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Dementia, A Very Short Introduction. By Kathleen Taylor ⁃ US 5.8 million people with Alzheimer’s with 400,000 developing it in 2019 ⁃ Worldwide 50 million people with Alzheimer’s ⁃ Top causes of death heart disease 9 million, stroke 6 million, COPD 3 million, pneumonia 3 million Alzheimer’s 2 million ⁃ Dementia diagnosis: A person must be impaired in at least two different cognitive domains and so impaired that it is seriously interfering with her ability to manage her life. Cognitive domains include memory, language, attention, problem-solving, and orientation ( the questions of when, where and who one is ) ⁃ Most common forms of dementia are vascular dementia, frontotemporal dementia, dementia with Lewy bodies, and most frequent of all Alzheimer’s. ⁃ Dementia comes from the Latin demens , from or out of the mind ⁃ Routines, good health care, exercise, and nutrition, and being lovingly cared for in a safe and familiar environment, can keep symptoms stable, or at least slow the rate of decline. ⁃ Page 10 various forms of dementia and symptoms ⁃ By the time a person is worried enough to have approached the medical profession and obtained a diagnosis of dementia, neurodegeneration will already be well underway ⁃ In 1965 8% of the world population was over 60, in 2015 it was 12%. The same figures for Japan are 10% and 33% ⁃ Chapter 2 what causes dementia? ⁃ Amyloid plaques and tau tangles are defining characteristics of Alzheimer’s disease ⁃ Affected very early in the disease is the nucleus basalis of Meynert ⁃ The strongest connection to date between Alzheimer’s in neurotransmitters is acetylcholine ACh ⁃ In Alzheimer’s sprain levels of ACh drop early on ⁃ Some research suggests that acetylcholinesterase, the protein which breaks down ACH after use, can generate a toxic protein fragment capable of damaging brain cells. The most successful treatment of dementia has been done by blocking acetylcholinesterase. Four standard drug shown on page 27 ⁃ Amyloid proteins especially when mis folded like to stick together ⁃ Key claim from Hardy Higgins paper from 1992 in Science is that too much amyloid protein builds up in the brain and that this then causes whatever else goes wrong ⁃ Many scientist still favor in part because the core ideas so attractively simple and optimistic: if a single protein is the root cause, successful drug treatments would only need to interfere with that protein ⁃ Glossary of various terms. CT computer tomography are fancy x-rays they combine multiple images taken at different levels around the location to make a 3-D image of the brain. MRI magnetic resonance imaging scans that can be used for the type of matter in an area, structural MRI they can see changes such as tissue loss, tumors, problems with white matter or damage to blood vessels and can also be used to detect changes in blood flow- functional MRI. MEG magnetoencephalography measures the brains magnetic fields. EEG electroencephalography measures its electrical signals. PET, positron emission tomography proving extremely useful in studying neurodegenerative disease ⁃ Medical wish list is a bio marker ⁃ Page 43 genetic test discussion. Good result APOE3. APOE4 is the bad result which may boost dementia risk by between 10 and 30 times ⁃ Chapter 3, Beyond amyloid ⁃ A lot of years, a lot of research into amyloid, not much progress in treating dementia, so some wonder: are we looking at the wrong cause ⁃ US national Institute of health is now spending more than half of it’s all timers budget of around $2 billion on topics other than tau and amyloid beta ⁃ Part of the problem is researchers tend to research what they have tools available for, what might be known as the hammer problem ⁃ A separate problem may be that we’re treating the problem too late because neurodegeneration needs to be addressed early ⁃ Essentially people no longer feel that there is one protwin to rule them all, amyloid is not the only problem. For instance lifestyle seems to influence when and perhaps whether people get dementia. It is may be possible to delay onset and progression by living healthily ⁃ People can have Alzheimer’s without having dementia ⁃ One new area of research is inflammation and immunity in the brain ⁃ One promising area of research is immuno therapy which aims to use the body to own weapons against rogue cells or in the case of dementia abnormal proteins ⁃ Starting on page 66 there’s a discussion of the blood brain barrier which is the layer of cells which separate brain tissue from the network blood brain vessels: around 400 miles tubing crammed into the confines of a human skull. The total surface area of the blood brain barrier is thought to be around 20 m², about 10 times as big as the skin. Yet the cells are so thin it makes up less than 1% of the brains total volume. ⁃ On page 68 there’s a further discussion of microglia which affectively monitor signal and fix things in the brain. I’m doing a very poor job of summarizing this research because it is a very complex. One concern might be that the microglia over prune synapses leading to reduce function. ⁃ Essentially chapter 3 says there’s a lot of other areas of research outside amyloid now but it may be better to focus on lifestyle choices in aid of prevention, while the research continues to search for a cure ⁃ Chapter 4 risk factors ⁃ Older population today’s are less affected by dementia than in previous decades ⁃ There are varying trends rising dementia prevalence in Japan low prevalence in India, stable incidence in Nigeria, large regional differences in China ⁃ Lifetime risk: the risk of developing dementia, stroke, or Parkinson’s disease was 48% in women and 36% in men when they were aged 45 ⁃ Concerns and all the studies to follow relate to selection bias, experimenter bias ⁃ While there are potential things we can do to improve our chances, many things are outside of our control including selecting our parents, our genes, our childhood environments etc. ⁃ Risk factors are generally three categories: genetic, environmental, physiological ⁃ Early retirement, lest intellectually demanding careers, and lack of hobbies have all been linked to a greater chance of developing dementia. Potential reverse causation. ⁃ Getting older is the biggest risk factor for dementia. Nearly 10,000,000 people acquire the condition every year. By 2050 more than 150 million are likely to have it. ⁃ Figures from the UK: among people age 60 to 64 the prevalence of dementia is just under 1%, by age 65 to 69 it is 1.7%, by age 75 to 79 more than 6%, by 85 to 89 18%, people age 95 or older more than 40% ⁃ Note it is biological, not chronological, age which is the risk factor for dementia. For example caloric restriction may improve biological age ⁃ Reasons for improving results in western countries: toxin such as lead have been reduced, nutrition has been improved, better housing and infrastructure have helped lower social stresses. Smoking rates have dropped from nearly 1/2 to less than 1/6. Level of air pollution has fallen in western in other countries. Smoking and pollution are known risks for dementia. Both cost oxidizing stress and damage the heart lungs and blood vessels ⁃ The particulates in car exhaust which include carbon, sodium, and ammonium particles is thought to be especially damaging ⁃ The percentage of people drinking alcohol has also fallen by about 5%, worldwide, since the year 2000 ⁃ Poor health, both mental and physical, raises the chance of cognitive decline. Vascular, lungs, and kidney disease, poverty and chronic stress, alcohol dependence and abuse, smoking and pollution, poor diet, and more. These factors bias the human brain toward mental illness, physical diseases and cognitive impairment. Thus preventing and treating ill health should lead to fewer people with dementia. ⁃ Better treatments for stroke, heart disease, and traumatic brain injury have reduce their impact on long-term cognitive function. Screening for and treating high blood pressure, high cholesterol, and diabetes has also led to reductions in cardiovascular and cerebrovascular disease including stroke. These are major risk factors for dementia ⁃ In a stroke, large blood vessels like the cerebral arteries can tear, hemorrhagic stroke, or block up, ischemic stroke. Stroke is a major cause of death and disability and having one can double the risk of dementia. ⁃ What’s good for the heart is therefore good for the brain, as a healthy heart promotes a strong cerebral blood flow. Exercise, which helps the heart to work better, is said to be one of the best ways of protecting aging brains. ⁃ Another common risk factor for dementia is diabetes. Either high or low blood sugar and especially rapid swings between the two stress brain cells and can weaken the blood brain barrier. Untreated they may raise the risk of cognitive decline in dementia by around 50%. Untreated diabetes is a severe health hazard but the risks are much reduced if the illness is well managed ⁃ Regarding diet the healthiest of those, like the Mediterranean diet, which include more fruit and veg, nuts, whole grains, and fish, and less meat, sugar, and heavily processed food ⁃ Random fact bacterial meningitis kills around a 10th of the people it infects ⁃ Unsurprisingly, many factors start to raise the risk for dementia involve inflammation. The list includes major surgery especially in elderly patients and when general anesthetics are involved. ⁃ With the brain as with muscle strength use it or lose it seems to be the rule ⁃ Sensory feelings, such as poor sense of smell and hearing loss are frequently found in people at high risk of dementia. Physical inactivity also reduces brain inputs. This is one more reason why exercising by way of a walk in the park may be more beneficial than walking on the treadmill in the gym because the environment is richer ⁃ One of the more consistent, and consistently puzzling, findings in dementia research is that education and lifelong learning are protective. Highly educated people still get dementia, but they tend to get it later, and when it is finally diagnosed a decline may be faster. It is as if the habit of thinking tops up cognitive reserve, allowing people to withstand the effects of neurodegeneration for longer ⁃ A job which is challenging but not overwhelming:; leisure activities such as gardening, singing or playing an instrument; volunteering; learning a language or reading a newspaper – all may help if done long-term, especially if done in company ⁃ Good long-term relationships with family, partners, and friends also seem to buffer the risk of cognitive decline ⁃ Depression is a risk factor as researchers found many people with depression show signs of chronically elevated cytokines ⁃ Again and again we see how risk factors interweave. Socializing, keeping mentally and physically active, good self-care, and having strong close relationships are protective against depression ⁃ Big picture there are two clear strategies. First detect and treat people with relevant health issues like depression, high blood pressure, or diabetes as early as possible. Second try to stop people falling into ill health in the first place ⁃ Chapter 5: diagnosis ⁃ The DSM-5 identifies and discusses 13 types of major neurocognitive disorder, distinguishing them by their pattern deficits across a group of six mental functions known as neurocognitive domains ⁃ Complex attention: more than just noticing things, this includes the ability to stay focused and multitask ⁃ Executive function: often thought of as planning and decision making, this also includes mental flexibility and self control ⁃ Learning and memory: symptoms include repetitive conversations, rapidly forgetting new information, and the inability to remember one’s intentions for long enough to carry them out ⁃ Language: both understanding and using language can be affected ⁃ Perceptual motor: deficits in this domain often affect the ability to use familiar objects, navigate familiar routes, and make sense of a space when it looks different, for example towards sundown ⁃ Social cognition this domain includes theory of mind, empathy, morality, and emotion recognition and control. Can lead to disorders of mood and motivation, or to social deficits ranging from awkwardness to frankly antisocial behavior ⁃ To be a diagnosed with a major NCD, the equivalent of dementia, people must be so seriously impaired in one or more domains that their performance on cognitive testing is at least two standard deviation‘s below the average; that is, in the lowest 2.5% of the population ⁃ The problem must be severe enough to “interfere with independence in every day activities“ DSM-5, p602. And the dysfunction must not be due either to delirium, or to some other disorder such as major depression ⁃ To end on a positive note, notes on rules to live by: eat well, sleep well, exercise, keep busy, socialize, stay in touch with nature, and try to reduce exposure to stress, trauma, and dangerous substances in food, drink, and air