Statins May Slow Cognitive Decline in Women With AD

LONDON — Statin use is associated with slower cognitive decline in some patients with Alzheimer’s disease (AD), particularly in women with elevated low-density lipoprotein cholesterol (LDL-C).In a registry-based analysis of more than 1200 patients with AD or mixed AD (mixed AD and vascular dementia), women with elevated LDL-C who were taking statins experienced a slower rate of decline on the Mini-Mental State Examination (MMSE) compared with women not taking statins (beta coefficient, 1.2 points per year). The association was not statistically significant in men with elevated LDL-C, and no sex differences were observed among patients with lower LDL-C levels.The findings suggest that sex and LDL-C levels may influence the relationship between statin use and cognitive decline, but the investigators cautioned that the results are preliminary.“These are still preliminary findings from an observational study, so we cannot say that statins directly caused the slower cognitive decline,” lead investigator Minjia Mo, PhD, of Karolinska Institutet in Stockholm, Sweden, told Medscape Medical News.“Some participants may have been previous statin users who discontinued treatment, introducing potential differences from randomized clinical trials, where treatment initiation and exposure are defined at randomization,” Mo said. “The association may also partly reflect differences in general health, cardiovascular care, or treatment adherence,” she added.The findings were presented on July 12 at the Alzheimer’s Association International Conference (AAIC) 2026.Potential Role for Precision TreatmentAlthough statins are widely prescribed to lower cholesterol and reduce cardiovascular risk, randomized clinical trials have not shown that they slow cognitive decline in patients with AD.Researchers have hypothesized that patients with greater vascular risk, including those with elevated LDL-C, may be more likely to experience cognitive benefits from lipid-lowering therapy. Biological differences between men and women could also influence treatment response.To investigate these potential differences, investigators assessed whether the association between statin use and cognitive trajectories varied by sex and baseline LDL-C levels in patients with AD or mixed AD.They analyzed data from the Swedish Registry for Cognitive/Dementia Disorders linked with the Stockholm Creatinine Measurements project and national health registers.The cohort included 1279 patients (mean age, 76 years; 58% women) with incident AD or mixed AD who had LDL-C measurements available within 6 months before a dementia diagnosis. Using longitudinal MMSE assessments, the investigators followed participants between 2007 and 2018.Overall, 585 patients were taking statins, including simvastatin (68%), atorvastatin (28%), and rosuvastatin (4%).Investigators tracked statin use over time and used statistical models to assess changes in MMSE scores while accounting for demographic and clinical factors.Stronger Signal in WomenStatin use was associated with a slower cognitive decline compared with nonuse (beta coefficient, 0.5 MMSE points per year; P = .009), with a stronger association observed among women (beta coefficient, 0.8 points per year; P = .001).Among those taking statins, women had higher LDL-C levels than men (mean, 3.3 mmol/L vs 2.9 mmol/L). Among patients with elevated LDL-C levels (≥ 3.36 mmol/L), the association was stronger (beta coefficient, 0.9 points per year; P = .014), particularly among those taking simvastatin (beta coefficient, 1.1 points per year; P = .005).After accounting for sex as an effect modifier, statin use was associated with a slower cognitive decline among women with elevated LDL-C levels (beta coefficient, 1.2 points per year; P = .005), whereas the association did not reach statistical significance among men with elevated LDL-C levels (beta coefficient, 0.9 points per year; P = .249). In analyses of simvastatin use, the findings were also consistent.No sex differences were observed among patients with lower LDL-C levels, and the investigators found no interaction between statin use, sex, and LDL-C.Possible ExplanationsThe stronger association observed among women with elevated LDL-C warrants further investigation, Mo noted.She suggested that patients with higher LDL-C levels may have a greater vascular risk and, therefore, more potential to benefit from lipid lowering.“In women, hormonal changes around menopause, especially the decline in estrogen, may also affect cholesterol levels, blood vessels, and brain health. However, these are only possible explanations, and our study was not designed to test the underlying mechanisms,” Mo said.The findings should be considered hypothesis-generating, she added.“The sample size, especially within the sex- and LDL-C-specific groups, was relatively small, so the estimates were less precise and need to be confirmed in larger studies,” she said.Preliminary but Intriguing FindingsThe analysis also explores whether the effects of statins vary according to biological sex and baseline LDL-C levels, Heather M. Snyder, PhD, senior vice president of Medical & Scientific Relations at the Alzheimer’s Association, who was not involved in the study, told Medscape Medical News.“This is an observational study, not a clinical trial, and represents the study team’s work being presented at a meeting to encourage scientific discourse and discussion,” Snyder said.She noted that previous studies evaluating statins and cognitive decline have produced mixed results, making the current findings an “interesting observation and a preliminary signal” that requires confirmation in larger and more representative populations.Snyder added that the study reinforces the importance of cardiovascular health for maintaining brain health.“What is good for the heart is good for the brain,” Snyder said, emphasizing that cardiovascular risk reduction remains an important target for preserving cognitive health.The study was funded by the Swedish Research Council, FORTE, ALF, the “New Innovative Roads Call” initiative from Leif Lundblad family and others, Cornell Foundation, Alzheimerfonden, and Demensförbundet. Snyder reported no relevant financial disclosures.