Topic Review: Alzheimer’s Disease

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    Written by Consensus
    September 19, 2021 16 min read
    TOPIC INTRO

    Why Alzheimer’s?

    Imagine cleaning your kitchen and you place a frying pan in the refrigerator. This happened to Fiona, the lead character in the 2006 film “Away From Her”. In isolation, it would be an absent-minded mistake. In the film, it’s an ominous revelation: Fiona has early-onset Alzheimer’s. That means she will lose her memories and sense of self. Fiona is not alone, she depicts what millions of people around the world suffer every day with Alzheimer’s Disease.

    Alzheimer’s is a neurodegenerative disease that results in gradual cognitive decline. What starts out as simple memory loss leads to confusion, paranoia, and the inability to carry on a conversation or even form words.

    In the U.S. alone, it’s estimated that over 5 million people suffer from Alzheimer’s. Despite its pervasiveness, scientists don’t seem close to a cure. While we’ve gained a better understanding of how Alzheimer’s affects the brain — the buildup of something called amyloid plaques — effective treatment for slowing or preventing Alzheimer’s are elusive.

    This has left many wondering about the causes of Alzheimer’s — whether they’re genetic or environmental — and what people can do, if anything, to decrease their chances of developing the disease. We at Metafact are here to answer those questions.

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    NUMBERS

    Meta-Index

    50,000,000 Number of people world-wide with dementia

    70% Proportion of those with dementia having Alzheimer’s Disease

    $1,000,000,000,000 Economic cost of dementia in 2018

    3 Seconds for someone in the world to be diagnosed with dementia

    $1,789,000,000 US National Institutes of Health research spending in 2018 on Alzheimer’s Disease

    0.8% Proportion of US research budget spent on Alzheimer’s Disease

    147,214 Number of research papers published relating to Alzheimer’s Disease

    134,602 US deaths in 2015 associated with Alzheimer’s Disease

    100 Number of anti-Alzheimer’s drugs that have failed in recent decades

    99.6% Failure rate of Alzheimer’s clinical trials during 2002-2012

     


    Alois Alzheimer
    ORIGIN STORY

    Dr Alois Alzheimer

    In 1906, Dr. Alois Alzheimer discovered never-before-seen changes in the brain tissue of Auguste Deter, a 55-year old woman who had recently died. For years Auguste had been suffering from an unknown mental condition involving significant memory declines, speaking and language problems, and bizarre, erratic behavior. An autopsy revealed the presence of abnormal protein clusters now referred to as amyloid plaques accumulated in her brain. These plaques are one of the two defining characteristics (the other being intracellular tangles made of tau protein within neurons) of what we now call Alzheimer’s disease (AD).

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    META-TRENDS

    Projected number of people with Alzheimer’s disease in the US

    Projected number of people with Alzheimer's disease in the US

                  ATLAS | Data: Neurology/Hebert et al

     


    META-TRENDS

    Change in selected causes of death in the US

    Change in selected causes of death in the US

                     ATLAS | Data: Neurology/Hebert et al

     


    THE CONSENSUS

    Is Alzheimer’s genetic?

    Read the full answers to this question hereWhen it comes to medical conditions, few could envision a malady more horrifying than one that slowly drains you of your cognitive abilities and memories. So naturally, many wonder whether the development of Alzheimer’s is a genetic, forgone conclusion, or if there are steps that can be taken to decrease one’s chances of developing the disease.

    About 85% of our experts agreed that genetics play a role in the development of Alzheimer’s, but it’s not always entirely clear to what extent genetics are involved. Erin Abner, an associate professor in the department of epidemiology at the University of Kentucky, explained that there are two forms of AD: early onset and late onset. Early onset occurs in a small percentage of cases and “is entirely genetic.”

    As for the other 95% of cases? Well, there are certain genes associated with them. “Sporadic AD … is strongly linked to the APOE gene, specifically the e4 allele,” wrote Abner. “People with either one or two copies of the APOE4 allele are between 4 and 12 times more likely to develop dementia due to AD compared to people without e4 allele. There are also many other genes (around 20) that have been linked to sporadic AD, but their individual effects are not nearly as strong as APOE. Overall, we estimate that about 70% of a person’s risk for sporadic AD is explained by genetics.”

    So if the other 30% is environmental, does that mean we can take meaningful steps to decrease our risk of developing AD? Margaret Gatz, a professor of psychology, gerontology and preventive medicine cited several studies suggesting “risk for developing Alzheimer’s disease is greater in those who do not engage in physical activity; in those with uncontrolled high blood pressure, diabetes, or obesity in midlife; and possibly among those exposed to greater air pollution.”

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    Are dementia rates in the US declining?

    THE CONSENSUS

    Are dementia rates in the US declining?

    Read the full answers to this question here. Given the years of research and the billions of dollars spent in search of a cure for Alzheimer’s, one would hope that we’ve made progress in both preventing and treating the disease. Many Metafact users were curious about whether dementia rates in the U.S. are actually declining.

    All of our experts agreed that rates are declining, with some caveats. First, it’s important to acknowledge that, while rates are going down, the overall number of dementia cases is increasing. That’s because the population contains more elderly adults than ever before.

    When we talk about “rates,” we’re discussing the percentage of cases compared to the total population. “From several studies in the United States and around the world, there is some evidence to suggest that the age-adjusted prevalence of dementia in older adults is now less than for prior generations,” wrote Jennifer Anne Deal, an epidemiologist at Johns Hopkins University. “There is also evidence from several studies that the incidence (that is, the new cases of dementia) is also less now than for prior generations.”

    That doesn’t mean we necessarily understand the reason for this rate decline. As John Goss, an associate professor at the Health Research Institute, University of Canberra, put it: “We are not entirely sure why, but it is encouraging news.”

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    THE CONSENSUS

    Is there a correlation between depression and later development of dementia?

    Read the full answers to this question here. For most dementia patients, the onset of symptoms is slow and gradual, which leads one to wonder if there are any cognitive symptoms that can signal oncoming dementia far in advance. One Metafact user asked whether there’s any link between depression and later development of  dementia.

    Most experts agreed there’s a correlation between dementia and depression, though it’s unclear whether this relationship is causal. Jen Yates, an assistant professor in mental health at the University of Nottingham, cited several studies noting such a correlation. “It might be that depression and dementia share common pathways within the brain, or alternatively it could be the acknowledgement that cognitive function is not at the same level that leads to feelings of sadness. Changes within the brain associated with dementia begin up to 15 years prior to symptoms being detected on neuropsychological tests, but people themselves may feel an awareness of such changes.” In other words, a dementia sufferer might be able to detect their cognitive decline far before it can be measured by medical experts.

    If there is a causal relationship between depression and dementia, does that mean antidepressants could decrease a person’s chances of developing the disease? Perhaps. “Some probably improve cognition,” wrote Donald R Royall, a psychiatrist at the University of Texas Health Science Center at San Antonio. “Others may adversely affect it. However, to prevent or delay dementia’s onset, they will have to improve [general intelligence]. I don’t think the current generation of antidepressants are ‘smart drugs.’ One sign of this is that the time course to functional recovery after ‘successful’ antidepressant treatment is similar to that of untreated major depression. Antidepressants are validated for their effect on mood, not cognitive impairment, and certainly not [general intelligence].”

    When in your life you experience depression may play a factor in the chances that you develop dementia. “Late life depression has a much stronger relationship with the subsequent development of dementia and that is likely due to the mood disorder being precipitated, at least in part, by evolving neurodegenerative (such as Alzheimer’s disease, Parkinson’s disease) and cerebrovascular disease that is part of the lengthy cascade into dementia,” wrote Brian Draper, a psychiatrist from UNSW Sydney. “So here, the depression is not causal of dementia, but a manifestation of the same underlying neuropathology occurring at an earlier time point.”

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    Can we help prevent Alzheimer's with diet?

    THE CONSENSUS

    Can we help prevent Alzheimer’s with diet?

    Read the full answers to this question here. Given that most Alzheimer’s cases aren’t entirely driven by genetics, it’s natural to wonder what can be done to decrease your chances of developing the disorder. More specifically, Metafact users wanted to know whether diet and exercise could help in preventing dementia.

    All of our experts agreed that a better diet decreases your chances of developing Alzheimer’s. Yoram Barak, an associate professor at the University of Otago, cited studies showing that the MIND diet — which consists largely of leafy vegetables, legumes, and berries — “lowered the risk of AD by as much as 53% in participants who adhered to the diet rigorously, and by about 35% in those who followed it moderately well.” Why is this diet so effective? Joseph Quinn, a professor of neurology from Oregon Health & Science University, pointed to the diet’s positive impact on vascular risk as a significant driver of its cognitive benefits.

    Rosanna Squitti, an expert from IRCCS Centro San Giovanni di Dio, pointed to several measures that could play a preventative role for dementia, including minimizing intake of saturated fats, an increase in the consumption of leafy vegetables, and 120 minutes of exercise each week. “Include aerobic exercise in the routine,” she wrote, “equivalent to 40 minutes of fast walking, three times a week.”

    Some experts noted the link between obesity, cardiovascular disease, and Alzheimer’s. “Obesity in middle age and early old age is a very strong risk factor for Alzheimer’s disease (AD),” wrote Auriel A Willette, an assistant professor of food science and human nutrition at Iowa State University. “Obesity often leads to decreased ‘good’ cholesterol, excess glucose in the blood that can cause pre-diabetes or type 2 diabetes, and other conditions that each raise AD risk.”

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    THE CONSENSUS

    Is there a link between bad sleep and dementia?

    Read the full answers to this question hereDiet wasn’t the only environmental factor Metafact users wondered about. What about sleep? Is there some sort of correlation between bad sleep and dementia, causal or otherwise?

    Yes, there is. “Sleep disturbances increase with advancing dementia severity, and may predict faster cognitive decline, mostly in the mild to moderate stages of Alzheimer’s dementia,” wrote Fabricio Ferreira de Oliveira, an affiliate professor of the department of neurology and neurosurgery at the Federal University of São Paulo. “Insomnia may also lead to more patient institutionalisation, increase risk of falls and mortality, and impact caregiver burden.”

    Most experts agreed that there’s not much concrete evidence as to whether lack of sleep causes dementia or is merely an early indicator of it. Andrew Lim, an assistant professor of neurology at the University of Toronto, cited animal studies showing that sleep disruption “can cause Alzheimer’s-related brain changes in animals.” Nadia Gosselin, an associate professor in the department of psychology at the University of Montreal, noted that “several studies show that poor sleep can alter the biomarkers of Alzheimer’s disease, but only about half of the epidemiological studies show an association between poor sleep and cognitive decline.”

    Why would poor sleep lead to dementia? It could be because one of the main benefits of sleep is cognitive repair. “Many of the protective mechanisms that the brain uses to maintain healthy function in aging are tied to sleep and to the night phase of the circadian rhythm, and sleep-wake cycle disruptions are one of the earliest signs of Alzheimer’s disease and dementia,” wrote Danielle Gulick, an assistant professor of physical therapy & rehabilitation sciences at the University of South Florida. Laurent Seugnet, a neuroscience researcher, had a similar assessment. “Sleep is important for neuronal plasticity, memory consolidation, and has also been shown recently to facilitate the elimination of toxic molecules such as beta-amyloid peptides [which make up plaques]” he wrote. “Thus it is almost certain that there is a bidirectional link between sleep disorders and dementia / Alzheimer’s.”

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    QUICK ANSWERS WITH CONSENSUS 
    • Does Cannabidiol oil likely to benefit someone with Alzheimers?  Rats maybe. Not enough evidence in humans. These studies suggest that Cannabidiol (CBD) oil may benefit someone with Alzheimer’s by exhibiting anti-inflammatory, anti-oxidation, neuroprotective activities, improving cognitive functions, and enhancing quality of life.
    • Does coffee lower the risk of Alzheimer’s? Not enough evidence. Some studies suggest that higher coffee consumption is associated with a reduced risk of Alzheimer’s disease and cognitive decline, while other studies indicate that the relationship is not statistically significant or that excessive consumption might increase the risk.
    • Can breaking down brain plaques prevent Alzheimer’s? No. Some studies suggest that breaking down brain plaques can prevent Alzheimer’s by reducing amyloid-β deposits and limiting neural damage, while other studies indicate that plaque clearance alone does not prevent progressive neurodegeneration.

     


    TOP ANSWER

    Do videogames prevent Alzheimer’s?

    Christopher Hertzog: An expert from Georgia Institute of Technology in Psychology

     

    Extremely Unlikely says Dr Christopher Hertzog, an expert in neuroscience from Georgia Institute of Technology. “It is possible that the mental exercise engaged by challenging video games can sharpen some aspects of the mind. But nothing has yet been found that slows, let alone prevents, Alzheimer’s disease (AD). The history of AD research shows that many hypotheses have been tested, many pharmaceuticals have been tested, all without meaningful effect on the disease and its progression. We do not understand the etiology of the disease and we have no way of combating it, at present. 

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    Does cooking with aluminum foil increase the risk for Alzheimers disease?

    TOP ANSWER

    Does cooking with aluminum foil increase the risk for Alzheimers disease?

    Robert A Yokel: An expert from University of Kentucky in Pharmacology, Toxicology

     

    Extremely Unlikely says Dr Robert Yokel, a toxicologist from the University of Kentucky. Cooking is a minor contributor to aluminium exposure for humans he says and Adequate kidney function protects against aluminum accumulation and toxicity. There is no good evidence that the consumption of aluminum from foods is associated with Alzheimer’s disease, nor is there convincing evidence that aluminum from any source is a significant contributor to Alzheimer’s disease.”

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    TAKEAWAYS
    1. Diet can help prevent Alzheimer’s, particularly the Mediterranean diet. That means you should eat lots of veggies, fruits, nuts, seafood (2 serves a week) and not much red-meat. Or just move to Italy, Spain or Greece.
    2. Coffee neither causes or prevents Alzheimer’s. Enjoy your latte.
    3. Brain games and video games good for cognition but doesn’t prevent Alzheimer’s. Sudoku anyone?
    4. Aluminium does not cause Alzheimer’s. Yes, you can still enjoy roasting with Aluminium foil.
    5. Good sleep is strongly linked to Alzheimer’s. Get >7-9hrs.
    6. Air pollution is strongly linked to Alzheimer’s. If you can, avoid being near busy roads for long periods of time at home or work. Or just wait til all cars become electric..that’ll take a while.

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