Padala Kalpana P, Padala Prasad R, McNeilly Dennis P, Geske Jenenne A, Sullivan Dennis H, Potter Jane F
Geriatric Research Education and Clinical Center, Central Arkansas Veterans Health Administration System, Little Rock, AR, USA.
Am J Geriatr Pharmacother. 2012 Oct;10(5):296-302. doi: 10.1016/j.amjopharm.2012.08.002. Epub 2012 Aug 22.
Statins are well-known for their cardiovascular benefits. However, the cognitive effects of statins are not well understood. We hypothesized that individuals with preexisting dementia would be more vulnerable to statin-related cognitive effects.
The aim of this study was to evaluate the impact on cognition of 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor (statin) discontinuation and rechallenge in individuals with Alzheimer's dementia (AD) on statins at baseline.
A 12-week prospective, open-label study was conducted in a geriatric clinic setting. Eighteen older subjects underwent a 6-week withdrawal phase of statins followed by a 6-week rechallenge. The primary outcome measure was cognition, measured by the Mini-Mental State Examination (MMSE); secondary outcome measures were the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) neuropsychological battery, Activities of Daily Living (ADL) scale, Instrumental ADL (IADL) scale, and fasting cholesterol. The change in outcome measures was assessed using repeated-measures ANOVA and paired t tests.
At the end of the intervention, there was a significant difference across time for MMSE score (P = 0.018), and total cholesterol (P = 0.0002) and a trend toward change across time for ADL (P = 0.07) and IADL (P = 0.06) scale scores. Further analyses using paired t tests indicated improvement in MMSE scores (Δ1.9 [3.0], P = 0.014) with discontinuation of statins and a decrease in MMSE scores (Δ1.9 [2.7], P = 0.007) after rechallenge. Total cholesterol increased with statin discontinuation (P = 0.0003) and decreased with rechallenge (P = 0.0007). The CERAD score did not show a change across time (P = 0.31). There was a trend toward improvement in ADL (P = 0.07) and IADL (P = 0.06) scale scores with discontinuation of statins, but no change with rechallenge.
This pilot study found an improvement in cognition with discontinuation of statins and worsening with rechallenge. Statins may adversely affect cognition in patients with dementia.
他汀类药物因其心血管益处而广为人知。然而，他汀类药物对认知的影响尚不完全清楚。我们假设，已患有痴呆症的个体可能更容易受到他汀类药物相关认知影响。
本研究旨在评估在基线时服用他汀类药物的阿尔茨海默病（AD）患者中，停用和重新使用3-羟基-3-甲基戊二酰辅酶A还原酶抑制剂（他汀类药物）对认知的影响。
在一家老年诊所进行了一项为期12周的前瞻性、开放标签研究。18名老年受试者经历了为期6周的他汀类药物撤药期，随后是为期6周的重新用药期。主要结局指标是通过简易精神状态检查表（MMSE）测量的认知；次要结局指标是建立阿尔茨海默病注册库协会（CERAD）神经心理成套测验、日常生活活动（ADL）量表、工具性ADL（IADL）量表和空腹胆固醇。使用重复测量方差分析和配对t检验评估结局指标的变化。
在干预结束时，MMSE评分（P = 0.018）、总胆固醇（P = 0.0002）随时间有显著差异，ADL（P = 0.07）和IADL（P = 0.06）量表评分随时间有变化趋势。使用配对t检验的进一步分析表明，停用他汀类药物后MMSE评分改善（Δ1.9 [3.0]，P = 0.014），重新用药后MMSE评分降低（Δ1.9 [2.7]，P = 0.007）。停用他汀类药物后总胆固醇升高（P = 0.0003），重新用药后降低（P = 0.0007）。CERAD评分随时间未显示变化（P = 0.31）。停用他汀类药物后ADL（P = 0.07）和IADL（P = 目标= 0.06）量表评分有改善趋势，但重新用药后无变化。
这项初步研究发现，停用他汀类药物后认知改善，重新用药后认知恶化。他汀类药物可能对痴呆症患者的认知产生不利影响。
