Are these early signs of a neurodegenerative process? Was it all a misunderstanding? Or did the media misinterpret his words? We would like to give him the benefit of the doubt, given he is the one developing and implementing policies within a ministry that has a key role to play in achieving the well publicised “vision 2030”. It seems logical that without good health care and a healthy population, there inevitably will not be much economic growth.

In 2015, I would believe that most of us would have heard about these two words: Alzheimer’s and dementia. Yet the difference between them might not be clear for all.

Dementia is defined as an acquired deterioration in cognitive abilities that impairs the successful performance of activities of daily living. Memory is the most common cognitive ability lost with dementia; 10% of persons >70 years and 20-40% of individuals >85 years have clinically identifiable memory loss. In addition to memory, other mental faculties are also affected in dementia. These include language, visuospatial and visuoconstructional abilities, attentional processes, information processing skills, working memory and higher-level thinking skills, also known as executive functions. The latter category encompasses skills carried out by the frontal lobes, for instance problem solving, planning and organisation, self-monitoring of goal directed behaviour, multitasking, decision-making, judgement and so on. I tend to describe that part of the brain as the CEO of a big corporation. Each dementia has a specific neuropsychological profile, with different levels of impairments identifiable in all or some cognitive domains.

Alzheimer’s disease is one type of dementia, typically the most common. In addition frontotemporal dementia, lewy body dementia, vascular dementia, HIV related dementia, Parkinson’s disease dementia and alcohol related dementia are a few of an exhaustive list of dementias. Even hypothyroidism can cause dementia in some cases. Alzheimer’s disease in itself is clinically characterised by rapid forgetting of information. The forgetfulness seen in the early stages of Alzheimer’s is often associated to “old age” and often goes unrecognised. It is only when the memory issue starts impacting day-to-day functioning that significant others start raising the alarm. People may have the Alzheimer pathology for years before they develop the dementia associated to it. Technically, health professionals can only diagnose Alzheimer’s disease as a dementia when it impacts a minimum of two or more activities of daily living. If it does not, then it is not a dementia. For comparison sake, it can be equated to HIV+ patients who have yet to develop AIDS. The typical neuropsychological profile seen in Alzheimer’s disease consists of impairments that initially target new learning and memory skills before spreading to language, where obvious word finding difficulties develop and finally compromises visuospatial and visuoconstructional skills. This is why the Clock Test is so informative in Alzheimer’s disease. Usually in Alzheimer’s dementia there are also several deficits in executive functioning skills, especially at the later stages.

So now that we understand the difference between the terms dementia, Alzheimer’s disease and Alzheimer’s dementia, we are better prepared to accept the misunderstanding that might have occurred in The Honourable’s mind. If it is possible for alcohol to affect the brain to the extent of causing a dementing process, then it would not be surprising that an opioid such as methadone, if used excessively could result in similar effects. However, to claim that methadone “causes” Alzheimer’s disease or Alzheimer’s dementia is a fallacy. To date there are still no known causes for Alzheimer’s. There are genes that have been found such as the apolopoprotein e4 (APOE e4), which indicate a stronger risk, but still no cause and effect relationship has been established. Several other studies have mentioned risk factors such as past head trauma, lifestyle (lack of exercise, smoking, diet lacking in fruits and vegetables), heart health as well as lifelong learning and social engagement (cognitive reserve is said to reduce the risk of AD) to name a few. Yet there is not a paper to date that has even made the remote claim that methadone causes Alzheimer’s disease. I will also point out that most of these studies are correlational by design. Studies of these type despite finding an association between two variables, do not account for cause and effect.

Substance abuse dementias, which include alcohol dementia and dementia related to the use of recreational drugs have been well documented. I can only imagine that misuse of methadone would fall in this category. I would like to stress the term misuse. It is also well documented that these dementias are reversible and that the prevalence is higher in the younger adult population. I would also note that the cognitive impairment seen in this type of dementia not only includes memory loss, but also, and most importantly, ability to concentrate (basic focused attention) working memory and information processing skills. The memory loss here is secondary to these deficits although it might possibly be the most noticeable aspect. One can imagine that if they do not pay attention and have trouble processing large amount of information efficiently, the encoding process would be flawed, therefore no memory trace would be present. However, people tend to think that their memory is impaired, when in reality it is a question of poor attention and information processing.

I do not wish to comment too much on the advantages of using methadone over naltrexone or vice versa, given that it is not my specialty and that the scientific literature has diverging opinions in order for us to draw definite conclusions. I would however, like to make a comment on the fact that naltrexone is significantly more efficient in the use of treating alcohol dependence, than that of opioid use disorder (the politically correct term to use). A recent Cochrane review (the gold standard of systematic review for medical research) by Mattick et al., (2009) has clearly demonstrated the effectiveness in the use of methadone in suppressing heroin use and retaining people in treatment. On the other hand a review by Minozzi et al., (2011) has shown that naltrexone was only as good as the placebo effect in treating opioid use disorder. More recent studies, such as the one conducted by Krupitsky and colleagues (2011), in contrast, demonstrated the efficacy of injectable extended-release naltrexone for opioid dependence, once again pointing out the divergence in opinion within experts in this field. Other research has focused on mortality rate following treatment with naltrexone or methadone. A study by Tait, Ngo and Hulse (2008) showed that mortality rates for naltrexone implant were similar to those for methadone, but increased mortality during methadone induction was avoided. It is interesting to compare this to a study published in Drug and Alcohol Review in January 2015. Louisa Degenhardt and colleagues from the University of New South Wales, University of Melbourne, King’s College London, Brown University and University of Washington, demonstrated that oral naltrexone patients had higher mortality than those treated with methadone. Total oral naltrexone mortality was significantly greater than for methadone in Western Australia and New South Wales. They estimate 25-29 deaths among 1097 oral naltrexone patients over two years and claim that this would “probably not have occurred if these patients had received methadone”. The major reason was higher mortality rate post-treatment cessation.

The one major drawbacks of naltrexone is the fact that it has a high level of treatment non-compliance and has been found most useful in patients with an extremely unusual level of social and environmental stability, very rarely seen within this patient group. That is why treatment with naltrexone has been provided through way of implants rather than orally, to improve compliance, and in that sense has been found to be quite successful. I finally note that methadone is listed in the WHO Model list of Essential Medicines whilst naltrexone is not. This list has been developed to provide a guideline as to the most important medication needed in a basic health system. I therefore believe that in any democratic state, the patient who are the ones using the drugs need to be provided with the education as to the advantages and disadvantages of both methadone and naltrexone. As a health practitioner I believe that treatment choice is one of the most important and intrinsic value of our professions. We can only provide the patient with their options and assist them in making an informed decision, instead of making the decision for them. Therefore, the use of both drugs, depending on the context, would be a more suitable option given our patient population, rather than having to decide between one or the other, especially when research is so divided.

I’d like to end by commenting on the latest breakthrough in Alzheimer’s treatment; the use of Solanezumab. Despite a failed trial in 2012, it is likely that in the next few years, Solanezumab could be prescribed to stop the cognitive decline associated with Alzhiemer’s disease. However, the current outcome measures being used in clinical trials to characterise the halt in cognitive decline are not reflective of day-to-day functioning. For it to be successful, research will have to focus on outcome measures such as functional improvement in day-to-day memory, rather than for example, an increase of 2 points on cognitive screening measures such as the Mini Mental State Examination. To date the most successful treatment approach to Alzheimer’s disease is the setting up of multidisciplinary clinics and the availability of community dementia services.  

Dr Vincent Oxenham is Consultant Clinical Neuropsychologist at the Macquarie University Hospital Clinic in New South Wales, Australia.