26 May 2023

Feel like catching up on the field over Memorial Day weekend? Here's some reading for you. Covering animal models to clinical trials, nine articles in the May issue of Nature Aging discuss current challenges and opportunities in dementia research.

In their perspective, Pranesh Padmanabhan and Jürgen Götz, University of Queensland, Brisbane, Australia, dispute that inadequate preclinical models are to blame for the long list of failed AD clinical trials, a mantra that is commonly heard in the field. Instead, they argue that scientists simply do not yet understand the etiology of the disease or when it is best to intervene in the disease progression.

On the latter, Michael Rafii and Paul Aisen, University of Southern California, Los Angeles and San Diego, respectively, review how advances in biomarkers, recruitment strategies, and cognitive testing have paved the way for some success in immunotherapy trials. They discuss how preclinical screening in cognitively normal older adults might facilitate optimum intervention. Indeed, in their perspective, scientists led by Wiesje van der Flier at Amsterdam University Medical Center envision a world in which AD pathology can by delayed, or better yet, completely prevented. The key? Personalized medicine approaches for prediction of disease onset.

Biomarkers will play a crucial role there, and as Oskar Hansson, Lund University, Sweden, and colleagues, outline in their review, these not only reduce costs associated with brain scans, but can help identify drugs or even lifestyle interventions that modify the disease process. One of those lifestyle factors might be social interaction, argue scientists led by Andrew Sommerlad, University College London. Over the years, evidence has grown that lack of a social network correlates with dementia, though whether it can cause the disease remains murky. Sommerlad and colleagues summarize the evidence, discuss the biology that might explain the correlation, and suggest how the knowledge might be used to slow or prevent disease.

In four comments, scientists expand on these themes. Suzanne Schindler at Washington University, St. Louis, compares the pros and cons of the different biomarker modalities currently available. Sarah Lenz Lock and Lindsay Chura, AARP, and their colleagues tackle the problem of inequity in brain health across populations and suggest ways for society to improve on it. On the topic of sex and gender differences, Michelle Mielke, Wake Forest University School of Medicine, Winston-Salem, North Carolina, and colleagues shine a spotlight not on AD, but on other dementias, for which this subject has received scant attention. Last but not least, scientists led by Tarun Dua at the World Health Organization, explain how the WHO blueprint for dementia research might be put into action. Check out the issue, and share your thoughts in the comment box below.—Tom Fagan