Healthy Lifestyle and all-cause and cause-specific dementia in Individuals with or without Type 2 diabetes: the roles of diabetes duration and insulin use

Abstract

Abstract Background Diabetes and dementia share common lifestyle risk factors, while few studies have examined the effect of seven healthy lifestyle factors as recommended by the diabetes management guidelines on all-cause and cause-specific dementia in individuals with type 2 diabetes (T2DM). Also, the roles of diabetes duration and insulin therapy in their association remain unclear. Methods This study analyzed data of 459 840 participants from the UK Biobank. We used Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CI) for the association of an overall healthy lifestyle score (derived from smoking, social connection, alcohol consumption, physical activity, sedentary, sleep duration and diet) with all-cause and cause-specific dementia of Alzheimer's disease (AD), Vascular dementia (VD) and Non-Alzheimer non-vascular dementia (NAVD), using people without T2DM as the reference group. We also analyzed the role of diabetes duration and insulin use on the association between lifestyle score and dementia. Results During a mean follow-up of 12.1 years, 5 268 incident dementia events were recorded. Using diabetes-free participants who had a lifestyle score of 5–7 as reference group, in diabetes-free participants, we observed a clear trend that higher healthy lifestyle score was related to lower risk of all-cause and cause-specific dementia. However, in people with T2DM, we did not observe such a trend with all-cause dementia. People with lifestyle score of 2–3, 4 and 5–7 all had around two-time risk of all-cause dementia (HR: 2.20–2.36), while those with a score of 0–1 had over three-time risk (HR: 3.14, 95% CI 2.34–4.21). After separating the analyses with dementia subtypes, a dose-response trend was only observed with VD (each two-point increase: 0.75, 0.61–0.93), and no significant association with AD (0.95, 0.77–1.16). The reduced risk of all-cause dementia, AD, VD, and NACD with higher lifestyle score was only observed in patients with diabetes duration less than 10 years, or in patients with no insulin use. Conclusions In people with T2DM, higher healthy lifestyle score was associated with lower risk of all-cause dementia, while the relationship with cause-specific dementia was inconsistent. A dose-response trend was only observed with VD, not with AD. The beneficial effect of healthy lifestyle was only observed in people with diabetes duration less than 10 years, or in those with no insulin use.