies have begun to explore the applicability of DBS in a widening array of psychiatric conditions including Alzheimer’s disease (AD) dementia [ 8 , 9 ]. The classical circuit of Papez consists of the hippocampal formation, fornix, mammillary bodies, mammillothalamic tract, anterior thalamic nucleus, cingulum, and the entorhinal cortex [ 10 ].…”

The Memory-Modifying Potential of Optogenetics and the Need for Neuroethics

“…Last but not least, optogenetic intervention has been recently tested as a potential treatment for various models of neurological disorders tested in animals. The latest evidence indicates that optogenetics, similar to DBS [63], shows potential for improving memory impairments observed in neurological conditions such as diencephalic amnesia and Alzheimer's disease through stimulating small thalamic nuclei [7]. Optogenetics has also contributed significantly to an improved understanding of the dysfunctional neural circuits underlying PTSD [64] and Parkinson's disease [65], inspiring novel circuit-inspired applications of DBS (ibidem).…”

Transcending the brain: is there a cost to hacking the nervous system?

“…Whilst the exact mechanism of DBS is still unclear, it is believed to involve disruption to the abnormal basal ganglia circuitry to restore normality ( Wichmann and DeLong, 2016 ). Alongside Parkinson’s disease, DBS is also investigated for use in depression, movement disorders, chronic pain, neuropsychiatric disorders, epilepsy, addictions and Alzheimer’s disease amongst other conditions ( Table 1; Nuttin et al , 1999 ; Volkmann et al , 2012 ; Munte et al , 2013 ; Delaloye and Holtzheimer, 2014 ; Falowski, 2015 ; Aldehri et al , 2018 ; Klinger and Mittal, 2018 ).…”