Dutch epidemiologist Albert Hofman. Photo courtesy Harvard Chan School of Public Health.

Dutch epidemiologist Albert Hofman spends a lot of time studying the causes of diseases. One of the diseases he is particularly interested in is what he refers to as “the other pandemic” or Alzheimer’s disease.

An estimated 50 million people around the world have dementia, a number expected to triple by 2050. That’s a staggering increase, but Dr. Hofman, an expert in vascular and neurologic diseases and chair of the Department of Epidemiology at Harvard T.H. Chan School of Public Health, remains optimistic.

That’s because new studies from the Netherlands and the United States show a declining risk of developing Alzheimer’s, the most common form of dementia.

Live a week, gain a weekend

In the 1800s, the global life expectancy at birth was about 35. In just two centuries, this number has more than doubled. In record countries such as Japan, the average life expectancy of women is today as high as 90. This rapid increase in how long we are expected to live is astonishing, Dr. Hofman said. “Every four years, we add one year to our life expectancy.  I summarized this for myself by saying, ‘You live a week and you gain a weekend.’”

Yet, an older population also means that the number of Alzheimer’s cases will increase. “After the age of 60, the risk of developing Alzheimer’s goes up,” Dr. Hofman said, and by the time we reach the age of 90, the chances are one in two of developing the disease.

The impact of Alzheimer’s disease is especially acute in countries like China and India, countries with a booming population that see a rapid increase in the proportion of elderly. Many of these countries are not prepared for the rise in the number of Alzheimer’s patients. “That’s why we call it the other pandemic,” he said.

15 million fewer cases

The reasons behind the increased likelihood for Alzheimer’s as we age remains a mystery. This is not solely a consequence of aging, Dr. Hofman believes, but an accumulation of risk factors.

In studying the causes for Alzheimer’s and dementia, Dr. Hofman gained crucial insights from large population-based cohort studies for age-related diseases, or studies that follow the same people over a period of time. He is the initiator of several large-population cohort studies like the Rotterdam Cohort study, which today includes 20,000 people and focuses on risk factors for cardiovascular and neurodegenerative diseases, including Alzheimer’s. In the data provided by the Rotterdam study, researchers saw a curious trend over the last three decades: a decline in the number of new patients diagnosed with Alzheimer’s disease.

Hofman followed up these findings by starting the Alzheimer’s Cohorts Consortium at Harvard in 2020, which combined the data of seven long-term cohort studies and involved 49,202 people from the US, Netherlands and other European countries. When researchers compared the data from these combined cases, they saw a decline in the number of new Alzheimer’s cases of between 10 percent and 15 percent per decade over the past 30 years.

They also discovered that the risk for men and women to develop Alzheimer’s is the same. “There are more women who have Alzheimer’s disease than men,” Dr. Hofman said, “but that is because women live longer.” In other words, while an aging population leads to more people diagnosed with Alzheimer’s overall, the risk of new cases is declining and if this declining trend continues, researchers estimate 15 million fewer cases in the US and Europe by 2040.

Population cohort studies are a valuable knowledge resource for epidemiology and medicine in general, but there are not that many in the world, Dr. Hofman said. It is easier in the Netherlands, and other European countries to follow people in a cohort study, he said, because the national governments maintain population registrations, including where people live.

Adopt a healthy lifestyle, now!

Scientists do not have a firm answer for the decline in new Alzheimer’s diagnoses. Dr. Hofman believes that non-genetic factors and in particular cardiovascular factors play a big role in Alzheimer’s disease. The vascular system, our circulatory system, is made up of blood vessels that carry oxygen-rich blood from the heart to other parts of the body. If the blood vessels are damaged, the lack of oxygen will cause the nerve cells to gradually die, leading to Alzheimer’s disease.

Dr. Hofman thinks a possible reason for the decline could be improved treatments of risk factors for heart disease and stroke since the 1970s and 1980s in Europe and the US, such as treating high blood pressure, lowering high cholesterol, no smoking and regular exercise. These preventive measures not only reduced the number of heart attacks and strokes, but also likely had a positive impact on the vascular system and brain health. The brain scans of patients who have been treated for blood pressure and cholesterol showed improvement over the years, Dr. Hofman said.

If the vascular risk factors play a major role in causing Alzheimer’s, adopting a healthier lifestyle can be a preventative measure that anyone can adopt.

Controversial drug

In teasing out the causes of Alzheimer’s, Dr. Hofman and his group are working on treatments that can lower or stabilize blood pressure, as large swings in blood pressure can increase the risk of developing Alzheimer’s.

And whereas Hofman and his group are focusing on preventative measures, the FDA recently approved the Alzheimer’s drug Aducanumab, the first treatment to attack the progression of the disease. The FDA’s approval created much consternation within the scientific community because of the controversies around the medication’s effectiveness and cost. Hofman belongs to this group of skeptics. “Perhaps, the positive side is that it will stimulate other companies to go on this path and strive to go on,” but he hopes that the European Medicines Agency will hold off on its approval and instead ask for more studies and clinical trials of the drug to provide complete evidence of the drug’s effectiveness.

Dinner with billionaires

Epidemiology is “the quantitative part of medicine,” Dr. Hofman said. It is this formalized way of studying the causes of a disease that fascinates him and which is why he chose to specialize in this field at the department of epidemiology at the Erasmus University in Rotterdam and Harvard in Boston in the late 1970s.

After his fellowship at Harvard, he returned to the Netherlands and later became chair of the biggest epidemiology department in the country. He maintained a connection to Harvard, and taught a summer course at the university for 25 years. In 2016, he returned to Harvard and became chair of the Department of Epidemiology. What makes Harvard and the Boston area appealing to him is the attitude toward science, or as he describes it, “the can-do mentality” and the “sense of urgency.” What’s more, Boston’s academic ecosystem is concentrated: “The Boston area has close to 20 percent of all postdoc positions in the whole of the US.”

When comparing the US research system to the Dutch research system, Dr. Hofman, thinks the educational infrastructure for PhD students in the US could serve as a model for Europe. “It is more developed in coursework, in the qualifying exams and in the in-person training,” he said. It is an educational infrastructure that provides students the opportunity to excel and to grow outliers.

The way the US funds science differs from the Netherlands. The US government, particularly the National Institutes of Health, funds and focuses on the important issues in medicine, but the role of private funds, benefactors, and foundations in the United States is “virtually absent” in the Netherlands.

“The dean and the president of Harvard advise me occasionally to go to the West Coast and to have dinner with a couple of billionaires, which is very nice. And very smart. I’ve never done a thing like that in Europe in the 30 years that I was chair there.”

He sees an opportunity for universities in the Netherlands to adopt this way of fundraising: “Most wealthy people are willing to support major causes in society.  Although we spend a lot of time here on fundraising I find it a very nice part of the American system.”

Read about other Dutch researchers in the United States.