Preventive Neurology

Dear Reader We have moved the preventive neurology unit blog to a new platform called substack . Google is discontinuing its Feedburner and has not added many new features to blogger for some time, which is why we have decided to move the site.  https://preventiveneurology.substack.com/  Thanks Gavin Giovannoni

Are you addicted to coffee? Do you need a reason to justify your addiction? Read on!  Photo by Jakob Owens on Unsplash I justify my coffee addiction (6-8 espresso shots per day) by claiming that I am preventing myself from developing Parkinson’s disease in the future. This is #PreventiveNeurology in practice. Sadly coffee consumption doesn’t protect you from getting Alzheimer’s disease or all-cause dementia. However, I was thrilled to note that it seems to protect you from developing chronic liver disease and dying from liver disease. The molecular mechanisms underlying this are plausible. Caffeine is a non-selective blocker of the A2aA receptor, activation of which stimulates collagen production by hepatic stellate cells, which are the primary mediators of fibrosis. But as decaffeinated coffee is also protective it may be the other ingredients in coffee such as chlorogenic acid, kahweol and cafestol, which protect against liver fibrosis. Whatever the mechanism underlying coffee’...

Photo by S L on Unsplash Human biology is systems biology; perturb one aspect of human biology and it will have downstream effects, which can be noted throughout the body. As you know sleep is critical for brain health; if you have poor sleep hygiene you are putting yourself at greater risk of developing dementia when you get older. Why?  In this study of cognitively normal older Chinese adults, spinal fluid soluble TREM2 (sTREM2) was associated with self-reported poor sleep hygiene using the Pittsburgh Sleep Quality Index. sTREM2 is shed from activated microglia or macrophages and is thought to be a marker of microglial activation. The implications are that this association may be causal, i.e. poor sleep is pro-inflammatory, both in the periphery and central nervous system and the latter contributes to driving neurodegeneration. Could improved sleep hygiene be anti-inflammatory? Or is the microglial activation simply a response to poorer clearance of CNS debris, which occurs when...

Congratulations to  Al Sandrock , from Biogen, for never giving up on science and for being a  risk-taker extraordinaire .   Photo by Markus Winkler on Unsplash The FDA’s controversial approval of aducanumab for the treatment of Alzheimer’s disease on Monday has caused a shitstorm. The main reason is that in November the FDA’s independent advisory committee voted against recommending approval; they said the data failed to demonstrate persuasively that aducanumab slowed cognitive decline. In a NY Times article Dr Lon Schneider, director of the California Alzheimer’s Disease Center at the University of Southern California and one of the aducanumab site investigators said “This should not be approved, because substantial evidence of effectiveness hasn’t been shown and there’s very little potential that this will address the needs of patients.” What the FDA has done is use the so-called Accelerated Approval Pathway , which allows them to approve a drug for a serious ...

In summary, any form and any amount of alcohol consumption is unhealthy for the brain. Photo by Hush Naidoo on Unsplash He was only 64 when his daughter noticed that his forgetfulness had started to impact on his ability to function independently. Her father had forgotten to pay the gas and electricity bill and social services had contacted her as next of kin to find out why. It was clear that years of excessive alcohol was having an impact on his memory. The scenario above is one that is played out across society thousands of times if not hundreds of thousands of times. This is why the study below from the UK biobank is so worrying; when it comes to brain volume, a crude measure of the brain's neuronal and cognitive reserve, there is no safe alcohol consumption limit. Importantly, comorbidities such as high blood pressure and obesity interacted with alcohol consumption to reduce brain health. Not surprisingly binging on alcohol made things worse and this was over and above the vo...

Since stating my intention to join the  #BackTo21  campaign to get my BMI back to what it was when I was 21 years of age, I have had several emails and direct messages on social media questioning the wisdom of my intention.  Photo by NeONBRAND on Unsplash It is clear that despite BMI being a relatively poor metric of health there is overwhelming evidence that at a population level it predicts poor health outcomes. Importantly there is new data that indicates the target BMI for the prevention of type 2 diabetes and the metabolic syndrome depends on your ethnicity. For people of South Asian origin, there is a call to reset the BMI cutoff to 23.9, which for most people is within the normal range. At the same time, there is a call to classify obesity as an important social determinant of health. Arnaud Chiolero argues below for using BMI as a socioeconomic indicator. Do you agree? Isn’t it quite amazing that in a previous era corpulence was a sign of affluence, whereas in th...

Do you have mild hypertension? If you don't know get measuring.  Photo by Mufid Majnun on Unsplash Defining mild-to-moderate hypertension as a disease when it is largely asymptomatic and is really only a risk factor for diseases as a result of end-organ damage caused by hypertension is a triumph of preventive medicine.  In medicine we define a disease as a clinicopathological correlate, i.e. there are clinical findings associated with a specific pathology that is unique and separates the specific disease from other disorders, which may mimic it. When mild-to-moderate hypertension develops there are usually no specific symptoms and when diagnosed early there is little of no end-organ signs of damage. In other words, hypertension is part of the prodrome for diseases that manifest many years later. However, the medical profession treats hypertension as a disease in itself. Why? I think it is because the epidemiological evidence showing hypertension is associated with poor o...

I had a terrible night last night. One of my patients who has been under my care for over a decade was admitted to a district hospital with life-threatening sepsis and has to have emergency surgery. It is touch and go if this patient will survive. I kept tossing and turning and rehearsing events that led up to their admission and kept wondering if anything could have been done to prevent the sepsis from progressing to a stage when it required surgery. The result is I had a very poor night’s sleep and feel terrible this morning; irritable, tired, groggy and foggy as if I have a hangover. What damage has this caused? Photo by engin akyurt on Unsplash It is clear that sleep is a physiological must; acute sleep deprivation is a major life-threatening stressor and kills. This is why it is used as a method of torture. Chronic sleep deprivation is also a stressor and also kills, only more slowly. The paper by Eide and colleagues below shows how one night’s sleep deprivation impairs the brain...

Photo by Mark Paton on Unsplash We know that exercise is important for brain health has the potential to delay, or prevent, all cause-dementia in the general population. Hearing loss has recently also been identified as an important and potentially modifiable risk factor for dementia. Are hearing loss and physical activity related to each other? This study below shows in elderly people that hearing loss is associated with a worse physical activity profile. Is this association or causation? Is hearing loss part of the dementia prodrome and hence is associated with other prodromal features of dementia such as poor motivation, social isolation, lower mood, etc., which lead to less activity? Or is less activity in old age related to a lifetime of less activity and hence a higher risk of dementia and is simply associated with loss of hearing? Does hearing loss impact one's ability to exercise? Does less environmental auditory feedback make it less likely that you go out and exercise? I...

Photo by i yunmai on Unsplash It looks like we have to rethink what a healthy BMI is!  This study below shows that above a BMI of 23 kg/m2 there is a linear increase in risk of severe COVID-19 leading to admission to hospital and death, and a linear increase in admission to an ICU across the whole BMI range, which is not attributable to excess risks of related diseases. The important thing to point out is that the relative risk due to increasing BMI is particularly notable in people younger than 40 years and of black ethnicity . This means that if your BMI (weight/height (m)-squared) is above 23 you should probably do something about it. In parallel to this, I read an article a few weeks ago that said you need to get back to what you weighed when you were aged 21. If I did this I would need to lose 13kg (2 stones) and my BMI would be 22. So I am going to get on the case and will be joining the #BackTo21 challenge and in so doing maximising my chances of doing okay if I ever get...

Photo by sk on Unsplash The stress response is hardwired into the primate genome. Clearly, the acute stress response is critical for the survival of the fittest. In comparison, a chronic stress response comes at a price. Some people like to think of stress as some subjective phenomenon that you measure on a Lickert scale from 0 (no stress) to 7 (severe or intolerable stress). However, the stress response is biological with glucocorticoid production being the biomarker of choice for measuring stress; i.e. the area-under-the-cortisol-curve over time is how we measure chronic stress. In the field study below of female baboons, chronic glucocorticoid exposure predicted life expectancy. A hypothetical female who maintained glucocorticoid levels in the top decile for her age across adulthood would be expected to lose 5.4 years of life relative to a female who maintained glucocorticoid in the bottom decile for her age. With the life expectancy of the average baboon being 35-45 years of age ...

Photo by engin akyurt on Unsplash "I was told to try the Snack-All-Day diet plan, but it has been a disaster. I was eating 7 or 8 small snacks per day but instead of losing weight, I have gained weight. Why?"   It is quite clear that obesity is a major public health problem and contributes to a substantial burden of disease at a population level. Why do we get obese? This is complex, but a lot of it can be explained by the food environment we live in and the change in our eating habits over the last 3 or 4 generations. The study below shows that the extent of the postprandial dip in glucose, which occurs 2-3 hours after a meal predicts hunger, a shorter time until the next meal and greater additional energy intake at 3-4 hours.  The reason why we get low blood glucose 2-3 hours after a meal is that there is too much insulin released relative to the amount of sugar or glucose in the baseline meal. In other words, our bodies produce too much insulin in anticipation of the...

The role sleep plays in normal human brain physiology is becoming more clear as the link between abnormal sleep and dementia gets stronger. Here is yet another epidemiological study linking reduced sleep in middle age to a higher risk of dementia. Quin Stevenson on Unsplash Is the association between reduced sleep and dementia causal or is it due to reverse causation? Sleep is required to consolidate memories and to allow the brain to cleanse itself, i.e. flush out all the intracellular debris that could aggregate to cause Alzheimer’s disease. Therefore, sleep deprivation by impairing memory consolidation and not allowing you to clear the brain's intracellular debris properly could lower your threshold for developing dementia in the future. Reverse causation states that people who are destined to develop dementia have pathology that starts decades before dementia manifests, for example, amyloid deposition and neurofibrillary tangles. The pathology affects parts of the brain that c...

Kinga Cichewicz on Unsplash The study below found that people who experience unconscious wakefulness most often and for longer periods of time had nearly double the risk of dying from cardiovascular disease during an average of between 6 and 11 years’ follow-up when compared to the risk in the general population. The association was particularly strong in women and less clear in men. Unconscious wakefulness also referred to as cortical arousal, is a normal part of sleep. It occurs spontaneously and is part of the body’s ability to respond to potentially dangerous situations, such as noise or breathing becoming obstructed. A full bladder, pain, limb movements, trauma, temperature, light, noise, sleep disorders, acid reflux, depression and anxiety can also be triggers. Clearly, unconscious wakefulness is a major modifiable risk factor for cardiovascular disease and is also a risk factor for all-cause dementia. Isn’t it about time we took this seriously and started a public health campai...

It is obvious, yet it is not. We need to ban sugar! Rod Long on Unsplash When I was on a road tour of the Southern USA in 2012 with my family, we went to the ‘Golden Corral’ all-you-can-eat buffet one morning for breakfast. The Golden Corral, like so many other fast-food and convenience-food outlets, was a church or cathedral to sugar. A place where you go to worship on the altar of sugar one of the most addictive substances known to man. I was horrified at how many obese Americans were eating at the Golden Corral, the types of food they were eating and the quantity they were eating.  Buffet Bar at the Golden Corral The rapid change in our diets driven by the cheap supply of processed carbohydrates has resulted in metabolic chaos, which is causing the obesity crisis and the cascade of health problems stemming from the resulting hyperinsulinaemia. The following international study confirms that the intake of foods with a high glycemic index is associated with increased cardiovascul...