tag:theconversation.com,2011:/uk/topics/early-onset-alzheimers-disease-59278/articlesEarly onset Alzheimer's disease – The Conversation2024-02-01T05:31:46Ztag:theconversation.com,2011:article/2223742024-02-01T05:31:46Z2024-02-01T05:31:46ZAlzheimer’s may have once spread from person to person, but the risk of that happening today is incredibly low<figure><img src="https://images.theconversation.com/files/572598/original/file-20240131-25-8grmtv.jpg?ixlib=rb-1.1.0&rect=107%2C71%2C5883%2C3907&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/alzheimers-disease-mri-1025800153">Atthapon Raksthaput/Shutterstock</a></span></figcaption></figure><p>An article published this week in the prestigious journal <a href="https://www.nature.com/articles/s41591-023-02729-2">Nature Medicine</a> documents what is believed to be the first evidence that Alzheimer’s disease can be transmitted from person to person.</p>
<p>The finding arose from long-term follow up of patients who received human growth hormone (hGH) that was taken from brain tissue of deceased donors. </p>
<p>Preparations of donated hGH were used in medicine to treat a variety of conditions from 1959 onwards – including in Australia from the mid 60s. </p>
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<p>The practice stopped in 1985 when it was discovered around 200 patients worldwide who had received these donations went on to develop <a href="https://www.vdh.virginia.gov/epidemiology/epidemiology-fact-sheets/creutzfeldt-jakob-disease-cjd/">Creuztfeldt-Jakob disease</a> (CJD), which causes a rapidly progressive dementia. This is an otherwise extremely rare condition, affecting roughly one person in a million.</p>
<h2>What’s CJD got to do with Alzehimer’s?</h2>
<p>CJD is caused by prions: infective particles that are neither bacterial or viral, but consist of abnormally folded proteins that can be transmitted from cell to cell. </p>
<p>Other prion diseases include kuru, a dementia seen in New Guinea tribespeople caused by eating human tissue, scrapie (a disease of sheep) and variant CJD or bovine spongiform encephalopathy, otherwise known as mad cow disease. This raised <a href="https://en.wikipedia.org/wiki/United_Kingdom_BSE_outbreak">public health concerns</a> over the eating of beef products in the United Kingdom in the 1980s.</p>
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<a href="https://theconversation.com/people-who-lived-in-the-uk-in-the-mad-cow-disease-years-may-now-be-able-to-give-blood-the-risk-of-vcjd-is-tiny-183521">People who lived in the UK in the 'mad cow disease' years may now be able to give blood. The risk of vCJD is tiny</a>
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<h2>Human growth hormone used to come from donated organs</h2>
<p>Human growth hormone (hGH) is produced in the brain by the pituitary gland. Treatments were originally prepared from purified human pituitary tissue.</p>
<p>But because the amount of hGH contained in a single gland is extremely small, any single dose given to any one patient could contain material from around <a href="https://www.cdc.gov/mmwr/preview/mmwrhtml/00000563.htm">16,000 donated glands</a>. </p>
<p>An average course of hGH treatment lasts around four years, so the chances of receiving contaminated material – even for a very rare condition such as CJD – became quite high for such people.</p>
<p>hGH is now manufactured synthetically in a laboratory, rather than from human tissue. So this particular mode of CJD transmission is no longer a risk. </p>
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<img alt="Scientist in a lab" src="https://images.theconversation.com/files/572600/original/file-20240131-25-f3bxeg.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/572600/original/file-20240131-25-f3bxeg.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/572600/original/file-20240131-25-f3bxeg.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/572600/original/file-20240131-25-f3bxeg.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/572600/original/file-20240131-25-f3bxeg.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/572600/original/file-20240131-25-f3bxeg.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/572600/original/file-20240131-25-f3bxeg.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
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<span class="caption">Human growth hormone is now produced in a lab.</span>
<span class="attribution"><a class="source" href="https://unsplash.com/photos/woman-standing-in-front-of-the-sink-aelk4Tn0vlI">National Cancer Institute/Unsplash</a></span>
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<h2>What are the latest findings about Alzheimer’s disease?</h2>
<p>The Nature Medicine paper provides the first evidence that transmission of Alzheimer’s disease can occur via human-to-human transmission. </p>
<p>The authors examined the outcomes of people who received donated hGH until 1985. They found five such recipients had developed early-onset Alzheimer’s disease. </p>
<p>They considered other explanations for the findings but concluded donated hGH was the likely cause.</p>
<p>Given Alzheimer’s disease is a much more common illness than CJD, the authors presume those who received donated hGH before 1985 may be at higher risk of developing Alzheimer’s disease.</p>
<p>Alzheimer’s disease is caused by presence of two abnormally folded proteins: amyloid and tau. There is <a href="https://actaneurocomms.biomedcentral.com/articles/10.1186/s40478-017-0488-7">increasing evidence</a> these proteins spread in the brain in a <a href="https://pubmed.ncbi.nlm.nih.gov/8086126/">similar way to prion diseases</a>. So the mode of transmission the authors propose is certainly plausible. </p>
<p>However, given the amyloid protein deposits in the brain <a href="https://www.nia.nih.gov/news/estimates-amyloid-onset-may-predict-alzheimers-progression">at least 20 years</a> before clinical Alzheimer’s disease develops, there is likely to be a considerable time lag before cases that might arise from the receipt of donated hGH become evident.</p>
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Read more:
<a href="https://theconversation.com/size-of-brain-area-linked-with-cognitive-decline-even-in-people-with-no-other-warning-signs-of-alzheimers-disease-217729">Size of brain area linked with cognitive decline – even in people with no other warning signs of Alzheimer’s disease</a>
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<h2>When was this process used in Australia?</h2>
<p>In Australia, donated pituitary material <a href="https://www.health.gov.au/sites/default/files/documents/2022/07/the-cjd-review-final-report.pdf">was used</a> from 1967 to 1985 to treat people with short stature and infertility. </p>
<p><a href="https://www.health.gov.au/sites/default/files/documents/2022/07/the-cjd-review-final-report.pdf">More than 2,000 people</a> received such treatment. Four developed CJD, the last case identified in 1991. All four cases were likely linked to a single contaminated batch. </p>
<p>The risks of any other cases of CJD developing now in pituitary material recipients, so long after the occurrence of the last identified case in Australia, are <a href="https://www.mja.com.au/journal/2010/193/6/iatrogenic-creutzfeldt-jakob-disease-australia-time-amend-infection-control">considered to be</a> incredibly small.</p>
<p>Early-onset Alzheimer’s disease (defined as occurring before the age of 65) is uncommon, accounting for <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4356853/">around 5%</a> of all cases. Below the age of 50 it’s rare and likely to have a genetic contribution. </p>
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<img alt="Older man places his hands on his head" src="https://images.theconversation.com/files/572596/original/file-20240131-17-v3sclo.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/572596/original/file-20240131-17-v3sclo.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/572596/original/file-20240131-17-v3sclo.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/572596/original/file-20240131-17-v3sclo.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/572596/original/file-20240131-17-v3sclo.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/572596/original/file-20240131-17-v3sclo.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/572596/original/file-20240131-17-v3sclo.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
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<span class="caption">Early onset Alzheimer’s means it occurs before age 65.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/depressed-elderly-man-covers-his-face-1999395698">perfectlab/Shutterstock</a></span>
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<h2>The risk is very low – and you can’t ‘catch’ it like a virus</h2>
<p>The Nature Medicine paper identified five cases which were diagnosed in people aged 38 to 55. This is more than could be expected by chance, but still very low in comparison to the total number of patients treated worldwide. </p>
<p>Although the long “incubation period” of Alzheimer’s disease may mean more similar cases may be identified in the future, the absolute risk remains very low. The main scientific interest of the article lies in the fact it’s first to demonstrate that Alzheimer’s disease can be transmitted from person to person in a similar way to prion diseases, rather than in any public health risk.</p>
<p>The authors were keen to emphasise, as I will, that Alzheimer’s cannot be contracted via contact with or providing care to people with Alzheimer’s disease.</p>
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Read more:
<a href="https://theconversation.com/young-onset-alzheimers-can-be-diagnosed-from-as-early-as-30-and-the-symptoms-are-often-different-209561">Young-onset Alzheimer’s can be diagnosed from as early as 30 – and the symptoms are often different</a>
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<p class="fine-print"><em><span>Steve Macfarlane is affiliated with HammondCare, a not-for-profit aged care provider. </span></em></p>Scientists have published the first evidence that Alzheimer’s can be transmitted from person to person. Patients received human growth hormone from the tissue of donated brains.Steve Macfarlane, Head of Clinical Services, Dementia Support Australia, & Associate Professor of Psychiatry, Monash UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1831152022-05-17T19:59:28Z2022-05-17T19:59:28ZThe 29,000 younger Australians living with dementia are getting lost between disability services and aged care<figure><img src="https://images.theconversation.com/files/463491/original/file-20220517-16-4xwcif.jpg?ixlib=rb-1.1.0&rect=32%2C21%2C7126%2C4754&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><a class="source" href="https://image.shutterstock.com/image-photo/closeup-senior-asian-woman-sitting-600w-1912015441.jpg">Shutterstock</a></span></figcaption></figure><p>There are up to <a href="https://www.dementia.org.au/statistics">29,000 people aged under 65</a> living with dementia in Australia. Our <a href="https://content.iospress.com/articles/journal-of-alzheimers-disease/jad215360">new research</a> shows people with young onset dementia experience delays to diagnosis and a faster decline in their cognitive abilities than older people with the condition. </p>
<p>They must also tackle a challenging maze of accessing support services across both a disability system inexperienced with their care and an aged-care system not suited to meet their needs. </p>
<p>Using the strengths of both sectors could prevent people with young onset dementia from falling through the cracks.</p>
<h2>When dementia meets busy lives</h2>
<p>People with young onset dementia (defined as <a href="https://www.dementia.org.au/information/about-dementia/types-of-dementia">any form of dementia</a> that begins before age 65) are usually in their 50s and early 60s. They experience progressive memory loss, difficulty with planning and decision-making, personality changes, and/or language difficulties. </p>
<p>Many people with young onset dementia (also referred to as <a href="https://www.dementia.org.au/information/about-you/i-have-younger-onset-dementia">younger onset</a> or early onset dementia) have dependent children, ageing parents, high-pressure jobs and significant financial responsibilities. </p>
<p>Dementia in younger people is also often misdiagnosed (most commonly as a psychiatric illness like depression), with a <a href="https://www.cambridge.org/core/journals/international-psychogeriatrics/article/abs/time-to-diagnosis-in-youngeronset-dementia-and-the-impact-of-a-specialist-diagnostic-service/45B348182C8E1E675D88940B723F9EED">four-year average wait for an accurate diagnosis</a>. </p>
<p>All this leads to <a href="https://pubmed.ncbi.nlm.nih.gov/20735892/">much higher rates of psychological distress and poorer well-being</a> among young people with dementia and their family members than their older counterparts.</p>
<p>We <a href="https://content.iospress.com/articles/journal-of-alzheimers-disease/jad215360">systematically reviewed</a> 30 studies on Alzheimer’s disease, vascular dementia and frontotemporal dementia. Our analysis demonstrated younger people with dementia experience a faster progression of their symptoms than older people with dementia. </p>
<p>Studies that tracked symptoms over time showed that, while younger people generally maintained better physical health than older people while living with dementia, their thinking and language difficulties can worsen quickly. </p>
<p>This has an important impact on their care and support needs – and how often these needs are assessed.</p>
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Read more:
<a href="https://theconversation.com/where-you-live-affects-your-dementia-risk-180240">Where you live affects your dementia risk</a>
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<h2>A tipping point at 65</h2>
<p>Because the likelihood of developing dementia <a href="https://www.dementia.org.au/statistics">rises sharply with age</a>, most people with dementia are older than 65. </p>
<p>The unique needs of younger people with dementia prompted the federal government to move funding for their care and support services to the <a href="https://agedcare.royalcommission.gov.au/system/files/2020-06/DEH.0001.0001.0014.pdf">National Disability Insurance Scheme</a> (NDIS) in 2016. Older people with dementia continue to be supported by the aged-care system.</p>
<p>This division means people with young onset dementia sit at the intersection of two complex service systems. They can access services to support their independence and community participation via the NDIS, but dementia-specific services and housing are still largely delivered by the aged-care sector. </p>
<p>Aged-care providers face difficulty providing tailored support services due to complex eligibility rules, and many have <a href="https://www.pc.gov.au/__data/assets/pdf_file/0004/219433/subpp0313-ndis-costs.pdf">withdrawn</a> their specific programs for young onset dementia.</p>
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<a href="https://images.theconversation.com/files/463492/original/file-20220517-18-34r1gs.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="street sign shows medicare and ndis" src="https://images.theconversation.com/files/463492/original/file-20220517-18-34r1gs.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/463492/original/file-20220517-18-34r1gs.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=337&fit=crop&dpr=1 600w, https://images.theconversation.com/files/463492/original/file-20220517-18-34r1gs.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=337&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/463492/original/file-20220517-18-34r1gs.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=337&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/463492/original/file-20220517-18-34r1gs.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=424&fit=crop&dpr=1 754w, https://images.theconversation.com/files/463492/original/file-20220517-18-34r1gs.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=424&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/463492/original/file-20220517-18-34r1gs.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=424&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
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<span class="caption">People diagnosed with dementia before they turn 65 get lost between NDIS and aged care.</span>
<span class="attribution"><span class="source">Shutterstock</span></span>
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Read more:
<a href="https://theconversation.com/genetic-testing-should-i-get-tested-for-alzheimers-risk-97065">Genetic testing: Should I get tested for Alzheimer's risk?</a>
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<h2>An annual NDIS review is not enough</h2>
<p>The disability sector has <a href="https://journals.sagepub.com/doi/abs/10.1177/00048674211011699">little experience</a> with delivering dementia care. Most NDIS participants are aged under 35 years and live with disabilities such as autism, intellectual disabilities and hearing impairments that <a href="https://www.abs.gov.au/articles/characteristics-national-disability-insurance-scheme-ndis-participants-2019-analysis-linked-data#:%7E:text=Of%20the%20337%2C300%20NDIS%20participants,of%20the%20rest%20of%20population.">remain relatively stable over their lifetime</a>. </p>
<p>The sometimes rapidly progressive nature of young onset dementia means care needs can change more quickly than the standard yearly reviews offered by the NDIS. So even when people with young onset dementia receive adequate funding to suit their needs, these needs may change quickly. And there is a major shortage of disability service providers with dementia expertise with whom they can <a href="https://journals.sagepub.com/doi/full/10.1177/00048674211011699?casa_token=hcCykl9JwR0AAAAA%3AQTGANy0GQgZQWMOQ9cczNQ_aozg7WbFguNYyOhMyJB9Et88leP36Nq5S-aIkGqHcDrX5PxWbxB2WjQ">spend their funding</a>. </p>
<p>This is especially true in rural and remote areas, where there may only be one or two people with young onset dementia across a large geographical area.</p>
<p>Strict eligibility rules about the “significance” of disability can also <a href="https://www.aph.gov.au/DocumentStore.ashx?id=ed5bf4a7-5d53-4432-a9cf-003aff149ffa&subId=515021">delay NDIS access</a>. People newly diagnosed with young onset dementia may have mild impairments – but there are <a href="https://www.bmj.com/content/350/bmj.h3029.full">major benefits</a> to early intervention.</p>
<p>Young people with dementia and their families frequently have to navigate their own care needs and educate the providers they encounter along the way. This can increase their stress. </p>
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<h2>Aged care isn’t the answer</h2>
<p>Despite the difficulties people with young onset dementia and their families experience, our research tells us they want their care to <a href="https://journals.sagepub.com/doi/full/10.1177/00048674211011699?casa_token=hcCykl9JwR0AAAAA%3AQTGANy0GQgZQWMOQ9cczNQ_aozg7WbFguNYyOhMyJB9Et88leP36Nq5S-aIkGqHcDrX5PxWbxB2WjQ">remain in the disability system</a> rather than revert back to the aged-care system. The NDIS philosophy of a strengths-based approach to maximise independence <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5517136/">is valued</a>.</p>
<p>The disability sector needs to be better equipped to support people with young onset dementia and others who have progressive impairments. </p>
<p>Training for the disability workforce about progressive neurological conditions including dementia would be a good first step. </p>
<p>Beyond training, <a href="https://naca.asn.au/wp-content/uploads/2018/11/Improving-the-Interface-Between-the-Aged-Care-and-Disability-Sectors.pdf">better integration</a> of the aged and disability sectors could have mutual benefits. </p>
<p>The disability sector can learn and grow from the rich dementia expertise of the aged care workforce. And the aged care sector can benefit from the disability sector’s experience with delivering strengths-based and goal-directed care. Hours of testimony from the <a href="https://agedcare.royalcommission.gov.au/sites/default/files/2021-03/final-report-volume-1.pdf">Royal Commission into Aged Care Quality and Safety</a> highlight how desperately this is needed.</p>
<p>Flexibility in funding rules around the 65-year-old NDIS cutoff point could see co-delivered services capitalise on these respective strengths. </p>
<p>Flexibility could also ensure people aged close to 65 years at the time of their dementia diagnosis can make informed choices about the sector from which they will seek support. Then suitable care that can adjust to their changing needs will stop them falling through the cracks.</p>
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Read more:
<a href="https://theconversation.com/serving-up-choice-and-dignity-in-aged-care-how-meals-are-enjoyed-is-about-more-than-whats-on-the-plate-179669">Serving up choice and dignity in aged care – how meals are enjoyed is about more than what's on the plate</a>
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<img src="https://counter.theconversation.com/content/183115/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Monica Cations receives funding from the National Health and Medical Research Council Medical Research Future Fund and the South Australian Hospital Research Foundation.</span></em></p>Younger people with dementia are more likely to experience quicker disease decline. But annual NDIS reviews don’t capture their changing needs.Monica Cations, Senior Research Fellow, Flinders UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1577132021-03-24T16:24:09Z2021-03-24T16:24:09ZDementia: is processed meat another risk factor?<figure><img src="https://images.theconversation.com/files/391378/original/file-20210324-23-jiuuiq.jpg?ixlib=rb-1.1.0&rect=6%2C0%2C4259%2C2845&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">The equivalent of one bacon rasher was associated with 44% increased dementia risk.
</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/cooking-great-outdoors-by-frying-sausages-130267775">stocksolutions/ Shutterstock</a></span></figcaption></figure><p>The evidence of a link between processed meat and cancer is now strong enough for some organisations to recommend <a href="https://www.wcrf-uk.org/uk/preventing-cancer/cancer-prevention-recommendations">not eating any</a>. There’s also increasing evidence of a link between processed meat and <a href="https://pubmed.ncbi.nlm.nih.gov/21831992/">type 2 diabetes</a>. And now, a new study has added to the list of woes for lovers of processed meat by linking it to an increased risk of dementia. But this latest association may not be quite so convincing.</p>
<p>The <a href="https://academic.oup.com/ajcn/advance-article-abstract/doi/10.1093/ajcn/nqab028/6178922">new study</a>, from the University of Leeds, used data from the UK Biobank, which is a biomedical database containing detailed genetic and health information from nearly half a million people, aged 40 to 69. The researchers measured how frequently participants reported consuming processed and unprocessed meat, and then monitored cases of dementia over an eight-year period. </p>
<p>During this period, 2,896 participants developed dementia. The researchers calculated that eating 25g of processed meat per day – the equivalent of one rasher of bacon – was associated with a 44% increased risk of dementia. And for those who developed dementia, processed meat was associated with a 52% increased risk of Alzheimer’s disease - the main cause of dementia. By contrast, they found that consuming 50g a day of unprocessed red meat such as beef, pork, or veal was protective, and was associated with reducing the risk of dementia by 19% compared to people eating meat up to once a week.</p>
<p>To find opposite health effects for processed meat and unprocessed meat is unusual, especially given that <a href="https://pubmed.ncbi.nlm.nih.gov/26514947/">many studies</a> show that both processed meat and red meat increase cancer risk. So what might be going on here?</p>
<p>Studies that examine an association between the consumption of a specific food and an increased risk of a disease are not proving that there is a causal link. <a href="https://pubmed.ncbi.nlm.nih.gov/32738937/">Many factors</a> are linked to an increased risk of dementia, and only a small selection of these can be evaluated in any one study. This makes it difficult to draw firm conclusions about what may be the cause for an observed effect. </p>
<p>The Leeds study used a broad definition of processed meats. It not only included ham, bacon and sausages, but also more highly processed meat products, such as meat pies, kebabs, burgers and chicken nuggets. It’s likely that people who consume these highly processed meat products will also have a taste for other highly processed foods, such as crisps or cakes, that are part of the typical western diet. </p>
<figure class="align-center ">
<img alt="An assortment of unhealthy foods, including a hamburger, soda, crisps, chocolate, and candy." src="https://images.theconversation.com/files/391460/original/file-20210324-15-12p8mie.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/391460/original/file-20210324-15-12p8mie.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/391460/original/file-20210324-15-12p8mie.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/391460/original/file-20210324-15-12p8mie.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/391460/original/file-20210324-15-12p8mie.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/391460/original/file-20210324-15-12p8mie.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/391460/original/file-20210324-15-12p8mie.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">An unhealthy diet may also be to blame.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/unhealthy-products-food-bad-figure-skin-1354124945">beats1/ Shutterstock</a></span>
</figcaption>
</figure>
<p>So highly processed meat products may simply be a representative marker for an unhealthy diet and it may be this, rather than bacon, ham or sausages, that is increasing the dementia risk. Research shows an unhealthy western diet is linked to an <a href="https://pubmed.ncbi.nlm.nih.gov/32717151/">increased risk of Alzheimer’s disease</a>. It’s thought that the adverse effects of a poor diet on the <a href="https://pubmed.ncbi.nlm.nih.gov/31837645/">gut microbiota</a> (the community of trillions of microbes in our gut which help us maintain our wellbeing) are linked with neurological disorders, including dementia.</p>
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Read more:
<a href="https://theconversation.com/your-gut-microbiome-may-be-linked-to-dementia-parkinsons-disease-and-ms-144367">Your gut microbiome may be linked to dementia, Parkinson's disease and MS</a>
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<p>Also, the degree to which the meat was cooked was not considered in this study. A high cooking temperature can increase meat’s <a href="https://pubmed.ncbi.nlm.nih.gov/26393643/">negative impact</a> on health. Most processed meats, such as sausages and <a href="https://theconversation.com/bacon-how-you-cook-it-could-partially-lower-cancer-risk-152723">bacon</a>, are cooked at high temperatures until brown. This browning is an indicator that toxic compounds, called advanced glycation end-products (AGEs), have formed on the surface of the meat. AGEs cause neuro-inflammation in the brain. And in <a href="https://pubmed.ncbi.nlm.nih.gov/32444539/">animal models</a> and <a href="https://pubmed.ncbi.nlm.nih.gov/31561370/">human studies</a> this is strongly linked to an increased risk of Alzheimer’s disease. </p>
<p>In a <a href="https://pubmed.ncbi.nlm.nih.gov/20497781/">survey of 549 foods</a>, fried bacon had by far the highest levels of AGEs. Although levels were high in steak, they were still ten times lower than for bacon. Levels of AGEs were lower still in other red meats (although still high compared to most other foods) and depended on how the meats were cooked. Because the way people eat meat varies so much, it’s perhaps not surprising that at the moment there is <a href="https://pubmed.ncbi.nlm.nih.gov/32456281/">no clear consensus</a> as to whether or not there is a link between eating meat and decreased cognitive function. </p>
<p>One of the distinguishing features of the participants in the Leeds study who developed dementia was that they were more likely to be men. Although dementia is overall more common in women, among those under 65 it’s more common in men. A main cause for this so-called <a href="https://www.scie.org.uk/dementia/symptoms/young-onset/key-issues.asp">early onset dementia</a> is thought to be <a href="https://pubmed.ncbi.nlm.nih.gov/23878613/">traumatic brain injury</a>, which occurs more in men living in regions of <a href="https://pubmed.ncbi.nlm.nih.gov/14511388/">socioeconomic deprivation</a>. The relatively young age of the study’s participants means that most of those with dementia would be classed as having early onset dementia, but brain injury was not assessed as a possible cause in this study.</p>
<p>As well as eating more processed meats, the participants in the study who developed dementia were also more likely to be economically deprived, less educated, smokers, less physically active, more likely to have a history of stroke, and a family history of dementia. Perhaps this is the more important finding from the study. </p>
<p>A high consumption of highly processed meats may simply be a representative marker of a less healthy lifestyle overall - something a single study cannot address in any detail. If so, then public health campaigns that address these <a href="https://pubmed.ncbi.nlm.nih.gov/24385661/">broader issues</a> are crucial for people from deprived backgrounds, to help reduce their overall risk of dementia. Merely reducing their consumption of bacon butties is likely to have far less effect.</p><img src="https://counter.theconversation.com/content/157713/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>I am the author of two books on the Mediterranean diet: The Mediterranean Diet: Health and Science (2011) and More Healthy Years - Why a Mediterranean Diet is best for you and for the planet (2020).</span></em></p>If so, it’s just one lifestyle risk among many others.Richard Hoffman, Associate lecturer, Nutritional Biochemistry, University of HertfordshireLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1208752019-08-13T22:17:17Z2019-08-13T22:17:17ZRethinking the approach to fighting Alzheimer’s disease<figure><img src="https://images.theconversation.com/files/286129/original/file-20190729-43114-1vwk6qg.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C5760%2C3828&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Hundreds of clinical trials have been conducted over the past 10 years to find a cure for Alzheimer's disease. They all failed.</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/">Shutterstock</a></span></figcaption></figure><p>The idea of seeing a loved one decline and lose their ability to recall their most treasured memories is devastating. However, it is a fact of life for an increasing number of Canadians. A group of experts on population health convened by the Alzheimer Society of Canada in 2015 estimated that <a href="https://alzheimer.ca/sites/default/files/files/national/statistics/prevalenceandcostsofdementia_en.pdf">nearly one million Canadians will have Alzheimer’s disease in 2031</a>. </p>
<p>Alzheimer’s is the most common form of dementia and no treatment has yet been found, despite the best efforts of researchers. This is what drives the massive funding of clinical trials searching for a way to stop the disease. Despite hundreds of drug trials however, there have been no new treatments approved by the U.S. Food and Drug Administration since 2003. It’s clear that a better understanding of the disease is needed, as well as a re-evaluation of how treatment is developed.</p>
<p>So, what makes the search for a treatment so difficult?</p>
<p>As a first year doctoral student in psychology at the Université du Québec à Montréal (UQAM) in <a href="https://professeurs.uqam.ca/professeur/bedard.marc-andre/">Marc-André Bédard’s laboratory</a>, I use nuclear imaging to investigate Alzheimer’s disease. My research aims to better understand changes in <a href="https://doi.org/10.1016/S0166-4328(00)00259-X">a neurotransmitter called acetylcholine</a> in people with early Alzheimer’s disease. Acetylcholine is a chemical that allows neurons to communicate with other neurons, muscles, glands and so on. </p>
<p>The main drugs prescribed for Alzheimer’s disease respond to the degeneration of neurons responsible for the transmission of acetylcholine through the brain. The neurons that transmit it are found in the Meynert basal nucleus, a small area located at the front of the brain. The death of these neurons is believed to be <a href="http://doi.org/10.1126/science.7058341">the cause of the attention and memory disorders</a> found in Alzheimer’s disease. The drugs help compensate for the loss of these neurons by increasing acetylcholine transmission, but <a href="https://www.cochrane.org/CD001190/DEMENTIA_donepezil-people-dementia-due-alzheimers-disease">they have little impact on disease progression</a>.</p>
<h2>A hypothesis under fire</h2>
<p>Currently, the search for treatments that can slow or stop the progression of Alzheimer’s disease is mainly based on the <a href="https://doi.org/10.1126/science.1566067">amyloid cascade hypthesis</a>. According to this theory, the disease begins when the body does not clean amyloid proteins properly, leading to a build-up of microscopic plaques in the brain. </p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/280589/original/file-20190620-149810-1ghz1so.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/280589/original/file-20190620-149810-1ghz1so.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=450&fit=crop&dpr=1 600w, https://images.theconversation.com/files/280589/original/file-20190620-149810-1ghz1so.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=450&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/280589/original/file-20190620-149810-1ghz1so.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=450&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/280589/original/file-20190620-149810-1ghz1so.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=566&fit=crop&dpr=1 754w, https://images.theconversation.com/files/280589/original/file-20190620-149810-1ghz1so.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=566&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/280589/original/file-20190620-149810-1ghz1so.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=566&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">The amyloid cascade hypothesis to explain the causes of Alzheimer’s disease is being increasingly criticized.</span>
<span class="attribution"><span class="source">Shutterstock</span></span>
</figcaption>
</figure>
<p>These plaques accumulate for decades, even before the first symptoms of Alzheimer’s disease appear. They then cause the dysfunction of tau, another protein found in neurons, producing <a href="https://doi.org/10.1016/j.bbadis.2004.08.014">neurofibrillary tangles</a> inside the neurons resulting in their death. </p>
<p>However, more and more researchers <a href="https://doi.org/10.1186/s40478-014-0135-5">are critical of this hypothesis</a>.</p>
<p>About one in five seniors has a significant accumulation of plaques and yet will never develop Alzheimer’s. There are even cases where tau tangles have been found in the absence of plaques, which calls into question the sequence of events predicted by the hypothesis. In addition, treatments that have been developed to cleanse or prevent amyloid production have either had no effect on the progression of Alzheimer’s disease or have accelerated the cognitive decline. </p>
<p>Alzheimer’s may be more complex than originally thought, and plaques might be a consequence of earlier changes rather than the driving force of the disease.</p>
<h2>Reproducing Alzheimer’s in rodents</h2>
<p>Before a new drug is used on humans, it must first be tested on animals to see if it is effective and safe. The animals used, usually rats or mice, must develop a pathology that resembles Alzheimer’s in humans. </p>
<p>In the case of Alzheimer’s, the disease is caused in the test subject by genetic manipulation. For example, researchers have created rodents that carry a gene that causes the accumulation of plaques similar to those seen in humans. This causes the rodents to have memory and attention problems similar to patients with Alzheimer’s.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/280587/original/file-20190620-149847-1cie8bw.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/280587/original/file-20190620-149847-1cie8bw.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=338&fit=crop&dpr=1 600w, https://images.theconversation.com/files/280587/original/file-20190620-149847-1cie8bw.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=338&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/280587/original/file-20190620-149847-1cie8bw.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=338&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/280587/original/file-20190620-149847-1cie8bw.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=424&fit=crop&dpr=1 754w, https://images.theconversation.com/files/280587/original/file-20190620-149847-1cie8bw.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=424&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/280587/original/file-20190620-149847-1cie8bw.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=424&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">To improve research, better animal models must be found to better represent the mechanisms of Alzheimer’s disease.</span>
<span class="attribution"><span class="source">Shutterstock</span></span>
</figcaption>
</figure>
<p>Animal experiments are based on the premise that the effects of treatments on artificially diseased animals are similar to those on humans. However, <a href="https://doi.org/10.1016/j.ebiom.2018.12.006">many animal models of Alzheimer’s disease recreate the amyloid cascade hypothesis</a>, which is imperfect. </p>
<p>Since the causes and symptoms are not perfectly recreated, a treatment that works in rodents may not work in humans. It also means that drugs that may be effective in humans may not be effective in animals. </p>
<p>To improve research, it is necessary to find better animal models to better represent the mechanisms of Alzheimer’s disease in humans without relying on genetic mutation. This would make them more similar to Alzheimer’s progression in humans, since <a href="https://www.ncbi.nlm.nih.gov/pubmed/23634826">95 per cent of human cases are not purely caused by genes</a>. Such models could help develop treatments that would be effective in both animals and humans.</p>
<h2>The challenges of clinical research</h2>
<p>The choice of patients in clinical trials can also pose serious challenges. One option is using people with mild Alzheimer’s. However, these patients have already lost most neurons in the basal forebrain, leaving no chance of recovering mental functions without using drugs such as the ones currently employed.</p>
<p>It is also thought that the mechanisms behind Alzheimer’s could be more difficult to halt since the cascade of events — plaques and tangles — might be too developed to be stopped. </p>
<p>That is why recent trials have been conducted in patients with pre-symptomatic Alzheimer’s disease. These people are very likely to develop the disease and have signs such as plaques, <a href="https://doi.org/10.1002/ana.21509">even if no symptoms can be detected</a>. </p>
<p>This allows researchers to measure the impact of the treatment on the odds of developing Alzheimer’s symptoms over the years. Such trials follow at least 1,000 participants over about two years in the hopes of detecting even small changes — requiring enormous investments.</p>
<h2>Prevention: the best cure</h2>
<p>Given these challenges, preventative methods are gaining interest. Among these, <a href="https://doi.org/10.1017/S0033291708003681">physical activity such as exercise could help to slow or even prevent the onset of the disease through its antioxidant effects</a>.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/280580/original/file-20190620-149806-ftzn26.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/280580/original/file-20190620-149806-ftzn26.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/280580/original/file-20190620-149806-ftzn26.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/280580/original/file-20190620-149806-ftzn26.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/280580/original/file-20190620-149806-ftzn26.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/280580/original/file-20190620-149806-ftzn26.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/280580/original/file-20190620-149806-ftzn26.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Light activities such as walking improve brain health and reduce the risk of developing Alzheimer’s disease.</span>
<span class="attribution"><span class="source">Shutterstock</span></span>
</figcaption>
</figure>
<p>Intense physical activity may be daunting and in some cases impossible for some seniors. Dr. Nicole L. Spartano and her colleagues at Boston University have found that <a href="https://neurosciencenews.com/brain-aging-physical-activity-12018/">each hour of light physical activity, such as walking, would improve brain health and potentially reduce the risk of developing Alzheimer’s disease</a>.</p>
<p>So far, the search for a miracle cure for Alzheimer’s has failed, despite enormous efforts by scientists and researchers. To overcome this challenge, researchers must rethink their approach towards developing and testing drugs. Until then, prevention with diet, social interaction, physical activity and staying cognitively active are the best-known ways of fighting this terrible disease.</p>
<p>[ <em><a href="https://theconversation.com/ca/newsletters?utm_source=TCCA&utm_medium=inline-link&utm_campaign=newsletter-text&utm_content=expertise">Expertise in your inbox. Sign up for The Conversation’s newsletter and get a digest of academic takes on today’s news, every day.</a></em> ]</p><img src="https://counter.theconversation.com/content/120875/count.gif" alt="La Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Étienne Aumont has received funds from the Fonds de Recherche Du Québec - Santé. </span></em></p>Alzheimer’s disease is the most common form of dementia. Despite all efforts, no treatments have been found yet. To increase the odds, we need to rethink our approach and try to better understand it.Étienne Aumont, Étudiant en neurosciences, Université du Québec à Montréal (UQAM)Licensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1141142019-04-25T10:43:50Z2019-04-25T10:43:50ZNo cure for Alzheimer’s disease in my lifetime<figure><img src="https://images.theconversation.com/files/267411/original/file-20190403-177181-1xjl0a1.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">In most cases, scientists are still unsure of what causes Alzheimer's disease.</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-vector/colorful-vector-illustration-scientists-researching-brain-1188871114">FGC / Shutterstock.com</a></span></figcaption></figure><p>Biogen recently announced that it was abandoning its late stage drug for <a href="https://theconversation.com/what-causes-alzheimers-disease-what-we-know-dont-know-and-suspect-75847">Alzheimer’s</a>, <a href="https://www.statnews.com/2019/03/21/biogen-eisai-alzheimer-trial-stopped/">aducanumab</a>, causing investors to <a href="https://www.cnbc.com/2019/03/21/biogen-shares-plunge-more-than-25percent-after-ending-trial-for-alzheimers-drug-aducanumab.html">lose billions</a> of dollars. </p>
<p>They should <a href="https://blogs.sciencemag.org/pipeline/archives/2018/06/12/an-alzheimers-statement?r3f_986=https://www.google.com/">not have been surprised</a>. </p>
<p>Not only have there been more than <a href="https://www.scientificamerican.com/article/why-alzheimer-s-drugs-keep-failing/">200 failed trials</a> for Alzheimer’s, it’s been clear for some time that researchers are likely decades away from being able to treat this dreaded disease. Which leads me to a prediction: There will be no effective therapy for Alzheimer’s disease in my lifetime.</p>
<p>Clinically, I am an emergency physician. But my research interests <a href="https://doi.org/10.1016/j.ajem.2016.08.018">include diagnostic biomarkers</a>, which are molecular indicators of disease, and a diagnostic test for Alzheimer’s is something of a holy grail. </p>
<p>Alzheimer’s sits right at the confluence of a number unfortunate circumstances. Stick with me on this – it’s mostly bad news for anyone middle-aged or older, but there’s a reward of sorts at the end. If you understand why there won’t be much headway on Alzheimer’s, you’ll also understand a bit more why modern medicine has been having fewer breakthroughs on major diseases.</p>
<h2>We don’t know what causes this disease</h2>
<p><a href="https://pdfs.semanticscholar.org/a5b7/42b5a09aae2d5ef53e7129174715dd9e1226.pdf">For decades</a> it was widely believed that the cause of Alzheimer’s was the build-up of abnormal proteins called <a href="https://doi.org/10.1038/d41586-018-05719-4">amyloid</a> and <a href="https://www.sciencemag.org/news/2016/05/tau-protein-not-amyloid-may-be-key-driver-alzheimer-s-symptoms">Tau</a>. These theories dominated the field and led some to believe we were <a href="https://www.webmd.com/alzheimers/news/20180725/new-drug-shows-promise-against-alzheimers">on the verge of effective treatments</a> – through preventing or removing these abnormal proteins. But had the theories been correct we would likely have had at least one or two positive clinical trials. </p>
<p>In retrospect, the multi-decade <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5797629/">amyloid</a> fixation looks like a <a href="https://www.amazon.com/Dogmatism-Science-Medicine-Dominant-Monopolize/dp/0786463015">mistake</a> that could have been avoided. Although there is a correlation between amyloid and risk of Alzheimer’s, there are elderly people whose brains have <a href="https://news.northwestern.edu/stories/2016/11/elderly-discovered-with-superior-memory-and-alzheimers-pathology/">significant amounts of the protein</a> and yet are <a href="https://www.statnews.com/2016/11/14/alzheimers-brain-amyloid-plaque/">cognitively intact</a>. <a href="https://doi.org/10.1212/01.wnl.0000219668.47116.e6">Versions of this observation</a> date back to at least <a href="https://doi.org/10.1016/0022-510X(68)90154-8">the 1960s</a>. That’s one reason why researchers <a href="https://doi.org/10.1186/s40478-014-0135-5">have questioned the enthusiasm</a> for this one hypothesis. </p>
<p>It was always possible that the classic plaques and tangles first seen by <a href="https://doi.org/10.1093/brain/awv316">Alois Alzheimer</a>, and now known to be made of abnormal proteins, were <a href="https://doi.org/10.1016/j.jalz.2013.11.003">epiphenomena of aging</a> and not the cause of the disease. Epiphenomena are characteristics that are associated with the disease but are not its cause.</p>
<figure>
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<figcaption><span class="caption">Changes occurring in the brain of people with Alzheimer’s disease.</span></figcaption>
</figure>
<p>But even more convincing that researchers are closer to the beginning than the end in understanding the cause of Alzheimer’s is the long list of alternative theories. This now includes but is not limited to: <a href="https://www.npr.org/sections/health-shots/2018/09/09/645629133/infectious-theory-of-alzheimers-disease-draws-fresh-interest">infection</a>, <a href="https://www.the-scientist.com/features/what-causes-alzheimers-41982">disordered inflammation</a>, abnormal <a href="https://doi.org/10.1177/193229680800200619">diabetes-like</a> metabolism and numerous environmental <a href="https://doi.org/10.2174/1567205012666150204121719">toxins</a>. </p>
<p>And the past few years have seen more evidence for <a href="https://www.medicalnewstoday.com/articles/322223.php">viral</a>, <a href="https://www.newscientist.com/article/2191814-we-may-finally-know-what-causes-alzheimers-and-how-to-stop-it/">bacterial</a> and <a href="https://doi.org/10.3233/JAD-132681">fungal infections</a>. These <a href="https://doi.org/10.1016/S0140-6736(96)10149-5">viral</a> and <a href="http://blogs.discovermagazine.com/d-brief/2019/01/23/dental-infection-may-spur-alzheimers-disease/#.XJ5dG5hKhhE">bacterial</a> hypotheses were portrayed as eureka moments. But this begs the question: How did powerful tools of epidemiology miss associations with things like cold sores and gum disease? </p>
<h2>Not one disease with one cause</h2>
<p>When Occam’s razor – the principle that the simplest solution is often the best – is applied to this laundry list of possible causes, it leads to some profound implications. Either <a href="https://www.sciencedaily.com/releases/2018/12/181204183713.htm">Alzheimer’s is not one disease</a>, or many factors can contribute to triggering or promoting it. Some authorities have been trying to make such arguments <a href="https://doi.org/10.1002/ana.21736">for some time</a>.</p>
<p>Either of these would be bad news, since we would need to develop multiple effective treatments, possibly in combination. </p>
<p>Unfortunately, our biomedical system is designed for the development and testing of one drug at at time. Combinations of drugs dramatically increase the number of clinical trials needed to test for efficacy and toxicity. </p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/267412/original/file-20190403-177190-19zc6dk.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/267412/original/file-20190403-177190-19zc6dk.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=375&fit=crop&dpr=1 600w, https://images.theconversation.com/files/267412/original/file-20190403-177190-19zc6dk.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=375&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/267412/original/file-20190403-177190-19zc6dk.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=375&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/267412/original/file-20190403-177190-19zc6dk.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=471&fit=crop&dpr=1 754w, https://images.theconversation.com/files/267412/original/file-20190403-177190-19zc6dk.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=471&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/267412/original/file-20190403-177190-19zc6dk.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=471&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">These are just some of the risk factors for Alzheimer’s disease.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-vector/risk-factors-disease-icon-design-infographic-1014218830">iLoveCoffeeDesign / Shutterstock.com</a></span>
</figcaption>
</figure>
<h2>We’ve ignored the biology of aging</h2>
<p>For 50 years after Alzheimer described the <a href="https://doi.org/10.1093/brain/awv316">first patient</a>, the disease was considered relatively rare. Called pre-senile dementia, it struck relatively early and sometimes ran in families. The much more common dementia of old age - senile dementia - was considered part of <a href="https://doi.org/10.1002/ana.21915">aging</a>. </p>
<p>But here’s the thing – regardless of type, Alzheimer’s has a powerful age-related association. This is true even for patients with early-onset inherited form of Alzheimer’s. Give someone the worst possible genome for Alzheimer’s – including the dreaded <a href="https://www.nia.nih.gov/health/alzheimers-disease-genetics-fact-sheet">APOE e4 gene</a> that may be associated with a 10-fold increase in risk - and that person still needs to age a bit before developing the disease.</p>
<p>Combine the long list of risk factors with the powerful age association and Alzheimer’s comes into focus. Neurons may be the high-wire act of cell types, and the senescence of aging inexorably wears on them. Any one of many cellular insults may accelerate neurons toward earlier cell death. The worst of these may be a particularly bad gene you inherited from your parents, but all are additive to a greater or lesser degree. </p>
<p>If correct, this conception of the disease means we’re even further away from an effective treatment.</p>
<p>Aging is not disease. It is the normal arc of life and an ineluctable part of being human (“dust unto dust”). As such, the biology of aging <a href="https://www.medpagetoday.com/neurology/alzheimersdisease/75075">didn’t get</a> the attention that was bestowed on organ systems and diseases during the golden years of research funding. </p>
<p>In retrospect, I think this may have been a grave mistake. If you list the risk factors for the major diseases of modern life – heart disease, diabetes, dementia – the most powerful is almost always age. </p>
<p>Bottom line: We also lack an understanding of the basic science of Alzheimer’s most important risk factor.</p>
<h2>We can’t even accurately diagnose this disease</h2>
<figure class="align-left zoomable">
<a href="https://images.theconversation.com/files/267415/original/file-20190403-177190-lu75rw.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/267415/original/file-20190403-177190-lu75rw.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/267415/original/file-20190403-177190-lu75rw.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=908&fit=crop&dpr=1 600w, https://images.theconversation.com/files/267415/original/file-20190403-177190-lu75rw.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=908&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/267415/original/file-20190403-177190-lu75rw.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=908&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/267415/original/file-20190403-177190-lu75rw.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=1140&fit=crop&dpr=1 754w, https://images.theconversation.com/files/267415/original/file-20190403-177190-lu75rw.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=1140&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/267415/original/file-20190403-177190-lu75rw.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=1140&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Alois Alzheimer’s patient Auguste Deter in 1902. Hers was the first described case of what became known as Alzheimer’s disease.</span>
<span class="attribution"><a class="source" href="https://upload.wikimedia.org/wikipedia/commons/1/1d/Auguste_D_aus_Marktbreit.jpg">Wikimedia</a></span>
</figcaption>
</figure>
<p>While it is widely known that it is not possible to diagnose Alzheimer’s accurately during life, a dirty little secret of Alzheimer’s research is that a significant fraction of patients cannot be categorized <a href="https://n.neurology.org/content/38/11/1682.short">even on autopsy</a>. The classic plaques and tangles that Alois Alzheimer saw through his microscope may <a href="https://doi.org/10.1002/ana.410300410">not be accurate</a> biomarkers of this disease.</p>
<p>The single absolute requirement for the development of therapies is an accurate diagnostic. You can’t begin to develop a drug if you can’t accurately identify who has and does not have the disease. Alzheimer’s is the quintessential example of this, as it is very difficult to diagnose. In living patients, diseases like <a href="https://www.nhlbi.nih.gov/health-topics/vascular-dementia">vascular dementia</a> and <a href="https://www.nia.nih.gov/health/what-lewy-body-dementia">Lewy body dementia</a> can be indistinguishable from Alzheimer’s. Some of the newest technologies are actually based on imaging amyloid, which some studies show <a href="https://www.statnews.com/2016/11/14/alzheimers-brain-amyloid-plaque/">may not be a reliable diagnostic test</a>.</p>
<h2>Lead times for new therapies are longer than predicted</h2>
<p>It takes a long time for the Food and Drug Administration to approve a drug. From the moment a possible drug is first conceived, it is often <a href="https://www.medicinenet.com/script/main/art.asp?articlekey=9877">more than 10 years</a> until it is available. </p>
<p>The brain has few if any <a href="https://www.npr.org/sections/health-shots/2018/03/07/591305604/sorry-adults-no-new-neurons-for-your-aging-brains">repair</a> mechanisms. So when we talk about Alzheimer’s treatments, we mean prevention not reversal. </p>
<p>The natural history of Alzheimer’s is such that preventive therapy will need to be started early in the course of the disease. This will add years to the drug development cycle. A decade from discovery to bedside would be good news for an Alzheimer’s drug.</p>
<p>But history teaches us that the delays could be even worse. Shortly after the discovery of genetic engineering in the early 1980s, it was common to tell patients with diseases like sickle cell that a genetic cure was just a <a href="https://www.statnews.com/2018/06/06/drug-development-speed-new-medicines/">few years away</a>. The sickle cell abnormality and its location in the genome had been known for <a href="http://www.bloodjournal.org/content/63/2/249.short?sso-checked=true">some time</a>. The organ system involved is easy to access. Thirty years later we have still not successfully cured diseases like sickle cell, and the hubris of those early predictions are painful memories for older physicians like myself. </p>
<p>The situation with Alzheimer’s looks much worse than sickle cell disease looked back in the 1980s. We don’t know the cause – which is likely multifactorial - and its in a hard to get at organ. And neurological diseases are a particular challenge because the brain is protected behind something called the blood-brain barrier. Even if you have a potentially effective drug, it may not reach its target.</p>
<p>Add all of these considerations together and the long road stretches out ahead. </p>
<p>But no drug for the foreseeable future does not mean there’s nothing to do. There is some indication that healthy lifestyle efforts may <a href="https://theconversation.com/what-causes-alzheimers-disease-what-we-know-dont-know-and-suspect-75847">prevent Alzheimer’s</a>. And even if they don’t, they’re likely effective in preventing <a href="https://www.mayoclinic.org/diseases-conditions/vascular-dementia/symptoms-causes/syc-20378793">vascular dementia</a>, which is <a href="https://www.mayoclinic.org/diseases-conditions/dementia/symptoms-causes/syc-20352013">almost as common</a>.</p><img src="https://counter.theconversation.com/content/114114/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Norman A. Paradis does not work for, consult, own shares in or receive funding from any company or organization that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>After the failure of multiple drug trials the outlook for an Alzheimer’s drug is bleak. This shouldn’t be a surprise. We don’t know the cause or even how to diagnose the disease.Norman A. Paradis, Professor of Medicine, Dartmouth CollegeLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1023302018-09-11T21:39:06Z2018-09-11T21:39:06ZIs that ‘midlife crisis’ really Alzheimer’s disease?<figure><img src="https://images.theconversation.com/files/235321/original/file-20180906-190656-5q9c2h.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Early-onset Alzheimer's disease presents unique challenges, when a patient is still working or parenting children.The personality changes involved can result in job loss or divorce before a diagnosis is made. </span> <span class="attribution"><span class="source">(Shutterstock)</span></span></figcaption></figure><p>Imagine you tell your 55 year-old mom you’re going to get married and she’s too disorganized to help you with the wedding preparations. Or you put your kids on the bus to elementary school and the 57 year-old driver forgets the route. </p>
<p>These are real scenarios, drawn from my clinical work with patients who have young-onset Alzheimer’s disease. </p>
<p>This is the other face of dementia — no white hair or wrinkles. And it is relatively common. Approximately <a href="http://alzheimer.ca/en/Home/About-dementia/Dementias/young-onset-dementia">five per cent of Alzheimer’s patients are younger than 65</a>. </p>
<p>While the underlying pathology of both young-onset and late-onset Alzheimer’s is the same — the <a href="http://alzheimer.ca/en/Home/About-dementia/Alzheimers-disease">abnormal accumulation of proteins called amyloid and tau in the brain</a> — there are significant differences in how the two diseases are experienced. </p>
<p>Patients who are under 65, for example, often have <a href="https://doi.org/10.1177/1533317512454711">difficulties with language, visual processing and organizing and planning</a>. They have less of the classic memory complaints.</p>
<p>There is also <a href="https://jhu.pure.elsevier.com/en/publications/age-at-onset-of-alzheimers-disease-relation-to-pattern-of-cogniti-4">accumulating evidence that young-onset Alzheimer’s progresses faster</a>. </p>
<h2>Dementia confused with depression</h2>
<p>The path to a diagnosis of Alzheimer’s or other dementia is often long, meandering and riddled with misdiagnosis. </p>
<p>A correct diagnosis is essential for every patient but especially important for younger people. They are often still working and at risk of losing their jobs. They may have young children. When they tell people that something isn’t quite right, they are told they are depressed or must be going through a midlife crisis. </p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/235313/original/file-20180906-190639-9a7jae.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/235313/original/file-20180906-190639-9a7jae.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=401&fit=crop&dpr=1 600w, https://images.theconversation.com/files/235313/original/file-20180906-190639-9a7jae.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=401&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/235313/original/file-20180906-190639-9a7jae.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=401&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/235313/original/file-20180906-190639-9a7jae.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/235313/original/file-20180906-190639-9a7jae.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/235313/original/file-20180906-190639-9a7jae.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Personality changes involved in Alzheimer’s disease can be misinterpreted as indifference, or cause conflict in relationships.</span>
<span class="attribution"><span class="source">(Shutterstock)</span></span>
</figcaption>
</figure>
<p>Many times, younger patients will notice changes in their cognition at very early stages. They may notice increased difficulty in organization or planning. They may forget how to do complex tasks or forget appointments. Cognitive impairment is more obvious when completing highly demanding tasks at work or co-ordinating family logistics. </p>
<p>When a young person goes to see their doctor and reports such changes in cognition, the “d” word brought up is usually depression and not dementia. </p>
<p>Until the correct diagnosis is made, there can be many misinterpretations of their changes in thinking — resulting in conflicts with family, friends and colleagues.</p>
<h2>Divorce before diagnosis</h2>
<p>Initially, a change in personality can be misinterpreted by the partner as indifference, as a midlife crisis or as something else. </p>
<p>There can be a changing of roles within a couple and it is not uncommon for separation or divorce to occur before a diagnosis is even made. </p>
<p>If young children are involved, it can be difficult for them to understand the change in their parent’s personality.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/235312/original/file-20180906-190665-q9fsj6.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/235312/original/file-20180906-190665-q9fsj6.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/235312/original/file-20180906-190665-q9fsj6.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/235312/original/file-20180906-190665-q9fsj6.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/235312/original/file-20180906-190665-q9fsj6.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/235312/original/file-20180906-190665-q9fsj6.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/235312/original/file-20180906-190665-q9fsj6.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Anne Hunt looks to her husband, Bruce, to be reminded if she already added sugar or not to her dough in their home in Chicago on July 13, 2018. Diagnosed with Alzheimer’s in 2016, Anne, who once ran a Chicago cooking school, now has to separate the ingredients into two different sections of the kitchen to prevent errors.</span>
<span class="attribution"><span class="source">(AP Photo/Annie Rice)</span></span>
</figcaption>
</figure>
<p>Getting services for young-onset Alzheiner’s can be especially challenging. There are very few programs that cater to people with dementia under the age of 65. </p>
<p>Support for caregivers and family members of these patients is also lacking. There is a dire need for specialized programs and long-term care facilities that can accommodate those under 65.</p>
<h2>‘Use it or lose it’</h2>
<p>Although we have no cure for any patients with Alzheimer’s, there are clinical trials that are targeting the abnormal proteins that build up during the disease. </p>
<p>There is symptomatic medication — such as acetylcholinesterase inhibitors — that can help memory. </p>
<p>We also promote a healthy lifestyle that includes aerobic exercise because <a href="https://doi.org/10.1111/jgs.15241">evidence shows this can slow neurodegeneration</a>. We want people to remain cognitively active and go on learning to help their brain reserve. </p>
<p>Although patients with young-onset Alzheiner’s are impaired in some activities, there are many other activities that they can participate in. “Use it or lose it” is the motto we should live by when it comes to the brain and preserving its function.</p>
<p>Young-onset Alzheimer’s is not the only dementia that typically affects the young. <a href="https://www.alz.org/alzheimers-dementia/what-is-dementia/types-of-dementia/frontotemporal-dementia">Frontotemporal dementia</a> also strikes young people. And although there are differences in presentation in these two illnesses, many of the challenges facing patients are the same.</p>
<p>Ongoing research is required to better understand this disease. While we search for a cure, we need to appreciate the special needs of this population. We need to target research and services to better serve patients and their families.</p><img src="https://counter.theconversation.com/content/102330/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Carmela Tartaglia receives funding from CIHR, NIH, Biogen, Eli Lilly, Roche, AstraZeneca. She is affiliated with the Alzheimer's Society of Toronto. </span></em></p>Alzheimer’s disease affects many people under the age of 65. The ‘young-onset’ version of the disease is often misdiagnosed as depression or dismissed as a midlife crisis.Carmela Tartaglia, Clinician-Scientist, University Health Network and Associate Professor, University of TorontoLicensed as Creative Commons – attribution, no derivatives.