The Case for Prevention in Dementia

Dementia is now the leading cause of death in Australia.

That sentence still surprises most of my patients when I say it out loud in a consultation. For years dementia sat behind ischaemic heart disease in the national mortality tables, and most people still assume it does. As of 2024, it does not. Dementia accounted for 9.4 per cent of all deaths in Australia last year, overtook heart disease as the single largest cause, and has been the leading cause of death for Australian women since 2016. The number of Australians dying from dementia has increased by almost 40 per cent in a decade. Roughly 433,000 Australians are now living with it. On current trajectories that number will more than double by 2065.

This is the disease that medicine has been chasing a cure for, with limited success, for the better part of forty years.

This article is the first in a series that argues for a different way of thinking about it. It argues that the future of dementia care, for our patients and for ourselves, lies in prevention rather than in the search for a cure. And it argues that the science behind that claim is now strong enough that it should change how each of us approaches the second half of life.

What the drugs do, and what they don’t

The two most recently approved drugs for Alzheimer’s disease, lecanemab and donanemab, are the high-water mark of decades of pharmaceutical effort. It is worth being clear about what they actually achieve, because the public discussion is often muddled by either dismissal or hype.

Both are monoclonal antibodies given by intravenous infusion. They bind to amyloid-beta, the protein that forms the plaques that are one of the two pathological hallmarks of Alzheimer’s disease. PET scans before and after treatment show the plaques being cleared. The biology is doing what the drugs are designed to do.

What is less clear is whether clearing the plaques translates into a meaningful clinical benefit. In the pivotal trials, both drugs slowed cognitive decline by roughly a quarter to a third over eighteen months, measured on cognitive scales that most patients and families would not recognise as a noticeable difference in everyday life. The disease still progressed. It just progressed a little more slowly.

That benefit, modest as it is, comes at real cost. Around one in five patients on these drugs develop amyloid-related imaging abnormalities, micro-bleeds or fluid accumulation in the brain, which are usually asymptomatic but can be severe and have caused fatalities. The drugs are approved only for early disease. Patients with established dementia derive no benefit at all. And the cost, when these drugs become available in Australia, will be in the tens of thousands of dollars per year.

These are not failures. They are real drugs, doing real things, in a disease that has resisted treatment for generations. But they are not a cure. The reason they are not a cure, the reason no drug at this stage of the disease is ever likely to be a cure, comes down to a single biological fact that this entire series is built around.

Why the drugs cannot do more

By the time a patient walks into a GP’s office with memory complaints, when the first cognitive symptoms appear, the disease has typically been progressing silently for fifteen to thirty years.

This is not a guess. It is one of the most robust findings in modern neurology. Studies of patients with genetic forms of Alzheimer’s disease, where the timing of symptom onset can be predicted from family history, show that amyloid plaques begin accumulating in the brain a full two decades before the first cognitive change. Tau pathology, the second hallmark protein, follows roughly a decade later. By the time symptoms emerge, hippocampal volume has measurably shrunk, networks of neurons have been pruned, and irreplaceable cells have died.

This matters enormously, because a drug that clears amyloid in a sixty-five-year-old with mild cognitive impairment is doing useful work, but it is doing that work in a brain that has already sustained two decades of accumulated damage. You can clear the plaques. You cannot un-die the neurons. You cannot un-prune the synapses. You cannot un-shrink the hippocampus.

This is why the best disease-modifying drugs at this stage of disease will only ever be able to slow further decline. It is a worthwhile goal. Every additional year of preserved function matters. But it is not, and biologically cannot be, a reversal of the disease.

It is also why the cure narrative, as it is usually framed in the media, is misleading. The hope for dementia treatment is real, but it lies almost entirely in pushing intervention earlier, into the silent decades before symptoms appear. And that, in turn, means the hope lies in prevention.

The window we already have

If the disease begins fifteen to thirty years before symptoms, then for most people the relevant window of intervention is midlife. Forty to sixty-five. The years when most of us assume our brain health is fine because we are not yet noticing problems.

This is the window in which modifiable risk factors are actively shaping the trajectory of every brain. Whether blood pressure is well controlled. Whether sleep is consolidated and of adequate length. Whether the brain is being aerobically exercised. Whether vascular and metabolic health is being protected or eroded. Whether hearing loss is being identified and corrected. Whether engagement, learning and social connection are being sustained. Whether the menopausal transition is being managed thoughtfully.

These are not vague lifestyle suggestions. They are interventions whose evidence base, taken together, dwarfs anything that pharmacology has produced.

The prevention evidence

The 2024 Lancet standing commission on dementia is the most authoritative recent summary of this evidence. It identified fourteen modifiable risk factors that, taken together, account for roughly 45 per cent of dementia cases worldwide. They include hypertension, hearing loss, smoking, obesity, depression, physical inactivity, diabetes, excessive alcohol, traumatic brain injury, air pollution, social isolation, less education in early life, untreated vision loss, and elevated LDL cholesterol. The Australian Institute of Health and Welfare’s local analysis, using a more conservative list of six risk factors, attributes 43 per cent of the Australian dementia disease burden to modifiable factors.

These figures are striking. They say that close to half of all dementia, in the world’s best current estimates, is theoretically preventable.

The strongest randomised evidence we have comes from the FINGER trial in Finland, which took adults at elevated risk of cognitive decline and randomised them to either standard advice or a two-year, multi-domain lifestyle intervention covering diet, exercise, cognitive training and vascular risk management. The intervention group showed measurably better cognitive trajectories at the end of the trial, and that benefit persisted at long-term follow-up.

Population-level evidence points in the same direction. Several high-income countries, the United States, the United Kingdom, Sweden, the Netherlands, have seen age-adjusted dementia incidence fall over recent decades, even as total dementia deaths have risen with population ageing. The most likely explanation is the cumulative effect of better treatment of vascular risk factors: blood pressure, cholesterol, smoking. We are watching the prevention hypothesis play out at population level in real time.

This is not soft evidence. It is the strongest signal in dementia research today, and it is being routinely underdiscussed in favour of the louder, less productive drug development story.

The honest caveats

None of this is a guarantee. Risk reduction is probabilistic, not deterministic. Some cognitive change with advancing age appears to be a genuine biological process, not entirely modifiable. Genetic risk matters, though it turns out to be much more modifiable in practice than the word “genetic” usually suggests, and I will come back to this in a later article. We do not yet have randomised trial evidence for every component of the prevention package, and the 45 per cent figure is calculated as if every risk factor could be eliminated, which is not realistic.

But the magnitude of preventable risk, somewhere between 40 and 65 per cent by current estimates, is in a different league from anything that drug development has delivered or is likely to deliver in the foreseeable future. This is where the evidence sits.

Practical steps for this week

If you take nothing else from this article, take these four.

1. Know your blood pressure. Buy a home monitor, take readings over a week, seated, arm supported, before coffee, and bring the average to your next appointment. Blood pressure is the single most important modifiable risk factor for dementia in midlife.
2. If you are over fifty and have not had a recent hearing test, book one. Hearing loss is one of the largest single contributors on the Lancet commission’s list, and the intervention, hearing aids, is straightforward and effective.
3. Identify the one health risk you have been avoiding. The weight that has crept up. The blood test you have been putting off. The conversation with your GP about the family history. The exercise you do not do. Most prevention failures are not failures of knowledge. They are failures of starting.
4. Make a longer appointment with your GP to talk specifically about your individual brain health risk profile. This is not the same conversation as a standard health check. It is a conversation about the next thirty years of your brain.

Where this series is going

This is the first article in a series that will work through the evidence on dementia prevention one piece at a time. The articles that follow will tackle the major modifiable levers: the vascular brain, the metabolic brain, the role of movement, the importance of sleep, the female brain through the menopausal transition, the underrated contribution of hearing and social engagement, the science of brain plasticity and cognitive reserve, and the supplements and medications that actually have evidence behind them. Each piece will end with practical steps you can act on this week, rather than a list of generalities. The closing article will pull all of it together into a decade-by-decade prevention framework.

A cure for dementia may still come. But waiting for it is not a plan. The evidence we have now says, with increasing confidence, that the brain you have at eighty is, to a substantial degree, the brain you build from here.