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.
Highlights
Dementia refers to a group of brain disorders that affect memory, reasoning, judgment, executive function, praxis, visuospatial abilities, and language that are not ascribed to delirium or another major psychiatric disorder (Bouchard, 2007)
Gratwicke et al (2017) recently conducted a randomized, double-blind, crossover clinical trial that involved evaluating the results of six patients with Parkinson’s disease dementia (PDD) who were treated with nucleus basalis of Meynert (NBM)-deep brain stimulation (DBS)
In the Phase II trial report of fornix-DBS in patients with Alzheimer’s disease (AD), patients with LOAD showed a trend of clinical benefit, while there was a trend of faster cognitive deterioration in patients with EOAD (Lozano et al, 2016)
Summary
Dementia refers to a group of brain disorders that affect memory, reasoning, judgment, executive function, praxis, visuospatial abilities, and language that are not ascribed to delirium or another major psychiatric disorder (Bouchard, 2007). STN-DBS improved his motor symptoms, while NBM-DBS improved his global cognitive functions, such as memory, attention, concentration, alertness, drive, spontaneity, and social communication (Freund et al, 2009) The mechanism for these improvements may be related to the stimulation of a largely degenerated nucleus, as low-frequency stimulation (20 Hz) can excite residual NBM neurons (Nandi et al, 2008; Wu et al, 2008). Gratwicke et al (2017) recently conducted a randomized, double-blind, crossover clinical trial that involved evaluating the results of six patients with PDD who were treated with NBM-DBS. We still need more evidence to confirm our hypothesis In both trials, a limitation was that the patients continued acetylcholinesterase inhibitor therapy, so the potential physiological effects of NBM-DBS on the cholinergic system may have been partially disguised (Kuhn et al, 2015a; Gratwicke et al, 2017).
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