Davunetide sex-dependently boosts memory in prodromal Alzheimer's disease.

IF 5.8 1区医学 Q1 PSYCHIATRY Translational Psychiatry Pub Date : 2024-10-02 DOI:10.1038/s41398-024-03118-0

Illana Gozes, Jason Blatt, Alexandra Lobyntseva

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Abstract

Background: The tauopathy inhibitor, davunetide shows sex-dependent efficacy in women suffering from progressive supranuclear palsy. Extending these findings to prodromal Alzheimer's disease, we submitted a double-blind, placebo-controlled, 12 weeks/16 weeks follow-up, davunetide clinical trial results in amnestic mild cognitive impairment (ClinicalTrials.gov ID NCT00422981), to a sex-dependent analysis.

Methods: One hundred forty-four individuals, separated into eight groups (1:2 placebo-and 2 doses, 5 mg davunetide/daily or 15 mg davunetide/twice-daily, with matching placebo intranasal volumes), were evaluated.

Results: Significant dose-dependent cognitive increases were observed in men compared to women with a test of delayed (12 ss) visual matching to the sample. In a test of semantic working memory and attention (digit span), women showed a significant low-dose placebo effect, ensuing in a high dose significant davunetide improvement, over the matched placebo. Correlating anxiety with cognition showed sex-opposing results, with women depicting significant anxiety correlations with delayed matching to sample.

Discussion: In conclusion, sex-specific prodromal Alzheimer's drug development is encouraged, with davunetide playing a lead initiative role.

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达伍内肽能提高前驱阿尔茨海默氏症患者的记忆力，但这与性别有关。

背景：tauopathy抑制剂达呋奈肽对患有进行性核上性麻痹的女性具有性别依赖性疗效。为了将这些发现推广到阿尔茨海默病的前驱期，我们提交了一项双盲、安慰剂对照、12周/16周随访、达武内肽治疗失忆性轻度认知障碍的临床试验结果（ClinicalTrials.gov ID NCT00422981），并进行了性别依赖性分析：方法：将144人分为8组（1:2安慰剂和2个剂量，5毫克达武尼肽/天或15毫克达武尼肽/天两次，同时配合安慰剂鼻内用量）进行评估：在对样本进行延迟（12 秒）视觉匹配测试时，男性的认知能力明显高于女性。在语义工作记忆和注意力（数字跨度）测试中，女性表现出显著的低剂量安慰剂效应，而高剂量达芙尼肽则比匹配的安慰剂有显著改善。将焦虑与认知相关联的结果与性别相反，女性在延迟与样本匹配的情况下表现出显著的焦虑相关性：总之，我们鼓励开发针对不同性别的阿尔茨海默氏症前驱期药物，其中达呋奈肽将发挥主导作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Translational Psychiatry PSYCHIATRY-

CiteScore

11.50

自引率

2.90%

发文量

484

审稿时长

23 weeks

期刊介绍： Psychiatry has suffered tremendously by the limited translational pipeline. Nobel laureate Julius Axelrod''s discovery in 1961 of monoamine reuptake by pre-synaptic neurons still forms the basis of contemporary antidepressant treatment. There is a grievous gap between the explosion of knowledge in neuroscience and conceptually novel treatments for our patients. Translational Psychiatry bridges this gap by fostering and highlighting the pathway from discovery to clinical applications, healthcare and global health. We view translation broadly as the full spectrum of work that marks the pathway from discovery to global health, inclusive. The steps of translation that are within the scope of Translational Psychiatry include (i) fundamental discovery, (ii) bench to bedside, (iii) bedside to clinical applications (clinical trials), (iv) translation to policy and health care guidelines, (v) assessment of health policy and usage, and (vi) global health. All areas of medical research, including — but not restricted to — molecular biology, genetics, pharmacology, imaging and epidemiology are welcome as they contribute to enhance the field of translational psychiatry.