Neuroscience Research Group (NRG), Universal Scientific Education and Research Network (USERN), Tehran, Iran.
School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
CNS Neurosci Ther. 2023 May;29(5):1434-1443. doi: 10.1111/cns.14117. Epub 2023 Feb 14.
There are contradictory findings regarding the effect of statin drugs on amyloid β (Aβ) deposition as one of the main hallmarks of Alzheimer's disease (AD), along with tau pathology. We aimed to longitudinally investigate the therapeutic and preventive role of statin drugs by examining the brain Aβ deposition and metabolism rate in AD, mild cognitive impairment (MCI), and healthy controls (HC).
The data of 828 subjects including 178 HC, 492 MCI, and 158 AD individuals were obtained from ADNI. The baseline and longitudinal [ F] AV45 and 18-fluorodeoxyglucose (FDG) PET standard uptake value ratio (SUVR) measures were investigated among statin users and non-users.
Our results showed that there is no significant difference in baseline Aβ deposition and metabolism rate between statin users and non-users among HC, MCI, and AD subjects. While there was no significant effect of statin on metabolism rate, there was a significant difference in Aβ deposition change after 4 years (from baseline) between statin users and non-users within HC subjects (p = 0.011). The change of Aβ deposition at 4 years from baseline was -2.0 ± 6.3% for statin users and 1.4 ± 4.7% for non-users. There was no significant association between statin duration use with baseline and longitudinal Aβ deposition and metabolism rate. However, statin dosage was significantly associated with Aβ deposition in 2 years (r = -0.412, p = 0.021) in the HC group. Moreover, our analysis showed a significant correlation between total statin exposure (duration×dosage) and Aβ deposition in 2 years visit (r = -0.198, p = 0.037) in HC subjects. Furthermore, we investigated the longitudinal changes within each group of statin users and non-users separately in linear mixed models. Our findings showed that there are no significant changes in AV45 and FDG SUVR among both groups.
The present longitudinal analysis revealed that using statins might be beneficial in slowing down or stabilizing the Aβ deposition due to aging in subjects without cognitive impairment. However, once the clinical symptoms of cognitive impairment appear, statins fail to slow down Aβ deposition. Overall, our findings revealed that statin users might have slower Aβ aggregation than non-users.
他汀类药物对淀粉样蛋白 β（Aβ）沉积的影响存在矛盾的发现，Aβ 沉积是阿尔茨海默病（AD）的主要标志之一，与 tau 病理学有关。我们旨在通过检查 AD、轻度认知障碍（MCI）和健康对照（HC）中的脑 Aβ 沉积和代谢率，来纵向研究他汀类药物的治疗和预防作用。
从 ADNI 中获得了 828 名受试者的数据，包括 178 名 HC、492 名 MCI 和 158 名 AD 个体。研究了他汀类药物使用者和非使用者的基线和纵向 [ F] AV45 和 18-氟脱氧葡萄糖（FDG）正电子发射断层扫描标准摄取比值（SUVR）测量值。
我们的结果表明，在 HC、MCI 和 AD 受试者中，他汀类药物使用者和非使用者的基线 Aβ 沉积和代谢率之间没有显著差异。虽然他汀类药物对代谢率没有显著影响，但在 HC 受试者中，他汀类药物使用者和非使用者在 4 年后（从基线开始）的 Aβ 沉积变化有显著差异（p=0.011）。他汀类药物使用者的 Aβ 沉积在 4 年内从基线下降了 2.0±6.3%，而非使用者为 1.4±4.7%。他汀类药物使用时间与基线和纵向 Aβ 沉积和代谢率之间没有显著关联。然而，他汀类药物的剂量与 HC 组中 2 年内的 Aβ 沉积显著相关（r=-0.412，p=0.021）。此外，我们的分析显示，HC 受试者中总他汀类药物暴露（持续时间×剂量）与 2 年内的 Aβ 沉积之间存在显著相关性（r=-0.198，p=0.037）。此外，我们在线性混合模型中分别对每个他汀类药物使用者和非使用者组的纵向变化进行了研究。我们的研究结果表明，两组之间的 AV45 和 FDG SUVR 均无显著变化。
本纵向分析表明，在没有认知障碍的受试者中，使用他汀类药物可能有助于减缓或稳定因衰老导致的 Aβ 沉积。然而，一旦出现认知障碍的临床症状，他汀类药物就无法减缓 Aβ 沉积。总的来说，我们的研究结果表明，他汀类药物使用者的 Aβ 聚集速度可能比非使用者慢。
