Charting Alzheimer's Disease and Dementia: Epidemiological Insights, Risk Factors and Prevention Pathways

Abstract

Alzheimer's disease (AD), the most common cause of dementia, is a complex and multifactorial condition without cure at present. The latest treatments, based on anti-amyloid monoclonal antibodies, have only a modest effect in reducing the progression of cognitive decline in AD, whereas the possibility of preventing AD has become a crucial area of research. In fact, recent studies have observed a decrease in dementia incidence in developed regions such as the US and Europe. However, these trends have not been mirrored in non-Western countries (Japan or China), and the contributing factors of this reduction remain unclear. The Lancet Commission has delineated a constrained classification of 12 risk factors across different life stages. Nevertheless, the scientific literature has pointed to over 200 factors-including sociodemographic, medical, psychological, and sociocultural conditions-related to the development of dementia/AD. This narrative review aims to synthesize the risk/protective factors of dementia/AD. Essentially, we found that risk/protective factors vary between individuals and populations, complicating the creation of a unified prevention strategy. Moreover, dementia/AD explanatory mechanisms involve a diverse array of genetic and environmental factors that interact from the early stages of life. In the future, studies across different population-based cohorts are essential to validate risk/protective factors of dementia. This evidence would help develop public health policies to decrease the incidence of dementia.

Keywords: Alzheimer’s disease; epidemiology; prevention; public health; risk factors.

Figure 1

Dementia pathways and main modifiable risk factors across lifespan. The familial dementia category represents a minimal percentage of cases directly explained by autosomal gene mutations. In contrast, modifiable factors may exert their effects on different biological systems of the organism (genes, immunological response, and brain connectivity) at different lifespan periods, raising the likelihood of sporadic dementia/AD. In addition to their weighted specific effects, risk factors may interact in a synergistic and complex way with different lifestyle habits (e.g., diet, sleep), population factors (e.g., air pollution, health system), or unknown conditions converging at late life (represented by the dotted area). Modifiable risk factors may interact with genes (epigenetic pathway is shown in yellow), boosting the probability of AD/dementia compared to those sporadic cases without these traits (green line). It should be noted that dementia onset can vary significantly between individuals at different paths, but it is represented in a simplified visual manner for the readers (see red dotted area).

Figure 2

Coping against dementia: resilience and resistance mechanisms. The term resistance implies slower or delaying the onset of AD-associated neuropathology represented by blue color. However, resilience refers to the brain’s capacity to maintain cognitive and functional performance against pathology, with cognitive reserve being the most known form. Thus, people with higher CR (brown line) may show better performance than those with lower CR when facing similar levels of pathology.