Subramaniam Saravanan, Blake David T, Constantinidis Christos
Department of Neurobiology & Anatomy, Wake Forest School of Medicine, Winston-Salem, NC, USA.
Brain and Behavior Discovery Institute, Department of Neurology, Medical College of Georgia, Augusta University, Augusta, GA, USA.
J Alzheimers Dis. 2021;83(2):491-503. doi: 10.3233/JAD-210425.
Memory and cognitive impairment as sequelae of neurodegeneration in Alzheimer's disease and age-related dementia are major health issues with increasing social and economic burden. Deep brain stimulation (DBS) has emerged as a potential treatment to slow or halt progression of the disease state. The selection of stimulation target is critical, and structures that have been targeted for memory and cognitive enhancement include the Papez circuit, structures projecting to the frontal lobe such as the ventral internal capsule, and the cholinergic forebrain. Recent human clinical and animal model results imply that DBS of the nucleus basalis of Meynert can induce a therapeutic modulation of neuronal activity. Benefits include enhanced activity across the cortical mantle, and potential for amelioration of neuropathological mechanisms associated with Alzheimer's disease. The choice of stimulation parameters is also critical. High-frequency, continuous stimulation is used for movement disorders as a way of inhibiting their output; however, no overexcitation has been hypothesized in Alzheimer's disease and lower stimulation frequency or intermittent patterns of stimulation (periods of stimulation interleaved with periods of no stimulation) are likely to be more effective for stimulation of the cholinergic forebrain. Efficacy and long-term tolerance in human patients remain open questions, though the cumulative experience gained by DBS for movement disorders provides assurance for the safety of the procedure.
作为阿尔茨海默病和年龄相关性痴呆神经退行性变后遗症的记忆和认知障碍是重大健康问题，其社会和经济负担日益加重。深部脑刺激（DBS）已成为一种减缓或阻止疾病进展的潜在治疗方法。刺激靶点的选择至关重要，已被作为记忆和认知增强靶点的结构包括帕佩兹环路、投射至额叶的结构（如腹侧内囊）以及胆碱能前脑。近期人类临床和动物模型结果表明，刺激Meynert基底核可诱导神经元活动的治疗性调节。益处包括增强整个皮质的活动，以及改善与阿尔茨海默病相关的神经病理机制的可能性。刺激参数的选择也至关重要。高频、连续刺激用于治疗运动障碍，作为抑制其输出的一种方式；然而，在阿尔茨海默病中尚未假设存在过度兴奋，较低的刺激频率或间歇性刺激模式（刺激期与无刺激期交替）可能对胆碱能前脑的刺激更有效。尽管DBS治疗运动障碍积累的经验为该手术的安全性提供了保障，但人类患者的疗效和长期耐受性仍是悬而未决的问题。
