Abstract
BACKGROUND: 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). METHODS: The data of 828 subjects including 178 HC, 492 MCI, and 158 AD individuals were obtained from ADNI. The baseline and longitudinal [(18) F] AV45 and 18-fluorodeoxyglucose (FDG) PET standard uptake value ratio (SUVR) measures were investigated among statin users and non-users. RESULTS: 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. CONCLUSION: 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.