Volume 3 Issue 5, May 2023

A major transformation in dementia diagnosis and care appears imminent and will depend on three major types of biomarkers: molecular imaging, blood-based biomarkers and cerebrospinal fluid biomarkers. Each modality has unique strengths and limitations that suggest its optimal uses in research, clinical trials and clinical diagnosis.

Studies have identified sex and/or gender differences in Alzheimer’s disease, but few have examined other dementias. We highlight sex and gender differences in other dementias, discuss sociocultural factors and provide a framework for future global studies.

The Global Council on Brain Health summarizes disparities that occur among the opportunities of different groups for adopting and sustaining brain-healthy behaviors across the lifespan. Here, we highlight challenges for people to maintain a healthy mind throughout their lives and suggest solutions for society to help people to achieve greater equity in brain health.

The World Health Organization (WHO) blueprint for dementia research provides a roadmap to addressing the challenges in the field and reshaping our approach to dementia research. This Comment focuses on how to operationalize the drivers of research highlighted in the blueprint to make research more equitable, impactful and global.

The mysteries behind immune aging and its related inflammation are being unmasked. Jin et al. reveal that the defective turnover of damaged mitochondria in CD4⁺ T cells from older individuals results in the exacerbated secretion of mitochondrial DNA, which fuels inflammaging and impairs immune responses.

Despite the central role of immune regulation in tissue repair, the contribution of immune dysfunction to regenerative failure in aging is mostly unknown. We discovered a mechanism of immune modulation that operates during skeletal muscle regeneration that is compromised in aged animals and can be harnessed to improve regenerative capacity in aging.

Moderately cold temperatures trigger the removal of aggregation-prone proteins in the invertebrate model Caenorhabditis elegans and cultured human cells, preventing the accumulation of pathological aggregates linked with age-related neurodegenerative disorders such as amyotrophic lateral sclerosis and Huntington’s disease.

This Perspective describes the clinical relevance of animal models in dementia for translational research. The authors emphasize incorporating aging as a component in model organisms to understand its contribution to disease pathogenesis.

This Perspective outlines a strategy to move towards a future with personalized medicine for Alzheimer’s disease by empowering patients in orchestrating diagnosis, prediction and prevention of the onset of dementia.

This Review provides an update on the most promising blood-based biomarkers relevant to Alzheimer’s disease and how they can be used to substantially improve the diagnostic and prognostic work-up in clinical practice and trials.

This Review highlights the need for targeting Alzheimer’s disease in the preclinical stage for an effective therapeutic strategy. The authors provide an update on candidate therapies in development, current preclinical Alzheimer’s disease trials, recruitment challenges and future directions.

This Review provides evidence-based update on the association between social interaction and risk of dementia. The authors propose a policy framework to promote social interaction as a preventative strategy against dementia.

Moderate cold temperature extends lifespan, but the mechanisms involved are not fully understood. Here, the authors show that moderate cold temperature eliminates aggregation-prone proteins through PSME3-activated proteasomes in both C. elegans and human cells.

Telomere shortening is a hallmark of aging and genetic telomerase deficiency causes premature aging phenotypes and reduces lifespan. Here the authors show that gut-specific telomerase expression is sufficient to rescue aging phenotypes and extend the lifespan of telomerase-deficient zebrafish, as well as ameliorate signs of aging in wild-type animals.

By showing that the immune modulator MANF is induced after muscle injury in young but not aged mice and is essential for regenerative success, this study reveals a new link between immune dysfunction and regenerative decline in muscle aging.

Chronic inflammation is a sign of immune system aging. Here the authors show that T cells from older adults contribute to inflammation due to CISH-mediated enhanced proteasomal degradation of a component of the proton pump V-ATPase, resulting in reduced lysosome function and the release of mtDNA and other amphisomal content.

Technologies could aid active and healthy aging but their development and implementation requires knowledge of user preferences. In this study, the authors conducted a Swedish national survey across three generations to understand attitudes toward technologies.