Dementia is a major public health challenge that is caused by a range of neurodegenerative disorders and that has debilitating effects on the cognitive function and daily lives of affected individuals. Alzheimer’s disease (AD) is the most common form of dementia, and accounts for over 60% of cases. Aging is the biggest risk factor for dementia. According to the World Health Organization (WHO), over 55 million people worldwide live with dementia, and this is forecast to rise to 78 million by 2030 owing to the growing older adult population, which will have marked social and economic effects. The current lack of a cure for dementia and the burden it places on individuals, caregivers and healthcare systems worldwide underscores the urgent need for a timely diagnosis, prevention and therapy strategies. In this issue, Nature Aging introduces a collection of Reviews, Perspectives and Comments that cover the most recent advances in dementia research.

Targeting a disease requires an understanding of the underlying mechanisms. Animal models of AD have been instrumental in our understanding of the disease mechanisms and exploration of therapeutic targets. However, they have been often criticized for a lack of translational success owing to a long history of drug failures. In a Perspective in this issue, Padmanabhan and Götz provide a defense for using animal model systems to study AD, and advocate for incorporating aging into experimental design to enhance the translational value of animal models.

Molecular imaging techniques, such as positron emission tomography, that have been used for decades to establish the presence of brain pathology and track disease progression have recently been complemented by analyses of fluid biomarkers in cerebrospinal fluid or blood, which are becoming increasingly accurate for prognosis and diagnosis. With the recent approval of two disease-modifying treatments that target amyloid pathology (aducanumab and lecanemab), the need for accurate AD biomarker testing in clinical practice is going to increase. In a Comment, Schindler and Atri highlight the accuracy and robustness of the use of cerebrospinal fluid biomarkers in AD research, clinical trials and diagnosis, and their utility as a benchmark for the development of novel blood-based biomarkers (BBBMs). In recent years, BBBMs have been shown to display high diagnostic accuracy and distinguish AD from other neurodegenerative diseases. In their Review, Hansson and colleagues provide a comprehensive update on the development of BBBMs, discussing their path to implementation in clinical practice; how they can facilitate the identification of individuals with pre-symptomatic AD for clinical trials; and how they can improve detection of disease-modifying effects of novel drugs or lifestyle interventions.

Given the long prodromal phase of the disease, identifying individuals who are at risk of AD before the clinical presentation of the symptoms offers an opportunity to treat patients before substantial damage has occurred and may help to prevent or delay the onset of dementia. In their Perspective, van der Flier and colleagues propose a strategy for a future with personalized medicine for AD that includes effective and patient-orchestrated diagnosis, prediction and prevention, arguing that empowering the public and patients with dementia to be more actively engaged in managing their health can help to prevent or delay disease onset. In a Review, Rafii and Aisen discuss the recent results of anti-amyloid immunotherapy trials in patients with symptomatic AD and how this therapeutic strategy is being tested in asymptomatic individuals at risk of developing AD, in phase 3 trials.

In parallel to the development of pharmacological treatments, there is growing awareness about the importance of the environment, social factors and behavior for the risk of dementia. Lifetime social participation can reduce the risk of dementia by increasing cognitive reserve, reducing stress and depression, and promoting healthy lifestyles. In their Review, Sommerlad and colleagues highlight that greater social participation in mid-life and late life is associated with a 30–50% lower risk of subsequent dementia, and point to the need for future research, prevention efforts and policy focus on the potential of social participation to mitigate the effects of neuropathology for brain health. Mielke and colleagues discuss in a Comment the contributions of sex, gender, race and ethnicity in dementia risk globally, especially in low- and middle-income countries, and the need for future research to take these factors into account for diagnostic and intervention purposes. In their Comment, Lock and colleagues highlight the societal barriers to a healthy brain and present recommendations from the Global Council on Brain Health for achieving greater brain health equity. Dua and colleagues, in another Comment, provide an insight into the WHO’s blueprint for dementia research, which advocates for global prioritization of dementia research through coordinated efforts in standardized, timely and high-quality evidence generation, empowering people with lived experience, addressing inequity and diversity, and sustainable funding.

In conclusion, effective diagnosis, prevention and therapy strategies are essential in addressing the global burden of dementia. A comprehensive approach that combines advances in diagnostic techniques, lifestyle interventions and personalized therapeutic interventions is emerging and will transform how we approach dementia care, and facilitate early detection, prevention and better management of dementia. The growing prevalence of dementia emphasizes the need for continued research, collaboration and investment in this field to improve the quality of life of those living with dementia and their caregivers.