Monthly Archives: April 2018

How reliable are genetic tests?

How reliable are genetic tests?

Increasingly, genetic tests can be ordered by the general public; they are called direct-to-consumer tests. Because they market to large number of consumers and because they don’t need to undergo the same quality tests, they can be ordered by consumers online.

These tests, such as 23andme or ancestry determine your ancestry and even whether you carry a predisposition for a large number of medical conditions in the future. Many of us want to know what the future brings. Hence, these tests have become bestsellers.

However, how scientific are these tests? If I would order such a test online, how reliable is it?

I will never forget the case of a middle-aged woman who saw me to assess an ovarian cyst. The cyst did not look suspicious. However, at the end of the consultation, my patient mentioned that she had done the 23ANDme test. I reviewed the results and it stated that the patient tested positive for BRCA2.

dna 1811955 1921

BRCA is a gene, when mutated increases the risk of breast and ovarian cancer significantly. The lifetime risk of ovarian cancer in the general population is 1.3%. By contrast, in carriers of BRCA, the risk developing ovarian cancer is between 40% and 60%.

Until then, I was not even aware that this test offered a BRCA test. I certainly got alarmed. Here I saw a patient with an ovarian cyst that at first sight looks unsuspicious but she has a BRCA mutation. Based on the mutation alone, I had to consider this patient high-risk for ovarian cancer.

I picked up the phone to discuss the case with a colleague who also is knowledgeable in this area. He confirmed that the test result needs to be taken serious. However, to be on the safe side and in order to avoid over-treating the patient, we agreed to repeat the test through scientific avenues.

We were both completely taken by surprise when the test result did not confirm BRCA. It virtually confirmed that the patient received a false positive test result through 23ANDme.

Two months later, the cyst has disappeared and no surgery was required. The patient remains well.

A study published in March 2018 has shown that up to 40% of direct-to-consumer tests are false positive. The percentage of tests that miss a diagnosis (false negative tests) is unknown.

The upshot of this story is that …

  1. Direct-to-consumer tests are not reliable to test for cancer risk. They don’t undergo the same scrutiny that tests have to go through that are ordered by your doctor.
  2. I expect that direct-to-consumer tests not only show false positive results but also have false negative results, where the cancer mutation is missed.
  3. In my practice, we only offer tests to check for cancer genes. They fulfill very high scientific standards, undergo ruthless quality checks and are accurate.


When the Doctor’s Mother Has Cancer

When the Doctor’s Mother Has Cancer

CreditStuart Bradford

“I want you to talk to me like I’m one of your patients, not like I’m your mother.”

My mom’s familiar voice came over the car’s speakers via the Bluetooth connection to my phone as I drove home. She had left a voicemail an hour earlier asking me to call her back, which was never a good sign. My mother, still working as an administrator in Rhode Island at age 74, was not the type to mince words, nor ask for a return call to discuss trivialities. I asked her what was going on.

“I had a cold that wasn’t getting any better, so I went to an urgent care clinic to get some antibiotics.”

I avoided the temptation to remind her that most colds were viral, and that antibiotics don’t alter their duration. Naturally, she knew that I would tell her that, and thus she didn’t mention she was going to urgent care in the first place. So it goes with mothers and sons, particularly when one of those sons is a doctor. She continued.

“They took a chest X-ray, and my doctor called me the next day to tell me they found a ‘shadow’ in my left lung and that I needed to get a CT scan of my chest.”

By this point I was holding my breath, bracing myself for what would come next: The beginning of every cancer story, when the seemingly innocent cough, dizziness or common cold takes a sinister turn and the unexpected replaces what was expected.

“She called me this afternoon and told me I have lung cancer, and I have to schedule a biopsy.”

I only vaguely processed the other cars on the road and the clouds breezing past the gray sky, the rest of the world moving on as mine suddenly stood still.

“O.K.,” I said, buying time to find some of the words I had heard family members of my own patients use for reassurance. “There are still a lot of things a mass in the lungs could be, like an infection, or scar tissue. It’s not cancer yet, until a biopsy shows that it’s cancer.” So the saying in oncology goes: “Tumor is a rumor, tissue is the issue.” I continued. “You haven’t gotten a biopsy, right?”

“Well, no. But my doctor seemed pretty sure this was cancer.”

“It’s not cancer yet,” I said, more son than doctor, trying to convince myself as much as her.

Over the next few days, I played an unfamiliar role. Rather than doctor providing information, I became the family member trying to obtain it, and also attempting to help schedule a procedure in an unfamiliar hospital many states away.

My mother’s doctor faxed me the report from the CT scan, which described a lobulated mass over three centimeters long, typical of cancer. Scheduling the biopsy proved more challenging, though, and after several phone calls the best the interventional radiology department could provide was a tentative date, 10 days in the future.

We entered the purgatory of waiting for a diagnosis. As those days passed, my mother formulated a number of “If this is cancer” questions: “If this is cancer, what are the next tests I will need? Will I need surgery? Chemotherapy? Can I keep working? When will we know?”

Until the diagnosis was made, I could answer only in generalities, and speculate.

Three days after the biopsy of the mass in her lung, the one that looked ominous as a cumulonimbus cloud on her CT scan, my phone buzzed with her message: “The test was positive. Call me, I’m home.”

I never imagined that the diagnosis would arrive by text. Then again, perhaps texting allowed her, and me, some distance from the new truth that had just dawned. I ducked away from my own clinic full of cancer patients to reach her.

“I just talked to my doctor. The biopsy showed cancer.” It was the first time she had used the word, and I noted again how she distanced herself from it, as if the biopsy had the cancer, not her.

“Did your doctor mention what kind of cancer?” I asked. She read the unfamiliar words from the paper on which she had taken notes.

“Adenocarcinoma. Consistent with pulmonary origin.” There was silence on the phone line as we both processed the information. “What is the next step?” she asked.

The next step was to determine how far the cancer had spread — its stage. In this respect, lung cancer is quite different from the cancer I treat, leukemia. Leukemia doesn’t have a stage, as it appears throughout the blood and bone marrow at diagnosis. If we did try to tag a stage to leukemia, it would be stage 4 or stage 0: Either you’ve got it, or you don’t.

The staging for lung cancer is predicated on the tumor’s size, whether it has spread to lymph nodes, the location of those lymph nodes, or whether it has metastasized to another organ or to the bones. This is assessed by additional scans, and often more biopsies. I explained this to her and asked whether she wanted the tests performed closer to her home in Rhode Island, or where I live and practice, in Cleveland.

“What do you want?” she asked.

It was hard to answer. I just wanted her better.

She decided to have her staging and consultations at my hospital, and flew west the following week to begin her appointments, starting with an M.R.I. of the brain to check if the cancer had spread there, some lab tests and a PET/CT scan.

Positron emission tomography or PET scans involve injection into the veins of a radionuclide “tracer” attached to glucose. Cells in the body that are active (and thus consuming glucose), such as cancer cells, accumulate the tracer and “light up” on the scan. The test can thus show both the main tumor and areas where the tumor has spread. Other cells that are active, which can occur with infection or inflammation, can also light up, though, leading to false positive results, meaning the scan shows cancer erroneously.

The next day we met first with the surgeon, who showed her the M.R.I. scans on the computer screen in his clinic room. He told her that her brain was free of cancer, and that it was “young” appearing.

She was thrilled with both details and visibly relaxed. “That was my biggest fear, that it had spread to my brain.”

Next, he showed the PET scans. “Here’s the tumor we saw on the CT scan,” he said, pointing at a fiery, globular mass. “And here are a couple of lymph nodes in your mediastinum,” in the middle of the chest, pointing at two smaller flames where the cancer had spread.

Instead of stage 1 lung cancer, meaning cancer that was confined to the initial mass and could be removed surgically, she had stage 3 and would need to receive chemotherapy and radiation therapy. Then, only if the cancer regressed, would she be eligible for surgery.

It also meant the chance she would be cured had just plummeted manifold.

“I want to be sure that those lymph nodes really have cancer in them,” the surgeon said as much to her as to himself as he considered the PET scan. “I’ll arrange for you to have a biopsy by a pulmonologist.”

She met next with a medical oncologist, a lung cancer specialist and close friend who also coached my son’s baseball team. In the cruelest of ironies, he had recently lost his own mother to stage 4 lung cancer, and he regarded me and my mother with that special kind of empathy reserved for those who are equally embattled cancer soldiers and their caregivers. He walked us through his treatment plan and also paused as he reviewed the PET scan. “We’ll biopsy those lymph nodes before starting any of this,” he said, reinforcing what the surgeon had said.

Two days later, my mother underwent the additional biopsy, and an hour after that, the pulmonologist called me.

“The lymph nodes were totally clear,” he said over the phone. “No cancer. The PET scan was a false positive.”

I repeated the words back to him to make sure I had heard them correctly, and then choked up as a wave of relief washed over me. She was back to stage 1, and would just need surgery. I told her the good news in the recovery area, following the biopsy.

Walking from the procedure, my mother and I ran into the medical oncologist and told him the biopsy results. This man, whose own mother was denied any chance of cure for her lung cancer, was selflessly overjoyed at our good fortune. He hugged us in congratulations.

“I have to wonder,” my mother asked him, “would I have been treated with chemotherapy and radiation elsewhere, based only on the PET scan results?”

He nodded, grimacing. “Unfortunately, that happens a lot.”

My mother underwent surgery, and has now returned to work. She had a great outcome, but she also had a strong, connected advocate, in me, and the means to travel to a specialty cancer center. I was happy for her, but the experience was discomfiting. It left me wondering how commonly cancer patients are treated inappropriately because they don’t have that same access, based on tests that aren’t always accurate.

Microbes aren’t the enemy, they’re a big part of who we are

Essays on health: microbes aren’t the enemy, they’re a big part of who we are

July 4, 2017 6.08am AEST

This militaristic understanding of immunity reflected the culture of the 20th century, which was dominated by nation building and world wars between “us” and “them.” It was a time when “survival of the fittest” came to be seen as the driver of evolution and competition and war were considered a natural part of what it is to be human.

But a radical shift in understanding the relationship between humans and microorganisms occurred with the discovery that only 50% of the cells in our bodies are human. The rest are microbes, such as bacteria, yeasts (members of the fungus family), viruses, and even insects. Together, these make up the microbiome.

There are millions of microorganisms in our gut. from

The 23,000 genes that comprise the human genome pale in comparison with the 3.3 million genes in the microbes that live in our guts. These produce proteins that help us digest food and support our immune systems.

Through the gut-brain axis, these genes even influence mood and memory. The gut-brain axis is a set of communication pathways between the gut and brain occurring largely through the actions of the gut microbiome.

Because we have evolved with microorganisms inside us, we now have specialised communities in our guts, on our skin, and in our mouths. Our microbes are understood to be so critical to our existence, many scientists consider us to be symbiotic organisms, made up of the host, the microbiome and the environment. This holy trinity is what they call the “holobiont”.

Considering human life as a function of the microbiome and our environment allows us to acknowledge that we may be affected by entities that harbour different evolutionary needs. For example, our food choices don’t just affect human health through nutrients and caloric balance, but also through their impacts on the gut microbiome.

Microbes and diet

The food we eat feeds our gut microbes and directly impacts their survival. Within two days of changing diet, our gut species change. Different gut bacteria thrive on different diets. For instance, Prevotella strains consume carbohydrates while Bacteroidetes prefer some fats, and Candida prefer glucose over protein. So, some species starve and others thrive based on what we eat.

The species in ours guts are also proving to be relevant to health and disease. Prevotella, for instance, has been linked to improved glucose tolerance and is much more prevalent in the guts of hunter-gatherer societies (such as the Hadza people in Tanzania) than those in Western societies. The reduction of Prevotella in gut-bacteria in Western populations is thought to partially explain modern epidemics such as diabetes and obesity.

The Hadza people of Tanzania have a much higher prevalence of glucose-tolerating Prevotella bacteria in their guts than those in Western societies. Woodlouse/Flickr, CC BY

It shouldn’t surprise us then, that microbes can shape our food choices to ensure their own survival. Some metabolites, the small byproducts of microbial digestion, can make us feel hungry, full or crave certain foods. However, the evidence in humans is so far somewhat circumstantial. A study of chocolate-craving and chocolate-indifferent people found different microbial metabolites in their urine, suggesting different bacteria were present in the gut.

Metabolites are important in terms of function, because we know these can send signals to the brain. Signals to regulate eating behaviour are also transmitted via the vagus nerve that runs between the brain and the gut. At least two human studies have shown blocking the vagus nerve induces weight loss in obesity, while stimulating it in rats has led to overeating.

Microbes and behaviour

Behaviour is also a function of the holobiont, not just the human host. Some metabolites are neuroactive, which means they can travel along the gut–brain axis and affect human mood, mental health and behaviour.

Much of the work exploring direct microbe-related behaviour has been done in mice and rats. These studies have had some pretty interesting results though. They’ve shown that behaviour can be transferred through poo transplants, that animals bred without any bacteria show unusual social and emotional behaviours, and that serotonin – the brain chemical associated with mood and depression – is produced largely in the gut. Together, these findings indicate a strong evidence base for the fact that the microbiome can affect host behaviour.

The best human evidence comes from the observed impacts of food on mood and behaviour – and microbes are the likely explanation. A good example is a study of healthy women some of whom consumed yogurt with a certain probiotic for one month. The researchers had the participants lie in a functional MRI scanner while they were shown pictures of faces with different emotions.

Those who had received the yogurt had reduced activity in the emotional processing brain regions, suggesting a dampening of the stress response, than those who didn’t have yogurt.

Research suggests the gut microbiome may have a role in the development of autism spectrum disorders (ASD). from

The protective value of a whole-food diet for depression also points to the importance of gut microbes for brain health. Mood disorders that can accompany conditions such as irritable bowel syndrome and inflammatory bowel diseases are thought to be related to microbial disruption in the bowel.

Recent research has also suggested the gut microbiome may have a role in the development of autism spectrum disorders (ASD). Research has found people with ASD have significantly higher numbers of Candida species in their intestines, for instance. Although determining causation is complicated, these microbes reduce the absorption of carbohydrates and release ammonia and other toxins which are thought to contribute to autistic behaviours.

There is also emerging evidence showing that differences in gut bacteria in children are related to behavioural problems, and potentially to future mental health risk.

There are numerous reports of changed gut bacteria in people experiencing mental illness such as schizophrenia and depression, as well as neurological disorders such as Parkinson’s disease. However, it is difficult to establish causation.

A compelling argument is made by studies that show microbiota transplants from people to mice actually change the behaviour of the recipient mice. One study used microbiota from people experiencing irritable bowel syndrome (IBS) and showed the mice who received the transplants experienced the same anxious behaviour that often accompanies IBS.

Changing the game

Many of our microbes aren’t good or bad, but they become bad because we change the game. from

We are ecosystems, whose members are intricately balanced by cooperation and competition. Many of our microbes are neither good nor bad. But they become bad because we change the game, giving them the opportunity to be bad.

For example, we are increasingly interfering in the ecosystem by using antibiotics and sanitisers, hormone and immune system treatments, cosmetic and plastic surgery, or biomedical implants and devices such as contact lenses or heart valves.

Although sanitation and nutrition have greatly improved in much of the world, antibiotic overuse has led to the rise of antibiotic resistant bacteria. Antibiotics also change what is in our microbiome. Many women would be familiar with Candida infections (thrush) that flourish after they use antibiotics, for instance.

Biomedical implants, contact lenses and dentures provide warm, moist and nutritious conditions for colonisation by microbes. Increased oestrogen use in birth control pills and other hormone treatments has been shown to promote yeast infection and reduce immune efficiency.

In fact, the hygiene hypothesis argues that infections help build our immune system and the proliferation of sanitising disinfectants in our homes could be contributing to skin allergies and respiratory conditions.

Body odours aren’t inherently unhealthy. from

Our definitions of good and bad are cultural as much as biological. For example, body odours and stale breath which are caused by microbes are not inherently unhealthy, but the market for antiperspirants, deodorisers and mouthwash is flourishing. Increasing skin conditions, allergies and illness could be the result of our attempts to control and groom our microbes, good and bad.

Our diets have also changed rapidly and the flow–on changes to both human and microbial health are apparent. Non–communicable disease epidemics such as obesity and heart disease are clear consequences of highly processed foods and increasingly inactive lifestyles.

The changing modern diet may also have effects over generations, as we pass on our microbial communities to our children. Research in mice has found some bacterial strains could not recover in the grandchildren of mice fed low–fibre western diets, even when a high–fibre diet was reintroduced. It may not be long then, before the modern western diet will have irrevocably changed the gut bugs and health of future humans.

Rethinking the metaphor

For most of the twentieth century, we were at war with microbes. Vigilant immune systems defended against vicious and sneaky microbial attacks. The cold and flu medication Codral, as just one example, famously helped us “soldier on.”

We have to rethink this militaristic metaphor. If we are a complex ecosystem which relies on the microbes in it, we cannot wage war against them. If microbes are part of our immune systems, who is fighting whom?

How we talk about our microbes reflects how we think about ourselves and others. As holobionts, we need to figure out how to live with all the members of our bodies. How might our worlds (and bodies) be different if we behave as resilient communities where the “others” are different selves, rather than invaders, terrorists, colonisers, or competitors?

Prostate cancer testing: has the bubble burst?

Smoke Signals

This mimics the situation with mammography and thyroid cancer screening – too much overdiagnosis leading to harm. Just as we have just discovered about Australian banks, self interest and financial benefit occurs in medicine just as it does elsewhere in society. Any attempt to reduce unnecessary testing and treatment will be severely resisted by those with the most to gain. 

Smoke Signals

Prostate cancer testing: has the bubble burst?

August 9, 2017 4.03pm AEST

Two new studies are bursting the bubble about the value of screening men for prostate cancer. from

In 2010, I wrote a free book on prostate cancer testing with two colleagues, Alex Barratt (an epidemiologist) and Martin Stockler (a clinical oncologist), Let sleeping dogs lie? What men should know before getting tested for prostate cancer. It has been downloaded just short of 38,000 times, the highest of any item in Sydney University’s open access repository.

Clearly, there is understandably immense concern about prostate cancer. In 2014, 3,102 Australian men died from the disease, making it the second leading cause of cancer death in males after lung cancer (4,947 deaths).

Media reporting about prostate cancer testing has long emphasised screening as highly sensible. This is consistent with other early-detection cancer-control messages about “finding it early”.

However, news reports often neglect to mention or minimise adverse consequences of interventions following the surgery and radiation that can follow a positive screening test, like long-term sexual impotence and incontinence.

Read more: Most people want to know risk of overdiagnosis, but aren’t told

There’s also a pitch to gender equity (“women have their cancer tests, and men have this one”). Those questioning testing have been vilified, and epidemiological details framed as an inferior form of knowledge than clinical experience.

Ten years ago, a study of Australian media reports found 10% of a large sample of statements in news reports were inaccurate or misleading and concluded:

Despite near universal lack of support for prostate cancer screening of asymptomatic men by leading international and Australian cancer control agencies, Australians are exposed to an unbalanced stream of encouragement to seek testing. This coverage includes inaccurate information which ignores scientific evidence and the general lack of expert agency support.

Since we published our book, many men have contacted me thanking us for writing it. But I’ve also been taken aside by others with this message: “Look, I know about all the controversy about prostate cancer testing but my husband had the test and his doctor said he was so lucky that they found it early because it was very advanced and if they’d left it any longer, he’d have almost certainly died from it.”

I reply that I of course have no idea what the test and subsequent biopsy showed and so I could not possibly comment. In some cases, this will be true, but as we shall see, in many more cases it won’t be.

Why are men unlikely to question advice?

People who have been told by a specialist urologist that they are at serious risk of death are naturally unlikely to question what they are told. Having climbed on board the testing, biopsy and radical treatment “train” and being still alive to tell their story, they have what is often called “survivor joie de vivre”.

They are utterly convinced that the cancer discovery and radical intervention (surgical prostate removal or radiation therapy) has saved their lives. They can be evangelical about their luck, even when 77% live with sexual impotence three years after surgery. As some will tell you, “you can’t have sex in a coffin”.

But such accounts do not tell us whether testing and subsequent intervention really save lives. Here, the evidence needs to come from longitudinal studies of men who are found to have elevated prostate specific antigen (PSA) test results (including men who have not been tested) and who are then randomised into different treatments (including no treatment).

Seven years after we summarised available knowledge on this in our 2010 book, we now have results from two recent clinical trials to help us make even stronger informed decisions: the Prostate Testing for Cancer and Treatment (ProtecT) – 10 years of follow-up – and Prostate Cancer Intervention versus Observation Trial (PIVOT) – 20 years of follow-up.

Read more: Latest research shows surgery for early stage prostate cancer doesn’t save lives

Two Australian oncologists, Ian Haines and George Miklos, have given us an important, excoriating summary of these two studies. They conclude the data:

… completely undermine the stratospheric spin associated with prostate cancer being a death sentence. They are unambiguous in their implications … The bottom line? Men with early stage abnormalities of the prostate who do not undergo surgery or radiation treatment, but whose condition is monitored for any progression of the cancer, live just as long as men who opted for complete removal of the prostate and who now live with its immediate consequences, including incontinence, intimacy issues, bowel problems and intervention regret.

What do the data say?

The Australian Institute of Health and Welfare (AIHW) collates all incidence and mortality data for all cancers. This figure shows the median age of death in men from various cancers and all causes of death combined for 2014, the latest available year.

This shows that prostate cancer is very clearly a disease that mostly kills very late in life. The average age of death for prostate cancer in Australia is 82 years, while the median age for all male cancers combined (other than prostate cancer) is 75 – considerably younger.

Sixty percent of men who die from the disease are aged 80 or over with 87% aged 70 or more. Just 2.1% (65 men) who died from the disease were aged under 60, and three (0.1%) were aged under 50.

Significantly, the average age of death (from all causes combined) for an Australian man in 2014 was 78 years.

So men who die from any cause after that time – prostate cancer included – are already living longer than average. Prostate cancer is one disease in the Grim Reaper’s quiver at the end of our lives. As we all must will die from some cause, it’s worth reflecting on why so much attention should be given to a disease that stands out so obviously as one that kills most very late in life.
In 2014, prostate cancer killed 3,102 males out of 78,341 deaths from all causes (4%). It’s long been remarked that far more men die with prostate cancer than from it. We know from autopsy studies that around 40% of men in their 40s will have signs of prostate cancer, with this increasing to about 60% of men in their 60s. Clearly then, the great majority of men who develop prostate cancer will not die from it but from something else.

Yet the drive to promote prostate testing continues unabated, which is causing massive anxiety, intervention and significant decrements to the quality of life of men who are treated unnecessarily. Haines and Miklos point the finger at financial reasons for this over-treatment.

It will be even more difficult to dislodge early PSA testing, particularly in countries such as the United States, where it has now become deeply entrenched in a belief-based or business enterprise. After all, given the huge investments in proton-based radiation facilities (where it costs in excess of $300 million to just build a proton beam facility), or in robotic surgery machines, the financial incentives to repay the investment and to move to a for-profit situation are huge. A constant supply of patients is obligatory, and an increasing supply is preferable.

Many male doctors do not have PSA tests themselves. As more information emerges that challenges the wisdom of the promotion of prostate testing, we need to ask whether this bubble is near to bursting.

Little laugh

Six things you can do to reduce your risk of dementia

Six things you can do to reduce your risk of dementia

An ageing population is leading to a growing number of people living with dementia. Dementia is an umbrella term for a group of symptoms including memory impairment, confusion, and loss of ability to carry out everyday activities.

Alzheimer’s disease is the most common form of dementia, and causes a progressive decline in brain health.

Dementia affects more than 425,000 Australians. It is the second-ranked cause of death overall, and the leading cause in women.

The main risk factor for dementia is older age. Around 30% of people aged over 85 live with dementia. Genetic influences also play a role in the onset of the disease, but these are stronger for rarer types of dementia such as early-onset Alzheimer’s disease.

Read more: What causes Alzheimer’s disease? What we know, don’t know and suspect

Although we can’t change our age or genetic profile, there are nevertheless several lifestyle changes we can make that will reduce our dementia risk.

1. Engage in mentally stimulating activities

Education is an important determinant of dementia risk. Having less than ten years of formal education can increase the chances of developing dementia. People who don’t complete any secondary school have the greatest risk.

The good news is that we can still strengthen our brain at any age, through workplace achievement and leisure activities such as reading newspapers, playing card games, or learning a new language or skill.

Even playing cards can strengthen your brain. Photo by Inês Ferreira on Unsplash

The evidence suggests that group-based training for memory and problem-solving strategies could improve long-term cognitive function. But this evidence can’t be generalised to computerised “brain training” programs. Engaging in mentally stimulating activities in a social setting may also contribute to the success of cognitive training.

Read more: What is ‘cognitive reserve’? How we can protect our brains from memory loss and dementia

2. Maintain social contact

More frequent social contact (such as visiting friends and relatives or talking on the phone) has been linked to lower risk of dementia, while loneliness may increase it.

Greater involvement in group or community activities is associated with a lower risk. Interestingly, size of friendship group appears less relevant than having regular contact with others.

3. Manage weight and heart health

There is a strong link between heart and brain health. High blood pressure and obesity, particularly during mid-life, increase the risk of dementia. Combined, these conditions may contribute to more than 12% of dementia cases.

In an analysis of data from more than 40,000 people, those who had type 2 diabetes were up to twice as likely to develop dementia as healthy people.

Managing or reversing these conditions through the use of medication and/or diet and exercise is crucial to reducing dementia risk.

Exercise is protective for heart health and diabetes, as well as against cognitive decline. Photo by chuttersnap on Unsplash

4. Get more exercise

Physical activity has been shown to protect against cognitive decline. In data combined from more than 33,000 people, those who were highly physically active had a 38% lower risk of cognitive decline compared with those who were inactive.

Precisely how much exercise is enough to maintain cognition is still under debate. But a recent review of studies looking at the effects of taking exercise for a minimum of four weeks suggested that sessions should last at least 45 minutes and be of moderate to high intensity. This means huffing and puffing and finding it difficult to maintain a conversation.

Read more: Could too much sitting be bad for our brains?

Australians generally don’t meet the target of 150 minutes of physical activity per week.

5. Don’t smoke

Cigarette smoking is harmful to heart health, and the chemicals found in cigarettes trigger inflammation and vascular changes in the brain. They can also trigger oxidative stress, in which chemicals called free radicals can cause damage to our cells. These processes may contribute to the development of dementia.

The good news is that smoking rates in Australia have dropped from 28% to 16% since 2001.

As dementia risk is higher in current smokers compared with past smokers and non-smokers, this provides yet another incentive to quit once and for all.

6. Seek help for depression

Around one million Australian adults are currently living with depression. In depression, some changes occur in the brain that may affect dementia risk. High levels of the stress hormone cortisol have been linked to shrinkage of brain regions that are important for memory.

High blood pressure can increase the risk of dementia. Photo by on Unsplash

Vascular disease, which causes damage to blood vessels, has also been observed in both depression and dementia. Researchers suggests that long-term oxidative stress and inflammation may also contribute to both conditions.

Read more: You’ve been diagnosed with depression, now what?

A 28-year study of more than 10,000 people found that dementia risk was only increased in those who had depression in the ten years before diagnosis. One possibility is that late-life depression can reflect an early symptom of dementia.

Other studies have shown that having depression before the age of 60 still increases dementia risk, so seeking treatment for depression is encouraged.

Other things to consider

Reducing dementia risk factors doesn’t guarantee that you will never develop dementia. But it does mean that, at a population level, fewer people will be affected. Recent estimates suggest that up to 35% of all dementia cases may be due to the risk factors outlined above.

This figure also includes management of hearing loss, although the evidence for this is less well established.

The contribution of sleep disturbances and diet to dementia risk are emerging as important, and will likely receive more consideration as the evidence base grows.

Even though dementia may be seen as an older person’s disease, harmful processes can occur in the brain for several decades before dementia appears. This means that now is the best time to take action to reduce your risk.

What is overdiagnosis and why should we take it seriously in cancer screening?

Public Health Res Pract. 2017 Jul 26;27(3). pii: 2731722. doi: 10.17061/phrp2731722.

What is overdiagnosis and why should we take it seriously in cancer screening?

Author information

Centre for Values, Ethics and the Law in Medicine, University of Sydney, NSW, Australia,
Centre for Values, Ethics and the Law in Medicine, University of Sydney, NSW, Australia.


Overdiagnosis occurs in a population when conditions are diagnosed correctly but the diagnosis produces an unfavourable balance between benefits and harms. In cancer screening, overdiagnosed cancers are those that did not need to be found because they would not have produced symptoms or led to premature death. These overdiagnosed cancers can be distinguished from false positives, which occur when an initial screening test suggests that a person is at high risk but follow-up testing shows them to be at normal risk. The cancers most likely to be overdiagnosed through screening are those of the prostate, thyroid, breast and lung. Overdiagnosis in cancer screening arises largely from the paradoxical problem that screening is most likely to find the slow-growing or dormant cancers that are least likely to harm us, and less likely to find the aggressive, fast-growing cancers that cause cancer mortality. This central paradox has become clearer over recent decades. The more overdiagnosis is produced by a screening program, the less likely the program is to serve its ultimate goal of reducing illness and premature death from cancer. Thus, it is vital that health professionals and researchers continue an open, scientific inquiry into the extent and consequences of overdiagnosis, and devise appropriate responses to it.

Likelihood that a woman with screen-detected breast cancer has had her “life saved” by that screening.

Arch Intern Med. 2011 Dec 12;171(22):2043-6. doi: 10.1001/archinternmed.2011.476. Epub 2011 Oct 24.

Likelihood that a woman with screen-detected breast cancer has had her “life saved” by that screening.



Perhaps the most persuasive messages promoting screening mammography come from women who argue that the test “saved my life.” Because other possibilities exist, we sought to determine how often lives were actually saved by mammography screening.


We created a simple method to estimate the probability that a woman with screen-detected breast cancer has had her life saved because of screening. We used DevCan, the National Cancer Institute’s software for analyzing Surveillance Epidemiology and End Results (SEER) data, to estimate the 10-year risk of diagnosis and the 20-year risk of death–a time horizon long enough to capture the downstream benefits of screening. Using a range of estimates on the ability of screening mammography to reduce breast cancer mortality (relative risk reduction [RRR], 5%-25%), we estimated the risk of dying from breast cancer in the presence and absence of mammography in women of various ages (ages 40, 50, 60, and 70 years).


We found that for a 50-year-old woman, the estimated risk of having a screen-detected breast cancer in the next 10 years is 1910 per 100,000. Her observed 20-year risk of breast cancer death is 990 per 100,000. Assuming that mammography has already reduced this risk by 20%, the risk of death in the absence of screening would be 1240 per 100,000, which suggests that the mortality benefit accrued to 250 per 100,000. Thus, the probability that a woman with screen-detected breast cancer avoids a breast cancer death because of mammography is 13% (250/1910). This number falls to 3% if screening mammography reduces breast cancer mortality by 5%. Similar analyses of women of different ages all yield probability estimates below 25%.


Most women with screen-detected breast cancer have not had their life saved by screening. They are instead either diagnosed early (with no effect on their mortality) or overdiagnosed.

The heterogeneity of cancer

The heterogeneity of cancer

  • H. Gilbert Welch

Cancer used to be so simple. It started as a wayward cell that then underwent a stepwise progression: from in situ to local, local to regional and, finally, regional to distant disease. At least, that is what I was taught in medical school…some (gulp) 40 years ago.

Narod and Sopik suggest a wildly different paradigm. Local growth and distant metastasis are independent phenomena. Local control of cancer (e.g., efforts to minimize local recurrence) has no effect on its tendency to metastasize. If a cancer is destined to spread to distant sites, it will have already done so.

Call it the “bad cancers are bad” model. Or, alternatively, “good cancers are good.”

Oddly enough, in 1955 a cancer surgeon at the Cleveland clinic—George Crile Jr.—foretold this complexity on the pages of Life magazine:

In clinical practice to say that a person has cancer gives as little information about the possible course of his disease as to say that he has an infection. There are dangerous infections that may be fatal and there are harmless infections that are self-limited or may disappear. The same is true of cancers. Cancer is not a single entity. It is a broad spectrum of diseases related to each other only in name. [1]

Narod and Sopik are not suggesting that size, stage, and nodal status are unassociated with the propensity to metastasize, rather that we have gotten the direction of causality wrong. The conventional model has been that large tumors are more likely to metastasize because they have a large pool of cancer cells to disseminate. Narod and Sopik instead suggest that these tumors became large because they are more aggressive cancers and thus are more likely to metastasize. Large, late-stage, node positive lesions are simply valuable markers for “badness.”

The corollary is that small, early-stage, node negative lesions are valuable markers for “goodness.” But not always. Which brings us to the conundrum of DCIS.

It would be simplest if all DCIS was pseudodisease—cancer not destined to ever cause problems for our patients. Most DCIS is pseudodisease, but as Narod documented in earlier work [2], about 3% of women with DCIS will die from breast cancer in the next 20 years. Over half of these women did not experience an in-breast invasive recurrence prior to death.

In other words, bad breast cancers are bad—from the get go.

This phenomenon explains the limited ability of mammography to reduce breast cancer mortality. The lack of value in finding microscopic breast cancers (like DCIS) is one of the least well-recognized findings from the ten randomized trials of mammography. Only one trial addressed this important question, the second Canadian trial [3]. The control group received an annual clinical breast exam: a standardized, thorough (5–15 min per patient) physical exam of the breast generally done by specially trained nurses. The intervention group received the same thorough clinical exam each year plus a mammogram. In other words, Canada 2 tested the additional value of detecting abnormalities that cannot be felt. Given the finding of no difference in breast cancer mortality between the two groups, the lesson is clear: there is no obvious value to finding breast cancers that are so small they cannot be felt (such as most DCIS).

Overdiagnosis is made possible by cancers at the other end of the spectrum. Overdiagnosis is the detection of cancers that are very good–so good that patients would be better off not having them detected. Overdiagnosis doesn’t limit the ability of mammography to reduce breast cancer mortality—instead it’s a side-effect of the effort.

Such heterogeneity in cancer poses huge challenges for our effort to catch the disease early. It’s been described as the “barnyard pen of cancers” (an analogy that likely originates with Crile). We are trying to catch birds, rabbits, and turtles. We can’t catch the birds early, because they have already gone—these are the most aggressive cancers, those that have already spread by the time they are detectable. We are able to catch the rabbits—the more slowly progressive cancers—but their earlier detection may not help much, because they weren’t destined to metastasize anyway. And then there are the turtles. There’s no need catch them, because they’re not going anywhere anyway

Quantifying the benefits and harms of screening mammography.

JAMA Intern Med. 2014 Mar;174(3):448-54. doi: 10.1001/jamainternmed.2013.13635.

Quantifying the benefits and harms of screening mammography.

Author information

The Dartmouth Institute for Health Policy and Clinical Practice, The Geisel School of Medicine at Dartmouth, Hanover, New Hampshire.


Like all early detection strategies, screening mammography involves trade-offs. If women are to truly participate in the decision of whether or not to be screened, they need some quantification of its benefits and harms. Providing such information is a challenging task, however, given the uncertainty–and underlying professional disagreement–about the data. In this article, we attempt to bound this uncertainty by providing a range of estimates-optimistic and pessimistic–on the absolute frequency of 3 outcomes important to the mammography decision: breast cancer deaths avoided, false alarms, and overdiagnosis. Among 1000 US women aged 50 years who are screened annually for a decade, 0.3 to 3.2 will avoid a breast cancer death, 490 to 670 will have at least 1 false alarm, and 3 to 14 will be overdiagnosed and treated needlessly. We hope that these ranges help women to make a decision: either to feel comfortable about their decision to pursue screening or to feel equally comfortable about their decision not to pursue screening. For the remainder, we hope it helps start a conversation about where additional precision is most needed