Archana Singh-Manoux: Preventing cognitive decline for healthier aging

Over the last 150 years our life expectancy has doubled, leading to a surge in cognitive impairment among older adults. But for Archana Singh-Manoux, Inserm research director and recipient of the Coups d'Élan Prize from the Bettencourt-Schueller Foundation, nothing is set in stone. A number of risk and protective factors are potential targets for preventing this decline. The foundations of healthy aging are laid throughout our lives!

© Inserm/François Guénet

"My dream is to identify the risk factors for age-related cognitive decline that we can influence, so that we can then implement a prevention campaign, like the campaigns that have led to a decline in the prevalence of cardiovascular diseases," cheerfully explains Archana Singh-Manoux, epidemiologist at the Center of Research in Epidemiology and Statistics (CRESS)* based at the Hôtel-Dieu Hospital in Paris. This survey, which has been recognized by the Coups d'Élan Prize for French Research, awarded by the Bettencourt-Schueller Foundation, has led to Singh-Manoux working between London and Paris for the last fifteen years. It's a hectic life, but "I love what I do!" assures the epidemiologist, whose career path has been somewhat unusual.

In 1985 when she left school in India, where she was born, "I was expected to get married and stay at home, but I wanted to be independent," she explains. "So I sought out a qualification that I could rapidly make use of and enrolled at the Indian Institute of Management Ahmedabad, a prestigious business school." Her studies led her to working on microcredit, which at the time was just emerging in India; but she already knew that she wanted to work in public health instead. The only problem was that this field was still unknown in her country. She therefore opted for a related subject, social psychology, which she studied first in New Delhi and then in France, at the Paris Nanterre University, where she obtained her Ph.D. in 1998. "But that wasn't really what I wanted to do either," she recalls. "So in 2000, I saw a postdoctoral position advertised at University College London, in one of the world's leading research groups for population health, and I had the nerve to apply despite having no qualifications and no experience in epidemiology."

Untapped cognitive data

The group was working on the Whitehall II British cohort study, which has collected clinical, social, socioeconomic, psychological, and perceived health data, among other information, from over 10,000 people who have been followed since 1985. "The research primarily focused on cardiovascular disease, but there was also untapped cognitive data,", recalls Singh-Manoux. On that basis, she threw herself into studying cognitive aging: the decline in intellectual ability. Now she had found her calling! And to extend her one-year contract, she obtained her first funding from the National Institutes of Health, the American equivalent of Inserm—funding which she is still receiving today. At the time, it was thought that cognitive decline, accompanied for example by memory loss or attention problems, began at the age of 60. As the epidemiologist explains, "the studies were only carried out in people aged 65 or older, which is too late because the damage is already done. They showed that people were affected to very different degrees. But with Whitehall II, we had access to data from people who had been followed since the age of 35, which allowed us to investigate whether the signs of decline could be seen at an earlier stage." For four years, Archana Singh-Manoux delved into this data in London, before deciding to return to France with her family. Her return could hardly have gone more smoothly. In 2004, she was appointed to a Chair of Excellence post, passed the Inserm competitive recruitment assessment, and won a European Research Council (ERC) grant. This allowed her to put together her own team in the Epidemiology and Biostatistics Inserm unit, first at the Saint-Maurice Hospital near Paris, and then at the Center for Research in Epidemiology and Population Health (CESP) in Villejuif, where she remained until last December. But fortunately she did not leave London entirely behind. With approval from Inserm, she remains responsible for the cognitive aging component of the Whitehall II cohort, and hops over the Channel to work in London for four days a month. In 2012, this Franco-British research swept away the established idea of the late onset of cognitive decline. Study of data from the Whitehall II cohort confirmed not only that the decline is greater in older adults, but most importantly that memory and the ability to reason and understand begin to weaken from the age of 45. This was a valuable insight since, as the epidemiologist highlights, "behavioral and pharmacological interventions aiming to limit cognitive aging are likely to be more effective if they are used from the onset of the decline."

From scientific data to preventive messages

The study of cognitive decline immediately took on a new dimension. "For the last five years or so, we have known that dementia involves changes in the brain that take place fifteen to twenty years before the disease is diagnosed," Singh-Manoux explains. "So to understand aging, we have to study the life course." In other words, it is crucial to look at what happens before the early symptoms of dementia are apparent. The researcher has therefore helped develop the cognitive component of the general-purpose French Constances cohort study, which is being run in partnership with Inserm, and which includes 200,000 people between the ages of 18 and 69. However, as the cohort study was launched in 2012, and participants only undergo overall assessment every five years, it is still too early to derive life course data from it. In the meantime, epidemiologists have had to be creative. "In addition to Whitehall II, we are working on studies like ARIC (Atherosclerosis Risk in Communities Study) and the Framingham study, which were developed in the United States for cardiovascular disease," the researcher notes. "This has given us access to potential risk factors measured early in life." And this approach recently made it possible to draw a link between hypertension and dementia.

Normal blood pressure is 120 mmHg (millimeters of mercury) and "we know that from 140 mmHg, hypertension should be treated, as it is associated with an increased risk of cardiovascular disease. But we've shown that for dementia, the critical threshold is 130 mmHg," she adds. "So there's now a debate about whether people should be treated earlier in order to prevent dementia, independently of the cardiovascular risk." A debate that illustrates the researcher's approach: focusing on producing solid scientific data as a basis for clear preventive messages.

It was with this in mind that at the start of the year, she incorporated a clinical component into her research. A number of neurologists have been added to her team, which joined the Center for Research in Epidemiology and Statistics in January, and will move to the Hôtel-Dieu when renovation work on the hospital is complete. The Bettencourt-Schueller Prize therefore comes at an ideal time. "It will allow us to take on a statistician and help us move to new premises," she concludes with delight.

Key dates

  • 1988. Bachelor's degree in Psychology, New Delhi, India
  • 1998. Ph.D. in Psychology from Paris Nanterre University, Paris X
  • 2000-2004. Postdoctoral student at University College London, United Kingdom
  • 2007. HDR Inserm (French accreditation to supervise research)
  • 2015. Inserm Research Prize

Note : *Inserm unit 1153/Université Paris Diderot/Université Paris 13/Université Paris Descartes/Inra