Deep Brain Stimulation: A Potential Treatment for Dementia in Alzheimer's Disease (AD) and Parkinson's Disease Dementia (PDD)

Abstract

Damage to memory circuits may lead to dementia symptoms in Alzheimer's disease (AD) and Parkinson's disease dementia (PDD). Recently, deep brain stimulation (DBS) has been shown to be a novel means of memory neuromodulation when critical nodes in the memory circuit are targeted, such as the nucleus basalis of Meynert (NBM) and fornix. Potential memory improvements have been observed after DBS in patients with AD and PDD. DBS for the treatment of AD and PDD may be feasible and safe, but it is still preliminary. In this review, we explore the potential role of DBS for the treatment of dementia symptoms in AD and PDD. Firstly, we discuss memory circuits linked to AD and PDD. Secondly, we summarize clinical trials and case reports on NBM or fornix stimulation in AD or PDD patients and discuss the outcomes and limitations of these studies. Finally, we discuss the challenges and future of DBS for the treatment of AD and PDD. We include the latest research results from Gratwicke et al. (2017) and compare them with the results of previous relevant studies, and this would be a worthy update of the literature on DBS for dementia. In addition, we hypothesize that the differences between AD and PDD may ultimately lead to different results following DBS treatment.

Modulation of Human Memory by Deep Brain Stimulation of the Entorhinal-Hippocampal Circuitry

“…In addition, DBS has been explored as a potential treatment for a wide variety of neuropsychological diseases, including diseases characterized by cognitive impairment and memory loss-mainly AD (Lv et al, 2018;Posporelis et al, 2018), though a few trials have been conducted in Parkinson's disease dementia (Lv et al, 2018) and traumatic brain injury (TBI) (Kundu et al, 2018) as well. The DBS research in AD patients has focused largely on long-term (months to years), continuous stimulation with the hope that it could reverse or at least slow the progression of the disease (Table 1), whereas the research with patients with epilepsy has primarily studied whether brief stimulations within well-defined memory paradigms have an overall positive or negative effect on subsequent memory performance for that task (Table 2).…”

Deep Brain Stimulation for Alzheimer's Disease: Stimulation Parameters and Potential Mechanisms of Action

“…This may be related to their structures and roles in the brain. They are involved in different circuit systems, including the base forebrain cholinergic system, the Papez circuit, and the trisynaptic circuit (Lv et al, 2018 ; Yu et al, 2019 ). There is currently no human clinical study of the EC as a target of stimulation in AD, and only animal studies support the EC as a target of DBS.…”

“…Figure 2 shows a schematic representation of these targets in the brain. AD is also considered to be a disease of the neural circuit, as neurons and neural circuits associated with cognitive function are damaged, and the Papez circuit is degraded (Lv et al, 2018 ). The Papez circuit is the main pathway of the limbic system and plays a vital role in the formation and storage of memory.…”

The Neurological, Multisystemic, PolyGenomic and Multipathological Basis of Aging (the ‘Autonomic’ Hypothesis)

“…The identification of the multi-level nature of brain function is one of the primary objectives of the EC's Human Brain Project however there is not, as yet, a fundamental understanding or agreement of such phenomena. Nevertheless there is widespread interest in using such techniques [162] (biofeedback, neurofeedback, neuromodulation, brainwave coherence, transcranial magnetic stimulation, and deep brain stimulation use electrical stimuli to stimulate the basal ganglia) to treat Multiple Sclerosis [163,164], Parkinsonism [165], Alzheimer 's disease [166][167][168], Migraine [169], Premenstrual Syndrome [170], etc.…”