July 31, 2024

expert reaction to 2024 Lancet Commission report on dementia prevention, intervention, and care

A report published in the Lancet looks at dementia prevention, intervention and care. 

Dr Sarah-Naomi James, Senior Research Fellow, MRC Unit for Lifelong Health and Ageing at UCL, said:

“The Lancet commission update on Dementia prevention, Intervention and Care is commendable, thorough and written with great care by the curated respected experts.  The previous Lancet commissions have been instrumental in encouraging researchers and policy makers, worldwide, to understand that there may be influences across the life course that increase, or decrease, the risk of developing dementia. This is important as, by understanding and acting on true risk factors of dementia, we can indeed delay, or prevent some cases of dementia. I welcome the important note in this review that risk factors often cluster in individuals, and therefore interventions ought to be taken with a holistic approach, appreciating the biological, lifestyle and societal influences on our health, and co-produced with key stakeholders in communities.

“However, whilst there is indeed evidence that shows these life course factors are linked with dementia, we still have fundamental gaps in our understanding. For example, we are still lacking substantial evidence of if, and how, these factors are causing dementia. We don’t know how these factors (such as blood pressure) are affecting dementia risk, and which aspects of dementia pathology, type and development are conferring this risk. Our evidence base also may be inadequate to capture other important influences on dementia, such as very early life influences (e.g. brain development in utero or in adolescence) and the role of reproductive health.

“Overall, while more evidence is warranted to understand the ‘flesh of the details’ to help optimise prevention efforts specifically orientated to reduce dementia risk or delay dementia onset, the recommended actions presented here (e.g., ensure good quality education, encourage lifelong exercise participation) ought to be encouraged in any case, by anyone interested in encouraging people to live healthier lives, throughout their life course.”

Prof David Attwell, Director of the BHF-UK DRI Centre for Vascular Dementia Research at the UK Dementia Research Institute, and Jodrell Professor of Physiology at UCL, said:

“I welcome this updated version of earlier Lancet Commission reports on dementia. Vascular contributions to dementia are given higher prominence compared to the 2020 report, with the recognition that vascular health and hence dementia risk can be negatively affected by diabetes, cholesterol level, hypertension, smoking, obesity, air pollution and head injury. More mechanistic assessment of how vascular dysfunction leads to dementia (beyond correlations between vascular dysfunction and stroke) could have been included, and could aid prediction of interventions that might prevent or slow dementia onset. Key questions remain over whether a decrease of cerebral blood flow or a breakdown of blood-brain barrier function makes a larger contribution to dementia. In Alzheimer’s disease, affected parts of the brain suffer a 45% decrease in cerebral blood flow (1) which is expected to impair cognition, and this is generated by constriction of capillaries by a specialised cell type known as pericytes (2). Consistent with this, use of drugs that dilate the blood vessels may delay the onset of Alzheimer’s disease (3) and similarly delay vascular dementia caused by cerebral small vessel disease (4). In contrast, drugs correcting blood-brain barrier dysfunction have yet to reach routine clinical use (but see 5), making it hard to assess the contribution of the blood-brain barrier to dementia onset.”

1. https://pubmed.ncbi.nlm.nih.gov/27327500/
2. https://pubmed.ncbi.nlm.nih.gov/31221773/
3. https://pubmed.ncbi.nlm.nih.gov/38324745/
4. https://pubmed.ncbi.nlm.nih.gov/37222252/
5. https://pubmed.ncbi.nlm.nih.gov/36812346/

Prof Sandrine Thuret, Professor of Neuroscience at King’s College London said:

“The latest crucial report from the Lancet Commission reveals that nearly half of dementia cases could be prevented or delayed by addressing 14 modifiable risk factors, with high cholesterol being one of its newly identified contributors. Although diet has not been represented on the summary figure (9), now with high cholesterol, together with obesity and diabetes as previously identified modifiable risk factors, this underscores further the crucial role of a healthy diet in mitigating dementia risk.

“From tackling vascular risk factors -e.g. with healthy diet and exercise- to ensuring cognitive activity and social engagement throughout life, these findings highlight the intersection of daily habits and long-term brain health, emphasizing that comprehensive, lifelong health strategies from early years -to be led by individuals and supported by government policies- can significantly impact dementia prevention.”

(from our colleagues in Germany) Prof Klaus Ebmeier, Foundation Chair of Old Age Psychiatry, University of Oxford, said:

“The third report of the Lancet Standing Committee on Dementia Prevention, Intervention, and Care aims to “influence policy, knowledge, clinical practice and the research agenda”. The committee makes recommendations for all stages of life to reduce the risk of dementia. It recommends measures such as better schooling, use of hearing aids and screening for vision loss, improved cardiovascular prophylaxis e.g., by reducing smoking and low-density lipoproteins in the blood, as well as reducing air pollution, effective treatment of depression, and the creation of age-appropriate and supportive social environments and housing. The committee points out that the elimination of fourteen risk factors could “theoretically” prevent almost half of dementia cases and that this “gives hope”. This wording is somewhat more cautious than it was in previous reports. The scope of the epidemiological research methods used to identify the causes of dementia is limited. In particular, the described correlations between risk factors and dementia do not imply causality (“some associations might be only partly causal”).

Unfortunately, press coverage typically boils down to the headline “half of all dementia cases are preventable”, which leads to “fake news” and false hopes, and gives patients the impression that dementia is at least partly a “lifestyle choice” because they have not taken adequate care of their health.

“My comments, in a nutshell:

• There is no doubt that the measures proposed by the Commission are laudable, if only because they improve health and well-being in general (who would object to more education, less air pollution, treating depression, or improving people’s physical health?).
• For practical and ethical reasons, it is mostly impossible to conduct randomized control trials that could prove the causality of the risk factors and therefore the effectiveness of such proposed interventions in dementia prevention. Newer genetically inspired methods (Mendelian Randomization) have generally confirmed many of the postulated risk factors as non-causal. The non-causal nature of the identified correlations often means that manipulation of such risk factors will not result in a prevention of dementia cases:

• • The diagnosis of dementia comes at the end of a decades-long disease development, which is often accompanied by behavioural changes such as social withdrawal, depression, and sensory changes (reduced sense of smell, hearing, and speech comprehension disorders). Early changes in the central nervous system during development before a diagnosis of dementia can, for example, lead to disorders of speech comprehension and to hearing aids being perceived as too difficult and frustrating to use. This may be the reason why hearing loss is only associated with later dementia if patients do not use hearing aids. It is therefore possibly not the lack of hearing aid use that leads to dementia, but an early limitation of information processing in people who later develop dementia prevents them from being able and wanting to use their hearing aids. On the other hand, early prodromal symptoms may mask causal risk factors. We know that over twenty years before a diagnosis of dementia, future patients slowly lose weight. Initially (twenty years before diagnosis) there is a (plausible) association of being overweight with later dementia, later (about ten years before diagnosis) there is no correlation, and finally, in the last years before diagnosis, underweight is associated with higher dementia risk.^[1] It is not clear whether the slow weight loss before diagnosis is due to reduced appetite (without the sense of smell, food becomes tasteless, and depressive mood is often accompanied by loss of appetite and weight), or due to a limited ability to eat well enough, or due to other brain and metabolic changes. Certain “risk factors” may thus only be early symptoms occurring before the dementia diagnosis (apparent ‘reverse causality’). Avoiding or removing them is therefore generally unlikely to reduce dementia incidence.

• • Risk factors may be correlated with the actual causes of dementia, but are not themselves the cause of the disease. Education, as an easily collected measure, may only be a “marker” for other (unrecorded) causes of dementia that are based on genetics (“cognitive reserve”), developmental disorders (before, during, and after birth), or social circumstances/poverty. Therefore, such actual causes being equal, increasing the length of schooling will not necessarily reduce the risk of dementia.

• • Education demonstrates another problem with risk factors: because dementia diagnosis is based on cognitive tests, academic experience protects against a pathological test result and reduces the risk of a dementia diagnosis (“cognitive reserve”). Although this may delay a diagnosis, the rate of cognitive deterioration and changes in the brain is largely unaffected.

• The plausibility of the proposed interventions is no proof of their practical significance. A theme that unites some of these suggestions is the maxim “use it or lose it”, which of course is well known from exercise physiotherapy. Patients consequently want to know which exercises can stop or even prevent the worsening of their dementia. There is no reliable evidence base for such interventions in dementia treatment or its prevention. It is unproven that school attendance, increasing sensory (audio-visual) input, sports, exercise, or a social and friendly environment can prevent dementia by enriching brain activity (exercise may of course improve cardio-vascular health which in turn is known to affect dementia risk, see 4. below). The correlations described can equally be explained by the interference of pre-diagnostic dementia changes with the activities mentioned (seemingly reverse causality) or by the accumulation of such healthy activities in already privileged and healthier parts of the population.
• It would be wrong to conclude from the above that dementia cannot be prevented. The strongest argument for this is the 13 percent reduction in dementia incidence per decade described in the research literature of this century.^[2] The most likely explanation for this phenomenon is the generally better health of the younger generations, possibly due to greater prosperity, better obstetrics, and health care, including the aforementioned targeted prevention of cardiovascular diseases and their risk factors, e.g., high blood pressure and smoking. The calculated 45 percent of preventable or delayed dementia cases is an optimal value that is unlikely to be achieved. The true figure is more likely to be around 10 percent per decade, but only if prosperity and general healthcare quality continue to improve.
• Two other recommendations about the treatment of dementia (especially Alzheimer’s disease) in this report are noteworthy and, in my opinion, entirely justifiable:
• • The authors justify a conservative uptake of the newer monoclonal antibody anti-amyloid-beta treatments, with their limited evidence base and effect, their significant side effects, and unknown long-term effects. They emphasize the costs of personnel, imaging studies, and special blood tests, and the need for long-term monitoring for side effects.^[3]
  • Similarly, “Biomarkers in cerebrospinal fluid or blood should be used clinically only in people with dementia or cognitive impairment to confirm or rule out a diagnosis of Alzheimer’s disease.”^[4] They also remind us that “biomarkers have only been validated in predominantly white populations,” so this “limits generalizability and raises health equity concerns.”

[1] Kivimäki et al. Body mass index and risk of dementia: analysis of individual-level data from 1·3 million individuals. Alzheimers Dement 2018

[2] Wolters et al. Twenty-seven-year time trends in dementia incidence in Europe and the United States: the Alzheimer Cohorts Consortium. Neurology 2020 [To avoid any misunderstanding, total dementia diagnoses are still increasing because the oldest part of the population pyramid is growing disproportionately]

[3] Which has just been confirmed by the European Medicines Agency (“European Medicines Agency rejects breakthrough Alzheimer’s drug”, Oliver Barnes in Financial Times, 26^th July 2024)

[4] Dementia itself is diagnosed exclusively clinically, i.e. after a personal examination with cognitive tests and an assessment of the patient’s independence in daily life.

Prof Claudia Cooper, QMUL Centre for Psychiatry and Mental Health, said:

“This commission highlights 14 potential risk factors to target in reducing dementia risk. Their selection is based on those with the strongest evidence from research studies. While reducing obesity, diabetes and hypertension are included, a healthy diet, though an important determinant of these, is not, because the evidence directly linking it to dementia risk in research studies is not as strong – perhaps understandably, given the timespan over which this relationship, likely to be life-long, would need to be studied. 

“The report is thus helpful as a guide to reducing one’s individual risk, but the playing field is not level. The socioeconomic conditions in which a person lives profoundly affect their chances of getting dementia – through the diet they eat, the healthcare they receive and even the degree of pollution in the air they breathe. 

“While it is possible for all of us to take actions that decrease our dementia risk, none of us can know the risk level from which we start – put another way, the age at which we would get dementia, if at all, if we didn’t take these actions. There are no guarantees.” 

Prof Masud Husain, Professor of Neurology, University of Oxford, said:

“The conclusions from this research are very important for all of us, but particularly for health policy makers and government. If we did simple things well such as screening for some of the factors identified in this report, with adequate resources to perform this, we have the potential to prevent dementia on a national scale. This would be far more cost effective than developing high-tech treatments which so far have been disappointing in their impacts on people with established dementia.”

Prof Terry Quinn, Professor in Cardiovascular Aging at the University of Glasgow, said:

“The update to the Lancet Commission on Dementia provides important new evidence on the causes of dementia, and potential treatments. The main focus of the Commission paper is around understanding risk of developing dementia, and more importantly what can be done to reduce this risk.  There are some things that increase our risk of dementia that we can do little about, for example getting older. However, the Commission identifies 14 risks that are common, but not inevitable. The authors estimate that by eliminating these risks around half of all cases of dementia could be prevented.

“The factors identified by the Commission operate at different levels, some are traditionally ‘medical’ such as treating high blood pressure, others fall within the remit of public health and government policy such as reducing air pollution, but many are actions that we all can take to improve our brain health, such as getting more exercise,  reducing alcohol and staying connected with friends and family. 

“An important aspect of the Commission is that it considered risk across our whole lifespan, for example improving early years education. This emphasises that it is never too early to start thinking about our brain health. Many of the issues highlighted by the Commission will be familiar as risks for other chronic conditions like heart disease and stroke, for example smoking. Simply knowing that these factors are a risk for future disease has not previously been sufficient to make people change their lifestyles. A major challenge going forward is taking the new knowledge from the Commission and using this to reduce risks at a global level.”

Prof Charles Marshall, Professor of Clinical Neurology, Queen Mary University of London, said:

“It’s vital that as a society we develop measures to keep people’s brains as healthy as possible, particularly as dementia is now the leading cause of death. It’s worth emphasising though that most of what determines whether an individual develops dementia is outside their control, and we should be careful not to imply that people with dementia could have avoided it if they’d made different lifestyle choices. It’s also important to note that when the report refers to the proportions of dementia cases that could be prevented, this is notional, and based on observational evidence. We don’t really have evidence that dementia cases are prevented by addressing any of these risk factors. We desperately need this type of evidence to guide health policy that could help to prevent some cases of dementia.”

Prof Tara Spires Jones, FMedSci; President of the British Neuroscience Association, Group Leader in the UK Dementia Research Institute, and Director of the Centre for Discovery Brain Sciences at the University of Edinburgh said:

“This study by Livingston and colleagues is an excellent up-to-date analysis of the research from around the world examining risk factors for developing dementia.  The data in the paper add compelling evidence for the ability to prevent dementia by addressing some of the 14 identified risk factors.  This type of research cannot conclusively link any of these factors directly to dementia, but contribute to the growing evidence that a healthy lifestyle including keeping your brain engaged through education, social activities,  exercise, and cognitively stimulating activities, and avoiding things like head injury and factors that are bad for your heart and lungs can boost brain resilience and prevent dementia.  There are new links in this report with vision loss and high cholesterol associating with dementia risk, which broadly fit with the previous research indicating that keeping your brain active and avoiding vascular risk factors that come with a sedentary lifestyle and poor diet is good for reducing dementia risk.  This study is important as it gives insight into ways that both individuals and governments can help reduce dementia risk. It also helps guide more fundamental neuroscience research into how these factors influence brain vulnerability to the diseases that cause dementia. While this excellent study estimates that up to half of dementia cases could be prevented by changing modifiable risk factors, it is important that we keep in mind that the other half of people with dementia likely developed brain disease for unavoidable reasons related to factors beyond their control like genetics.”  

Dr Susan Kohlhaas, Executive Director of Research at Alzheimer’s Research UK, said:

“Dementia devastates lives, and if nothing changes, one in two of us will be affected by it, either by developing it ourselves, caring for someone with it, or both. But dementia is not an inevitable part of ageing and that’s why finding ways to prevent people from ever developing it is crucial. To do this, researchers across the world have been tracking down the health and lifestyle factors linked to Alzheimer’s and other diseases that cause dementia.

“Age and genetics are the biggest risk factors for dementia. But today’s new analysis, which Alzheimer’s Research UK helped fund, confirms that there are at least 14 other health and lifestyle factors at play – accounting for almost half of all dementia cases. The good news is that this provides a huge opportunity to put in place measures, in early to mid-life, that keep our brains healthy and lessen the devastating impact of dementia on our society and our loved ones in future.

“Many of these factors are things individuals can do something about, such as smoking. But others, like air pollution and early childhood education, are bigger than individuals and communities. Tackling them will need structural changes to society to give everyone the best chance of a healthy life, free from the impact of dementia. Public health leaders must not ignore this message if they are truly committed to seizing this enormous opportunity.

“Alzheimer’s Research UK wants to see the Public Health and Prevention Minister, Andrew Gwynne MP, establish a prevention strategy that addresses the health and lifestyle factors linked to dementia – from what we eat and drink, to the air we breathe and the education we receive.

“Aside from government action, there are steps we can all take to help reduce our risk of dementia, but just one in three people in the UK know this. Alzheimer’s Research UK has developed three simple rules to protect your brain – love your heart, stay sharp, and keep connected to other people. Take our Think Brain Health Check-in to find out more about how you can reduce your dementia risk, by visiting www.thinkbrainhealth.org.uk.”

Fiona Carragher, Chief Policy and Research Officer at Alzheimer’s Society said: 

“Dementia is the UK’s biggest killer and a global crisis affecting more than 55 million people, but it’s never too early or too late to reduce your dementia risk. 

“This Lancet Commission study, part-funded by Alzheimer’s Society, identifies two new risk factors for developing dementia: untreated vision loss and high LDL cholesterol. 

“It also suggests that nearly half of dementia cases across the world could be delayed or prevented.  

“Some dementia risk factors, such as alcohol consumption and physical exercise, can be managed by changing your lifestyle, but many must be addressed on a societal level. Social isolation, education inequalities and air pollution are beyond individuals’ control and require public health interventions and joint action between Government and industry. 

“If we can support people to reduce their dementia risk and address the societal change needed, this could mean potentially hundreds of thousands fewer people in the UK will go on to develop dementia.”  

Dementia prevention, intervention, and care: 2024 report of the Lancet standing Commission’ by Gill Livingston et al. was published in The Lancet at 21:15 UK time on Wednesday 31 July.

DOI: 10.1016/S0140-6736(24)01296-0

Declared interests

Dr Sarah-Naomi James: No declarations of interest

Prof David Attwell: I have no interests to declare

Prof Sandrine Thuret: No COIs to declare.

Prof Klaus Ebmeier: I have no conflict of interest to declare.

Prof Claudia Cooper: No conflicts of interest

Prof Masud Husain: I don’t have any conflict of interest.

Prof Terry Quinn: No COI

Prof Charles Marshall: No relevant declarations of interest

Prof Tara Spires Jones: I have no conflicts with this study

Dr Susan Kohlhaas: ARUK part funded this work

Fiona Carragher: Alzheimer’s Society part funded the work

None others received.