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The dementia ‘tsunami’ is coming – but two potential medications offer hope
Sophie Scott
Clinical Articles iconClinical Articles

The dementia ‘tsunami’ is coming – but two potential medications offer hope

As our population continues to age, the number of people with dementia is set to skyrocket, a situation that geriatric medicine researcher A/Prof Michael Woodward has likened to a ‘tsunami that’s sadly almost bearing down on us’. Dementia already affects more than 400,000 Australians and is the second-biggest cause of death, but it’s predicted that this will grow to 589,000 by 2028 and more than one million by 2058. The debilitating condition causes a decline in memory, cognition and day-to-day functioning, a distressing process both for sufferers and their loved ones. Two new medications for dementia are currently being trialled, giving hope for more effective treatment. One is a monoclonal antibody gantenerumab, designed to remove the toxic protein amyloid from the brains of people with dementia. Although earlier trials have been disappointing, a higher dose is now being trialled in several thousand participants, including at Melbourne’s Austin Hospital.

Expert/s: Sophie Scott, Brooke Wylie
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Prof Malcolm Hopwood
Monographs iconMonographs

MDD: Management and Choosing Between Antidepressants

This article discusses a practical, evidence-based approach to the management of Major Depressive Disorder as it is likely to present in the real world setting.

Expert/s: Prof Malcolm Hopwood
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Dr Vivienne Miller
Clinical Articles iconClinical Articles

Assessing stroke risk – easier than saying “CHA2DS2-VA Score”!

General Practitioner Dr Vivienne Miller takes a look at what’s changed in the recently updated CHA2DS2-VASC Score for the determination of stroke risk factors from atrial fibrillation. The CHA2DS2-VA Score was updated from the CHA2DS2-VASC Score last year to exclude female sex (represented by Sc) in the determination of stroke risk factors from atrial fibrillation. The two scores are identical, apart from the exclusion of female sex, which is no longer considered an outright risk factor in stroke from atrial fibrillation, but more of a ‘risk modifier’ of this complication.1General Practitioner Dr Vivienne Miller takes a look at what’s changed in the recently updated CHA2DS2-VASC Score for the determination of stroke risk factors from atrial fibrillation. The CHA2DS2-VA Score was updated from the CHA2DS2-VASC Score last year to exclude female sex (represented by Sc) in the determination of stroke risk factors from atrial fibrillation. The two scores are identical, apart from the exclusion of female sex, which is no longer considered an outright risk factor in stroke from atrial fibrillation, but more of a ‘risk modifier’ of this complication.

Expert/s: Dr Vivienne Miller
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Dr Linda Calabresi
Clinical Articles iconClinical Articles

Fluoroquinolones and neuropathy, is that a thing?

How big is the risk of peripheral neuropathy with fluoroquinolones? That’s the question UK researchers were looking to answer with their large case-controlled study recently published in JAMA Neurology. And – cutting to the chase – what’s the answer? Well, the risk isn’t huge but there is certainly a risk. And the association is worth bearing in mind if a patient develops peripheral neuropathy because the timing of this side-effect can be unpredictable, making the link less obvious. According to the study which analysed details from a large UK primary care population database involving almost 1.4 million patients over seven years, taking oral fluoroquinolone increased the relative risk of developing peripheral neuropathy by 47% compared to not taking the drug. “The absolute risk with current oral fluoroquinolone exposure was 2.4 per 10,000 patients per year of current use,” the study authors wrote. And just to be sure the association wasn’t simply related to having an infection that needed antibiotics, the researchers also looked at all those patients who had received a different antibiotic, namely amoxicillin-clavulanate, to see if there was a similar association with this particular side-effect. But no – the problem just seemed to occur with the fluoroquinolones. “No significant increased risk was observed with observed with oral amoxicillin-clavulanate exposure,” they found. Aside from quantifying the risk of peripheral neuropathy with fluoroquinolones, which was the main aim of the study, researchers also found that the relative risk remained significantly increased up to 180 days after taking the drug. So, if a doctor is investigating the cause of a patient’s newly-developed peripheral neuropathy, they need to ask about fluoroquinolone use in the previous six months. The study findings also suggested certain patients might be more at risk of developing this adverse effect than others. The risk appeared to be greater among men and those aged older than 60 years. The risk also seemed to increase the longer a person took the drug. The findings seem to suggest increased caution needs to be taken when prescribing fluoroquinolones, especially given that they have other known potential side-effects such as tendon rupture and aortic aneurysm. “Health care professionals should consider these potential risks when prescribing fluoroquinolone antibiotic,” the study authors concluded. But, an accompanying editorial warns against getting the risk out of perspective. The editorial authors from the Mayo Clinic in the US point out that when a side-effect is very rare, it can be challenging to determine predisposing factors or potential confounders. There is also a lack of a strong hypothesis on the mechanism underlying fluoroquinolone-induced neuropathy. “It is clearly a rare event in a sea of fluoroquinolone use, and no clear pattern has been defined that differentiates it from other causes of peripheral neuropathies,” they wrote. However, they support the findings of the original study that there is an association, but suggest further research is needed before doctors start avoiding using these drugs.

Reference

Morales D, Pacurariu A, Slattery J, Pinheiro L, McGettigan P, Kurz X. Association Between Peripheral Neuropathy and Exposure to Oral Fluoroquinolone or Amoxicillin-Clavulanate Therapy. JAMA Neurol. Published online April 29, 2019. doi:10.1001/jamaneurol.2019.0887 Staff NP, Dyck PJB. On the Association Between Fluoroquinolones and Neuropathy. JAMA Neurol. Published online April 29, 2019. doi:10.1001/jamaneurol.2019.0886    
Expert/s: Dr Linda Calabresi
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Dr Linda Calabresi
Clinical Articles iconClinical Articles

Mindfulness yoga best for Parkinson Disease

Patients with Parkinson Disease can now be prescribed a mind-body therapy that has a strong evidence-base of effectiveness. According to a randomised clinical trial published in JAMA Neurology, a program of mindfulness yoga will not only improve motor dysfunction and mobility at least as well as a program of standard stretching and resistance exercises but it will also significantly lessen anxiety symptoms and improve quality of life. While clinical practice guidelines have almost uniformly recommended exercise for patients with Parkinson’s, to date there has been no robust evidence that yoga is any better than any other physical exercise program. While the fact that this study shows that mindfulness yoga is equivalent to a conventional exercise program in terms of motor symptoms is of interest, the researchers say it is the improvement in depression and anxiety symptoms that is of most importance. These symptoms are common in Parkinson disease and are a major factor affecting these patients’ quality of life. “Considering that [Parkinson Disease] is not only a physically limiting condition but also a psychologically distressing life event, health care professionals should adopt a holistic approach in [Parkinson Disease] rehabilitation,” they wrote. Much of the clinically and statistically significant improvement in anxiety and depression symptoms seen in the study, the researchers attribute to the mindfulness component of the yoga therapy. The moderate to large psychological benefit of mindfulness yoga was said to be ‘remarkable’, as the patients assigned to receive this intervention attended a mean of only six sessions. The actual study was neither huge nor of long duration, however it was randomised and had ‘adequate statistical power to detect a clinically meaningful effect.’ The Hong Kong researchers randomised almost 190 patients with mild to moderate, idiopathic Parkinson Disease to either a weekly, 90-minute session of mindfulness yoga or a weekly 60-minute session of stretching and resistance training exercises. The intervention went for a period of eight weeks and both groups were encouraged to perform 20-minutes of home-based practice twice a week over the duration of the program. The participants were assessed at baseline, at eight weeks (immediately after the intervention) and then at 20 weeks. The assessments were conducted by independent assessors who were not aware of which intervention the patient had undertaken. Interestingly while the effects of both the interventions on motor symptoms and mobility were very similar straight after program, with benefits lessening at the 20 week mark (three months after the intervention had finished), the psychological benefit of mindfulness yoga seen at eight weeks was just as pronounced 12 weeks later at the 20 week mark. This suggests that a relatively short program of mindfulness yoga might have longer term benefits in helping patients with Parkinson Disease manage stress and symptoms, the study authors said. But, of course, further research is needed to compare different mindfulness practices, the long-term effectiveness and compliance. Nonetheless, the study authors say these study findings are sufficiently strong for doctors to at least consider recommending this type of therapy to patients with Parkinson Disease. “Future rehabilitation programs could consider integrating mindfulness skills into physical therapy to enhance the holistic well-being of people with neurodegenerative conditions,” they concluded.

Reference

Kwok JYY, Kwan JCY, Auyeung M, Mok VCT, Lau CKY, Choi KC, et al. Effects of Mindfulness Yoga vs Stretching and Resistance Training Exercises on Anxiety and Depression for People With Parkinson Disease: A Randomized Clinical Trial. JAMA Neurol. 2019 Apr 8. DOI: 10.1001/jamaneurol.2019.0534
Expert/s: Dr Linda Calabresi
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Dr Linda Calabresi
Clinical Articles iconClinical Articles

Improving the Outlook for Cerebral Palsy Children

Despite the incidence of cerebral palsy decreasing, it is still Australia’s most common cause of physical disability in childhood, experts say. And with the condition affecting over two in every 1000 live births, it is more than likely a GP will be caring for these patients in their clinical practice. The authors of a review in the latest Medical Journal of Australia highlight areas where the treating health professional, including the GP can play a role in improving these children’s health outcomes as well as their quality of life. “While there is currently a limited range of evidence-based treatments that change the underlying pathology of cerebral palsy, there are many areas in which health care professionals can change the natural history of cerebral palsy and improve participation and quality of life for children with this condition,” they said. They refer to a framework for management of patients with cerebral palsy, known as the six Fs. These Fs help both clinicians and families of the affected child set realistic goals and develop appropriate pathways to meet them. The six Fs are: Function – encourage the child to try activities and celebrate not only what they can achieve but the attempt. Family –  the family environment is vitally important to the child’s health outcomes both physically and psychologically. Significant attention, support and resources need to be directed to this. Fitness – Overall physical fitness is at least as important as exercises directed at helping overcome the particular physical disability of a child with cerebral palsy. Fun – Caregivers need to ensure the child with cerebral palsy does not miss out on this key component of childhood. Friends – Social interaction and the development of quality relationships need to be incorporated as a management goal. Future – This is all about setting realistic goals and expectations and the mapping out plans of how to achieve them, keeping in mind the other five Fs. In addition to this very grounding framework of management, the review authors went on to describe the current state of play of treatment for the various physical manifestations of cerebral palsy. Spasticity and dystonia are the most common signs of the disease and along with physical therapies such as physiotherapy, occupational therapy, splints and orthotics there are a number of medications and even some surgical options for treatment. Baclofen, diazepam and Botulinum toxin A are well-known options to treat the spasticity and dystonia. But apparently there is emerging evidence for the use of other medications such as gabapentin and clonidine. There are also some highly specialised surgeries being performed for subsets of cerebral palsy children such as deep brain stimulation for children with dystonic and dyskinetic movement, selective dorsal rhizotomy for severe spasticity in the lower limbs and even intrathecal baclofen to avoid the side effects of oral baclofen. The review also highlights three potential problem areas for children with cerebral palsy that are of particular relevance for GPs caring for children with this condition. Hip displacement is more of a risk in children with cerebral palsy, and if it is missed it can result in hip dislocation. Regular clinical and radiographic assessment is recommended. “The pelvic x-ray is taken in a standardised supine position and is usually repeated between six and 12 months, depending on the severity of cerebral palsy and the rate of progression of migration of the femoral head out of the acetabulum,” they said. Referral is recommended once migration approaches 30% Another major issue to check for in children with cerebral palsy is pain, with evidence suggesting up to 75% of young patients are regularly experiencing this. The review authors recommend carers ask about this directly, as children may not volunteer this information despite chronic pain’s well-known effect on quality of life. Pain treatment is generally fairly standard, however specific treatments are available for pain arising from unique symptoms such as dystonia or spasticity. Finally, the review authors advise treating clinicians to watch out for feeding and swallowing problems, and as a consequence of these, deficiencies in nutrition. There is a wide range of potential issues concerning eating and drinking that can affect children with cerebral palsy, including swallowing difficulty, managing utensils, posture, risk of aspiration, sensory difficulties and even excessive drooling. All of these can be managed, but the key first step is identifying there is an issue before nutritional deficiencies manifest in comorbidities such as osteoporosis. Unfortunately, as yet, we still cannot cure cerebral palsy. However, with early interventions, close monitoring and targeted therapies the natural history of cerebral palsy is being altered for the better.

Reference

Graham D, Paget SP, Wimalasundera N. Current thinking in the health care management of children with cerebral palsy. Med J Aust. 2019 Feb; 210(3): 129-35. DOI: 10.5694/mja2.12106
Expert/s: Dr Linda Calabresi
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Dr Linda Calabresi
Clinical Articles iconClinical Articles

Preventing Alzheimer Disease

At first read, the study results seemed disappointing. Yet another promising premise fails to deliver when it comes to actual proof. But the researchers aren’t ready to give up on this hypothesis just yet. In fact, commentators on the study say the results offer ‘great hope’ and represent ‘a major leap forward.’ The SPRINT MIND study, recently published in JAMA was investigating whether intensive blood pressure control (to a systolic less than 120mmHg) worked better than standard blood pressure control (SBP<140mmHg) at reducing the risk of mild cognitive impairment and dementia. This randomised controlled trial was a component of the well-publicised Systolic Blood Pressure Intervention Trial (SPRINT) which looked at the effect of more intensive blood pressure control on cardiovascular and renal outcomes in addition to cognitive function in over 9000 people without a history of diabetes or stroke. Basically, what this study showed was that intensive blood pressure control to a target of less than 120mmHg did not reduce the incidence of probable dementia compared to lowering BP to a target of less than 140mmHg. Depressing, yes? No, say the study authors. Firstly, they say the study demonstrated no ill-effects of intensive BP lowering – which has been an issue of concern for some who have been worried that lowering the BP could decrease cerebral perfusion thereby harming cognitive function. In fact, the study authors showed quite the opposite was true. The intervention actually helped protect cognitive ability. “This is the first trial, to our knowledge, to demonstrate an intervention that significantly reduces the occurrence of [mild cognitive impairment], a well-established risk factor for dementia, as well as the combined occurrence of [mild cognitive impairment] or dementia,” they said. The study authors suggest the lack of benefit in dementia may be due to the fact the SPRINT study was terminated early following the demonstration of benefit of intensive BP control on cardiovascular outcomes and all-cause mortality. Because of this shortened time frame and the fact that there were fewer than expected cases of dementia, they suggest the study may have been ‘underpowered’ to show a result for lowering the risk of dementia. They also say there were fewer cases of dementia among the intensive treatment group compared with the standard treatment group (7.2 vs 8.6 cases per 1000 patient years) even though this wasn’t statistically significant. We cannot know whether this trend would have reached statistical significance had the intervention continued. An accompanying editorial views the study and the results with a good deal of positivity. “For older adults, almost all of who have concern about being diagnosed with Alzheimer Disease and related dementia, [this study] offers great hope,” the US epidemiologist, Dr Kristine Yaffe, said. She points out that this a readily modifiable risk factor, and we should be accelerating our efforts into investigating whether this, along with other vascular health interventions such as physical activity, can indeed prevent dementia, building on the positive results of this study. “The SPRINT MIND study may not be the final approach for prevention of Alzheimer disease or other cognitive impairment but it represents a major leap forward in what has emerged as a marathon journey.”

Reference

Yaffe, K. Prevention of Cognitive Impairment With Intensive Systolic Blood Pressure Control. JAMA [Internet]. 2019 Jan 28. DOI: 10.1001/jama.2019.0008 [Epub ahead of print]
Expert/s: Dr Linda Calabresi
The dementia ‘tsunami’ is coming – but two potential medications offer hope
Dr Linda Calabresi
Clinical Articles iconClinical Articles

Predicting and Preventing Dementia

Adolescent boys who struggle to understand how basic machines work and young girls who have difficulty remembering words are at increased risk of developing dementia when they’re older, new research has found. According to the longitudinal study published in The Journal of the American Medical Association, lower mechanical reasoning in adolescence in boys was associated with a 17% higher risk of having dementia when they were 70. With girls it was a lower memory for words in adolescence that increased the odds of developing the degenerative disease. It has been known for some time that the smarter you are throughout life, even as a child the less likely it is that you will develop dementia. Not a guarantee of protection – just a general trend. It has to do with cognitive reserve, the US researchers explain. “Based on the cognitive reserve hypothesis, high levels of cognitive functioning and reserve accumulated throughout the life course may protect against brain pathology and clinical manifestations of dementia,” they wrote. This theory has been supported by a number of studies such as the Scottish Mental Health Survey that showed that lower mental ability at age 11 increased the risk of dementia down the track. But what had been less well-defined was whether there were any particular aspects of intelligence in young people that were better predictors (or protectors) of dementia than others. This study goes some way to addressing this. Researchers were able to link sociobehavioural data collected from high school children back in 1960 with Medicare claims data over 50 years later that identified those people who had been diagnosed with Alzheimer's disease and related disorders. Interestingly, poor adolescent performance in other areas of intelligence such as mathematics and visualisation were also associated with dementia but not nearly to the extent of mechanical reasoning and word memory. So why is this so? The study authors say there are a few possible explanations. Maybe the poor performance in adolescence reflected poor brain development earlier in life, a risk factor for dementia. Or maybe these adolescents are more susceptible to neuropathology as they get older? Or maybe they are the adolescents who adopt poor health behaviours such as smoking and little exercise? “Regardless of mechanism, our findings emphasise that early-life risk stretches across the life course,” they said. And what can be done about it? That’s the million-dollar question. The researchers say the hope is if we know the at-risk group we can get aggressive with preventive management early. “Efforts to promote cognitive reserve-building experiences and positive health behaviours throughout the life course may prevent or delay clinical symptoms of Alzheimer's disease and related disorder.” An accompanying editorial takes this concept a little further. Dr Tom Russ, a Scottish psychiatrist says interventional research has identified a number of factors that can potentially influence cognitive reserve. These include modifiable health factors, education, social support, positive affect, stimulating activities and/or novel experiences, and cognitive training. As Dr Russ says, you can’t necessarily change all of these risk factors, and even the ones you can change may become less modifiable later in life. But as this study demonstrates, you may be able to work on a person’s cognitive reserve at different stages throughout their life to ultimately lower their risk of dementia.   Reference
  1. Huang AR, Strombotne KL, Horner EM, Lapham SJ, Adolescent Cognitive Aptitudes and Later-in-Life Alzheimer Disease and Related Disorders. JAMA Network Open [Internet]. 2018 Sep; 1(5): e181726. Available from: https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2701735 doi:10.1001/jamanetworkopen.2018.1726.
  2. Russ TC, Intelligence, Cognitive Reserve, and Dementia: Time for Intervention? JAMA Network Open [Internet]. 2018 Sep; 1(5): e181724. Available from: https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2701735 doi:10.1001/jamanetworkopen.2018.1724.

Expert/s: Dr Linda Calabresi
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Healthed
Clinical Articles iconClinical Articles

Study: Vitamin D unlikely to protect individuals from brain-related disorders.

New research from South Australian scientists has shown that vitamin D (also commonly known as the sunshine vitamin) is unlikely to protect individuals from multiple sclerosis, Parkinson's disease, Alzheimer's disease or other brain-related disorders. The findings, released today in the science journal 'Nutritional Neuroscience' reported that researchers had failed to find solid clinical evidence for vitamin D as a protective neurological agent. "Our work counters an emerging belief held in some quarters suggesting that higher levels of vitamin D can impact positively on brain health," says lead author Krystal Iacopetta, PhD candidate at the University of Adelaide. Based on a systematic review of over 70 pre-clinical and clinical studies, Ms Iacopetta investigated the role of vitamin D across a wide range of neurodegenerative diseases. "Past studies had found that patients with a neurodegenerative disease tended to have lower levels of vitamin D compared to healthy members of the population," she says. "This led to the hypothesis that increasing vitamin D levels, either through more UV and sun exposure or by taking vitamin D supplements, could potentially have a positive impact. A widely held community belief is that these supplements could reduce the risk of developing brain-related disorders or limit their progression." "The results of our in-depth review and an analysis of all the scientific literature however, indicates that this is not the case and that there is no convincing evidence supporting vitamin D as a protective agent for the brain," she says. >> Read more   Source: News Medical Net

Expert/s: Healthed
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Dr Linda Calabresi
Clinical Articles iconClinical Articles

Wealth a winner in preventing dementia

In what will be seen as a blow to cryptic crossword compilers the world over, it appears wealth is a better determinant of whether you keep your marbles than education. In a UK prospective study of over 6000 adults aged over 65 years, researchers found those people in the lowest quintile in terms of socioeconomic status were almost 70% more likely to get dementia than those categorised to be in the top fifth, over a 12 year follow-up period. Depressingly, this finding held true regardless of education level. “This longitudinal cohort study found that wealth in late life, but not education, was associated with increased risk of dementia, suggesting people with fewer financial resources were at higher risk,” the study authors said. On further analysis, researchers found the association between wealth, or the lack thereof and dementia was even more pronounced in the younger participants in the cohort. So what did the researchers think was the reason behind the link between poverty and dementia? One explanation was that having money allowed one to access more mentally stimulating environments including cultural resources (reading, theatre etc) and increased social networks that might help preserve cognitive function. While on the flip side, poverty (or ‘persistent socioeconomic disadvantage’ as the authors describe it) affects physiological functioning, increasing the risk of depression, vascular disease and stroke – all known risk factors for dementia. Other factors such as poor diet and lack of exercise also appear to more common among poorer people in the community. All this seems fairly logical, but what of the lack of a protective effect of education? Well, the researchers think this might be a particularly British phenomenon in this age group. “This might be a specific cohort effect in the English population born and educated in the period surrounding the World War II,” they suggested. A number of other studies have shown other results, with some, including the well-respected Canadian Study of Health and Aging-  showing the complete opposite – education protects against dementia. Consequently, the authors of this study, published in JAMA Psychiatry, hypothesise that perhaps this cohort of patients may have been unable to access higher education because of military service or financial restrictions but were able to access intellectually challenging jobs after the war. All in all, the study is an observational one and it is possible there are a number of confounding factors from smoking to availability of medical care that play a role in why poorer people are at greater risk of dementia. And while the researchers are not advocating older people give up their Bridge game and just buy lottery tickets, it would seem money is useful, if not for happiness, then at least for preserving brain power. Ref: JAMA Psychiatry doi:10.1001/jamapsychiatry.2018.1012

Expert/s: Dr Linda Calabresi
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Dr Wei Luan
Clinical Articles iconClinical Articles

Neuroscience in pictures: the best images of the year

To understand how the healthy brain works and what occurs in brain disease, neuroscientists use many microscopy techniques, ranging from whole-brain human MRIs to imaging within a single neuron (brain cell), creating stunning images in the process.

Expert/s: Dr Wei Luan, Dr Merja Joensuu, Ravi Kiran Kasula
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Dr Perminder Sachdev
Clinical Articles iconClinical Articles

Can lithium prevent dementia?

When people think of lithium, it’s usually to do with batteries, but lithium also has a long history in medicine. Lithium carbonate, or lithium salt, is mainly used to treat and prevent bipolar disorder. This is a condition in which a person experiences significant mood swings from highs that can tip into mania to lows that can plunge into depression. More recently, though, lithium has been explored as a potential preventive therapy for dementia. A recent paper even led some to question whether we should start putting lithium in drinking water to lower population dementia rates.
But despite early studies linking lithium to better cognitive function, there is currently not enough evidence to start using it as a preventive dementia strategy.

Lithium’s medical history

Lithium is a soft, light-silver metal present in many water systems, which means humans have always been exposed to it. Its concentrations in water range from undetectable to very high, especially in geothermal waters and oil-gas field brines. The high concentration of lithium in some natural springs led to it being related to healing. In the 19th century, lithium water was used to treat gout and rheumatism. Of course this was with little objective evidence of any benefit. Early attempts to treat diseases such as kidney stones with higher doses of lithium often led to lithium toxicity – potentially irreversible damage to the kidneys and brain. The landmark event in the medical history of lithium was a 1949 paper by Australian psychiatrist John Cade in the Medical Journal of Australia. This demonstrated its benefit in bipolar disorder, then known as manic-depressive illness. The psychiatric community took some time to absorb this finding – the US regulator the Food and Drug Administration only approved lithium for use in 1970. After that, lithium as a drug transformed psychiatric practice, especially in the treatment and prevention of bipolar disorder. This led to extensive research into the mechanisms of lithium in the brain.
Read more: What is bipolar disorder?

How lithium affects the brain

We don’t know exactly how lithium works, but we know it helps the way brain cell connections remodel themselves, usually referred to as synaptic plasticity. It also protects brain neurons by controlling cellular pathways, such as those involved in oxidative stress (where the brain struggles to control toxins) and inflammation. Animal studies have shown that long-term treatment with lithium leads to improvement in memory and learning. These observations led to studies of lithium’s protective effects on brain neurons in bipolar patients who had been taking it for a long time. One of these was a review of more than 20 studies, seven of which examined dementia rates in patients with mood disorders (such as bipolar) being treated with standard therapeutic doses of lithium. Five of these studies showed lithium treatment was related to low dementia rates. The review looked at four randomised controlled trials (comparing one group of patients on lithium with a group taking a placebo). These examined lithium’s effects on cognitive impairment (such as memory loss) or dementia over six to 15 months. One study did not show a statistically significant benefit on cognition but showed a biologically positive effect on the levels of a protein that promotes nerve cell growth. The other three showed statistically significant, albeit modest, beneficial effects of lithium on cognitive decline.
Read more: How we can protect our brains from memory loss and dementia

Lithium in water

A number of epidemiological studies – which track patterns and causes of diseases in populations – have linked lithium concentrations in drinking water with rates of psychiatric disease. In the above-mentioned review, nine out of 11 studies found an association between trace-dose lithium (low doses in drinking water but not detectable in blood of the people consuming it) and low rates of suicide and, less commonly, homicide, mortality and crime. More recently, researchers in Denmark conducted a nation-wide study linking dementia rates based on hospital records for people aged 50-90 with their likely exposure to lithium. This was based on the lithium levels in the waterworks predominantly supplying the region where they lived. Those with higher dementia rates came from regions with lower mean levels of lithium in the water than those without. This was 11.5 micrograms (µg) per litre compared to 12.2µg per litre. The Danish population is geographically stable and the health record linkage is excellent for such studies. The reliability and validity of dementia diagnosis in Danish health registers is also high. But the study had a number of limitations. The lithium intake was based on sampling of waterworks that provide water to only 42% of the population. The sampling was done for only four years (2009-2013) and extrapolated to a lifetime. Many potential, additional variables were not considered. For instance, a major source of lithium is diet, and some bottled water contains lithium. The study did not take this into account. An intriguing aspect of the results, for which no explanation was given, was that the relationship wasn’t linear. That is, lower doses (5.1-10µg per litre) increased the risk of dementia by about 20%, whereas exposure to levels over 15µg/L reduced the risk by about the same amount.

We’re not there yet

Observational studies (which make educated assumptions by observing a sample of the population) have considerable merit in the epidemiology of dementia, but have sometimes led to blind alleys. Aluminium is a useful example, with its preventive role in dementia still unclear after several decades of observations. A concern is lithium may take the same path.
Read more – In defence of observational science: randomised experiments aren’t the only way to the truth
Lithium was once widely used as an elixir and even as a salt substitute, but was discredited because of lack of effectiveness, marked toxicity and early death. We must wait for more observational studies with the rigour such studies warrant before we start clinical tests of its effects in drinking water. The ConversationWe must also study the potential harmful effects of lithium on the thyroid and the kidney, as these organs bear the brunt of long-term harms of lithium. For now, there is insufficient evidence to add lithium to the drinking water. Perminder Sachdev, Scientia Professor of Neuropsychiatry, Centre for Healthy Brain Ageing (CHeBA), School of Psychiatry, UNSW This article was originally published on The Conversation. Read the original article.
Expert/s: Dr Perminder Sachdev

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