Background and Objectives Type 2 diabetes and lifestyle factors have been associated with dementia risk, but the effect of a healthy lifestyle on diabetes-related dementia remains largely unknown. We aimed to investigate whether the increased risk of dementia among individuals with diabetes can be offset by a broad combination of healthy lifestyle factors.
Methods This prospective study used data from the UK Biobank cohort. An overall lifestyle score ranging from 0 to 7 was created, with 1 point for each of the 7 healthy lifestyle factors: no current smoking, moderate alcohol consumption, regular physical activity, healthy diet, adequate sleep duration, less sedentary behavior, and frequent social contact. Incident dementia was ascertained using linkage with electronic health records. Cox proportional hazards models were used to examine the associations between diabetes, healthy lifestyle score, and dementia incidence.
Results We included 167,946 participants aged 60 years or older without dementia at baseline (mean age 64.1 [SD 2.8] years, 51.7% female). During a median follow-up of 12.3 years, 4,351 developed all-cause dementia. Participants with diabetes, but not those with prediabetes, showed a higher risk of dementia than those with normoglycemia. Compared with diabetes-free participants who had a lifestyle score of 7, the hazard ratios (HRs) for dementia were 4.01 (95% CI 3.06–5.25) and 1.74 (95% CI 1.11–2.72) for those with diabetes who had a lifestyle score of 0–2 and 7, respectively. Among participants with diabetes, the HR for dementia comparing a lifestyle score of 7 vs 0–2 was 0.46 (95% CI 0.28–0.75). This finding corresponded to a reduction in the 10-year absolute risk of dementia from 5.22% (95% CI 3.94%–6.73%) to 1.72% (95% CI 0.92%–2.97%). The association between higher lifestyle score and lower dementia risk was independent of glycemic control and diabetes medication.
Discussion Adherence to a broad range of healthy lifestyle factors was associated with a significantly lower risk of dementia among participants with diabetes. Behavioral lifestyle modification through multifactorial approaches should be a priority for prevention and delayed onset of dementia in patients with diabetes.
- body mass index;
- glycated hemoglobin;
- hazard ratio;
- International Classification of Diseases;
- Swedish National Study on Aging and Care in Kungsholmen
The rising prevalence of dementia poses a significant burden on public health, social care, and the economy.1 Globally, around 50 million people live with dementia, and this number is predicted to triple over the next 30 years as the population ages.1 Type 2 diabetes, a worldwide epidemic that affects 1 in 10 adults (537 million),2 has been judged as a risk factor for dementia. It is estimated that diabetes confers a roughly two-fold greater risk of dementia and accounts for 1%–3% of individuals with dementia.3,4 This proportion continues to rise because of considerable improvements in treatment and demographic trends that are closely linked with prolonged survival of patients with diabetes.5
Thus far, there are no valid pharmacologic therapies to cure or reverse dementia. Although the US Food and Drug Administration approved aducanumab for treatment of Alzheimer disease in June 2021, its clinical efficacy and safety remains intensely controversial.6 Therefore, directing the focus toward prevention strategies by identifying modifiable risk factors has become a public health priority. Favorable lifestyle behaviors including no smoking, moderate alcohol consumption, regular physical activity, and healthy diet have been associated with a lower risk of dementia.4 These behaviors tend to cluster within populations and interact synergistically. Combining these lifestyle factors could strengthen the association with dementia.7,–,9 In the past few years, mounting evidence has suggested a role for emerging lifestyle factors such as sleep duration, sedentary behavior (e.g., television viewing time), and social contact, independently or in combination with other lifestyle factors.10,–,12 As relevant evidence gradually increases, incorporating these emerging factors into overall lifestyle profile will provide more useful information for lifestyle intervention.
Lifestyle management is a fundamental component of diabetes care.13 Prospective studies regarding the associations between lifestyle and health conditions among patients with diabetes have focused on cardiovascular outcomes and mortality,14,15 whereas data specific for dementia are lacking. Recently, engagement in leisure activities and a rich social network has been shown to mitigate the detrimental effect of diabetes on dementia risk.16,17 However, it remains unknown whether and to what extent a healthy lifestyle characterized by a broad combination of lifestyle factors could protect against diabetes-related dementia. Because patients with diabetes are at a higher risk of developing dementia and intensive diabetic control does not decrease the risk,4 understanding this feature is crucial to help tailor future interventions for dementia prevention in this population. In the current study, we aimed to examine the association of diabetes and an extended lifestyle score, which integrated traditional and emerging lifestyle factors, with dementia incidence using data from the UK Biobank. We hypothesized that a healthy lifestyle may counteract the increased risk of dementia in patients with diabetes.
Standard Protocol Approvals, Registrations, and Patient Consents
The UK Biobank study was approved by the North West Multi-Centre Research Ethics Committee. All participants provided written informed consent for the study.
Study Design and Population
The UK Biobank is a prospective, population-based cohort of more than 500,000 participants aged 40–70 years recruited between 2006 and 2010.18 Participants attended 1 of 22 assessment centers across the United Kingdom, where they completed touchscreen and nurse-led questionnaires, had physical measurements taken, and provided biological samples. Analyses were restricted to individuals aged at least 60 years at baseline, given that dementia generally occurs at older ages. Participants with type 1 diabetes identified based on self-reported medical history and hospital inpatient records were excluded to capture primarily people with type 2 diabetes. We also excluded participants with missing data on glycated hemoglobin (HbA1c), lifestyle variables, or covariates, as well as those with self-reported dementia at baseline or prevalent dementia diagnosis identified via hospital records (eFigure 1 in the supplement, links.lww.com/WNL/C329).
Healthy Lifestyle Score
We constructed a healthy lifestyle score based on 7 modifiable behavioral factors, including 4 traditional factors (smoking, physical activity, alcohol consumption, and diet) and 3 emerging factors (sleep duration, sedentary behavior, and social contact) assessed at baseline using a touchscreen questionnaire. Body mass index (BMI) was not included in the lifestyle score because weight change is a typical phenotype during diabetes progression and medical treatment could also result in weight change,19 and thereby, BMI may not serve as a valid measure for weight management. Details of the assessments of individual lifestyle factors can be found in eMethods in the supplement (links.lww.com/WNL/C329).
Participants scored 1 point for healthy category of each lifestyle factor on the basis of national recommendations if available. For smoking status, no current smoking was classified as healthy category. Regular physical activity was defined as at least 150 min/wk of moderate activity or 75 min/wk of vigorous activity or an equivalent combination.20 In accordance with previous UK Biobank studies,7,9 a healthy diet was defined as an adequate consumption of at least 4 of 7 food groups (an increased amount of fruits, vegetables, whole grains, and fish and a reduced amount of refined grains and processed and unprocessed meats) following recommendations on dietary priorities for cardiometabolic health (eTable 1 in the supplement, links.lww.com/WNL/C329).21 Given the reported U-shaped relationship between alcohol consumption and dementia risk,22,23 healthy drinking was defined as moderate alcohol consumption with up to 1 drink (14 g)/day for women and up to 2 drinks (28 g)/day for men.24 Likewise, because short and long sleep have been reported with a higher risk of dementia,11,25 adequate sleep duration (7–9 h/d) was classified as healthy category. We used television watching as the proxy for leisure sedentary behavior and defined a healthy level as <4 h/d26 The social contact index was assessed using information on the number in the household, frequency of friend/family visits, and participation in leisure/social activity.27 Participants who were active and moderately active were considered as having frequent social contact. The lifestyle score ranged from 0 to 7, with a higher score indicating higher adherence to an overall healthy lifestyle. This score has been used in a recently published study among individuals with type 2 diabetes from the UK Biobank.15 Because of small numbers of participants in extreme groups with low scores (0, 1, and 2), these groups were combined into 1 category. In sensitive analysis, we further constructed a weighted lifestyle score considering effect size (β coefficient) for individual lifestyle factors derived from the adjusted model: weighted lifestyle score = (β1× factor1 + β2 × factor2 +…+ β7 × factor7) × (7/sum of the β coefficients).
Ascertainment of Outcome
Incident dementia was ascertained using linkage with hospital inpatient records and death registry data. Date and cause of hospital admissions were obtained from record linkage to Health Episode Statistics (England and Wales) and the Scottish Morbidity Records (Scotland). The information on death was provided by the National Health Service Digital (England and Wales) and the National Health Service Central Register (Scotland). Detailed information regarding the linkage procedure is available online.28 Additional cases were retrieved from primary care records. Dementia was defined according to the ICD-9 and ICD-10 for Alzheimer disease, vascular dementia, and other dementia classifications (eTable 2, links.lww.com/WNL/C329).
Assessment of Prediabetes and Diabetes
The UK Biobank algorithms for identification of prevalent type 2 diabetes based on self-reported medical history and medication have been described.29 Admissions and diagnoses data of the hospital inpatient records were used to ascertain type 2 diabetes with the ICD-9 (250.00, 250.10, 250.20, or 250.90) and ICD-10 codes (E11). Participants who had self-reported or hospital diagnoses of type 2 diabetes were identified as diagnosed patients. Undiagnosed patients were determined according to the American Diabetes Association (ADA) criteria as HbA1c level ≥48.0 mmol/mol (6.5%).30 Prediabetes was defined as the HbA1c level of 39.0–47.0 mmol/mol (5.7%–6.4%) in participants without diabetes.
Area-based socioeconomic status was derived from the postcode of residence using the Townsend deprivation index, a composite measure of data on car ownership, household overcrowding, owner occupation, and unemployment.31 Ethnicity and educational attainment were self-reported and coded as dichotomized variables. Prevalent noncommunicable diseases (hypertension, heart diseases, stroke, head injury, hyperlipidemia, depression, schizophrenia, Parkinson disease, chronic obstructive pulmonary disease, chronic asthma, chronic liver diseases, and cancer) were ascertained during a nurse-led interview at baseline. We calculated morbidity count as 0, 1, 2, or ≥3. Medication use for diabetes, cholesterol, and hypertension was collected by self-reported touchscreen questionnaire or verbal interviews. BMI was calculated as weight in kilograms divided by the square of height in meters. The HbA1c level was measured by high-performance liquid chromatography using the VARIANT II Turbo analyzer (Bio-Rad Laboratories). APOE haplotypes were extracted from the genetic data and categorized into APOE ε4 carriers (any ε4 allele) and noncarriers. Diabetes duration was calculated from age at diagnosis of diabetes and age at baseline assessment for diagnosed patients and assumed 0 years for undiagnosed patients. Tests for cognitive function (reaction time test of symbol matching and visual pairs memory test) were completed through a touchscreen tool.
Baseline characteristics of the analytic sample were summarized as percentage for categorical variables and mean (SD) or median (interquartile range) for continuous variables. Cox proportional hazards models were used to estimate the hazard ratios (HRs) and 95% CIs for incident dementia associated with diabetes status and healthy lifestyle score. Follow-up time was calculated from the baseline date to diagnosis of outcome, death, or the censoring date (July 30, 2021), whichever came first. We then examined the association of the combination of diabetes and healthy lifestyle score (12 categories with no diabetes and a lifestyle score of 7 as reference) with dementia. Statistical interaction between diabetes and healthy lifestyle score was tested by fitting an interaction term in the models. We also estimated dementia risk according to diabetes and the number of traditional and emerging lifestyle factors. Models were adjusted for age, sex, education, ethnicity, Townsend index (in quintiles), morbidity count, BMI, medication for hypertension and cholesterol, APOE ε4 carrier status, and cognitive performance at baseline. For analyses on diabetes status, models were additionally adjusted for lifestyle score and vice versa. The proportional hazards assumption was assessed using the Schoenfeld residuals method and satisfied.
The association between healthy lifestyle score and incident dementia was further investigated among participants with and without diabetes, respectively. Absolute risk over a 10-year period was calculated as the cumulative incidence of dementia occurring in a given group using competing risk regression. Among participants with diabetes, models were additionally adjusted for HbA1c level (<53 or ≥53 mmol/mol [7.0%]), diabetes duration (<5, 5–9, or ≥10 years), and diabetes medication use (oral antidiabetic drugs only, insulin use, or neither). The dose-response relationship between healthy lifestyle score and dementia risk was tested using penalized splines. Stratified analyses among participants with diabetes were performed by age at diabetes diagnosis (<55 or ≥55 years), sex, education, BMI category (<30 or ≥30 kg/m2), APOE ε4 carrier status, morbidity count (≤1 or >1), HbA1c level, diabetes duration, and diabetes medication. Furthermore, the population attributable fraction was calculated to estimate the proportion of individuals with incident dementia that would be attributable to lifestyle factors, assuming a causal relationship.
Several sensitivity analyses were conducted to test the robustness of the results. Residual confounding by socioeconomic status was evaluated by further adjusting for employment and household income. The models were repeated after excluding participants who developed dementia within the first 3 years of follow-up to reduce potential reverse causality or excluding participants with prevalent diseases. The analyses were also run after excluding participants with undiagnosed diabetes in case that substantial change in lifestyle might occur after the awareness of diabetes. Proportional subdistribution hazards regression models were used to account for competing risk of death. To address bias from complete case analysis, missing values for exposure and covariates were imputed by multiple imputation with chained equations. All statistical analyses were performed with SAS, version 9.4 (SAS Institute Inc), and R, version 4.1.1 (R Foundation). A 2-sided p value < 0.05 was considered statistically significant.
The data used in this current study are available from the UK Biobank data resources, which can be found online.32 Permissions are required to gain access to the data resources, subject to successful registration and application process.
A total of 167,946 participants with complete data were included in this study; the mean age at baseline was 64.1 [SD 2.8] years, and 51.7% were women. Among the participants, 28,958 (17.2%) had prediabetes, and 12,769 (7.6%) had diabetes. Overall, 4.0%, 10.8%, 22.4%, 30.1%, 23.7%, and 8.9% of participants had 0-2, 3, 4, 5, 6, and 7 healthy lifestyle factors (scored 0–7), respectively. Baseline characteristics of the study population according to diabetes status are shown in Table 1. Compared with participants with normoglycemia, those with prediabetes or diabetes were older, less educated, more deprived, more likely to be men, non-White, APOE ε4 noncarriers, had higher levels of BMI, had more morbidities, and took more blood pressure– and cholesterol-lowering drugs. The prevalence of healthy lifestyle behaviors was lower in participants with prediabetes or diabetes. Cohort characteristics by healthy lifestyle score are presented in eTable 3 (links.lww.com/WNL/C329).
During a median follow-up of 12.3 years (1,992 730 person-years), 4,351 participants developed dementia. The risk of incident dementia was higher in participants with diabetes than in those with normoglycemia (Table 2). Additional adjustment for lifestyle score, morbidity count, BMI, medication, APOE ε4 carrier status, and background cognitive performance yielded an HR of 1.77 (95% CI 1.61–1.95). Prediabetes was not significantly associated with dementia risk. We therefore merged normoglycemia and prediabetes into a single category as no diabetes in subsequent analyses. For lifestyle factors, each showed an independent association with dementia except for diet (eTable 4, links.lww.com/WNL/C329). When all factors were combined, the HR for dementia for participants with a lifestyle score of 3, 4, 5, 6, and 7 compared with those with a score of 0–2 was 0.77 (95% CI 0.67–0.89), 0.68 (0.59–0.77), 0.62 (0.54–0.71), 0.57 (0.50–0.65), and 0.47 (0.39–0.55), respectively (Table 2). Each 1-point increment in the healthy lifestyle score was associated with an HR of 0.89 (95% CI 0.86–0.91).
Figure 1 shows the joint effect of diabetes and lifestyle factors on the risk of incident dementia. Participants with diabetes and a lifestyle score of 0–2 had a 4-fold greater risk of dementia than those with no diabetes and a score of 7 (HR 4.01, 95% CI 3.06–5.25). However, the risk was dramatically attenuated in participants with diabetes and a lifestyle score of 7 (HR 1.74, 95% CI 1.11–2.72). No significant interaction between diabetes and lifestyle score was observed (Pinteraction = 0.10). Analyses of the subtypes of dementia showed the same pattern for Alzheimer disease and vascular dementia (eTable 5, links.lww.com/WNL/C329). Importantly, there was no difference in the risk of Alzheimer disease between participants with and without diabetes who had a lifestyle score of 7 (HR 1.24, 95% CI 0.54–2.82). The association of diabetes and lifestyle factors with dementia remained unchanged in serial sensitivity analyses with the use of a weighted lifestyle score (eTable 6, links.lww.com/WNL/C329), with additional adjustment for employment and income, when participants who developed dementia during the first 3 years of follow-up or those with prevalent diseases were excluded (eTable 7, links.lww.com/WNL/C329), when missing exposure and covariates were imputed (eTable 8, links.lww.com/WNL/C329), or when the competing risk of death was taken into account (eTable 9, links.lww.com/WNL/C329). Further analysis stratified by APOE ε4 demonstrated that the joint effect of diabetes and lifestyle factors on dementia risk was more pronounced in APOE ε4 noncarriers than in APOE ε4 carriers (Pinteraction <0.001) (eTable 10, links.lww.com/WNL/C329).
There was a similar association of higher lifestyle scores with lower risks of incident dementia among participants without and with diabetes, with an HR per 1-point increment in lifestyle score of 0.89 (95% CI 0.87–0.91) and 0.86 (95% CI 0.81–0.92), respectively (Table 3 and eFigure 2, links.lww.com/WNL/C329). The 10-year absolute risk of dementia among participants without diabetes decreased from 2.39% (95% CI 2.02%–2.81%) for those with a lifestyle score of 0-2 to 1.09% (0.93%–1.27%) for those with a lifestyle score of 7 and correspondingly decreased from 5.22% (3.94%–6.73%) to 1.72% (0.92%–2.97%) among participants with diabetes. A similar pattern was found for separate traditional and emerging factors; however, the effect estimates for both were less remarkable than the extended score (eTable 11, links.lww.com/WNL/C329). We further divided participants into 3 lifestyle categories: favorable (lifestyle score 6–7), intermediate (score 4–5), and unfavorable (score 0–3). A favorable lifestyle was associated with an HR of 0.67 (95% CI 0.61–0.74) and 0.56 (95% CI 0.44–0.72) for dementia compared with an unfavorable lifestyle among participants without and with diabetes, respectively (Pinteraction = 0.032) (eTable 12 and eFigure 3, links.lww.com/WNL/C329).
Among participants with diabetes, consistent results were observed across stratification by age at diabetes diagnosis, sex, education, BMI category, APOE ε4 carrier status, morbidity count, HbA1c level, diabetes duration, and diabetes medication use (Figure 2). In the analyses restricting to patients with diagnosed diabetes, the results did not alter appreciably (eTable 13, links.lww.com/WNL/C329). Based on population attributable fraction analysis, 32.5% (95% CI 4.8%–55.5%) of dementia cases among participants with diabetes were attributed to all 7 lifestyle factors (eTable 14, links.lww.com/WNL/C329).
In this large prospective study, type 2 diabetes and an extended lifestyle score composing of 7 lifestyle factors were independently associated with risk of incident dementia. Participants with diabetes and a healthy lifestyle score of 0–2 had a significantly higher risk of dementia compared with those who had no diabetes and a lifestyle score of 7, but the risk was markedly attenuated among participants with diabetes and a lifestyle score of 7. There was a graded association between higher lifestyle scores and lower risks of incident dementia among participants without diabetes as well as among those with diabetes, irrespective of glycemic control and medication use.
Type 2 diabetes is an identified risk factor for dementia.4 In a pooled meta-analysis of 2.3 million individuals, type 2 diabetes was associated with a 60% greater risk of all-cause dementia.33 The estimate is similar to the result in this study, with an adjusted HR of 1.75 (95% CI 1.60–1.92). In contrast, previous studies on prediabetes and dementia risk are sparse, and the results are inconsistent. Data from the Kungsholmen Project showed an increased risk of dementia associated with prediabetes (defined using random plasma glucose) among older participants aged ≥75 years.34 Recently, the Whitehall II study and the Swedish National Study on Aging and Care in Kungsholmen (SNAC-K) did not show evidence of an association between prediabetes and dementia,16,35 which were in line with our results. It is possible that methodological differences in the assessment of prediabetes (e.g., using HbA1c, fasting or random plasma glucose), the follow-up duration, and differences in demographic characteristics of study populations may at least partially explain the discrepant findings.
Healthy lifestyle factors have been associated with a lower risk of dementia in largely healthy populations, and such association could be strengthened by integrating lifestyle factors together.7,–,9 However, previous observational studies on health effects of lifestyle factors in patients with diabetes have focused on cardiovascular outcomes and mortality; little is known about whether a combination of healthy lifestyle factors can offset the risk of dementia associated with diabetes, although cardiovascular disease and dementia share similar risk factors. Results from the SNAC-K study showed that the increased risk of dementia in patients with diabetes could be mitigated by active engagement in leisure activities or a rich social network.16 In a subsequent analysis based on the same cohort, the association between an active lifestyle combining education, work complexity, leisure activities, and social network and dementia in patients with diabetes was confirmed.17 Notably, these studies did not consider common lifestyle factors such as smoking, alcohol consumption, or diet. On the other hand, most of previous studies include 4 well-characterized traditional lifestyle factors (smoking, alcohol consumption, physical activity, and diet) to define an overall lifestyle, whereas several emerging factors that potentially affect dementia risk such as sleep, sedentary behavior, and social contact have rarely been taken into account.10,–,12 In this study, we created a lifestyle score incorporating both traditional and emerging lifestyle factors. Our results add new evidence by demonstrating that higher healthy lifestyle scores are associated with a dramatically decrease in dementia risk among patients with diabetes, and the estimates are greater than those derived from separate traditional and emerging components. Similarly, large intervention trials also suggest the beneficial effects of multidomain lifestyle modification on improving cognitive function or dementia incidence in elderly people at risk for dementia.36,–,38 Our findings, together with data from other studies, highlight the importance of comprehensive interventions targeting a broad range of lifestyle behaviors to optimize dementia prevention in patients with diabetes.
In the current study, although the relative risk of incident dementia across the increasing number of healthy lifestyle factors was comparable between participants with and without diabetes, the 10-year absolute risk reduction for dementia was definitely more remarkable among participants with diabetes (3.50% comparing 7 vs 0–2 healthy lifestyle factors) compared with those without diabetes (1.30%). Correspondingly, 1 case of dementia in 10 years would be prevented for each 29 participants with diabetes and 78 participants without diabetes who adhere to all 7 healthy lifestyle factors. In supplementary analysis, we detected a significant interaction between lifestyle category and diabetes, whereby the graded association between healthier lifestyle categories and lower risks of dementia was stronger in participants with diabetes than in those without diabetes. These findings imply that individuals with diabetes might benefit more than their nondiabetic counterparts from a healthy lifestyle. Given the rising epidemic of diabetes and longer survival after diabetes diagnosis, targeting lifestyle interventions to patients with diabetes might be an effective and feasible strategy to help achieve a considerable dementia burden reduction.
The mechanisms underlying the association between healthy lifestyle factors and lower risk of dementia in patients with diabetes are yet to be fully understood. Several hypotheses have been proposed involving reduced oxidative damage, antithrombotic and anti-inflammatory effects, increased cerebral blood flow, and upregulation of neurotrophic factors.39 Furthermore, a rich social support can help patients with diabetes cope with their health and make use of medical resources to maintain a healthy lifestyle. This favors better adherence to diabetes treatment and glycemic control,40 reducing the exposure to hyperglycemia, which is supposed as an important etiology of cognitive dysfunction in patients with diabetes.5
The strengths of our study include the large sample size, the prospective design with a long-term follow-up, and rich data resources. As a result, we could perform detailed analyses to explore dementia risk associated with diabetes and a wide combination of traditional and emerging lifestyle factors. Our results are robust in a series of sensitivity analyses. Several limitations also merit discussion. First, information on lifestyle behaviors was self-reported and might be prone to measurement error. However, possible measurement and classification errors are likely to have biased the association toward the null. Furthermore, lifestyle factors were extracted from baseline data, and lifestyle changes over time could not be captured. In addition, there were no data on lifestyle before the diagnosis of diabetes. People who adhered to a healthy lifestyle before diabetes onset probably had less severe diabetes and consequently a lower risk of dementia. In our study, nevertheless, we observed a consistent association between higher lifestyle scores and lower dementia risk irrespective of factors reflecting diabetes severity (e.g., HbA1c level, diabetes duration, or diabetes medication). Second, individuals excluded from the analysis due to missing data were generally comparable in baseline characteristics but seemed to be less educated and more deprived. Considering that the risk of dementia and health effects of lifestyle factors are greater in individuals with more socioeconomic deprivation,4,26 the influence of healthy lifestyle factors in this study would have been underestimated. Besides, sensitivity analysis using multiple imputation for missing exposure and covariates produced results consistent with the main analysis. Third, because the UK Biobank study collected nonfasting blood samples, prediabetes and diabetes were determined based on HbA1c measurements only. Therefore, a proportion of participants with prediabetes or diabetes might have been misclassified as normal or diabetes-free, leading to a dilution of the observed associations. Fourth, participants in the UK Biobank were primarily Caucasians. This might reduce the generalizability of the results to other populations. Fifth, although we adjusted for multiple confounding factors including genetic factors (APOE ε4 allele) and medication use, residual confounding from unknown or unmeasured factors could not be ruled out. Finally, because of the observational nature of this study, reverse causality still remains possible, although the results were similar after excluding incident cases occurring in the first 3 years of follow-up.
In conclusion, adherence to a healthy lifestyle incorporating emerging factors (sleep duration, sedentary behavior, and social contact) along with traditional lifestyle factors was associated with a substantial decrease in the risk of diabetes-related dementia. Our results highlight the significance of promoting an overall healthy lifestyle through multifactorial approaches for prevention or delayed onset of dementia, particularly in patients with diabetes. Future research is needed to determine how combined healthy lifestyle behaviors benefit cognitive outcomes in diabetes and the possible mechanisms.
This work was funded by the National Natural Science Foundation of China (82170870 and 82120108008), Shanghai Ninth People’s Hospital affiliated to Shanghai Jiao Tong University School of Medicine (YBKA201909), Shanghai Municipal Human Resources and Social Security Bureau (2020074), Clinical Research Plan of Shanghai Hospital Development Center (SHDC2020CR4006), and Innovative Research Team of High-level Local Universities in Shanghai (SHSMU-ZDCX20212501).
The authors report no relevant disclosures. Go to Neurology.org/N for full disclosures.
This research has been conducted using the UK Biobank resource (application number 77740). The authors thank participants and staff in the UK Biobank for their dedication and contribution to the research.
Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
Submitted and externally peer reviewed. The handling editor was Linda Hershey, MD, PhD, FAAN.
↵* These authors contributed equally to this work as first authors.
Editorial, page 927
- Received March 18, 2022.
- Accepted in final form July 27, 2022.
- © 2022 American Academy of Neurology