The Lancet Commission on dementia prevention, intervention, and care has produced three major reports — 2017, 2020, and 2024. Each report identified modifiable risk factors and estimated the population-attributable fraction: the proportion of dementia cases theoretically preventable through their modification. The framework has become the canonical evidence base for dementia prevention, and the 40% headline number — the aggregate preventable fraction — has become the statistic that anchors public-facing longevity-psychiatry conversations.
The 2017 report identified nine modifiable risk factors. The 2020 update added three more (alcohol consumption, air pollution, traumatic brain injury), bringing the canonical list to twelve. The 2024 update added two more — high LDL cholesterol in midlife and untreated vision loss in later life — bringing the total to fourteen. The list is not closed. As more rigorous epidemiological work accumulates, factors will be added or revised. The framework is a moving target that reflects the state of the evidence at each point.
Population-attributable fraction (PAF) is the methodological core. PAF estimates what proportion of dementia cases would not occur if a given risk factor were eliminated from the population. The calculation depends on the relative risk associated with the factor and the prevalence of the factor in the population. A high-relative-risk factor that is rare contributes less to total preventable burden than a moderate-risk factor that is common. The PAF framework is therefore a population-level guide, not a single-patient predictor.
The 40% aggregate figure is not the simple sum of individual PAFs. The factors interact — many co-occur, many share underlying mechanisms, many have overlapping effects on cognition. The Commission’s methodology adjusts for this overlap to produce the combined estimate. The interpretation is: if every modifiable risk factor were eliminated from the population, approximately 40% of dementia cases would not occur. The remaining 60% reflects non-modifiable factors (age, genetics, irreducible biology) and modifiable factors not yet identified.
The clinical implication of the framework is the discipline of working through the factors systematically, in every patient, in the acceleration window. Not as a checklist to be sped through. As an actual workup that produces specific interventions for the specific patient in front of you. The patient with untreated hearing loss, undiagnosed sleep apnea, hypertension above goal, and ongoing depression has four high-leverage interventions available — each one delivered changes the trajectory.
The fourteen factors cluster naturally into three groups, and the stages that follow address each cluster in turn. The high-impact cluster is dominated by hearing loss and depression — non-vascular, non-metabolic factors that each carry large individual effect. The vascular and metabolic cluster contains hypertension, diabetes, obesity, physical inactivity, and LDL cholesterol — where the work of psychiatry overlaps the work of cardiology and endocrinology. The environmental and behavioral cluster contains alcohol, smoking, air pollution, and vision loss — the factors that are partly individual behavior and partly structural environment.
The framework also has known omissions. Sleep apnea, perhaps the highest-yield unenumerated factor, is not on the Lancet list — partly because the epidemiology is harder to extract from co-occurring obesity and cardiovascular disease. Chronic systemic inflammation, measured by CRP, IL-6, and related markers, is not yet on the canonical list but is associated with elevated risk and may be modifiable. Cognitive engagement and purpose appears partially as education, but the lifelong-engagement dimension is underrepresented. The framework is the foundation, not the ceiling.
The next three stages address the three clusters in detail. The fundamental orientation is: the framework is a clinical workup, not a public-health slogan. Every factor on the list is a question to ask of every patient in the acceleration window. Each affirmative answer is an intervention opportunity.