Intranasal insulin therapy for Alzheimer disease and amnestic mild cognitive impairment: a pilot clinical trial.
Intranasal insulin therapy for Alzheimer disease and amnestic mild cognitive impairment: a pilot clinical trial.
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DOI：
10.1001/archneurol.2011.233
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发表时间：
2012-01
影响因子：
--
通讯作者：
Gerton, Brooke
中科院分区：
文献类型：
--
作者：
Craft, Suzanne;Baker, Laura D.;Montine, Thomas J.;Minoshima, Satoshi;Watson, G. Stennis;Claxton, Amy;Arbuckle, Matthew;Callaghan, Maureen;Tsai, Elaine;Plymate, Stephen R.;Green, Pattie S.;Leverenz, James;Cross, Donna;Gerton, Brooke
研究鼻内胰岛素给药对遗忘型轻度认知障碍或阿尔茨海默病（AD）成人的认知、功能、脑葡萄糖代谢和脑脊液生物标志物的影响。随机、双盲、安慰剂对照试验。退伍军人事务医疗中心的临床研究单位。意向治疗样本包括104名患有遗忘型轻度认知障碍（n = 64）或轻度至中度AD（n = 40）的成人。受试者接受安慰剂（n = 30）、20 IU胰岛素（n = 36）或40 IU胰岛素（n = 38），持续4个月，使用鼻内给药装置（Kurve Technology，博瑟尔，华盛顿）给药。主要措施包括延迟的故事回忆评分和痴呆严重程度评定量表评分，和次要措施包括阿尔茨海默病评估量表认知子量表（ADAS-cog）评分和阿尔茨海默病合作研究-日常生活活动（ADCS-ADL）量表。一部分参与者在治疗前后接受了腰椎穿刺（n = 23）和氟脱氧葡萄糖F 18正电子发射断层扫描（n = 40）。结果指标采用重复测量协方差分析进行分析。20 IU胰岛素治疗改善了延迟记忆（P <0.05），两种剂量的胰岛素（20和40 IU）均保持了正常的功能能力（P <0.01）。两种胰岛素剂量也保留了年轻参与者通过ADAS-cog评分评估的一般认知和成年AD患者通过ADCS-ADL量表评估的功能能力（P <0.05）。胰岛素治疗组受试者的脑脊液生物标志物未发生变化，但在探索性分析中，记忆和功能的变化与脑脊液中Aβ42水平和tau蛋白/Aβ42比值的变化相关。安慰剂组受试者的顶颞叶、额叶、楔前叶和楔叶区域的氟脱氧葡萄糖F18摄取减少，胰岛素进展最小。未发生治疗相关严重不良事件。这些结果支持遗忘型轻度认知障碍患者和AD患者鼻内胰岛素治疗的长期试验。
To examine the effects of intranasal insulin administration on cognition, function, cerebral glucose metabolism, and cerebrospinal fluid biomarkers in adults with amnestic mild cognitive impairment or Alzheimer disease (AD). Randomized, double-blind, placebo-controlled trial. Clinical research unit of a Veterans Affairs medical center. The intent-to-treat sample consisted of 104 adults with amnestic mild cognitive impairment (n = 64) or mild to moderate AD (n = 40). Participants received placebo (n = 30), 20 IU of insulin (n = 36), or 40 IU of insulin (n = 38) for 4 months, administered with a nasal drug delivery device (Kurve Technology, Bothell, Washington). Primary measures consisted of delayed story recall score and the Dementia Severity Rating Scale score, and secondary measures included the Alzheimer Disease’s Assessment Scale–cognitive subscale (ADAS-cog) score and the Alzheimer’s Disease Cooperative Study–activities of daily living (ADCS-ADL) scale. A subset of participants underwent lumbar puncture (n = 23) and positron emission tomography with fludeoxyglucose F 18 (n = 40) before and after treatment. Outcome measures were analyzed using repeated-measures analysis of covariance. Treatment with 20 IU of insulin improved delayed memory (P < .05), and both doses of insulin (20 and 40 IU) preserved caregiver-rated functional ability (P < .01). Both insulin doses also preserved general cognition as assessed by the ADAS-cog score for younger participants and functional abilities as assessed by the ADCS-ADL scale for adults with AD (P < .05). Cerebrospinal fluid biomarkers did not change for insulin-treated participants as a group, but, in exploratory analyses, changes in memory and function were associated with changes in the Aβ42 level and in the tau protein–to–Aβ42 ratio in cerebrospinal fluid. Placebo-assigned participants showed decreased fludeoxyglucose F 18 uptake in the parietotemporal, frontal, precuneus, and cuneus regions and insulin-minimized progression. No treatment-related severe adverse events occurred. These results support longer trials of intranasal insulin therapy for patients with amnestic mild cognitive impairment and patients with AD.
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影响因子：
9.9
作者：
Watson, GS;Peskind, ER;Craft, S
通讯作者：
Craft, S
影响因子：
5.7
作者：
Chen, Kewei;Langbaum, Jessica B. S.;Fleisher, Adam S.;Ayutyanont, Napatkamon;Reschke, Cole;Lee, Wendy;Liu, Xiaofen;Bandy, Dan;Alexander, Gene E.;Thompson, Paul M.;Foster, Norman L.;Harvey, Danielle J.;de Leon, Mony J.;Koeppe, Robert A.;Jagust, William J.;Weiner, Michael W.;Reiman, Eric M.
通讯作者：
Reiman, Eric M.
DOI：
10.1016/j.jalz.2009.07.038
发表时间：
2009-09
期刊：
Alzheimer's & dementia : the journal of the Alzheimer's Association
影响因子：
--
作者：
Schneider LS;Sano M
通讯作者：
Sano M
影响因子：
6.3
作者：
WORSLEY, KJ;EVANS, AC;NEELIN, P
通讯作者：
NEELIN, P
DOI：
10.1073/pnas.0809158106
发表时间：
2009-02-10
影响因子：
11.1
作者：
De Felice, Fernanda G.;Vieira, Marcelo N. N.;Klein, William L.
通讯作者：
Klein, William L.