Where the mind is without fear and the head is held high,
Where knowledge is free,
Where the world has not been broken up into fragments
By narrow domestic walls,
Where words come out from the depth of truth,
Where tireless striving stretches its arms towards perfection,
Where the clear stream of reason has not lost its way
Into the dreary desert sand of dead habit,
Where the mind is led forward by thee
Into ever-widening thought and action,
Into that heaven of freedom, my Father, let my country awake.
Rabindranath Tagore, Gitanjali, 1912
THE WHITE-ROBED MAN hands me a cup of chai while the midday sun pelts his calloused fingers. This is Hari Chand, a farmer in the village of Shahpur Kalan, in Ballabgarh, northern India. His ninety-four years of age asserts his status as village elder. And he’s not alone: nearby, several more elders stoop on wooden benches to smoke the customary hookah pipe, quietly chatting while offering me looks of curious bemusement.
Ballabgarh is a patchwork of twenty-eight villages located some thirty-five kilometres south of New Delhi. Its elderly inhabitants are mostly illiterate, impoverished farmers, many of whom have never left the village. I’m here to retrace the steps of a sixteen-year investigation, which started in 1988, when the US National Institute on Aging set out to widen the net for Alzheimer’s clues:
Other countries, cultures, ethnic or population groups, with different exposures and habits, may offer clues to the [cause] of the disease that are not apparent in Western industrialized nations. The need to search more aggressively and widely for potent modifiable risk factors requires movement beyond national boundaries.1
Looking around, I’m hard-pressed to think of a more suitable candidate for such an objective. Many of the villagers are bone thin; clearly malnourished. They live in crumbling sugar-cube houses or wooden shacks covered with corrugated metal sheets. They burn cow dung for fuel. Electricity is a luxury few possess. And water is supplied by a single cement basin and a few rusty pumps. But another difference seemed to be their resistance to dementia. Sporadic reports from New Delhi’s Centre for Ageing Research suggested that Alzheimer’s was ‘unusual’ in this part of India, that plaque and tangle pathology were ‘rarely found’ post-mortem.
‘My memory is good,’ Chand said proudly. ‘I think there are some people in Ballabgarh who don’t want to remember certain things, but I’ve never heard of anyone having problems with their memory.’ Chand has farmed these fields since he was ten years old. His memory stretches as far back as his teenage years, to the arguments his mother and father had when they had to borrow money to pay the British colonialists’ high taxes. Having retired at the age of eighty-five, Chand now spends his days in the company of his ten children, eight grandchildren and seven great-grandchildren. After reeling off all their names for me, he said that I’m not the first scientist to visit his town. Others had come with similar questions, not so long ago.
Leading the NIA study was Mary Ganguli, an Indian-born psychiatrist at the University of Pittsburgh, Pennsylvania (in collaboration with Vijay Chandra and colleagues at the Centre for Ageing Research and the Department of Community Medicine of the All India Institute of Medical Sciences). She had her work cut out. The study required a group of elderly people in a region where many don’t know their real age, family histories in a community where medical records are virtually non-existent, and cognitive tests in an area where few have ever put pen to paper or kept track of the Roman or Hindu calendar. It moved us from the realm of telephones and bank accounts to the era of spirits and storytelling around the fire. It was, at heart, a radical act of learning by unlearning, advancing by retreating.
‘They have the same cognitive functions as educated people,’ Ganguli explained over the phone. ‘It’s just about finding a reasonable way to tap them. It’s important because we might have learned all we’re going to learn, or most of what we’re going to learn, by only studying the risk factors for dementia among white people in wealthy countries.’
To overcome the cultural and educational disparity, Ganguli’s team devised ‘culture-fair’ tests of cognition. Since the villagers speak a phonetic dialect of Hindi, for example, they were asked to repeat certain sounds instead of reading or writing things down. Questions involving abstract mental arithmetic, like the subtracting seven task I did in chapter four, were personalised to questions about rupees and village bus fares. As an adaptation of the standard task ‘Write a sentence’, the researchers instead asked participants ‘Tell me something’–anything to gauge their ability to generate a complete thought.
A bewildered ‘What shall I tell you?’ was a common response, often leading, Ganguli wrote, to ‘awkward and pointless exchanges between interviewer and subject’. The experience resulted in the final version being ‘Tell me something about your house.’ Even the idea of taking a test was alien to many of them. When asked to memorise a list of words, most villagers simply laughed and asked, ‘What for?’ When told a story and asked to repeat it, many would say, ‘You call that a story? Let me tell you a story!’ before proceeding to embellish the original tale with great dramatic flair. When the interviewers insisted they follow the rules, they often replied, with sincere wonder, ‘Why?’
At one point the team tried something called the Boston Naming Test, a neuropsychological exam where the candidate is shown line drawings of various objects–a boat, a whistle, a kangaroo–and asked to name them. But the objects were completely unfamiliar to the villagers. Some even had difficulty with the concept of a drawing, and started grasping at the paper itself for more insight. So Ganguli decided to use 3-D models instead. One was a miniature model tree, which a member of her team had purchased in a children’s museum back in Pittsburgh. To avoid confusion, he’d cut the wooden base off before posting it to Ganguli.
‘Okay, what’s this?’ she asked when she presented it to them.
‘Broccoli,’ came the reply.
A different approach was clearly needed, and so she decided to focus on her subjects’ ability to perform normal day-to-day business. Not too much is expected of these elderly citizens–cooking, working the fields and tending the fire are all done by younger family members. Daughters-in-law are especially required to look after them. ‘At a certain age, many of the women hand over the pantry keys to their eldest daughter,’ Ganguli explained, ‘and then sit back and relax. They become ladies of leisure, if they can afford it, if there are enough daughters to do all the work.’
But these weather-beaten seniors do have some responsibilities, like watching over grandchildren, and overseeing festivals and marriages; so the team devised a new scoring system based on questions such as, ‘Does he express his opinion on important family matters?’, ‘Is she able to remember important festivals such as Holi, Diwali?’, ‘Does he ever lose his way in the village?’ The results confirmed what many had already declared. There was a curiously low level of Alzheimer’s in the village.
It was the BBC that first alerted me to this story. In February 2010 it ran an article headlined INDIAN VILLAGE MAY HOLD KEY TO BEATING DEMENTIA, in which the remarkably wholesome lifestyle of Ballabgarh’s residents was pointed to as the reason for their low rates. ‘The people of Ballabgarh are unusually healthy,’ it announced. ‘It is a farming community, so most of them are very physically active and most eat a low-fat vegetarian diet. Obesity is virtually unheard of. Life in this fertile farming community is also low in stress, and family support is still strong, unlike in other, more urban parts of India.’
But Ganguli told a different story. Despite all the effort that had gone into carefully developing the assessment tools, her instinct was that something was off–that an elusive, protective agent, somehow camouflaged amid the vicissitudes of Ballabgarhian life, was wishful thinking. There were too many ‘what ifs’; too few absolutes. The villagers’ diet, for instance, consists mainly of whole-wheat flatbreads, lentils, vegetables and yoghurt. Since everyone in the village eats this, whether it makes any difference is impossible to say. The idea of a stress-free life in Ballabgarh also seems fanciful. The villagers’ livelihood hinges on a capricious climate, with drought and crop failures giving Indian farming a notoriously high suicide rate. Indeed, during my visit, Chand explained how the Indian government is further assaulting their livelihood by buying the farmland cheap and urbanising it for foreign investors. Only by increasing their yield can they hope to survive as an industry–and so every day, said Chand, they pray, nerve-racked, that ‘the gods give the rain’.
To this day Ganguli has mulled over what else it could be. Whether or not physical activity protects them is another unknown, not assessed by the study–though Ganguli lends more credence to this possibility than any other. ‘It’s quite possible. They’re an active community. They walk everywhere. They don’t have cars. When they were younger many of them worked the fields, which is hard physical labour, so that might be protective.’ Chand told me he spent ten to twelve hours a day ploughing the fields; sometimes his family even slept in the fields. ‘And we know that everything that’s good for the heart is good for the brain. The trouble is–and I’m sure you’ve come across this–Alzheimer’s pathology begins in our brain when we are much younger, decades before symptoms start. So we would need to perform a trial where we make half the younger villagers follow the same exercise protocol for the next forty or fifty years to see if it really reduces their risk.’
Genetics might play a role. Ganguli’s team genotyped more than 4,000 villagers–aged fifty-five to ninety-five–and found that the APOE4 gene is rare here compared to more developed parts of the world. But even this explanation had pitfalls: APOE4 increases the risk of heart disease as well; did the APOE4 carriers die of heart disease before they could get symptoms of Alzheimer’s? Which begged another question. Was this all just a function of India’s low life expectancy, which according to the latest average is sixty-two?
To understand the answer, it’s important to know the difference between disease prevalence and disease incidence. Prevalence is the proportion of people at any given time with the condition: a kind of snapshot of a population. Incidence is the rate at which new cases of disease occur in the population over a defined period of time: one year, for instance. The relationship between incidence and prevalence is duration, and for Alzheimer’s, it’s duration of survival. Two populations might therefore have the same incidence of Alzheimer’s but prevalence would be higher in the population that lives longer.
In the west, we maintain elderly people in good health, meaning they can live a long time with dementia. In India and other developing nations, however, cultural influences can preclude this kind of sustained healthcare. The children often keep their parents at home, do all the housework, feed them, wash them and nurse them if they get sick. As Chand’s eldest son explained to me, ‘From when we first start walking, from the very first time our parents hold our hand, it is our duty to look after them. When they get old, they need our hand, our support–no matter how sick they become. This is our culture.’ Rather than being a product of low life expectancy, then, it’s possible that underreporting, due to the low expectations of Ballabgarh’s elders and the unparalleled level of respect and care they receive from the young, may have concealed many cases of Alzheimer’s from Ganguli’s study.
I liked the way Ganguli viewed this riddle. It reminded me of something I’d almost forgotten. Science is messy, its tools forever incomplete. In the lab we’re largely cocooned from this. Everything comes neatly packaged in IKEA-style kits. If something doesn’t work, it’s usually the fault of the scientist. And when a tool isn’t up to the challenge, we often just wait for one that is. We push boundaries from the comfort of clearly defined lines. But Ganguli and her team scrapped all that. They were going back to basics, back to the styles of Joseph Priestley and Alfred Russel Wallace–intrepid explorers, poking in the dark for the eurekas only this approach can dispense.
She mentioned a similar study, carried out in 1995, in which researchers compared Alzheimer’s prevalence between African Americans living in Indianapolis and Nigerian Africans in the city of Ibadan, Nigeria.2 The contrast was powerful for essentially neutralising genetic differences–the African Americans had migrated to America during the slave trade 200 years earlier, which is arguably not enough time for intermarriages to outweigh environmental influences. Lo and behold, Alzheimer’s prevalence was lower in Nigeria than in Indianapolis. Again, nobody really knows why. Evidently something in the environment is at play.
Another report, published a few years earlier by the same group, supports that suspicion. They looked at a population of Cree Indians in Winnipeg, Manitoba.3 It may be Canada, but the native Cree live in sovereign reservations with a culture and tradition all of their own. Most of the men continue to hunt and fish well into old age. Many of the women maintain an interest in elaborate crafts like sculpting and quillwork. They still embrace modern society (the buffalo-hide tipis are just for show) and yet the prevalence of Alzheimer’s remains unusually low. If an undiscovered guardian is somewhere in their environment, the most ‘striking impression’, the report noted, was the ‘continuity of activities of the elderly Native subjects’. Keep active, in other words. Stay busy.
The rejection of cultural differences has consequences, too. A 1996 study published by the National Institute on Aging, entitled ‘Prevalence of dementia in older Japanese-American men in Hawaii’, found that elderly Japanese people living in America have higher rates of Alzheimer’s than those living in Japan.4 Nearly 4,000 participants aged seventy-one to ninety-three were involved, impressive even by today’s standards. Though the cause of the discrepancy was never determined, researchers largely attribute it to the western diet–especially because Alzheimer’s rates in Japan have shot up since the gradual westernisation of the country’s diet. ‘Genetics loads the gun, lifestyle pulls the trigger’ is a popular biology adage. It reconciles the argument over nature versus nurture, and each of these studies is a stark reminder of it.
Before I left Ballabgarh, I saw another group of elders sitting in a circle beneath a wooden shelter. They were playing card games, laughing merrily while their children worked in the acres of paddy fields around them. In spite of so much uncertainty, it definitely seemed that they were doing something right.
While the search for that ‘something’ continues, research into the ancient Indian spice turmeric, commonly used in curry powder, has flourished. This spice, derived from the roots of Curcuma longa, a yellow flowering plant native to the monsoon forests of South East Asia, possesses surprising therapeutic properties that may help explain India’s low Alzheimer’s rates.
In the early 2000s nutritionists noticed that turmeric’s most active ingredient, a compound known as curcumin, dismantles beta-amyloid plaques in a petri dish.5 A few years later, Fusheng Yang, a neurologist at the University of California Los Angeles, fed curcumin to Alzheimer’s mice and showed that it does indeed enter the brain and destroy plaques.6 Further tests found that curcumin might even stop tangles forming. Following this work, in 2013, Muaz Belviranli at Selçuk University, Turkey, demonstrated that curcumin fed to old rats improved their spatial memory and reduced the cellular damage associated with ageing.7 To date, there are more than 1,000 published studies with similar findings, and researchers have spent the last decade eagerly trying to reproduce the effects in humans.
The results, unfortunately, remain speculative. In 2006 researchers at the National University of Singapore tested 1,010 elderly Asians–Chinese, Malays and Indians–aged sixty to ninety-three, and discovered that those who ate curry ‘often or very often’ scored higher on cognitive tests than those who ‘never or rarely’ did.8 But with such a vast age range and diverse ethnic mix it’s hard to rule out other influences. The data from Alzheimer’s patients has been equally ambiguous, with only a few studies showing positive effects. Nevertheless, since most human studies have measured curcumin’s effect in months, not years, the evidence from cell and animal models needn’t be dismissed. In fact many scientists believe the prime obstacle is the spice’s transience: since curcumin doesn’t absorb well into blood (over 60 per cent is excreted in stool) the question remains whether it would have an impact if its blood levels could be raised and maintained.
Mark Taylor, a chemist at the University of Lancaster, England, is now trying to develop methods to bind curcumin on to the surface of nanoparticles: a form of nanotechnology made using molecules of fats, proteins, iron, even gold.9 This so-called nanocurcumin will hopefully increase curcumin’s absorption in the body, allowing more of it to reach the brain and work its magic. If it ever is concluded that curcumin guards Ballabgarh’s population from Alzheimer’s, we shall look back in wonderment at the measures we employed to mimic something so simple.
As it happens, Chand and his elderly companions consume turmeric often. In India the average consumption of curcumin is 80–200 milligrams per day (I myself can’t remember the last time I ate a meal containing the ingredient). In clinical trials researchers used doses of up to 4 grams a day for six to twelve months. When compared to a lifetime of cultural habit, though, even this dose might be too little too late, and so it’s difficult to draw any firm conclusions about curcumin’s therapeutic value–larger, lengthier, more sophisticated trials are required. But still, Ganguli told me the evidence is encouraging, and she’s as sceptical by nature as they come.
This story speaks to a higher truth not mentioned enough. Science doesn’t seek to prove hypotheses; it seeks to disprove them. Every finding has scores of older, closely related findings trailing behind, each having been disproved, amending the scientific narrative. Even completely new discoveries must be fallible in some way, ready to be updated when a better idea comes along. Science orbits the truth; it doesn’t live there. The twentieth-century philosopher Karl Popper understood this better than anyone. He’s famous for proclaiming that a discovery ‘must be falsifiable: and in so far as it is not falsifiable, it does not speak about reality’.10 But I’ve always preferred something else he said: ‘Science must begin with myths, and with the criticism of myths.’ Is the feeling that Chand’s and the other elders’ lifestyle protects them from Alzheimer’s just that–a feeling, speculation, a myth?
Possibly. Only when Ganguli and others have falsified and criticised enough will we know for certain. But that scientists are now combing the world for answers fills me with hope. It shows just how far we are willing to go.