Mika Kivimaki’s research while affiliated with University College London and other places

Background The progressive nature of dementia and the complex needs means that people living with dementia require tailored approaches to address their changing care needs over time. These include physical multimorbidity, psychological, behavioural, and cognitive symptoms and possible risks arising from these and helping family caregivers. However, provision of these interventions is highly variable between and within countries, partly due to uncertainty about their efficacy and scarce resources. In the 2024 update of the Lancet Commission we aimed to summarise published evidence about the effect of non‐pharmacological interventions for people with dementia and their carers on cognition, neuropsychiatric symptoms and other person‐centred outcomes. Method We reviewed and summarised evidence according to expert consensus opinion. Result There is moderate‐quality evidence from a Cochrane review of 25 studies for effect of cognitive stimulation therapy on cognition; 1.99 (1.24‐2.74) Mini‐Mental State Examination points higher compared to control groups, and clinically relevant improvements in communication and social interaction. Multicomponent interventions for family carers reduce family carer depression, burden, or stress and are cost‐effective but remote delivery of these interventions was not better than care as usual. A meta‐analysis of 7 studies of tailored activity programmes for people with dementia found a moderate effect on improving quality of life (standardised ES Cohen’s d 0.79, 0.39–1.18; 7 studies, n = 160), decreasing neuropsychiatric symptoms (0.62; 0.40–0.83) and decreasing carer burden (0.68, 0.29–1.07) but there is little evidence on cost‐effectiveness. Exercise interventions were not effective in improving neuropsychiatric symptoms, cognition or functioning. We discuss evidence for other treatments for specific neuropsychiatric symptoms. Conclusion There is developing evidence for benefit of psychological and social interventions on key outcomes including cognition, neuropsychiatric symptoms and quality of life, with sufficient strength of evidence and cost‐effectiveness to justify these being implemented and offered routinely to people with dementia. Interventions generally should be tailored to specific symptoms and individualised to patient preferences and goals. Most interventions have been tested in majority ethnic populations in high income countries: future interventions should be co‐designed with local communities to ensure that they are appropriate for the context, culture, beliefs and practices.

Background The 2020 Lancet Commission on dementia prevention, intervention and care estimated that up to 40% of dementia cases could be prevented by tackling 12 potentially modifiable risk factors, namely less education, hearing loss, hypertension, physical inactivity, diabetes, social isolation, excessive alcohol consumption, air pollution, smoking, obesity, traumatic brain injury, depression. As more evidence on risk factors emerges, the Lancet standing commission on dementia met to update evidence on established dementia risk factors and to consider the evidence for other risk factors. Method We used a lifecourse approach to understand how to reduce risk or prevent dementia, as many risks operate at different timepoints in the lifespan. We considered evidence for when in the lifecourse a risk factor was relevant to development of dementia as well as the size of the effect and strength of the evidence. Our interdisciplinary, international, multicultural group of experts adopted a triangulation framework, prioritising systematic reviews and meta‐analyses, performing new meta‐analyses where needed and debated and agreed on the best available evidence and its consistency. We considered whether there was evidence of disparities in impact of risk factors based on demographic characteristics, particularly ethnicity and socioeconomic status. Result Evidence for two new risk factors was considered strong enough to include this in our lifecourse model. We will present evidence for incorporation of these risk factors, including strength of evidence and potential mechanisms. We will also discuss risk factors for which evidence was not strong enough. Conclusion As more evidence about risk factors emerges we can increase our understanding of how dementia develops and how to potentially prevent it. Understanding the landscape of dementia prevention research is also helpful to appreciate where further evidence is needed and what form of evidence would be most helpful in advancing our understanding.

Background Our authors from around the world met to summarise the available knowledge, decide which potentially modifiable risk factors for dementia have compelling evidence and create the most comprehensive analysis to date for potentially modifiable risk factors to inform policy, give individuals the opportunity to control their risks and generate research. Method We incorporated all risk factors for which we judged there was strong enough evidence. We used the largest recent worldwide meta‐analyses for risk factor prevalence and relative risk and if not available the best data. We performed new meta‐analyses for depression and hearing loss relative risks. We used all 37,000 participants aged ≥ 45 years from HUNT, Norwegian longitudinal population‐based study, to estimate communalities (risk factors clustering) as people frequently have multiple risk factors. Four principal components explained 51% of total risk factors variance. We then calculated weighted population attributable fraction (PAF) estimates. Result We will present each potentially modifiable dementia risk factor’s prevalence, communality, relative risk, unweighted and weighted PAFs and our new lifecourse infographic. Conclusion Our results give hope suggesting many dementias can be prevented or delayed. Many risk factors are linked to deprivation, for example, where people live and exposure to air pollution, or finding affordable healthy food within walking distance and having the resources and skills to prepare it. We have more evidence that longer exposure to a risk has more effect, for example in diabetes, and that risks have more effect in otherwise vulnerable people, for example air pollution. Thus, it is important to redouble efforts to treat existing conditions in communities and people with multiple risks where approaches beyond individual treatment or behaviour change have potentially larger impact. While association is not causation, the effect on cognition of multicomponent, hearing aid and hypertensions RCTs, and naturalistic changes with reduction in air pollution, cigarette smoking, social contact, hearing and vision corrections and work cognitive stimulation, continue to suggest causal relationships with dementia. Socially disadvantaged groups in all countries are more at risk and should be prioritised for intervention. There is more evidence that risks are also modifiable for people at increased genetic risk.

Background/Objectives: This study examined the association between adherence to the Mediterranean dietary approaches to stop hypertension Intervention for Neurodegenerative Delay (MIND) diet, its components, and recurrent depressive symptoms (DepSs). Methods: The analyses included 4824 participants (73% men, mean age = 61; SD = 5.9) from the British Whitehall II cohort study. The MIND diet scores were derived from a validated 127-item food frequency questionnaire in 2002–2004. DepSs were assessed by the Center for Epidemiologic Studies Depression Scale (score ≥ 16) or by use of antidepressant drugs, and recurrence was defined as having DepSs in at least two of the four repeated measurements in the 2002–2004, 2007–2009, 2012–2013, and 2015–2016 follow-up phases. Results: Recurrent DepSs were observed in 13.3% of the participants over 13 years of follow-up. After adjusting for potential confounders, participants in the highest tertile of the MIND diet score (where a higher score represents a higher diet quality) had 26% lower odds of experiencing recurrent DepSs (OR = 0.74; 95% CI 0.58–0.93) compared to those in the lowest tertile. In mutually adjusted analyses of 14 MIND diet components in relation to recurrent DepSs, independent associations were observed for green leafy vegetables (OR = 0.59, 95% CI: 0.45–0.78), other vegetables (OR = 0.43, 95% CI:0.24–0.77), and berries (OR = 0.74, 95% CI: 0.61–0.89). Conclusions: In this British prospective cohort, good adherence to the MIND diet, particularly to the recommendations for vegetables and berries, was associated with a lower risk of recurrent depressive symptoms, independent of socio-economic, health behavior, and health status factors, including baseline cognitive impairment and antecedents of DepSs.

Objectives To identify trajectories of work ability from pre-COVID to post-COVID-19 pandemic period and to examine work unit characteristics associated with these trajectories. Methods The study population was a cohort of Finnish public sector employees (n=54 651) followed from 2016 until 2022. We used trajectory analysis to identify trajectories of work ability and multinomial regression to examine their associations with prepandemic work unit characteristics and pandemic-related changes at workplaces. Results We identified three trajectories of work ability: (1) suboptimal work ability decreasing over time (12%); (2) relatively consistent good work ability (73%) and (3) consistent optimal work ability (15%). The strongest associations with belonging to the suboptimal work ability trajectory were found for employees in work units characterised by high job strain (OR 2.29, 95% CI 1.82 to 2.88), poor team climate (OR 0.74, 95% CI 0.64 to 0.86) and low organisational justice (OR 0.64, 95% CI 0.57 to 0.72) when compared with the most optimal trajectory. The least favourable work ability trajectory was also associated with team reorganisation (OR 1.22, 95% CI 1.04 to 1.44) and a low share of those working from home (OR 0.86, 95% CI 0.78 to 0.94) during the pandemic. Conclusion Prepandemic psychosocial risk factors and pandemic-induced changes at work were associated with poor and declining work ability during the COVID-19 pandemic. Employers and occupational health services should better identify and support vulnerable employees to enhance their work participation.

Background The trajectories of anthropometric and body composition measures (important predictors of diabetes) are rarely explored before diabetes diagnosis. Our study aimed to compare trajectories of fat mass (FM), fat-free mass (FFM), body mass index (BMI), and waist circumference (WC) preceding type 2 diabetes mellitus (T2DM) to aging trajectories of individuals without diabetes during follow-up. Methods We used data from the Whitehall II study, a prospective cohort of British civil servants. 5-yearly BMI and WC were available for up to 20 years, while 5-yearly FM and FFM measures were available for up to 10 years. Linear mixed models with a backward timescale (from diabetes diagnosis or end of follow-up) were performed stratified by sex and adjusted for age, occupational grade, ethnicity, and lifestyle factors. Results A total of 1674/990 (anthropometric/body composition analysis) women (233/81 incident diabetes) and 3917/2710 men (479/217 incident diabetes) 49.81 [0.08]/60.91 [0.9] (mean [SE]) years of age at baseline were included. All outcomes were higher in cases compared to controls. Women’s FM, BMI, and WC followed a quadratic increase in both groups with a faster increase among incident diabetes cases (dBMI 0.04 [0.01] kg/m2/year, dFM 0.19 [0.09] kg/year, dWC 0.2 cm/year [0.05]). FFM decreased linearly with similar slopes in cases and controls. Men’s FM, BMI, and WC also showed a quadratic increase with faster increase in incident cases compared to controls (dBMI 0.03 [0.01] kg/m2/year, dFM 0.23 [0.04] kg/year, dWC 0.08 [0.02] cm/year). FFM followed a quadratic decrease in both groups with a slower rate (0.06 [0.03] kg/year) in incident cases. Conclusions Incident diabetes cases have higher anthropometric and body composition measures 10-20 years before diabetes diagnosis compared to controls. Furthermore, incident cases showed faster increases in these measures except for FFM that decreased during follow-up with similar or lower speeds in cases than controls. Key messages • Traditional anthropometric measures do not capture the underlying changes in body composition. • The inclusion of body composition in risk calculators may result in more precise diabetes prediction.

Background The transition to retirement is a significant turning point in life, which may lead to changes in food habits. Objective To examine changes in red meat, fish, vegetables and fruit consumption during the retirement transition and whether these changes vary between sociodemographic groups. Methods The data were from the Whitehall II study, a cohort of 10 308 British civil servants aged 35–55 years at study induction (1985–1988). Data collection has taken place every 2–3 years. Food consumption (n=2484–2491) was assessed with the Food Frequency Questionnaire in the periods before (max. 16 years) and after retirement (max. 16 years). Changes in preretirement and postretirement consumption were compared in the total cohort and subgroups by sex, marital status, preretirement occupation status and financial hardship using linear regression analyses with generalised estimating equations. Results Weekly red meat consumption was stable before retirement but increased after retirement (p=0.02), especially among women, single and lower occupational status participants. Fish consumption increased during the follow-up and the increase was steeper before retirement than postretirement period (p=0.02). Vegetable and fruit consumption also increased during the entire follow-up, but more strongly during preretirement than postretirement period (p<0.001 for both). Conclusion The transition to retirement is accompanied by favourable (increase in fruit, vegetable and fish) and unfavourable (increase in red meat) dietary changes, varied to some extent by sex, marital status and preretirement occupational status. Our findings suggest that attention should be paid to this transitional phase to promote eating habits in accordance with the recommendations for retirement.

Background: Depression is a pressing public health issue and may be affected by multifaceted urban living, yet the specific urbanicity elements associated is unclear. Using a multidimensional urbanicity scale, we explored the association between urbanicity and its components with the risk of depressive symptoms. Methods: This study used data from four waves of the China Health and Retirement Longitudinal Study, including 12,515 participants aged ≥45 years at baseline in 2011 in 450 rural and urban communities, and 8,766 with 7 years of follow-up. Multilevel logistics regression and Cox proportional hazards regression models examined the cross-sectional and longitudinal associations between urbanicity and depressive symptoms. Results: Living in areas with the highest tertile of urbanicity was associated with a 61% lower risk of depressive symptoms cross-sectionally (odds ratio (OR): 0.39, 95% confidence interval (CI): 0.30-0.50) and 33% lower risk longitudinally (hazard ratio (HR): 0.67, 95% CI: 0.58-0.77) compared to those living in areas with the lowest tertile of urbanicity. Among components, higher population density (OR: 0.92, 95% CI: 0.87-0.97), better education (OR: 0.94, 95% CI: 0.89-0.99), transportation (OR: 0.95, 95% CI: 0.92-0.98), sanitation (OR: 0.96, 95% CI: 0.93-0.98) was associated with lower odds of depressive symptoms, while greater population educational and socioeconomic diversity (OR, 1.08; 95% CI, 1.03-1.13) had opposite effect. Better economic conditions (HR: 0.94, 95% CI: 0.90-0.98) and availability of social services (HR, 0.96; 95% CI, 0.93-0.99) were longitudinally associated with reduced risk of developing depressive symptoms during 7 years of follow-up. Additionally, differences in associated components were found between urban and rural residents and between midlife and older adults. Conclusions: Our findings underscore the complex links of urban living with depressive symptoms among middle-aged and older adults, highlighting the need to consider a multidimensional urbanicity perspective to understand the urbanicity-mental health nexus. Tailored urban planning policies should consider the associated urbanicity components, along with temporal effectiveness, urban-rural disparities, and age group differences.

Aim The 2021 European Society of Cardiology prevention guidelines recommend the use of (lifetime) risk prediction models to aid decisions regarding initiation of prevention. We aimed to update and systematically recalibrate the LIFEtime-perspective CardioVascular Disease (LIFE-CVD) model to four European risk regions for the estimation of lifetime CVD risk for apparently healthy individuals. Methods and Results The updated LIFE-CVD (i.e., LIFE-CVD2) models were derived using individual-participant data from 44 cohorts in 13 countries (687,135 individuals without established CVD, 30,939 CVD events in median 10.7 years of follow-up). LIFE-CVD2 uses sex-specific functions to estimate the lifetime risk of fatal and non-fatal CVD events with adjustment for the competing risk of non-CVD death, and is systematically recalibrated to four distinct European risk regions. The updated models showed good discrimination in external validation among 1,657,707 individuals (61,311 CVD events) from eight additional European cohorts in seven countries, with a pooled C-index of 0.795 (95%CI 0.767-0.822). Predicted and observed CVD event risks were well calibrated in population-wide electronic health records data in the UK (CPRD) and Netherlands (ELAN). When using LIFE-CVD2 to estimate potential gain in CVD-free life expectancy from preventive therapy, projections varied by risk region reflecting important regional differences in absolute lifetime risk. For example a 50-year-old smoking woman with a SBP of 140 mm Hg was estimated to gain 0.9 years in the low risk region versus 1.6 years in the very high risk region from lifelong 10 mm Hg SBP reduction. The benefit of smoking cessation for this individual ranged from 3.6 years in the low risk region to 4.8 years in the very high risk region. Interpretation By taking into account geographical differences in CVD incidence using contemporary representative data sources, the recalibrated LIFE-CVD2 model provides a more accurate tool for the prediction of lifetime risk and CVD-free life expectancy for individuals without previous CVD, facilitating shared decision-making for cardiovascular prevention as recommended by 2021 European guidelines.