Today’s open access research materials present a statistical exercise that uses broad epidemiological data to determine the impact of individual lifestyle choices and environmental factors to the incidence of dementia. The results are not declaring that, say, particulate air pollution is responsible for 2% of dementias. Rather if the statistics point out that particulate air pollution is associated with 2% of cases, smoking with 5%, and hearing loss with 8%, then one starts to see priorities in the choices that people should be making to better manage their health over the long term.

Summing all of the impacts together – to see a 30-40% contribution of lifestyle and environment to incidence of dementia – also provides an assessment of the degree to which dementia is a lifestyle disease. To which it is avoidable with sensible choices regarding health and surrounding environment. Alzheimer’s disease in particular involves a number of mechanisms that look suspiciously like those involved in type 2 diabetes, a condition that is near entirely a lifestyle issue resulting from excess fat tissue. Nonetheless, Alzheimer’s disease and other dementias are clearly not determined by obesity to the same degree. The risk spreads out over choices and influences that touch on chronic inflammation (fat, smoking, air pollution), cognitive reserve (education), physical damage to brain tissue and surrounding channels for cerebrospinal fluid drainage (hypertension, head injury). It is a matter of many smaller contributions that cause harm through a range of quite different mechanisms.

While senolytic drugs that remove senescent cells in the brain will probably make a sizable difference to dementia incidence, via greatly reducing inflammation in brain tissue, it remains the case that comparatively little else can be done at present other than slowing the decline through better life-long health. More and better regenerative therapies, and more and better therapies that target the underlying molecular damage of brain aging are needed.

Dementia prevention, intervention, and care: 2020 report of the Lancet Commission

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.

The number of people with dementia is rising. Predictions about future trends in dementia prevalence vary depending on the underlying assumptions and geographical region, but generally suggest substantial increases in overall prevalence related to an ageing population. For example, according to the Global Burden of Diseases, Injuries, and Risk Factors Study, the global age-standardised prevalence of dementia between 1990 and 2016 was relatively stable, but with an ageing and bigger population the number of people with dementia has more than doubled since 1990.

However, in many high income countries (HIC) such as the USA, the UK, and France, age-specific incidence rates are lower in more recent cohorts compared with cohorts from previous decades collected using similar methods and target populations and the age-specific incidence of dementia appears to decrease. All-cause dementia incidence is lower in people born more recently, probably due to educational, socio-economic, health care, and lifestyle changes. However, in these countries increasing obesity and diabetes and declining physical activity might reverse this trajectory. In contrast, age-specific dementia prevalence in Japan, South Korea, Hong Kong, and Taiwan looks as if it is increasing, as is Alzheimer’s in LMIC, although whether diagnostic methods are always the same in comparison studies is unclear.

Cognitive reserve is a concept accounting for the difference between an individual’s clinical picture and their neuropathology. It is divided into neurobiological brain reserve (eg, numbers of neurons and synapses at a given timepoint), brain maintenance (as neurobiological capital at any timepoint, based on genetics or lifestyle reducing brain changes and pathology development over time) and cognitive reserve as adaptability enabling preservation of cognition or everyday functioning in spite of brain pathology. Early-life factors, such as less education, affect the resulting cognitive reserve. Midlife and old-age risk factors influence age-related cognitive decline and triggering of neuropathological developments. Consistent with the hypothesis of cognitive reserve is that older women are more likely to develop dementia than men of the same age, probably partly because on average older women have had less education than older men. Cognitive reserve mechanisms might include preserved metabolism or increased connectivity in temporal and frontal brain areas.

Risk factors in early life (education), midlife (hypertension, obesity, hearing loss, traumatic brain injury, and alcohol misuse) and later life (smoking, depression, physical inactivity, social isolation, diabetes, and air pollution) can contribute to increased dementia risk. Good evidence exists for all these risk factors although some late-life factors, such as depression, possibly have a bidirectional impact and are also part of the dementia prodrome. 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.