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Exploit population imaging to unravel resistance to Alzheimer's disease

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Tailored lifestyle for dementia prevention

Dementia affects millions of people worldwide and may be caused by various brain pathologies. Lifestyle habits may help nurture the brain and prevent symptoms.

Late-life cognitive impairment and dementia represent one of the most pressing health challenges of our time. Dementia involves memory loss, confusion and difficulties with thinking, caused by underlying brain pathologies, such as Alzheimer’s disease (AD) or vascular damage. With the annual cost of dementia care rising, there is a need for prevention strategies. While there is currently no cure, research shows that up to 40 % of dementia cases could be preventable by addressing modifiable risk factors such as hypertension, obesity and hearing loss. However, it is important to understand if these factors simply delay the symptoms of dementia by supporting overall brain health or actually reduce the underlying disease processes in the brain.

Gardening the ageing brain

Undertaken with the support of the Marie Skłodowska-Curie Actions programme, the DIVERT-AD project aimed to explore how lifestyle and social factors relate to specific types of brain pathology, and how their effects vary across individuals. Using a simple analogy, the principal investigator Julia Neitzel at Erasmus University Medical Center(opens in new window) in the Netherlands explains: “If the brain were a garden, dementia prevention strategies resemble general maintenance such as watering, fertilising, and weeding. These certainly help overall brain health and thus reduce dementia cases. However, to continue the analogy, they may not address specific bugs and pests, as well as AD-typical changes that damage key crops, such as memory and cognition.” The research team studied the association between selected cognitive, physical and social factors and dementia risk across different community cohorts from the US and Europe. To move prevention forward, additional efforts are needed to identify risk factors that specifically influence AD pathology.

Sleep and exercise matter

One promising, but currently under-recognised, AD-specific risk factor may be poor sleep and disrupted circadian rhythms. In a recent study published in JAMA Neurology(opens in new window), DIVERT-AD researchers found that fragmented sleep and irregular 24-hour activity rhythms were associated with greater amyloid accumulation over time. This was particularly prominent in individuals who carry the APOE4 gene, a known risk factor for AD. However, most studies still focus on clinically diagnosed sleep disorders, while everyday behavioural aspects, such as sleep hygiene and routines, are often overlooked. While some lifestyle factors may not directly target AD pathology, they still play a critical role in cognitive health. In a large meta-analysis(opens in new window), the DIVERT-AD team showed that higher education and physical activity were associated with reduced dementia risk. These factors appear to offer resilience against cognitive decline, most likely through effects on vascular health and brain reserve.

Rethinking future prevention strategies

Although DIVERT-AD results come from observational data and no causal conclusions can be drawn, they point towards a more refined prevention framework that distinguishes between risk factors that influence general cognitive decline from those that may contribute to AD-related changes. “Clinical trials testing interventions may remain impractical due to their long duration, but observational research can still offer valuable guidance,” states Neitzel. The project advocates tailored approaches that consider genetic background, age, and individual lifestyle patterns. Future efforts include pooling large cohort datasets to allow for better risk stratification, as well as using AI techniques to identify patterns that may predict who is most likely to develop AD.

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