Advances in brain biomarkers reveal how some people maintain cognitive function despite Alzheimer’s, stroke and other brain diseases - with implications for global dementia prevention.
Researchers are gaining unprecedented insight into why some people remain mentally sharp well into old age, even when their brains show signs of injury or disease typically linked to dementia.
A new comprehensive review of cognitive resilience - the brain’s ability to maintain thinking and memory despite ageing, injury or neurodegenerative disease - highlights how advances in brain imaging and blood-based biomarkers are transforming dementia research and prevention strategies worldwide. The review, published in The Lancet Neurology and led by UNSW Sydney’s Centre for Healthy Brain Ageing (CHeBA) in collaboration with Neuroscience Research Australia (NeuRA), explores the concept of cognitive resilience and the biological processes that may help explain it.
Until recently, the true extent of brain pathology could only be confirmed after death. Now, modern neuroimaging, electroencephalography, and cerebrospinal fluid and blood biomarkers allow researchers to study Alzheimer’s disease, Lewy body disease and cerebrovascular disease in living people, and to track how these changes relate to cognitive function over time.
“Dementia is not an inevitable consequence of brain pathology,” says Co-Director of CHeBA Professor Henry Brodaty. “Some individuals show remarkable cognitive resilience, maintaining cognitive abilities despite a substantial burden of disease in the brain.”
Resilience, not just pathology
Large community-based studies have shown that common neuropathologies - including Alzheimer’s disease, Lewy body disease, TDP-43 protein inclusions and vascular disease - are strongly associated with dementia, but not deterministically so. In other words, the presence of disease does not always predict cognitive decline.
This observation has led researchers to focus on cognitive resilience, defined in the review as “cognitive performance that is better than expected given a person’s degree of brain injury or disease across the lifespan.” Understanding what underpins this resilience - and how it can be strengthened - is now a major goal of ageing and dementia research.
From autopsy to real-time measurement
Previously, cognitive resilience could only be inferred by comparing a person’s cognitive performance with brain pathology identified at autopsy. Advances in biomarkers now allow resilience to be measured in real time and followed longitudinally.
These tools are enabling researchers to examine how psychosocial factors, clinical characteristics and biological mechanisms interact to protect cognition, even in the presence of neurodegenerative and vascular disease.
The review also clarifies long-standing confusion in the field by distinguishing between related concepts such as cognitive reserve, brain reserve and brain maintenance, using internationally agreed definitions developed by leading experts in cognitive ageing.
Social determinants and global equity
A key focus of the review is the role of social determinants of health - including education, socioeconomic conditions and access to healthcare - in shaping cognitive resilience across the lifespan.
This has major implications for low- and middle-income countries (LMIC), which are disproportionately affected by dementia but remain under-represented in cognitive resilience research.
“Optimising vascular health across the lifespan may offer particularly powerful cognitive benefits in low- and middle-income countries, where vascular disease contributes more heavily to cognitive decline,” says Dr Alice Powell from CHeBA, lead author and neurologist.
“While there is growing evidence from high-income countries that multicomponent interventions - combining lifestyle, vascular risk management and cognitive strategies - can enhance resilience, these approaches have yet to be rigorously tested in LMIC settings,” she says.
A pathway to prevention
By integrating cognitive testing with imaging and fluid-based biomarkers, researchers can now better identify who is resilient, why they are resilient, and how interventions may help preserve cognition even when brain disease is present.
The authors emphasise that consistent definitions, standardised measurement and greater inclusion of diverse populations are essential to translating cognitive resilience research into effective, equitable dementia prevention strategies.
Understanding why some brains withstand damage better than others, they conclude, may unlock new ways to slow or prevent cognitive decline - offering hope not just for individuals, but for ageing populations worldwide.
Contact details:
Heidi Douglass
(02) 9385 0410
