Prevent Stroke to Prevent Dementia?

Daniel M. Keller, PhD

October 31, 2019

DUBAI, United Arab Emirates — To reduce the incidence of dementia, societies will need to reduce the incidence of strokes, a multinational panel of experts concluded here at the XXIV World Congress of Neurology.

Because there are modifiable risk factors for stroke, it should be possible to lessen the occurrence and impact of dementia, they say.

Disability-adjusted life years (DALYs) from stroke begin to increase in midlife for both women and men, followed approximately at ages 65 to 69 years by a rising trend in DALYs from Alzheimer's disease and other dementias for both sexes — but more so for men.

Given increasing populations, "the age-standardized rates of dementia have not changed even though… the absolute numbers of people with dementia has increased quite sharply," said William Carroll, MBBS, MD, president of the World Federation of Neurology (WFN) and consultant neurologist at the University of Western Australia in Perth.

Estimates are that the number of people living with dementias in the Americas in 2050 will increase by 248% (9 million recently to 31 million people), in Africa by 300% (3 million to 12 million), in Europe by 90% (11 million to 21 million), and in Southeast Asia by 226% (22 million to 72 million).

"The problem is about how countries and people and nations are going to manage this increased number of people suffering from dementia," he said, given that the human, financial, and societal burdens of dementia are already very large.

Because stroke is a risk factor for dementia, one logical approach to prevent dementia is to address hypertension, a major cause of stroke, as well as smoking, diabetes, and lifestyle. Climate change and air pollution have also become risk factors.

"If we reduce the rate of stroke, the argument goes, we may be able to reduce the face of dementia; if not stop it then at least reduce the severity of the dementia," Carroll predicted.

The Alzheimer's Disease International 2018 report gives a figure of 50 million people worldwide living with dementia in 2018. A new case occurs every 3 seconds. By 2050 the prevalence is expected to triple to 152 million people – two thirds of whom will live in developing countries.

During the news conference, Najeeb Qadi, MD, of King Faisal Specialist Hospital and Research Centre in Riyadh, Saudi Arabia, illustrated the link between stroke and dementia. He said the top three types of dementia are Alzheimer's disease (47%), mixed dementia (34%), and vascular dementia (9%).

The prevalence of vascular dementia doubles every 5 to 10 years after age 65, and it surpasses Alzheimer's disease after age 85 years. Qadi said dementia occurs in 20% to 30% of people within about 3 months of a stroke, with an additional 25% developing dementia over the next 3 years.

"Usually, we don't see pure neurodegenerative disease or pure vascular insult. In fact, we see a combination," he said, where vascular insults plus Alzheimer's disease hasten progression of dementia. "This is why mixed dementia prevalence is increasing more and more with the longevity of individuals."

He cited the Nun Study, published in JAMA in 1997, which showed that lacunar infarcts in the basal ganglia, thalamus, or deep white matter raised the risk of dementia 20.7-fold compared with women without infarcts. "This is why we put a lot of emphasis on how to prevent a vascular dementia or Alzheimer's disease," he said.

Modifiable risk factors are hypertension, smoking, diabetes, chronic atrial fibrillation, blood cholesterol, obesity, poor diet, excessive alcohol consumption, and lack of exercise. Potential beneficial factors are education, cognitive training, social interaction, reducing depression, ability to hear, and following a Mediterranean diet. One estimate is that for every 1000 hypertensive patients treated with anti-hypertensive drugs for 5 years, 19 cases of dementia may be prevented.

Qadi concluded that multimodal risk factor reduction may have greater benefit than focusing on a single one. Factors that are not modifiable are age, sex, genetics, a previous vascular event, and a high fibrinogen level.

Michael Brainin, MD, PhD, of Danube University in Krems, Austria and president of the World Stroke Organization (WSO), pointed out that stroke accounts for just over 67% of all deaths from neurologic disorders and that it is the second leading cause of death after cardiovascular disease, accounting for 16.8% of all deaths in 2015.

Stroke incidence and mortality have a very skewed geographic distribution in terms of East vs West. "This is a striking phenomenon which is going on for a while, and this disparity [is] increasing, so we see a huge increase in incidence rate in China and other Asian countries," he said. Some regions in Eastern Europe also have high incidences.

An interesting finding is that household socioeconomic status (SES) influences infant gray matter volume even before 1 year of age, with a gradient of increasing volume as SES increases from low to mid to high levels.

Another factor is air pollution worldwide. In the Americas, about 5% to 15% of cerebrovascular disease is attributable to air pollution, whereas in India, China, and parts of Africa the figures range between 25% and 35%. "Now, we are talking about modifiable risk factors," Brainin said. "We still have hope that outdoor air pollution is a modifiable risk factor."

He said small particles less than 2.5 μm (micrometers) do more damage to the brain than to the heart, and particles this size cannot be filtered out by typical masks. They can go through the skin and into the arteries and be a cause of atherosclerosis.

"So, this is the link between air pollution and stroke and diseases of vessels," he explained. There is a demonstrated dose effect of exposure to increasing levels of small-particle air pollution and annual relative risk of mortality from ischemic heart disease and from stroke.

When the effects of modifiable lifestyle risk factors are added to medical ones like blood pressure, cholesterol, fasting plasma glucose, and impaired kidney function, Brainin said, 80% of the strokes in the world can be predicted. "This is a huge number...If we're able to modify the risk profile in this population, we might prevent an equal percentage — or maybe, let's say half of it over time," he said.

As part of that effort, the WSO has initiated a project called Cut Stroke in Half. "We have reasonable hopes to implement strategies to modify these risk factors" to reduce stroke incidence, he said.

Adesola Ogunniyi, MBBS, University College Hospital, Ibadan, Nigeria gave a perspective on the challenges of stroke and dementia in Africa, reporting that stroke is the second most important cause of disability in Africa. Prevalence rates range from 58 per 100,000 people to 851 per 100,000, one of the highest rates in the world.

Just between 2000 and 2012, stroke DALYs increased 120%. Drivers of the increase were an aging population, uncontrolled or inadequately controlled hypertension, pollution, and changing lifestyles leading to poor diet and lack of physical activity.

Two studies from Sub-Saharan Africa, one in Nigeria and the other in Ghana, link stroke with cognitive impairment and dementia.

"They reported that about 45% of individuals who've had a stroke will develop some cognitive problems," Ogunniyi said. "The majority of them will have cognitive impairment between 35% and about 40%. Well, about 10% to 14% of them will develop dementia." He cited risk factors of age, low education, and cognitive decline.

He said prevalence rates of dementia in Africa used to be very low, about 2%, "but recent studies are reporting much higher rates of about 11%." Dementia in Sub-Saharan Africa is estimated to increase by 260%, with numbers rising from about 2.1 million individuals in 2015 to about 7.6 million in 2050, again, driven by age, air quality, hypertension, and the presence of other vascular factors.

A Success Story and Proof of Concept

In 2000, several brain health advocates persuaded the government of Ontario, Canada's largest province with 14 million people, to invest in stroke by building more stroke units, dementia clinics, and to promote risk factor control through public campaigns.

After a while, they saw that outcomes were better, fewer people were dying of stroke, and had less disability. Even if a person had a warning of a stroke and went to a stroke prevention clinic, the chance of dying that year decreased by 26%. If a stroke could be avoided altogether, the person was less likely to develop dementia.

One of the leaders of this effort, Vladimir Hachinski, MD, DSc, Western University, London, Canada, said that over a 12-year period in Ontario there was a decrease of 32% in the incidence of stroke, accompanied by a 7% decrease in dementia.

"If you multiply over the tens of thousands of people who have a dementia diagnosis each year in Ontario, that's a large number," he said. Going forward, the working group will take a much more comprehensive view, looking at environmental factors like pollution, social factors, economic factors, access to care, as well as individual factors.

Identifying asymptomatic people at risk of a stroke is critical in preventing dementia. From 12 studies of incident stroke involving 1.3 million participants, researchers saw that a stroke doubled the chance of developing dementia (hazard ratio 2.18; 95% confidence interval, 1.90 - 2.50; P < .001).

This is the first time such a project has been attempted because it takes many people working together on a common goal. Part of the effort will be an open science platform hosted by the Montreal Neurological Institute and Hospital, which will also provide analytics. But a key point is that the information must be shared. A second piece of the project is that Statistics Canada will make data widely available. And third, there is a dementia plan for Canada.

"We now have the ability to look at Big Data by artificial intelligence, and we can be answering questions that were not possible to answer before," Hachinski said. "And it could be that small changes in a large number of factors could have a bigger impact than any big change in any one factor."

He added that one approach that has been proven to work right now is to build stroke units. "Then the new thing we added was the stroke prevention clinics... and you don't have to build them. Just organize clinics where people can get that care," he said. They can be implemented at low cost and will go a long way to prevent stroke and, therefore, dementia.

If these preventive measures were a drug, "we would all be queuing up at the pharmacy to get hold of that because the effect is so huge," WSO President Brainin said. "This is so obvious and just needs to be implemented in an intelligent way and the way that reaches most people."

Some Ways Forward

Ultimately, it would be best to prevent stroke and not to have to treat it, and prevention efforts need to start early, a point emphasized by Alla Guekht, MD, PhD of the Russian National Research Medical University in Moscow.

"We need to educate those people who are now at age of 20 or 15 and older…[about the] need to change their lifestyle now if we want some impact in 30 years' time," she said. "It would be too late to start…all the measures and all the initiatives and all the interventions when the person is old enough."

Qadi made the point that stroke units do not do patients any good if paramedics just take them to the closest hospital. "You have to take them to the centers with the stroke unit where they're properly equipped," he said.

Although stroke units are the best places to treat strokes, "the problem is even then it's getting the message out into the community," WFN President Carroll said. "Nowadays, with social media and other forms of communication, it's going to be easier."

He said that when he heard that some countries were going to establish units to do thrombolysis and thrombectomy, he disagreed with that approach — that preventive measures should be the first efforts.

But he said he came to recognize that "you can educate the population much faster if you open a dramatic stroke unit, and then talk about stroke and get the topic on the table. And so we may have to think smarter and more intelligently about how we get these messages out into the community in the population at large."

Another problem with stroke is denial and delay, that is, the need for a patient to present for treatment as soon as possible after stroke symptoms begin. Hachinski noted that a fundamental difference between strokes and heart attacks is that heart attacks are painful, and thus people more readily go to the hospital. But with stroke, if "the symptoms go away, the danger doesn't," he said.

Cardiologists have been successful in reducing mortality from heart attacks, and now more people are living with heart failure because of it. The outcome of stroke may be even more devastating for survivors, being unable to move well, speak, or understand speech or its emotional content. So prevention is key.

"So it can only be the knowledge that this now is a stroke that causes you to call 9-1-1, and this knowledge goes...through to schools and through the education of the young generation," Brainin emphasized.

Carroll said the need for public education about stroke prevention is a worldwide problem with some local variations. "That's what we need to concentrate on because there is a real opportunity. Then we can get a double whammy — that we can reduce the rate or the severity of dementia as well as that of stroke if we adopt them."

These efforts will take coordination and community cooperation, but as the Canadian example illustrates, such efforts can bear fruit in a relatively short time. Quoting what he said was an African proverb, Hachinski encapsulated what is needed for success: "If you want to go fast, go alone. If you want to go far, go together."

The World Stroke Organization has issued a proclamation, endorsed by all the major international organizations focused on global brain and cardiovascular health, calling for the joint prevention of stroke and dementia. An article, "The Berlin Manifesto," summarizes the evidence to translate it into action.

The presenters have disclosed no relevant financial relationships. There was no funding for the topic under discussion.

XXIV World Congress of Neurology (WCN) 2019: Presented October 28, 2019.

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