Vasiliki Orgeta, Kenneth Rockwood, Clive Ballard, Adesola Ogunniyi, Robert Howard, Alistair Burns, Elizabeth L Sampson, Andrew Sommerlad, Naaheed Mukadam, Jonathan Huntley, Gill Livingston, Geir Selbæk, Karen Ritchie, Nick C. Fox, Quincy M. Samus, Carol Brayne, Laura N. Gitlin, Sube Banerjee, Eric B. Larson, Linda Teri, Jiska Cohen-Mansfield, Amit Dias, David Ames, Sergi G. Costafreda, Helen C. Kales, Lon S. Schneider, Claudia Cooper, and Mika Kivimäki
The number of older people, including those living with dementia, is rising, as younger age mortality declines. However, the age-specific incidence of dementia has fallen in many countries, probably because of improvements in education, nutrition, health care, and lifestyle changes. Overall, a growing body of evidence supports the nine potentially modifiable risk factors for dementia modelled by the 2017 Lancet Commission on dementia prevention, intervention, and care: less education, hypertension, hearing impairment, smoking, obesity, depression, physical inactivity, diabetes, and low social contact. We now add three more risk factors for dementia with newer, convincing evidence. These factors are excessive alcohol consumption, traumatic brain injury, and air pollution. We have completed new reviews and meta-analyses and incorporated these into an updated 12 risk factor life-course model of dementia prevention. Together the 12 modifiable risk factors account for around 40% of worldwide dementias, which consequently could theoretically be prevented or delayed. The potential for prevention is high and might be higher in low-income and middle-income countries (LMIC) where more dementias occur. Our new life-course model and evidence synthesis has paramount worldwide policy implications. It is never too early and never too late in the life course for dementia prevention. Early-life (younger than 45 years) risks, such as less education, affect cognitive reserve; midlife (45–65 years), and later-life (older than 65 years) risk factors influence reserve and triggering of neuropathological developments. Culture, poverty, and inequality are key drivers of the need for change. Individuals who are most deprived need these changes the most and will derive the highest benefit. Policy should prioritise childhood education for all. Public health initiatives minimising head injury and decreasing harmful alcohol drinking could potentially reduce young-onset and later-life dementia. Midlife systolic blood pressure control should aim for 130 mm Hg or lower to delay or prevent dementia. Stopping smoking, even in later life, ameliorates this risk. Passive smoking is a less considered modifiable risk factor for dementia. Many countries have restricted this exposure. Policy makers should expedite improvements in air quality, particularly in areas with high air pollution. We recommend keeping cognitively, physically, and socially active in midlife and later life although little evidence exists for any single specific activity protecting against dementia. Using hearing aids appears to reduce the excess risk from hearing loss. Sustained exercise in midlife, and possibly later life, protects from dementia, perhaps through decreasing obesity, diabetes, and cardiovascular risk. Depression might be a risk for dementia, but in later life dementia might cause depression. Although behaviour change is difficult and some associations might not be purely causal, individuals have a huge potential to reduce their dementia risk. In LMIC, not everyone has access to secondary education; high rates of hypertension, obesity, and hearing loss exist, and the prevalence of diabetes and smoking are growing, thus an even greater proportion of dementia is potentially preventable. Amyloid-β and tau biomarkers indicate risk of progression to Alzheimer's dementia but most people with normal cognition with only these biomarkers never develop the disease. Although accurate diagnosis is important for patients who have impairments and functional concerns and their families, no evidence exists to support pre-symptomatic diagnosis in everyday practice. Our understanding of dementia aetiology is shifting, with latest description of new pathological causes. In the oldest adults (older than 90 years), in particular, mixed dementia is more common. Blood biomarkers might hold promise for future diagnostic approaches and are more scalable than CSF and brain imaging markers. Wellbeing is the goal of much of dementia care. People with dementia have complex problems and symptoms in many domains. Interventions should be individualised and consider the person as a whole, as well as their family carers. Evidence is accumulating for the effectiveness, at least in the short term, of psychosocial interventions tailored to the patient's needs, to manage neuropsychiatric symptoms. Evidence-based interventions for carers can reduce depressive and anxiety symptoms over years and be cost-effective. Keeping people with dementia physically healthy is important for their cognition. People with dementia have more physical health problems than others of the same age but often receive less community health care and find it particularly difficult to access and organise care. People with dementia have more hospital admissions than other older people, including for illnesses that are potentially manageable at home. They have died disproportionately in the COVID-19 epidemic. Hospitalisations are distressing and are associated with poor outcomes and high costs. Health-care professionals should consider dementia in older people without known dementia who have frequent admissions or who develop delirium. Delirium is common in people with dementia and contributes to cognitive decline. In hospital, care including appropriate sensory stimulation, ensuring fluid intake, and avoiding infections might reduce delirium incidence.