Neurobiologic Rationale for Treatment of Apathy in Alzheimer's Disease With Methylphenidate.
Neurobiologic Rationale for Treatment of Apathy in Alzheimer's Disease With Methylphenidate.
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DOI：
10.1016/j.jagp.2020.04.026
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发表时间：
2021-01
期刊：
影响因子：
--
通讯作者：
Rosenberg PB
中科院分区：
文献类型：
--
作者：
van Dyck CH;Arnsten AFT;Padala PR;Brawman-Mintzer O;Lerner AJ;Porsteinsson AP;Scherer RW;Levey AI;Herrmann N;Jamil N;Mintzer JE;Lanctôt KL;Rosenberg PB
阿尔茨海默病(AD)的公共卫生负担不仅与认知症状有关，还与包括冷漠在内的神经精神症状有关。冷漠被定义为与先前的功能水平相比，目标导向活动的数量减少，影响30%-70%的阿尔茨海默病患者。以前治疗阿尔茨海默病患者冷漠的尝试--无论是非药理学的还是药理学的--都是不够的。儿茶酚胺能与哌醋甲酯已显示出令人鼓舞的结果，初步试验的冷漠在AD。了解动机行为背后的神经元回路及其对儿茶酚胺作用的依赖，有助于为哌醋甲酯治疗AD患者的冷漠提供理论基础。解剖学、生理学和行为学研究已经确定了控制动作、认知和情绪的平行皮质-基底神经节回路，并在动机行为中发挥关键作用。了解前额叶皮质背外侧区、眶内侧区和背内侧区对动机行为的不同贡献有助于解释为什么AD患者这些区域的退化会导致冷漠行为。我们认为，阿尔茨海默病患者前额叶皮质的退化会产生冷漠的症状。我们进一步提出，哌甲酯治疗可能通过增强前额叶-纹状体-丘脑皮质回路中去甲肾上腺素和多巴胺的作用来改善这些症状。
The public health burden of Alzheimer’s disease (AD) is related not only to cognitive symptoms, but also to neuropsychiatric symptoms, including apathy. Apathy is defined as a quantitative reduction of goal-directed activity in comparison to a previous level of functioning and affects 30%–70% of persons with AD. Previous attempts to treat apathy in AD—both nonpharmacologically and pharmacologically—have been wanting. Catecholaminergic treatment with methylphenidate has shown encouraging results in initial trials of apathy in AD. Understanding the neuronal circuits underlying motivated behavior and their reliance on catecholamine actions helps provide a rationale for methylphenidate actions in the treatment of apathy in patients with AD. Anatomical, physiological, and behavioral studies have identified parallel, cortical-basal ganglia circuits that govern action, cognition, and emotion and play key roles in motivated behavior. Understanding the distinct contributions to motivated behavior of subregions of the prefrontal cortex—dorsolateral, orbital-ventromedial, and dorsomedial—helps to explain why degeneration of these areas in AD results in apathetic behaviors. We propose that the degeneration of the prefrontal cortex in AD produces symptoms of apathy. We further propose that methylphenidate treatment may ameliorate those symptoms by boosting norepinephrine and dopamine actions in prefrontal-striatal-thalamocortical circuits.
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