Grande G, Qiu C, Fratiglioni L. Prevention of dementia in an ageing world: Evidence and biological rationale. Ageing Res Rev. 2020;101045. doi:10.1016/j.arr.2020.101045
At a glance
A narrative review of the literature summarizes the scientific knowledge on dementia prevention, identifying the 3 main strategies to prevent or delay the onset of dementia:
- targeted interventions on the body to protect the brain, in particular the prevention and treatment of cardiovascular diseases;
- compensatory interventions to combat brain aging, such as education and lifelong commitment to cognitively and socially stimulating activities;
- lifelong health promotion (physical activity, healthy balanced diet, elimination of risky behaviour such as smoking).
In addition, 5 pathways involved in the development and progression of dementia related to prevention strategies have been identified: neurodegeneration, inflammation, brain resilience, vascular damage, oxidative stress.
The review stresses that the biological and molecular mechanisms underlying the epidemiological evidence are still unclear in the literature.
What is already known
- Dementia is one of the main causes of disability and dependency among the elderly. In 2018 almost 50 million people had Alzheimer’s and other dementias and this number is set to double in the next 20 years.
- Aging and the development of dementia are closely related processes: old age is the main risk factor. At the same time, dementia is not an inevitable consequence of aging: there are many other factors at stake.
- Despite their role of genetic and environmental determinants, there are numerous protective factors, which act through compensation mechanisms
- Studies in neuropathology and neuroimaging have shown that neurodegeneration coexists with cerebrovascular lesions in most cases of dementia in older people.
- Over the past 40 years, clinical trials have failed to identify drugs that are effective in curing or even changing the disease process. On the other hand, we have a lot of epidemiological data that show the possibility to act on modifiable risk factors and protective factors.
Design and Method
The article is a narrative review of the literature, offering an overview of the topic of dementia prevention, with a look at the historical development of research on this topic and future research directions.
Interventions aimed at the body to protect the brain are focused primarily on the prevention and treatment of cardiovascular diseases. Cardiovascular disease (CVD) and dementia have a high prevalence in the elderly, tend to aggregate in the same person and share common risk factors such as hypertension, obesity, smoking and dyslipidemia. Atrial fibrillation, ischemic heart disease, and heart failure are among the most studied and with most evidence-based CVDs.
Compensatory interventions to combat brain aging, such as education and engagement in cognitive and social stimulating activities. Education is a factor that must be considered in its lifelong implications: the level of education achieved by young people influences many factors that can promote the development of dementia, such as the working environment and lifestyle. This is why research is focusing on life-long studies, showing that “it’s never too late” to introduce compensatory interventions for brain health. In old age the benefits of social interaction are well documented compared to the risk of developing dementia, but there may be a reverse causality.
Some promising studies investigate the interaction of psychosocial and lifestyle factors with genetic factors and health conditions.
Numerous longitudinal observational studies have shown the benefits of health promotion interventions: tobacco use is the major risk factor not only for cancer and cardiovascular disease, but also for dementia. Alcohol abuse is not only related to Wernicke-Korsakoff’s syndrome and alcoholism dementia, but seems to cause neurotoxicity and neuroinflammation and indirectly causes dietary deficiencies that impact on brain health. Moderate use, however, seems to be a protective factor. Physical activity is recommended by the WHO as the main protective factor against dementia, in particular aerobic activity seems to be more effective.
As far as nutrition is concerned, in the face of conflicting studies on individual foods, research has focused on dietary regimens: for example, the Mediterranean diet is associated with a reduced risk of dementia. In general, the results of promotion measures implemented in old age are less clear. Some studies have attempted to evaluate interventions that not only address one of these behaviors, but multi-domain interventions.
The narrative review does not aim to show “novelty”, but to describe the state of the art by bringing out reflections, doubts, interpretations and indications on the future paths to follow, starting from a critical reading of the most significant scientific p:ublications.
In particular the authors identify some critical elements in prevention:
- In order to be fully effective, preventive strategies need to be applied according to an approach that takes into account the different stages of life;
- preventive interventions that improve the risk profile in older people could delay the onset of dementia. To this end, multi-domain interventions can be considered as evidence for this hypothesis, as they show that even a late multi-domain intervention can reduce the rate of cognitive decline and possibly postpone the onset of dementia.
What the prospects
A key step for research is to clarify the biological and molecular mechanisms underlying the epidemiological evidence.
A key question for future studies is the sustainability and effectiveness of these preventive approaches in different geographical, economic and cultural contexts.
By Francesca Memini