Secrets of the ‘superagers’

Medical science has done exceedingly well in extending our lifespans, with the average age of death literally decades more than it was a century ago. But is the longer lifespan really worth it if our health can’t keep up? We’ve made little to no headway in stopping or delaying the onset of dementia, and although increasing numbers of people are living into their nineties, it’s estimated that around two-thirds of them have either dementia or mild cognitive impairment.

Most researchers working on dementia, and in particular Alzheimer’s, have focused on identifying disease pathology and pathogenesis, which they hope may lead to the development of drugs to target markers. But some have taken the opposite route, and have chosen to look at a rare group of people who live into their eighties and nineties but have the cognitive abilities of someone several decades younger. These are the so-called ‘superagers’.

Two studies recently presented at the American Association for the Advancement of Science focus on this group of healthy agers. One study showed significant anatomical differences in the brains of superagers, demonstrating that they shrink much more slowly than age-matched controls. Over 18 months the control brains lost volume in the cortex twice as fast as those of the superagers, making them less resistant to cognitive impairment and dementia.

The study also found that superagers have more of a type of cell known as the Von Economo (VE) neuron than normal elderly people. These VE neurons are found in the anterior cingulate, which is thought to play a role in attention and working memory. Researchers also found that anterior cingulate is considerably thicker in superagers. It’s not yet clear why superagers have more of these VE neurons and what role they play in improving the cognitive abilities of superagers.

Autopsy studies of superagers have also in some ways muddied the waters of Alzheimer’s research, as they show that superagers are not immune to the plaques of amyloid protein that are the hallmarks of the disease. Why some people who have amyloid pathology develop the cognitive impairments typical of Alzheimer’s disease, while some don’t, is not yet clear. But the finding may have some relevance as to why experimental drugs designed to clear amyloid from the brain have not to date proven successful in phase 2 and 3 trials in humans. It also might point to the fact that lifestyle factors play a more important role than previously suspected.

Do the superagers have anything to tell us about how we can increase our chances of a cognitively healthy old age? Another study – the 90+ Study, has been tracking people in their 90s for the past 15 years to try and elucidate whether there are any particular lifestyle patterns in those who live well in their older years. And it turns that there are.

One factor that seems to play an important role is having strong social networks. Superagers reported having more satisfying, high-quality relationships compared with cognitively average people of the same age. The finding mirrors that of several other studies that found social interactivity is a crucial predictor of longevity and delay of cognitive impairment.

Here are some other key findings of the 90+ study:

People who drank moderate amounts of alcohol or coffee lived longer than those who abstained;
People who were overweight in their 70s lived longer than normal or underweight people did;
Over 40% of people aged 90 and older suffer from dementia, and almost 80% are disabled. Both dementia and disability are more common in women than men;
About half of people with dementia over age 90 do not have sufficient neuropathology in their brain to explain their cognitive loss;
People aged 90 and older with an APOE2 gene are less likely to have clinical Alzheimer’s dementia, but are much more likely to have Alzheimer’s neuropathology in their brains.

Diet and dementia: what the research tells us

Dying and dementia are the two things people in their middle years tend to say they are most apprehensive about. The former is inevitable, but can the latter be avoided? A number of studies have shown an association between exercise, in particular resistance or muscle-building exercise, and a decreased risk of Alzheimer’s disease and other forms of dementia. The jury appears to be still out on the possible protective effects of brain training. But what about the food we eat?

Diet and dementia has been an intensive area of research, and the best way to learn anything from the myriad studies carried out with varying methods, objects and endpoints is to look at the meta-analyses and systematic reviews. The most recent review, published late last year, looked at all observational studies published between 2014 and 2016 on the relationship between diet and late-life cognitive disorders. This found evidence that combinations of foods and nutrients can act synergistically to provide stronger effects than found with any one particular ingredient. In particular, adherence to a Mediterranean-type diet – with its emphasis on plant-based foods, fish, poultry and olive oil – was associated with decreased rates of cognitive decline.

The review also finds another diet associated with a reduction or delay of Alzheimer’s disease: the emerging DASH – or Dietary Approach to Stop Hypertension – diet, which emphasises fruit, vegetables, whole grains and low-fat dairy foods. It includes meat, fish, poultry, nuts, and beans, but limits sugar-sweetened foods and beverages, red meat, and added fats. As its name suggests, it was originally designed to help in hypertension, which has in itself been linked to higher rates of dementia.

Combining the Mediterranean and DASH diets produces the MIND diet, or the Mediterranean-Dash diet Intervention for Neurodegenerative Delay, which has also been associated with lower rates of dementia in several studies. Put together by a team from the Rush University Medical Center in the US, the MIND diet, like the other two diets, emphasizes the importance of fresh fruit, vegetables, and legumes. But it also includes recommendations for specific foods, such as leafy greens and berries, which have been shown in studies to slow cognitive decline.

The MIND diet appears to be more effective at reducing cognitive decline than either the Mediterranean or DASH diets on their own. One prospective study of over 900 middle-aged and older people, followed for an average of nearly five years, found those with either moderate or high compliance to the MIND diet had significantly lower rates of Alzheimer’s disease diagnoses, with a reduction in risk of a third and a half, respectively, compared with the lowest levels of compliance. But for the DASH and Mediterranean diets, only study participants with high adherence saw an effect.

Another study of around 1000 people found that adherence to the MIND diet significantly slowed cognitive decline, and that those with the highest compliance managed to delay decline by an average of 7.5 years.

Systematic reviews of these dietary interventions do caution that it is very difficult to tease out possible confounders; that more long-term results are needed; and that observational studies can never show causality, only association. Of course, it’s notoriously difficult, and indeed probably impossible, to run a randomised trial of a dietary intervention over many years. That’s not to say we will never get evidence that most in the medical community consider definitive. After all, no randomised trials were ever carried out to prove the link between tobacco use and lung cancer, and yet today there is no doubt at all about the causality.

In the meantime, here are the fundamentals of the MIND diet:

What to eat:

Green leafy vegetables – kale, spinach, broccoli, collards and other greens, at least two servings a week;.
Other vegetables – a salad and at least one other vegetable every day;
Nuts – at least five times a week;
Berries – such as blueberries or strawberries, at least twice a week;
Beans – three times a week;
Whole grains – at least three servings a day;
Fish – at least once a week;
Poultry – two or more servings a week;
Olive oil.

What to avoid:

Butter and margarine – not more than one tablespoon daily;
Cheese – less than once per week;
Red meat – no more than three servings each week;
Fried food – less than once per week;
Pastries and sweets – no more than four times a week.

Medicare Benefits Schedule Review update

The MBS Review Taskforce continues its work into 2018, with the next round of public consultations expected for release in February.

In the meantime, a number of clinical committees have yet to begin. The Department of Health’s MBS Review team is currently accepting nominations from medical practitioners with the relevant background to participate on the following reviews:

Aboriginal and Torres Strait Islander Health, Neurology, Pain Management, Urology, Allied Health, Colorectal Surgery, Consultation Services, General Surgery, Mental Health Services, Nurse Practitioner & Participating Midwife, Ophthalmology, Optometry, Oral & Maxillofacial Surgery, Paediatric Surgery, Plastic & Reconstructive Surgery, Thoracic Surgery, Vascular Surgery

The MBS Review Taskforce also has an interest in participants (both specialists and consultant physicians) for the review of specialist consultation items.

The success of the MBS reviews is contingent on the reviews being clinician-led and the AMA encourages medical practitioners with the relevant skillset to consider nominating to the clinical committees. Follow the online links to learn more about the individual items under review by each committee.

For more information or to submit a nomination, contact the MBS Review team.

The AMA’s approach has always been to defer recommendations relating to specialty items to the relevant Colleges, Associations and Societies (CAS) and comment on the broader policy. As such, the AMA does not have direct representation on individual clinical committees but supports the commitment made by members who do contribute their expertise to the review.

Through feedback mechanisms involving the CAS, a member-based AMA Working Group and the Medical Practice Committee, the AMA has responded to every single MBS review consultation – raising issues from across our membership, while stressing where systematic improvements need to be made. The AMA Secretariat and the President have done this through direct representations with the Health Minister, the Department of Health and in writing to the Chair of MBS Review Taskforce.

Recent submissions highlighted a number clear deficiencies and significant variations in the MBS review process, signalling a need for absolute transparency from the Taskforce and leadership on the clinical committees through early engagement of the relevant CAS.

This year, the AMA will continue to press Government to ensure the reviews result in sensible reinvestment into the MBS while protecting clinical decision making. It is therefore crucial that each committee has the input of practicing clinicians and consistent, practical advice from the CAS.

The AMA continues to monitor the reviews with interest and update members along the way. The profession and the wider CAS are encouraged to do the same by engaging early with the clinical committees and public consultations. The full schedule of MBS reviews can be found on the Department of Health website: http://www.health.gov.au/internet/main/publishing.nsf/content/MBSR-about

For more information on AMA’s advocacy with the MBS reviews, contact Eliisa Fok
Senior Policy Adviser, Medical Practice efok@ama.com.au

Eliisa Fok
AMA Senior Policy Adviser

A silver lining to the rising tide of dementia

We’re all familiar with the studies and news reports that present dementia as a ticking public health time bomb in the heart of the developed world. And while it’s true that global dementia rates continue to rise due to ageing populations, a new study suggests that the actual per capita incidence may be in long-term decline. In other words, while the brute number of people with dementia may continue to increase due to demographic changes, the chances of anyone in particular developing the disease are in fact diminishing.

The study, published in JAMA Neurology, measured incident dementia in a population sample of 1350 people over the age of 70 and without dementia at enrolment, between 1993 and 2015. Dementia incidence declined in successive birth cohorts. In those born before 1920, incidence per 100-person years was 5.09, which dropped to 1.73 for those born in the latter half of the 1920s.

The researchers from the Albert Einstein College of Medicine in New York identified a tipping point in those born after 1929, in whom dementia incidence started dropping significantly.

They say their results are broadly consistent with previous studies, which saw a drop-off in the incidence of dementia from around 1990. That would be around the time when those born after 1929 were entering their 60s, at which point age-related dementia becomes more prevalent.

But they say it’s not easy to tease out why the decline in dementia incidence has occurred. Some experts have pointed out that it correlates with a trend towards greater levels of education, but the researchers say that adjusting for education levels did not attenuate the decline in dementia incidence.

Another potential explanation is improved cardiovascular health. Vascular risk factors increase the odds of dementia and the incidence of stroke has declined in recent decades, just as management of cardiovascular risk factors have improved. The researchers say this could partially explain the decline in dementia incidence, but not totally. Improved nutrition is another possible explanation, unexplored by the study. For the moment, why the decline has occurred remains, to some degree, a mystery.

The study authors also found an increased prevalence in diabetes over the years of the study. Dementia is linked to diabetes so this higher prevalence may, in the future, serve to increase the rates of dementia.

They say more work needs to done to further elucidate what’s happening and whether the decrease in dementia incidence will offset the increase due to the ageing population.

You can read the study here.

The lifestyle changes that can reverse Alzheimer’s disease

Last summer, a research group from the University of California, Los Angeles (UCLA) quietly published the results of a new approach in the treatment of Alzheimer’s disease. What they found was striking. Although the size of the study was small, every participant demonstrated such marked improvement that almost all were found to be in the normal range on testing for memory and cognition by the study’s end. Functionally, this amounts to a cure.

These are important findings, not only because Alzheimer’s disease is projected to become ever more common as the population ages, but because current treatment options offer minimal improvement at best. Last July, a large clinical trial found little benefit in patients receiving a major new drug called LMTX. And after that, another hopeful drug designed to target amyloid protein, one of the hallmarks of Alzheimer’s disease, failed its first large clinical trial as well. Just two months ago, Merck announced the results of its trial of a drug called verubecestat, which is designed to inhibit formation of amyloid protein. It was found to be no better than placebo.

The results from UCLA aren’t due to an incredible new drug or medical breakthrough, though. Rather, the researchers used a protocol consisting of a variety of different lifestyle modifications to optimise metabolic parameters – such as inflammation and insulin resistance – that are associated with Alzheimer’s disease. Participants were counselled to change their diet (a lot of veggies), exercise, develop techniques for stress management, and improve their sleep, among other interventions. The most common ‘side effect’ was weight loss.

The study is notable not only for its remarkable outcomes, but also for the alternative paradigm it represents in the treatment of a complex, chronic disease. We’ve spent billions of dollars in an effort to understand the molecular basis of Alzheimer’s in the hope that it will lead to a cure, or at least to more effective therapies. And although we have greatly enlarged our knowledge of the disease, it has not yielded many successful treatments.

The situation is analogous in kind, if not quite degree, to the many other chronic diseases with which we now struggle, such as diabetes and cardiovascular disease. While we do have efficacious medications for these conditions, none work perfectly, and all have negative effects. Our understanding of the cellular processes at the root of these diseases is sophisticated, but technical mastery – the grail of a cure – has remained elusive.

Acknowledging these difficulties, the researchers at UCLA opted for a different approach. Beginning from the premise that Alzheimer’s disease is a particular manifestation of a highly complex system in disarray, they sought to optimise the system by changing the inputs. Put another way, the scientists chose to set aside the molecular box which has proven so vexing, and to focus instead on the context of the box itself. Although we cannot say precisely how the intervention worked, on a cellular level, the important thing is that it did work.

The method isn’t entirely novel. Researchers have already shown that multi-faceted, comprehensive lifestyle interventions can significantly improve outcomes in cardiovascular disease, diabetes and hypertension. But it’s difficult for these approaches to gain traction for two reasons. First, these protocols are more challenging than simply taking a pill at bedtime. Patients need ongoing education, counselling and support to effect meaningful change. And second, the pharmaceutical mode of treatment is deeply embedded within our current medical system. Insurance companies are set up to pay for medication, not lifestyle change; and physicians are taught pharmacology, not nutrition.

Despite these difficulties, it’s time to start taking these approaches much more seriously. The prevalence of Alzheimer’s disease is expected to triple over the next three decades, to nearly 14 million in the United States alone. Diabetes and other chronic diseases are expected to follow a similar trajectory. Trying to confront this epidemic with medication alone will raise a new host of problems, from prohibitive cost to adverse effects, without addressing any underlying cause. We know that comprehensive lifestyle modification can work for many chronic diseases, in some cases as well as medication. It deserves more than passing mention at the end of an annual check-up – it’s time to make it a cornerstone in the treatment not only of Alzheimer’s disease, but of all chronic disease.

Dr Clayton Dalton is a medical resident at the Massachusetts General Hospital in Boston.

This article was originally published at Aeon and has been republished under Creative Commons.

The link between anticoagulation and dementia

Atrial fibrillation patients are much less likely to develop dementia if they are taking an anticoagulant, a large Swedish study has found.

Although the the increased risk of dementia in atrial fibrillation has been known for many years, until now it has been unclear whether anticoagulation modifies that risk.

The retrospective study is the largest yet to look at dementia and anticoagulation. It involved nearly half a million people, comprising everyone in Sweden who had been diagnosed with atrial fibrillation from 2006 to 2014, with a cumulative 1.5 million years of follow-up. The study found a surprisingly large number of people – 54% – were not taking an anticoagulant, the use of which is recommended to mitigate increased stroke risk.

But those who were on anticoagulation treatment had, on analysis, a 48% lower risk of developing dementia. The study results also suggested that the earlier a patient started on an anticoagulant, the less risk of developing dementia he or she had.

The researchers also found a greater effect in patients with higher risk of stroke according to their CHA2DS2-VASc score.

Despite previous suggestions that novel oral anticoagulants (NOACs) may be more effective at warding off dementia than warfarin, the researchers found no difference between the types of anticoagulant medications in dementia risk.

The researchers cautioned that because of the retrospective nature of the study, they could not demonstrate cause and effect. Randomised trials would never be done for ethical reasons, but given the biological plausibility of a causal effect, the results “strongly suggest” that anticoagulants protect against dementia, the authors said.

Other independent risk factors for dementia in the study were increasing age, Parkinson’s disease, earlier stroke and alcohol abuse.

Study co-author Dr Leif Friberg, an associate professor of cardiology at Stockholm’s Karolinska Institute, said the important implications from the findings were that patients should be started on anticoagulant treatment as soon as possible after diagnosis of atrial fibrillation and they should continue on the drugs.

“Doctors should not tell their patients to stop using oral anticoagulants without a really good reason. Patients start on oral anticoagulation for stroke prevention but they stop after a few years at an alarmingly high rate. If you know that AF eats away at your brain at a slow but steady pace and that you can prevent it by staying on treatment, I think most AF patients would find this a very strong argument for continuing treatment.”

Dr Friberg said atrial fibrillation patients often have a fatalistic view about stroke, thinking that either they’ll get it or they won’t. But they tend to be less fatalistic about dementia and are more likely to do what they can to ward off the disease. That may make risk of dementia a more compelling argument to ensure that patients stay on anticoagulation medication, Dr Friberg said.

You can read the study here.

SIDS and serotonin link confirmed

A new Australian study has confirmed abnormalities in serotonin, a common brain chemical, are linked to sudden infant death syndrome (SIDS).

SIDS is the leading cause of infant death (between the ages of one month and one year) in Australia and most of the developed world.

University of Adelaide’s Medical School conducted the Australian first study, investigating 41 cases of SIDS deaths, and found there were striking abnormalities in chemical serotonin within the brain. The study has been published in the Journal of Neuropathology & Experimental Neurology.

Dr Fiona Bright, the primary researcher, said the study was significant because it confirmed abnormalities in serotonin in the brain are most definitely linked to cases of SIDS.

“Our research suggests that alterations in these neurochemicals may contribute to brainstem dysfunction during a critical postnatal developmental period,” she said.

“As a result, this could lead to an inability of a SIDS infant to appropriately respond to life-threatening events, such as lack of oxygen supply during sleep.”

Her work builds on research conducted in the United States at the Boston Children’s Hospital and Harvard Medical School, where Dr Bright was based for 18 months during her combined studies.

The Sudden Infant Death Research Foundation Inc., now known as Red Nose, estimates that annually, 3,200 Australian families experience the sudden and unexpected death of a baby or child. They have been quick to welcome the results of a University of Adelaide study.

Risk reduction still remains the key preventer of SIDs. This includes evidence-based safe sleeping public health program. Since risk reduction campaigns began in 1989, the rate of SIDS in Australia has decreased by 80 per cent. Red Nose believes that an estimated 9,450 lives have been saved.

Dr Bright’s research also reinforces that risk factors are central to managing SIDS.

“Notably, the SIDS cases we studied were all linked to at least one major risk factor for SIDS, with more than half of the infants found in an adverse sleeping position and having had an illness one month prior to death,” Dr Bright says.

“Ultimately, we hope that this work will lead to improved prevention strategies, helping to save baby’s lives and the emotional trauma experienced by many families.”

For information on how to sleep baby safely to reduce the risk of sudden unexpected death in infancy, including SIDS and fatal sleeping accidents, visit https://rednose.com.au/section/safe-sleeping.

MEREDITH HORNE

Why some people get dementia and others don’t

New findings on resilience to memory loss have been presented at the World Congress of Neurology, which is currently being held in Kyoto, Tokyo.

The US-based 90+ study has been looking at the mental health of the oldest of the old since 2003, enrolling over 1,700 participants over the age of 90 along the way. Data showed that around 40% of study participants had a dementia disease, with women over-represented in that group.

However, there was surprisingly little correlation between Alzheimer’s pathology – typically a buildup of amyloid-beta protein plaques and tau protein tangles in the brain – and dementia symptoms.

“Interestingly enough, autopsies revealed that about half of the oldest-old without dementia have a high degree of Alzheimer’s neuropathology in their brains although they were mentally fit while alive,” says Professor Kawas of the University of California, a lead researcher for the study.

At the same time, among participants who did develop symptoms of cognitive loss, around half did not have typical Alzheimer’s pathology.

The findings mirror those from the work of Professor Carol Brayne, a leading UK dementia researcher who runs a brain bank and dementia epidemiology program at the University of Cambridge.

Professor Brayne has also found very little correlation between the classic features of Alzheimer’s disease and beta-amyloid accumulation in post-mortems on people who were well characterised before they died.

These findings are clearly significant for any research program hoping to banish dementia by targeting Alzheimer’s pathology such as amyloid-beta accumulation in the brain. But it also prompts the question of why some people are cognitively resilient to Alzheimer’s pathology – which may have genetic origins – while others aren’t.

The 90+ study shows that at least some of the difference is attributable to lifestyle. Participants who were resilient to cognitive loss tended to exercise more, drink more coffee, and watch less television.

In a phenomenon known as cognitive reserve, higher levels of education seemed to protect against cognitive loss in people who were shown on PET scans to have amyloid plaque in the brain.

“People with a low level of education had a four times higher statistical risk of contracting dementia than those with a higher level of education. Among those without plaque, the educational difference was irrelevant,” says Professor Kawas.

The researchers also found that one of the best predictors of dementia was having multiple comorbidities.

“Multiple pathologies are at the root of dementias of all ages,” says Professor Kawas. “In the oldest-old, the presence of multiple pathologies is associated with increased likelihood of dementia. The number of pathologies also seems to be relevant for the severity of the cognitive decline. We will therefore need to target multiple pathologies to reduce the burden of dementia.”

Despite these advances in our knowledge of the causes of dementia, there remains great uncertainty over what preventive measures should be taken. The best evidence is for physical exercise, with studies showing that it can play a role in postponing or slowing age-related cognitive decline. High blood pressure in middle age has also been shown to be associated with later cognitive decline. And given the findings on cognitive reserve and dementia, cognitive training may also have an effect, but studies have yet to show this.

A new report acknowledges that more research needs to done on the efficacy of preventive measures, but suggests diabetes and anti-depression therapies, lipid-reducing drugs, initiatives to improve sleep quality and social involvement, and addition of folic acid to the diet along with other nutritional interventions may all be of benefit.

Access abstracts from the World Neurology Conference here.

[Correspondence] PubMed should raise the bar for journal inclusion

A survey by Manca and colleagues1,2 found that predatory journals active in neuroscience and neurology outnumber those regularly indexed in the main biomedical databases. Furthermore, this analysis of predatory publishing (as of October, 2016) showed that over 10% of predatory journals in three important subdisciplines are indexed in PubMed (12% for rehabilitation, 11·4% for neurosciences, and 20·2% for neurology).1,2

[Perspectives] Taking a dose of Roald Dahl’s marvellous medicine

With more than 50 000 shows being staged by over 3000 artists in 300 venues, there are performances to suit all tastes at next month’s 70th Edinburgh Festival Fringe—but one show at the arts festival has a special sprinkling of literary magic. Tom Solomon, Professor of Neurology and Director of the Institute of Infection and Global Health at the University of Liverpool, UK, will entertain families with his Roald Dahl’s Marvellous Medicine show, which will introduce a new generation to Dahl’s tales, while allowing older readers to revisit their favourite books.