There were 2,519 nondemented individuals evaluated in 2001 with the CSI-D of which 1,808 were re-evaluated in 2004. The 711 participants not re-evaluated were deceased (33.6%), refused (34.2%), too sick (9.4%), or lost for other reasons (22.8%). This analysis was also restricted to the 1,146 participants who provided blood samples for ApoE genotyping. Of the 1,146 participants, 292 (25.5%) were on LLAs at baseline. Breaking down the types of LLAs used, 284 (97.3%) were only on statins, 3 (1.0%) were on both statin and another LLA, and 5 (1.7%) were solely on another LLA. For the analysis, we excluded the five participants who were only on a non-statin LLA. Approximately 41% of statin users were taking simvastatin, 41% atorvastatin, 8% pravastatin, 6% fluvastatin, 2% cerivastatin, and 2% lovastatin. shows demographic and baseline characteristics for both statin users and those participants not taking statins (statin nonusers). Level of education, presence of ApoE ε4 allele, and history of smoking were similar in both groups (p > 0.05). Baseline statin use was significantly associated with younger age, male sex, hypertension, higher body mass index (BMI), and prevalence of alcohol use, nonsteroidal anti-inflammatory drug use, stroke, diabetes, and heart disease (p < 0.05). Baseline statin non-users were significantly associated with elevated total cholesterol, LDL-C, and CRP levels (p < 0.05).
Demographics and baseline characteristics both overall and by baseline statin use
On the standardized cognitive change scores, statin users at baseline had a mean change of −0.14 SD while non-statin users had a mean change of 0.05 SD, a difference of 0.19 SD with statin users showing less cognitive decline than the nonusers (p = 0.0020).
Univariate analyses showed that only statin use, possession of an ApoE 4 allele, and hypertension were associated with cognitive decline after adjusting for age, sex, and education (p < 0.10). When these variables were included together in an ANCOVA model, hypertension was no longer significant. An interaction between baseline statin use and possession of ApoE ε4 allele was investigated but found not significant and not included in the final model. Results from the final model are shown in . After adjusting for age, gender, education, and the possession of ApoE ε4 allele, baseline statin use was associated with less cognitive decline (p = 0.0177). When adjusting for baseline cognitive score, an inverse association between statins and cognitive decline remains (p = 0.0046).
Results from final model showing the association of statin use at baseline with 3-year cognitive decline
A logistic regression model on incident dementia, in 2004 as the outcome using the same independent variables as in the model above, showed that statins may be associated with a reduction in incident dementia (OR = 0.32; p = 0.0673). The number of incident dementia cases was 3 (1.2%) for statin users and 29 (3.9%) for participants not taking statins. For this analysis, 32 (2.8%) participants were diagnosed with dementia and 960 (84.1%) participants were either diagnosed normal by clinical examination or in the good performance group based upon their CSI-D score. The remaining 149 (13.1%) participants, who were in the poor performance category in 2004, were excluded.
When LDL-C and CRP were included in the final model on cognitive decline (tables and ), there were no interactions with statin use with either variable (p = 0.7605 for LDL-C and p = 0.3216 for CRP). In both models, however, the main effects for statin use were significant.
Results from final model including the interaction between baseline statin use and LDL-C on 3-year cognitive decline
Results from final model including the interaction between baseline statin use and C-reactive protein (CRP) on 3-year cognitive decline
Of the 1,808 participants with 3-year follow-up, we compared the 1,146 participants included in the analyses to the 662 participants who were excluded from the analyses due to lack of blood samples. The rates of statin use at 2001 and the magnitude of cognitive decline between the two groups were similar.
We also investigated statin use over time. Of the 287 participants who were statin users in 2001, 212 (73.9%) were still statin users while 72 (25.1%) discontinued using statins during the follow-up wave in 2004. Of the 859 participants who were not using statins in 2001, 120 (14.1%) began using statins by 2004 while 730 (85.5%) still reported no use. The remaining subjects did not provide their medications at 2004. When the final model for cognitive decline used statin use over time instead of statin use at 2001, while both groups of 2001 statin users demonstrated less cognitive decline than statin nonusers, this difference was significant only for the statin users who had discontinued prior to the 2004 wave (). A comparison of the demographic, clinical, biochemical characteristics and statin use of the four types of statin use from 2001 to 2004 found no significant differences between the 72 participants who discontinued use and the 212 participants who continued use, which was the main comparison of interest.
Results from analysis of covariance model on cognitive decline by statin use over time after adjusting for age, sex, education, and ApoE ε4