Insights
Study reveals why memory declines with age

A recent international study that pooled brain scans and memory tests from thousands of adults has shed new light on how structural brain changes are tied to memory decline as people age.
The findings show that the connection between shrinking brain tissue and declining memory is nonlinear, stronger in older adults, and not solely driven by known Alzheimer’s-associated genes like APOE ε4.
This suggests that brain ageing is more complex than previously thought, and that memory vulnerability reflects broad structural changes across multiple regions, not just isolated pathology.
Alvaro Pascual-Leone, MD, PhD is senior scientist at the Hinda and Arthur Marcus Institute for Aging Research and medical director at the Deanna and Sidney Wolk Center for Memory Health.
The researcher said: “By integrating data across dozens of research cohorts, we now have the most detailed picture yet of how structural changes in the brain unfold with age and how they relate to memory.”
The study found that structural brain change associated with memory decline is widespread, rather than confined to a single region.
While the hippocampus showed the strongest association between volume loss and declining memory performance, many other cortical and subcortical regions also demonstrated significant relationships.
This suggests that cognitive decline in ageing reflects a distributed macrostructural brain vulnerability, rather than deterioration in a few specific brain regions.
The pattern across regions formed a gradient, with the hippocampus at the high end and progressively smaller but still meaningful effects across large portions of the brain.
Importantly, the relationship between regional brain atrophy and memory decline was not only variable across individuals but also highly nonlinear.
Individuals with above-average rates of structural loss experienced disproportionately greater declines in memory, suggesting that once brain shrinkage reaches higher levels, cognitive consequences accelerate rather than progress evenly.
This nonlinear pattern was consistent across multiple brain regions, reinforcing the conclusion that memory decline in cognitively healthy ageing is linked to global and network-level structural changes, with the hippocampus playing a particularly sensitive role but not acting alone.
Pascual-Leone said: “Cognitive decline and memory loss are not simply the consequence of ageing, but manifestations of individual predispositions and age-related processes enabling neurodegenerative processes and diseases.
“These results suggest that memory decline in ageing is not just about one region or one gene — it reflects a broad biological vulnerability in brain structure that accumulates over decades.
“Understanding this can help researchers identify individuals at risk early, and develop more precise and personalized interventions that support cognitive health across the lifespan and prevent cognitive disability.”
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Interview: Dr Matthew Bennett on building resilience and a pain-free healthspan

Harnessing the multi-dimensional capabilities of the human body is key to overcoming chronic pain and boosting longevity, say the authors of a new book.
While the primary focus of established health care systems is to target pain points through medication or surgery a more holistic approach is emerging, as US chronic pain doctor Matthew Bennett explains.
Published late last year by Dr Bennett and colleague Dr Sahar Swidan’s book, Mastering Chronic Pain: How Peak Resilience Unlocks Your Potential offers grounded insights into pain resolution.
Speaking to Agetech World from his New York base he said: “I’ve been treating patients in chronic pain for over 20 years.
“And, it becomes obvious that while some pain is very responsive to simple interventions, like a nerve block or a surgery, there’s a large number of people which that does not move the needle for.
“We used to look at it like, ‘Hey, the MRI shows this one spot that’s pushing on this one nerve. If we can take that spot off that nerve, everything’s going to be better’.
“And, that just doesn’t always play out that way. It’s become apparent that there are a lot of situations where the problem is more systemic.
“It’s really more of a metabolic problem, and pain is the expression of these system failures.”
‘Fight or flight’
The upstream drivers of acute pain can be numerous as Dr Bennett explains: “You can take as much pressure as you want off of nerves, but if your inflammatory system isn’t fixed, if the neurological system isn’t fixed, if your autonomic nervous system – meaning your fight-or-flight versus your rest-and-relaxation – isn’t balanced, if your gut biome is off, if your sleep is off – a lot of these problems aren’t going to improve.”
Key elements in developing a longevity-focused healthpsan – devoid of chronic pain and opioids – are simple, every day measures, focused on movement, sleep and breathing.
This includes developing the right muscles to create a ‘good deep core musculature’.
He continued: “An even bigger one is the way people breathe – the way they use their diaphragm.
“The diaphragm is a great big muscle that controls the deep core part of the spine. When the diaphragm’s not working correctly, the whole core musculature isn’t working right.
“You can’t get that stability in the lower spine, so other muscles jump in and try to do the work for you. That causes downstream problems.
“You need someone getting to that root cause,.. (and) we teach people how to do that, and they’ll have big breakthroughs.”
He continued: “Sleep is a big problem in people with chronic pain. There’s a lot of healing that occurs with deep sleep.
“Unfortunately, in a lot of pain states, sleep gets disrupted, and people can’t get into deep sleep, so the brain can’t clear itself of the byproducts of metabolism; that glymphatic system doesn’t work.
“Poor sleep also interferes with endocrine connectors; growth or sex hormones can be depleted. Obstructive sleep apnea can play a huge role. There’s just a big correlation between sleep disorders and chronic pain.”
Seeking calm
These key elements of Dr Bennett’s work – which has been described as ‘biopsychosocial’ – come concomitant with a keen focus on nervous systems, chronic inflammation and neuroplasticity.
Dr Bennett, co-founder of NoceViva, continued: “When we think about neurologics, one of the things that’s very far upstream of a lot of health is the balance between the fight-or-flight system and the rest-and-relaxation system – that autonomic nervous system.
“All of these things are ‘two-way streets’ with pain; meaning the pain can cause the dysfunction, and the dysfunction can cause the pain; it becomes this feedback cycle where things get entrenched in a bad loop.
“So, balancing that autonomic nervous system is a really helpful upstream fix to make. Simple things like breathwork. Some people do well with meditation.
“Some people do well with making sure they’re involved in hobbies. These are things that can help just calm that fight-or-flight system down.”
Nerves & neuroplasticity
Allowing ourselves to adjust to emerging health challenges is achievable in the right settings and with the right approach.
He continued: “The body’s nervous system has the ability to change. And it can change based on various inputs.
“The nervous system can become increasingly sensitised, or it can become de-sensitised. And so that’s one of the bigger things that we see in the chronic pain state, is this sensitisation that comes along with it.
“This neuroplasticity can make the nerves in the extremities more sensitive.
“It can also make the nerves in the central nervous system more sensitive – so nerves in the spinal cord, or even nerves in the brain can become hyper-sensitised – so they’re triggering more of a pain response in the person.
“But the same thing that can cause the system to go in what we would consider a bad direction, where it gets more sensitive, the neuroplasticity can actually become undone, and you can make the nerves less sensitive.”
AI to boost lifespan?
Looking ahead Dr Bennett foresees a future where a deeper understanding of the functional pathways of pain, combined with AI, stem cell therapies and regenerative biologics will all speak to a future of greater longevity for mankind.
“I think the more attentive we are to the root cause, the more attentive we are to functional pathways – when we start thinking about how the system really works? And we get out of just an algorithmic approach to things.
“We still have quite a ways to go. I think we are making progress. There was a time where we would not be thinking about any of this.
“I think everyone’s excited about what AI will bring. And are we going to be able to make some big steps? I think we’re able to intervene on a genetic level at this point.
“Will we be able to do it well enough to change lifespan? I would guess, yes, but by how much? I don’t know!”
News
Genetic influence on lifespan underestimated by half
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Four in ten cancer cases could be prevented globally, report finds

Up to four in ten cancer cases worldwide could be prevented, a new global analysis has found.
The study examines 30 preventable causes, including tobacco, alcohol, high body mass index, physical inactivity, air pollution, ultraviolet radiation and, for the first time, nine infections that can cause the disease.
Released ahead of World Cancer Day on 4 February, the analysis from the World Health Organization (WHO) and its International Agency for Research on Cancer (IARC) estimates that 37 per cent of all new cancer cases in 2022, around 7.1 million cases, were linked to preventable causes.
Drawing on data from 185 countries and 36 cancer types, the study identifies tobacco as the leading preventable cause of cancer, globally responsible for 15 per cent of all new cancer cases, followed by infections (10 per cent) and alcohol consumption (3 per cent).
Three cancer types, lung, stomach and cervical cancer, accounted for nearly half of all preventable cancer cases in both men and women globally.
Lung cancer was primarily linked to smoking and air pollution, stomach cancer was largely attributable to Helicobacter pylori infection (a bacterial infection of the stomach lining), and cervical cancer was overwhelmingly caused by human papillomavirus (HPV).
Dr André Ilbawi, team lead for cancer control at WHO and author of the study, said: “This is the first global analysis to show how much cancer risk comes from causes we can prevent.
“By examining patterns across countries and population groups, we can provide governments and individuals with more specific information to help prevent many cancer cases before they start.”
The burden of preventable cancer was substantially higher in men than in women, with 45 per cent of new cancer cases in men compared with 30 per cent in women.
In men, smoking accounted for an estimated 23 per cent of all new cancer cases, followed by infections at 9 per cent and alcohol at 4 per cent.
Among women globally, infections accounted for 11 per cent of all new cancer cases, followed by smoking at 6 per cent and high body mass index at 3 per cent.
Dr Isabelle Soerjomataram, deputy head of the IARC Cancer Surveillance Unit and senior author of the study, said: “This landmark study is a comprehensive assessment of preventable cancer worldwide, incorporating for the first time infectious causes of cancer alongside behavioural, environmental and occupational risks.
“Addressing these preventable causes represents one of the most powerful opportunities to reduce the global cancer burden.”
Preventable cancer varied widely between regions.
Among women, preventable cancers ranged from 24 per cent in North Africa and West Asia to 38 per cent in sub-Saharan Africa.
Among men, the highest burden was observed in East Asia at 57 per cent, and the lowest in Latin America and the Caribbean at 28 per cent.
These differences reflect varying exposure to behavioural, environmental, occupational and infectious risk factors, as well as differences in socioeconomic development, national prevention policies and health system capacity.
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