Dataset Information

Is metabolic-healthy obesity associated with risk of dementia? An age-stratified analysis of the Whitehall II cohort study.

ABSTRACT:

Background

Metabolically healthy obesity is hypothesized to be a benign condition but whether this is the case for dementia remains debated. We examined the role of age at assessment of metabolic-obesity phenotypes in associations with incident dementia.

Methods

Obesity (body mass index ≥ 30 kg/m²) and poor metabolic health (≥ 2 of elevated serum triglycerides, low HDL-C, elevated blood pressure, and elevated serum fasting glucose) were used to define four metabolic-obesity phenotypes (metabolically healthy (MHNO) and unhealthy non-obesity (MUNO), metabolically healthy (MHO) and unhealthy obesity (MUO)) at < 60, 60 to < 70, and ≥ 70 years using 6 waves of data from the Whitehall II study and their associations with incident dementia was examined using Cox regression.

Results

Analyses with exposures measured < 60, 60 to < 70, and ≥ 70 years involved 410 (5.8%), 379 (5.6%), and 262 (7.4%) incident dementia cases over a median follow-up of 20.8, 10.3, and 4.2 years respectively. In analyses of individual components, obesity before 60 years (HR 1.41, 95% CI: [1.08, 1.85]) but not at older ages was associated with dementia; unhealthy metabolic status when present < 60 years (HR 1.33, 95% CI: [1.08, 1.62]) and 60 to < 70 years (HR 1.32, 95% CI: [1.07, 1.62]) was associated with dementia. Compared to the metabolically healthy non-obesity group, the risk of dementia was higher in those with metabolically healthy obesity before 60 years (1.69; 95% CI: [1.16, 2.45]); this was not the case when metabolic-obesity phenotype was present at 60 to < 70 years or ≥ 70 years. Analyses at older ages were on smaller numbers due to death and drop-out but inverse probability weighting to account for missing data yielded similar results.

Conclusions

Individuals with metabolically healthy obesity before age 60 had a higher risk of incident dementia over a 27-year follow-up; the excess risk dissipates when metabolic health and obesity are measured after 70 years.

SUBMITTER: Machado-Fragua MD

PROVIDER: S-EPMC10644649 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature

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Publications

Is metabolic-healthy obesity associated with risk of dementia? An age-stratified analysis of the Whitehall II cohort study.

Machado-Fragua Marcos D MD Sabia Séverine S Fayosse Aurore A Hassen Céline Ben CB van der Heide Frank F Kivimaki Mika M Singh-Manoux Archana A

BMC medicine 20231114 1

<h4>Background</h4>Metabolically healthy obesity is hypothesized to be a benign condition but whether this is the case for dementia remains debated. We examined the role of age at assessment of metabolic-obesity phenotypes in associations with incident dementia.<h4>Methods</h4>Obesity (body mass index ≥ 30 kg/m<sup>2</sup>) and poor metabolic health (≥ 2 of elevated serum triglycerides, low HDL-C, elevated blood pressure, and elevated serum fasting glucose) were used to define four metabolic-obe ...[more]

PMID: 37957712

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Project description:Objective To test the hypotheses that physical activity in midlife is not associated with a reduced risk of dementia and that the preclinical phase of dementia is characterised by a decline in physical activity.Design Prospective cohort study with a mean follow-up of 27 years.Setting Civil service departments in London (Whitehall II study).Participants 10 308 participants aged 35-55 years at study inception (1985-88). Exposures included time spent in mild, moderate to vigorous, and total physical activity assessed seven times between 1985 and 2013 and categorised as "recommended" if duration of moderate to vigorous physical activity was 2.5 hours/week or more.Main outcome measures A battery of cognitive tests was administered up to four times from 1997 to 2013, and incident dementia cases (n=329) were identified through linkage to hospital, mental health services, and mortality registers until 2015.Results Mixed effects models showed no association between physical activity and subsequent 15 year cognitive decline. Similarly, Cox regression showed no association between physical activity and risk of dementia over an average 27 year follow-up (hazard ratio in the "recommended" physical activity category 1.00, 95% confidence interval 0.80 to 1.24). For trajectories of hours/week of total, mild, and moderate to vigorous physical activity in people with dementia compared with those without dementia (all others), no differences were observed between 28 and 10 years before diagnosis of dementia. However, physical activity in people with dementia began to decline up to nine years before diagnosis (difference in moderate to vigorous physical activity -0.39 hours/week; P=0.05), and the difference became more pronounced (-1.03 hours/week; P=0.005) at diagnosis.Conclusion This study found no evidence of a neuroprotective effect of physical activity. Previous findings showing a lower risk of dementia in physically active people may be attributable to reverse causation-that is, due to a decline in physical activity levels in the preclinical phase of dementia.

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Project description:ObjectiveTo examine the association of midlife and late life multimorbidity, including severity of multimorbidity, with incident dementia.DesignProspective cohort study.SettingCivil service departments in London (Whitehall II study, study inception in 1985-88).Participants10 095 participants, aged 35 to 55 at baseline.Main outcome measureIncident dementia at follow-up between 1985 and 2019. Cause specific Cox proportional hazards regression was used to examine the association of multimorbidity overall and at age 55, 60, 65, and 70 with subsequent dementia, taking into account the competing risk of death.ResultsThe prevalence of multimorbidity (≥2 chronic diseases) was 6.6% (655/9937) at age 55 and 31.7% (2464/7783) at age 70; 639 cases of incident dementia occurred over a median follow-up of 31.7 years. After adjustment for sociodemographic factors and health behaviours, multimorbidity at age 55 was associated with subsequent risk of dementia (difference in incidence rate per 1000 person years 1.56, 95% confidence interval 0.62 to 2.77; hazard ratio 2.44, 95% confidence interval 1.82 to 3.26). The association weakened progressively with older age at onset of multimorbidity. At age 65, onset of multimorbidity before age 55 was associated with 3.86 (1.80 to 6.52) per 1000 person years higher incidence of dementia (hazard ratio 2.46, 1.80 to 2.26) and onset between 60 and 65 was associated with 1.85 (0.64 to 3.39) per 1000 person years higher incidence (1.51, 1.16 to 1.97). Severity of multimorbidity (≥3 chronic diseases) at age 55 was associated with a 5.22 (1.14 to 11.95) per 1000 person years higher incidence of dementia (hazard ratio 4.96, 2.54 to 9.67); the same analyses at age 70 showed 4.49 (2.33 to 7.19) per 1000 person years higher incidence (1.65, 1.25 to 2.18).ConclusionMultimorbidity, particularly when onset is in midlife rather than late life, has a robust association with subsequent dementia. The increasingly younger age at onset of multimorbidity makes prevention of multimorbidity in people with a first chronic disease important.

Project description:Background Increased vagal modulation is a mechanism that may partially explain the protective effect of healthy lifestyles. However, it is unclear how healthy lifestyles relate to vagal regulation longitudinally. We prospectively examined associations between a comprehensive measure of 4 important lifestyle factors and vagal modulation, indexed by heart rate variability (HRV) over 10 years. Methods and Results The fifth (1997-1999), seventh (2002-2004), and ninth (2007-2009) phases of the UK Whitehall II cohort were analyzed. Analytical samples ranged from 2059 to 3333 (mean age: 55.7 years). A healthy lifestyle score was derived by giving participants 1 point for each healthy factor: physically active, not smoking, moderate alcohol consumption, and healthy body mass index. Two vagally mediated HRV measures were used: high-frequency HRV and root mean square of successive differences of normal-to-normal R-R intervals. Cross-sectionally, a positively graded association was observed between the healthy lifestyle score and HRV at baseline (Poverall≤0.001). Differences in HRV according to the healthy lifestyle score remained relatively stable over time. Compared with participants who hardly ever adhered to healthy lifestyles, those with consistent healthy lifestyles displayed higher high-frequency HRV (β=0.23; 95% CI, 0.10-0.35; P=0.001) and higher root mean square of successive differences of normal-to-normal R-R intervals (β=0.15; 95% CI, 0.07-0.22; P≤0.001) at follow-up after covariate adjustment. These differences in high-frequency HRV and root mean square of successive differences of normal-to-normal R-R intervals are equivalent to ≈6 to 20 years differences in chronological age. Compared with participants who reduced their healthy lifestyle scores, those with stable scores displayed higher subsequent high-frequency HRV (β=0.24; 95% CI, 0.01-0.48; P=0.046) and higher root mean square of successive differences of normal-to-normal R-R intervals (β=0.15; 95% CI, 0.01-0.29; P=0.042). Conclusions Maintaining healthy lifestyles is positively associated with cardiac vagal functioning, and these beneficial adaptations may be lost if not sustained.

Dataset Information

Is metabolic-healthy obesity associated with risk of dementia? An age-stratified analysis of the Whitehall II cohort study.

Background

Methods

Results

Conclusions

Publications

Is metabolic-healthy obesity associated with risk of dementia? An age-stratified analysis of the Whitehall II cohort study.

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