The American Heart Association (AHA) published a 2019 evidence-based statement for the safety and tolerability of statin use. Statins are associated with rare reports of cognitive impairment based on postmarketing data. These reports were generally non-serious and reversible which resulted in loss of memory, confusion, and other forms of impairment. Two clinical trials were highlighted (HPS and PROSPER) which assessed cognitive function from simvastatin 40 mg (5 years) or pravastatin 40 mg (3 years) vs placebo in their respective studies. The results suggest similar rates of cognitive impairment. Several reviews of clinical data also report mixed results whether there is a cognitive benefit or harm from statin therapy. Based on these findings, the AHA suggests there is no definitive evidence regarding the risk of statins and cognitive decline, among other central nervous system disorders. The panel did not address whether starting statins later in life affects cognitive risk or whether earlier initiation may reduce the likelihood of developing dementia. [1]
A 2023 scientific statement from the AHA also evaluates contemporary evidence regarding the effects of aggressive LDL-C lowering on the brain, specifically its impact on dementia. The statement highlights that despite some earlier studies suggesting potential cognitive impairment associated with statins, extensive analysis of RCTs and observational data does not substantiate these concerns. Instead, the data predominantly indicate no significant adverse cognitive effects linked to aggressive LDL-C reduction over the trial durations, which range from a median of 1.6 to 6.0 years. Similar to other guidelines, the panel did not address the impact of statin initiation timing on cognitive outcomes or dementia risk. [2]
A systematic review and meta-analysis published in 2025 examined the association between statin use and the incidence of dementia and Alzheimer’s disease (AD). The research synthesized data from 42 cohort studies encompassing a total of 6,325,740 participants. The findings revealed a significant association wherein statin use resulted in a 21% reduced risk of dementia (hazard ratio [HR] 0.79, 95% confidence interval [CI] 0.71 to 0.88) and a 29% decreased risk of AD (HR 0.71; 95% CI 0.60 to 0.85). Subgroup analyses revealed that statins are more effective in preventing dementia and AD in participants with a mean/median age under 70 years compared to those over 70 years. Specifically, the HR for dementia prevention in younger participants was 0.67 (95% CI 0.56 to 0.81) versus 0.86 (95% CI 0.78 to 0.95) in older participants (p= 0.02). For AD prevention, the HR was 0.47 (95% CI 0.44 to 0.50) in the younger group compared to 0.81 (95% CI 0.71 to 0.92) in the older group (p= 0.01). No significant differences emerged from stratified analyses based on sex, geographical territory, or the lipophilicity of statins. Despite significant heterogeneity across the studies, an overarching pattern suggested greater efficacy with higher statin dosages and extended exposure durations. Sensitivity analyses confirmed the robustness of these outcomes, especially under different diagnostic criteria for dementia/AD. The meta-analysis underscored the implications of the findings for clinical practice, particularly highlighting the importance of early initiation and sustained use of statins among younger populations to maximize cognitive protection. [3]
A 2025 narrative review examines the complex relationship between statin use and cognitive health. This review highlights the ongoing debates regarding whether statins confer neuroprotective benefits or pose a risk of cognitive impairment, with an emphasis on examining the biochemical and physiological mechanisms at play. Statins, known for their efficacy in lowering low-density lipoprotein cholesterol (LDL-C) and preventing cardiovascular disease (CVD), are scrutinized for their potential impact on mental functions due to the distinctive cholesterol homeostasis in the brain, the blood-brain barrier’s limited permeability to lipoproteins, and the varying lipophilicity of different statin formulations. Despite a prevalent belief in possible cognitive side effects, recent epidemiological studies, as cited in the review, suggest that statins may actually offer neuroprotective benefits, though these findings are hindered by biases such as selection bias, confounding variables, and reverse causation. Two pivotal randomized controlled trials, STAREE and PREVENTABLE, are currently underway and anticipated to fill gaps in the literature by providing rigorous, objective analyses of statins’ effects on cognition. Existing literature reveals mixed results, with early studies indicating potential cognitive disturbances associated with statin use, while more recent large-scale studies have failed to substantiate these concerns. Observational data, particularly from large cohorts, have suggested that statins may be linked to a reduced incidence of Alzheimer’s disease and other forms of dementia, although methodological limitations necessitate caution in interpreting these findings. The review underscores the need for further well-designed trials to elucidate the differential impacts of statin type, dose, and treatment duration on cognitive outcomes, as well as their effects on individuals with mild cognitive impairment, diabetes, chronic kidney disease, and other high-risk conditions. [4]
A 2015 systematic review evaluated RCTs and observational studies assessing whether statin use influences cognitive outcomes. Evidence summarized in the review indicates that initiation of statins in late life does not prevent cognitive decline or dementia over the subsequent 3 to 5 years. The authors also note that the current literature does not address whether mid-life or long-term statin use has beneficial cognitive effects, leaving uncertainty regarding potential advantages of earlier initiation. Although several observational studies that used time-updated statin exposure reported an apparent protective association, the review concludes that these findings are likely attributable to reverse causation, given that developing cognitive impairment can reduce adherence to or likelihood of statin prescribing. Overall, the review emphasizes that existing evidence does not support starting statins in late life to prevent cognitive decline, and that whether earlier initiation reduces dementia risk remains unaddressed by available studies. [5]
A 2019 poster abstract examined the complex interplay between lipid profiles, statin use, and cognitive function. This review included publications evaluating associations between cholesterol levels and/or statin use and cognition, focusing on both male and female subjects aged 45 and over. Among studies assessing cholesterol levels and cognition, a predominant number (n=21) indicated that elevated lipid profiles during midlife significantly heightened the risk of developing dementia and cognitive decline in later years (mean age <70 years). Conversely, 17 studies suggested that higher cholesterol levels could positively affect cognition in individuals aged over 70. Furthermore, 16 studies highlighted a link between higher HDL levels and improved cognitive function, alongside a protective role against dementia, while four studies found no association and one observed a potential connection between high HDL and increased neuritic plaques. In contrast, seven studies showed no correlation between cholesterol levels and cognitive performance. In a similar vein, the examination of statin use and cognitive outcomes yielded mixed results. Among the studies reviewed, seven demonstrated a lower risk of cognitive decline for statin users, whereas 23 studies reported potential negative effects of statins on cognition. Additionally, 18 studies did not find any significant association between statin use and cognitive decline. Overall, the results from studies assessing both lipid profiles and statin use underscore the need for more extensive longitudinal research to elucidate these relationships further. Notably, the follow-up duration in most statin-related studies did not exceed five years, leaving the long-term cognitive effects of statin use uncertain. Therefore, it is imperative to undertake additional longitudinal studies investigating the prolonged impact of statin therapy on cognitive decline, particularly spanning from mid to late life. [6]