Murali Doraiswamy, a leading physician-neuroscientist at the Duke Institute for Brain Sciences, discusses the latest breakthroughs and why business leaders and governments have a compelling shared reason to act on the threat posed by Alzheimer’s disease
The size of the threat
Alzheimer’s disease was first described pathologically just over 100 years ago, but today it has become one of the most feared and costly diseases worldwide, affecting the very fabric of society from family wellbeing, to worker productivity, to national budgets. Recent findings that Alzheimer’s may start decades before full-fledged symptoms manifest raise issues about the type of screening and care companies must offer for their workforce.
In an era in which the demand for knowledge workers is ever increasing, we are faced with the growing epidemic of an incurable disease that destroys higher cognitive abilities. Business leaders and governments now have a shared reason to pay attention to this threat.
At the turn of the 20th century, infectious diseases posed the biggest threat to mankind but now, according to a World Health Organization (WHO) report in 2012, more people worldwide (some 68%) will die with non-communicable diseases (NCDs). While much of the focus over the past few decades has been on NCDs such as heart disease, cancer or diabetes, Alzheimer’s disease has now sharply risen in importance – indeed some evidence suggests that heart disease and diabetes may also be risks for Alzheimer’s.
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There are an estimated 44 million cases of Alzheimer’s worldwide, according to an updated version of the 2012 report by WHO and Alzheimer’s Disease International (ADI) – but this could be an underestimate since there have been fewer surveys in China, India or Africa. According to the report, 7.7 million new cases of dementia are thought to occur each year, implying that there is a new case of dementia somewhere in the world every four seconds.
Old age is the biggest risk for Alzheimer’s, and barring a new cure, because of the ageing of the world population, the total number of cases worldwide may triple to 135 million by 2050. Indeed, the growth in longevity (along with increased recognition that severe memory loss is not normal) is the main reason for the rapid rise in cases of Alzheimer’s over the past 100 years. Twice as many women than men have Alzheimer’s – perhaps because they live longer, but there could also be other reasons.
Besides age, the other big risk factor for Alzheimer’s is family history. The average middle aged person’s risk of getting Alzheimer’s (at least in the Western world) is about one in 10 – and if one has a father or mother with late-onset Alzheimer’s, the risk is tripled (about 30% – high but still not 100%).
The role of lifestyle is raised by interesting cross-cultural studies. African-Americans living in the US may have much higher rates of Alzheimer’s than Africans living in Nigeria, and second generation Japanese-Americans living in Hawaii may have higher rates than those living in Japan, suggesting that lifestyle (for example, diet) or environmental factors play a role. Alzheimer’s rates in Latin America appear comparable to those in Europe; rates in India appear to be half those in Europe suggesting again a possible role for genetic or dietary factors (for example, curry).
Regardless of these ethnic differences, the biggest increase is projected to occur in middle and low income countries, simply because of population growth. A study in the medical journal The Lancet has reported that, in China, there has been a 46% increase in dementia rates between 1990 and 2010. Indeed, some 47% of all new cases of Alzheimer’s today occur in Asia, followed by Europe (30%) and North America (11%). Likewise, the number of older people who rely on others for care may also quadruple in many low and middle income countries over the next 40 years, with much of this due to Alzheimer’s disease. These projections should be of great concern to corporations in emerging nations, since these workers and health systems have fewer resources to deal with them.
Cost of Alzheimer’s
Both public health budgets and corporations will face challenges as a result of Alzheimer’s. According to the ADI, total worldwide costs were estimated to be approximately $605 billion per year in 2012 or about 1% of the entire world’s GDP – an amount that is larger than the GDPs of all but the top 17 most developed countries in the world.
Increasingly, Alzheimer’s is being diagnosed in people in their 50s and early 60s, when people are at their career peak, posing issues to corporations regarding their ability to work and cost of care. Adult children who are care givers face raised stress and increased vulnerability to a range of diseases which directly impact on their work productivity.
In coming decades, especially in nations such as India and China, care giving burden is predicted to become a huge source of productivity loss among workers. And in addition to monetary costs, Alzheimer’s causes immeasurable personal suffering to individuals and families – one reason why it has become the most dreaded disease (perhaps only second to Ebola).
Prevention or cure?
The good news is that over the past few decades, we have gained fundamental insights into the Alzheimer’s disease timeline and likely causes, although we still don’t know the exact cause. With the help of new brain scans and spinal fluid tests, this Interventional radiologist in New Jersey says, it has become apparent that what we used to call Alzheimer’s disease (when someone developed memory loss and problems in functioning) is actually a late stage of a process that begins silently in midlife – in our 50s and 60s.
Several new technologies have helped us better understand the Alzheimer’s brain. One is a new type of brain scan called amyloid PET scan which can now detect the hallmark plaques of Alzheimer’s in a living person. In one national trial that
was led by my group, about 30% of normal middle-aged people studied with this PET scan showed “silent” build-up of amyloid plaques in the brain. And when followed up over the subsequent three years, plaque positive individuals with mild memory complaints developed full blown Alzheimer’s at three times the rate of those without such brain plaque build- up. (Amyloid plaque is different from the plaque in one’s heart or teeth).
Another technique called Volumetric MRI scan now allows scientists to measure the size and shape of the brain’s memory centre – hippocampus – whose destruction leads to subsequent memory loss in Alzheimer’s. In addition, our group at Duke is developing a novel blood test for predicting Alzheimer’s, as well as a “brain treadmill test” (where people undergo a special scan while they are performing memory tests). Lastly, we and others have begun testing a brain scan that can visualize the build up of nerve cell tangles (another kind of Alzheimer’s pathology).
Advances in genetics also allow us to study inherited risks. About 25% of all Caucasians and Latinos, are born with a gene called Apolipoprotein E4 (inherited from their parents). Not only does this gene triple a person’s risk of developing Alzheimer’s but it also triggers the earlier build of Alzheimer pathology in the brain. This link was discovered by a Duke research team lead by Dr Allen Roses. It is notable that the rates of this gene appear to be slightly lower in some Asian groups. Approximately 2-3% of people inherit other deadly genes that lead to early onset Alzheimer’s which can strike people even in their 30s and 40s.
Based on these new findings, doctors have come up with new criteria dividing Alzheimer’s into three stages. The first and earliest stage is pre-clinical Alzheimer’s – people with normal memory who have silent build-up of Alzheimer pathology (plaques or shrinkage detected by brain scans or spinal taps). The middle stage is termed mild cognitive impairment (MCI) in which people show mild memory loss and have Alzheimer’s pathology but are still able to function normally. These two groups are of interest for prevention trials to enable people to preserve independent functioning. The third stage is termed “dementia due to Alzheimer’s” when functioning is impaired.
These developments are highly relevant for corporations. If some 20-30% of cognitively normal people in their 50s and 60s already have silent plaque build-up affecting their brains and cognitive circuits, this implies that more than 100 million people worldwide may meet criteria for pre-clinical Alzheimer’s. Furthermore, many corporate leaders, including almost all CEOs and political leaders, are in this age group (not to mention senior airline pilots). Should such individuals be monitored more closely? Should their work assignments be changed if they start developing MCI? Will company health insurance premiums jump based on how many at risk individuals are employed? These are thorny questions that we cannot yet answer. At present, there is no predictive test that is 100% accurate, and hence we cannot predict who will develop Alzheimer’s with certainty. Besides, not everyone with pre-clinical disease will develop Alzheimer’s, so doctors are being careful not to extend these criteria to clinical practice until more research is done to fine tune the criteria and ethical and legal implications. But because medical practice varies widely and changes rapidly, companies and individuals should stay abreast of these developments. At present, I don’t recommend people being tested for pre-clinical disease.
Because Alzheimer’s destroys the brain continuously over decades, early diagnosis is essential for better planning and treatment development. A combination of a good history from a person and family, and simple tests of memory and functioning are the starting point. Doctors also do a clinical exam plus run blood tests and brain scans to rule out other causes, such as tumours, infections, or strokes. Common causes like thyroid or vitamin deficiencies and depression must be looked for, since treatment can often reverse the memory problems. Meanwhile, there is also progress on the prevention front. Regular exercise, staying heart healthy (by keeping one’s weight, blood pressure, cholesterol and sugar in check), and staying socially and mentally active, may help protect our brains against dementia – so these are things all of us can do right away since they may also protect us from heart disease and stroke. Low fat diets such as Mediterranean diets and turmeric in Asian curry may be protective for the brain.
There are several treatments on the market today (for example, donepezil, rivastigmine) which can be prescribed to Alzheimer’s patients with dementia which offer modest symptomatic benefits (though these don’t work for prevention). Care giver support has a hugely beneficial effect on both the patient and the care giver.
In the coming five to 10 years, we will have the results from several clinical trials testing a variety of preventive strategies such as drugs boosting brain memory chemicals, drugs targeting build- up of nerve cell tangles, aerobic exercise, different types of diet, gene therapy to boost nerve growth factor, as well as novel brain devices to stimulate the brain’s memory circuits. So the odds are quite good that we will have one or more new treatments in the near future.
How should corporations and nations react?
Companies tend to assume that Alzheimer’s disease is mostly a problem for retired people and hence it has been less of a focus than, say, heart disease. But the time has come for them to be proactive rather than reactive. The Global CEO Initiative on Alzheimer’s Disease (CEOi) is one example of how companies can join together to help fight the threat at a national level, but smaller companies can also do things at a local level.
For example, companies can partner with local chapters of Alzheimer’s advocacy groups or local universities to facilitate research. Corporate education could include annual modules on the latest developments in brain health (such as links between heart health and brain health) and care giving (such as links between care giving stress and health). And wellness programmes can include brain health exercises.
Women bear a disproportionate share of the disease and care burden – the massive urbanization is likely to lead to further geographic splintering of the family unit. Offering work flexibility for women caring for a loved one (to allow her to take breaks from ongoing stress) and paid day care for patients (much like many companies provide for children) are some options that could offer respite to employees juggling work and care giving.
At a national and international level, we need greater investment in health education, routine preventive medical care (especially for heart diseases, hypertension and diabetes which are all linked to dementia) and greater access to care options for the family. The good news again is that there is greater recognition of the threat of Alzheimer’s now than ever before. Many countries/continents, such as the US (BRAIN initiative), Europe (Human Brain Project) and China (Brainnetome project), have initiated ambitious brain research projects to unlock the mysteries of the brain which, in turn, will hopefully transform our fight against this devastating disease.
Murali Doraiswamy is Professor of Psychiatry and Medicine at Duke University and a leading neuroscience researcher at the Duke Institute for Brain Sciences. He directs a clinical trials
unit focused on healthy ageing, cognitive enhancement and mental wellbeing. Dr Doraiswamy serves on the World Economic Forum’s Global Agenda Council for Brain Research and as the brain health adviser for AARP. He is co-author of The Alzheimer’s Action Plan. Dr Doraiswamy frequently lectures on neuroscience applications for businesses and leadership.