The need for a more holistic approach to dementia prevention
Authors: Jason R Smith, Jennifer A Deal
Journal: The Lancet Healthy Longevity (2024)

Public health action is needed to address the projected 2·7 times increase in global dementia prevalence in the coming decades.1Nichols E Steinmetz JD Vollset SE et al.Estimation of the global prevalence of dementia in 2019 and forecasted prevalence in 2050: an analysis for the Global Burden of Disease Study 2019.Lancet Public Health. 2022; 7: e105-e125Summary Full Text Full Text PDF PubMed Scopus (1396) Google Scholar This action should include targeting modifiable risk factors for dementia prevention.2Livingston G Huntley J Sommerlad A et al.Dementia prevention, intervention, and care: 2020 report of the Lancet Commission.Lancet. 2020; 396: 413-446Summary Full Text Full Text PDF PubMed Scopus (4728) Google Scholar An important measure of the preventative potential of risk factor reduction is the population attributable fraction (PAF), which estimates the proportion of dementia cases that could be prevented if a given exposure was eliminated in a population. The PAF incorporates the risk associated with the factor and its prevalence, which vary across populations and contexts. In The Lancet Health Longevity, Blossom C M Stephan and colleagues3Stephan BCM Cochrane L Kafadar AH et al.Population attributable fractions of modifiable risk factors for dementia: a systematic review and meta-analysis.Lancet Healthy Longev. 2024; 5: e406-e421Summary Full Text Full Text PDF Google Scholar report a systematic review and meta-analysis, in which they estimated global dementia PAFs for modifiable risk factors. Overall, they estimated that 32·0% to 55·0% of prevalent dementia cases were collectively attributable to seven modifiable factors (ie, low education, hypertension, obesity, smoking, physical inactivity, depression, and diabetes). Importantly, the authors included non-English language studies, which reduces potential reporting bias. Consistent with, and extending the 2020 Lancet Commission findings,2Livingston G Huntley J Sommerlad A et al.Dementia prevention, intervention, and care: 2020 report of the Lancet Commission.Lancet. 2020; 396: 413-446Summary Full Text Full Text PDF PubMed Scopus (4728) Google Scholar the study by Stephan and colleagues reaffirms the importance of addressing modifiable risk factors for reducing dementia risk. It highlights the vital role that clinicians, public health officials, and policy makers have in promoting and prioritising primordial prevention; for example, through lifestyle modification and social determinants. The authors provide one of the most comprehensive summaries of the dementia PAF literature to date. However, we believe that important limitations exist with regard to common approaches to calculating and combining PAFs, which should be addressed to advance knowledge in this area. We argue for a more holistic approach for PAF calculations that better incorporates key population characteristics of person, place, and time. In terms of person, we need a different approach to address how dementia risk factors cluster in individuals, as many risk factors frequently co-occur. For example, up to 60% of people with diabetes have comorbid hypertension,4American Diabetes AssociationHypertension management in adults with diabetes.Diabetes Care. 2004; 27: S65-S67Crossref PubMed Google Scholar and vascular risk factor clustering increases with age.5Martin SS Aday AW Almarzooq ZI et al.2024 heart disease and stroke statistics: a report of US and global data from the American Heart Association.Circulation. 2024; 149: e347-e913Crossref PubMed Scopus (36) Google Scholar Importantly, dementia risk increases with increasing vascular risk burden.2Livingston G Huntley J Sommerlad A et al.Dementia prevention, intervention, and care: 2020 report of the Lancet Commission.Lancet. 2020; 396: 413-446Summary Full Text Full Text PDF PubMed Scopus (4728) Google Scholar, 5Martin SS Aday AW Almarzooq ZI et al.2024 heart disease and stroke statistics: a report of US and global data from the American Heart Association.Circulation. 2024; 149: e347-e913Crossref PubMed Scopus (36) Google Scholar Current widely used methods6Norton S Matthews FE Barnes DE Yaffe K Brayne C Potential for primary prevention of Alzheimer's disease: an analysis of population-based data.Lancet Neurol. 2014; 13: 788-794Summary Full Text Full Text PDF PubMed Scopus (1746) Google Scholar to account for risk factor co-occurrence in the PAF, including those reported by Stephan and colleagues,3Stephan BCM Cochrane L Kafadar AH et al.Population attributable fractions of modifiable risk factors for dementia: a systematic review and meta-analysis.Lancet Healthy Longev. 2024; 5: e406-e421Summary Full Text Full Text PDF Google Scholar systematically underestimate the combined effects of risk factors.7Welberry HJ Tisdell CC Huque MH Jorm LR Have we been underestimating modifiable dementia risk? an alternative approach for calculating the combined population attributable fraction for modifiable dementia risk factors.Am J Epidemiol. 2023; 192: 1763-1771Crossref PubMed Scopus (3) Google Scholar This calculation is problematic as most older adults often have multiple risk factors. Therefore, the proportion of preventable dementia cases is likely to often be underestimated.2Livingston G Huntley J Sommerlad A et al.Dementia prevention, intervention, and care: 2020 report of the Lancet Commission.Lancet. 2020; 396: 413-446Summary Full Text Full Text PDF PubMed Scopus (4728) Google Scholar, 3Stephan BCM Cochrane L Kafadar AH et al.Population attributable fractions of modifiable risk factors for dementia: a systematic review and meta-analysis.Lancet Healthy Longev. 2024; 5: e406-e421Summary Full Text Full Text PDF Google Scholar Future research is needed to identify the best methods to combine PAF estimates in longitudinal settings. We also need tutorials with sample statistical code, preferably from individuals in ageing research with expertise in epidemiological methods, to help researchers easily implement these methods. With respect to place, because risk factor prevalence is a component of the PAF calculation, and prevalence will vary by location, the PAF is most relevant for public health planning when it is localised to the region in which the intervention will occur. We therefore urge researchers to report regional PAFs (eg, at city, state, division, and province levels) in addition to aggregate (eg, country and global) estimates when possible. Finally, regarding time, Stephan and colleagues rightly indicate that dementia prevention efforts require a life course approach. Both components of the PAF—risk factor prevalence and effect on dementia risk—vary over the life course. For example, hypertension is more common in later life (age ≥65 years) than midlife (age 45–64 years), but dementia is more strongly associated with hypertension in midlife than later life.8Smith JR Sharrett AR Pike JR et al.Dementia occurring over a 32-year follow-up attributable to hypertension observed at different ages: implications for dementia prevention.Alzheimers Dement. 2023; 19: 3435-3447Crossref PubMed Scopus (2) Google Scholar We urge researchers to clearly define their study population for PAF calculations; if the goal is to estimate the number of dementia cases that could be prevented by targeting hypertension in a population of older adults, then risk factor prevalence estimates, and their associations with dementia (eg, relative risk), should be restricted to the appropriate age group. We note that the use of aggregate data from multiple large data sources to calculate PAFs is becoming increasingly common; researchers should be aware that inaccurate use of prevalence estimates and pooled relative risks that do not directly map to the age of the target population (eg, applying a risk factor prevalence estimate for adults aged ≥18 years and pooled relative risk from studies in adults aged 45–80 years to a PAF calculation) could conservatively or non-conservatively bias estimates, depending on the risk factor. Furthermore, nuance in interpretating and translating these age-dependent effects into real-world settings is key, particularly if successful risk factor prevention efforts in midlife (45–64 years) could paradoxically increase dementia incidence in later life.9Chen Y Araghi M Bandosz P et al.Impact of hypertension prevalence trend on mortality and burdens of dementia and disability in England and Wales to 2060: a simulation modelling study.Lancet Healthy Longev. 2023; 4: e470-e477Summary Full Text Full Text PDF PubMed Scopus (4) Google Scholar The findings reported by Stephan and colleagues emphasise the considerable value that targeting modifiable risk factors has for reducing the risk of dementia in older adults. However, to advance this field, we urge researchers to consider person (effect of co-occurring risk factors), place (reporting PAF estimates specific to the regions in which interventions are likely to be deployed), and time (a life course approach) when calculating and reporting PAF. This holistic approach will ultimately improve the alignment of PAF analyses and messaging of outcomes with the theory and intent10Rockhill B Theorizing about causes at the individual level while estimating effects at the population level: implications for prevention.Epidemiology. 2005; 16: 124-129Crossref PubMed Scopus (0) Google Scholar of population-level approaches for the primary prevention of dementia. JRS reports support from an Epidemiology and Biostatistics of Aging Predoctoral Training Grant funded by the US National Institute on Aging (grant number NIA 5T32AG000247-27). JAD reports support from the US National Institutes of Health (grant number K01AG054693) and honoraria from Frontiers in Epidemiology, Velux Stiftung, and the Medical Education Speakers Network. Population attributable fractions of modifiable risk factors for dementia: a systematic review and meta-analysisGovernments need to invest in a life-course approach to dementia prevention, including policies that enable quality education, health-promoting environments, and improved health. This investment is particularly important in LMICs, where the potential for prevention is high, but resources, infrastructure, budgets, and research focused on ageing and dementia are limited. Full-Text PDF Open Access