Multi-Model Analysis of the Association between Osteoporosis and Cognitive Decline: From Prospective Cohorts

BACKGROUND: Previous studies have suggested the possible association between osteoporosis and cognitive decline, but the number of participants in these studies is small, and most of them have not been categorized in detail. OBJECTIVES: This study examined the association between osteoporosis and the risk of cognitive impairment and Alzheimer's disease (AD) and explored which populations are most affected. METHODS: We analyzed data from two prospective cohorts, the English Longitudinal Study of Ageing (ELSA) and the Health Retirement Study (HRS). We used multivariate regression, mixed-effects models, Cox models to assess the associations between osteoporosis and cognitive function at baseline, over time, and with AD risk. Subgroup analyses and sensitivity analyses were conducted. RESULTS: A total of 28,919 participants were enrolled (57.11% females). At baseline, memory scores were significantly lower in the osteoporosis group (β = -0.37, 95% confidence interval [95% CI]: -0.56, -0.18; p < 0.001), particularly in younger participants. Annually, memory scores also declined more rapidly in osteoporosis (β = -0.01, 95% CI: -0.18, -0.02; p = 0.018), especially in hypertension female. At baseline, osteoporosis was associated with a higher prevalence of AD (OR = 1.40, 95% CI 1.02-1.93; p = 0.039), particularly among men. Over time, the cumulative effect of osteoporosis on AD increased steadily (Log-rank p < 0.001). Younger males with osteoporosis showed high odds of developing AD. CONCLUSION: Osteoporosis was associated with a steeper decline in memory over follow-up, with evidence that this association was stronger among women with hypertension. Osteoporosis was also associated with a higher hazard of incident AD, and the association appeared stronger in men.