risk factors

Tau tangles why TBI increases risk of Alzheimer's

  • Mouse study shows tau tangles may be behind increased Alzheimer's risk for those who have suffered a traumatic brain injury.

We know that traumatic brain injury increases the risk of later developing neurodegenerative disorders such as Alzheimer's disease, but we haven't known why. New mouse studies suggest a reason.

In the research, mice who had a toxic form of tau protein (taken from mice who had suffered TBI) injected into their hippocampus, showed impaired memory and cognition. Moreover, levels of the aggregated tau protein not only increased in the hippocampus, but also in the cerebellum (which is quite some distance away from the hippocampus). This is consistent with other research showing that tau tangles spread from the initial injection site, using mice modeling Alzheimer's disease.

The study followed on from previous research showing that this form of tau protein increases after a traumatic brain injury and may contribute to development of chronic traumatic encephalopathy (a condition experienced by many professional athletes and military personnel).

The findings support the hypothesis that many of the symptoms of TBI may be down to an increase in these tau tangles, and that this may also be responsible for the increased risk for neurodegenerative disease. As an obvious corollary, it also suggests that the tau tangles are an important therapeutic target.

http://www.eurekalert.org/pub_releases/2016-01/uotm-tbi011216.php

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More evidence that stress increases risk of Alzheimer's

  • A stress hormone has been found to be associated with more amyloid-beta protein, in mice and human neurons.
  • The finding helps explain why stress is a risk factor for Alzheimer's.
  • A previous 38-year study supports this with the finding that women who scored highly in "neuroticism" in middle age, had a greater chance of later developing Alzheimer's.
  • This link was largely accounted for by chronic stress experienced by these women over the four decades.

A study involving both mice and human cells adds to evidence that stress is a risk factor for Alzheimer's.

The study found that mice who were subjected to acute stress had more amyloid-beta protein in their brains than a control group. Moreover, they had more of a specific form of the protein, one that has a particularly pernicious role in the development of Alzheimer's disease.

When human neurons were treated with the stress hormone corticotrophin releasing factor (CRF), there was also a significant increase in the amyloid proteins.

It appears that CRF causes the enzyme gamma secretase to increase its activity. This produces more amyloid-beta.

The finding supports the idea that reducing stress is one part of reducing your risk of developing Alzheimer's.

A neurotic personality increases the risk of Alzheimer's disease

An interesting study last year supports this.

The study, involving 800 women who were followed up some 40 years after taking a personality test, found that women who scored highly in "neuroticism" in middle age, have a greater chance of later developing Alzheimer's. People who have a tendency to neuroticism are more readily worried, distressed, and experience mood swings. They often have difficulty in managing stress.

The women, aged 38 to 54, were first tested in 1968, with subsequent examinations in 1974, 1980, 1992, 2000, and 2005. Neuroticism and extraversion were assessed in 1968 using the Eysenck Personality Inventory. The women were asked whether they had experienced long periods of high stress at each follow-up.

Over the 38 years, 153 developed dementia (19%), of whom 104 were diagnosed with Alzheimer's (13% of total; 68% of those with dementia).

A greater degree of neuroticism in midlife was associated with a higher risk of Alzheimer's and long-standing stress. This distress accounted for a lot of the link between neuroticism and Alzheimer's.

Extraversion, while associated with less chronic stress, didn't affect Alzheimer's risk. However, high neuroticism/low extraversion (shy women who are easily worried) was associated with the highest risk of Alzheimer's.

The finding supports the idea that long periods of stress increase the risk of Alzheimer's, and points to people with neurotic tendencies, who are more sensitive to stress, as being particularly vulnerable.

http://www.eurekalert.org/pub_releases/2015-09/uof-uhr091615.php

http://www.eurekalert.org/pub_releases/2014-10/uog-anp101414.php

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Sleeping on your side best for clearing waste from brain

  • Waste products accumulate as the brain functions.
  • The process of clearing this waste is most effective during sleep.
  • Accumulation of waste products such as amyloid-beta and tau proteins are involved in Alzheimer's.
  • Rat study shows sleeping on your side is best for removing waste from the brain.

This sounds like pseudoscience, but it appears in Journal of Neuroscience, so … Weirdly, a rat study has found that sleeping on the side (the most common posture for humans and other animals) is the best position for efficiently removing waste from the brain.

Brain waste includes amyloid-beta and tau proteins, whose build-up is a critical factor in the development of Alzheimer's disease.

The study used imaging of the glymphatic pathway, which clears waste products from the brain by filtering cerebrospinal fluid through the brain and exchanging it with interstitial fluid. The process is most efficient during sleep, and its efficiency is affected by the level of consciousness. The researchers compared glymphatic transport during sleep when anesthetized rodents’ brains were in three positions—lateral (side), prone (down), and supine (up).

Of course, these findings need to be confirmed in humans (which might be tricky!), but there is, after all, no harm in changing your sleep position, if you don't already sleep on your side (though I concede it can be a difficult thing to change).

Apart from providing a practical tip for fighting age-related cognitive decline and dementia, the finding also supports the idea that one of the purposes of sleep is to ‘clean up’ the mess that accumulates while we are awake.

The finding is also consistent with increasing evidence that sleep disturbances are a factor in the development and progression of dementia.

http://www.futurity.org/side-sleeping-brains-979872/

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[3956] Lee, H., Xie L., Yu M., Kang H., Feng T., Deane R., et al.
(2015).  The Effect of Body Posture on Brain Glymphatic Transport.
The Journal of Neuroscience. 35(31), 11034 - 11044.

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Better hygiene in wealthy nations may increase Alzheimer's risk

A comparison of Alzheimer’s prevalence across the world using 'age-standardized' data (which predict Alzheimer's rates if all countries had the same population birth rate, life expectancy and age structure) has found a strong correlation between national sanitation levels and Alzheimer's, with better hygiene associated with higher rates of Alzheimer’s.

This fits in with the idea that’s been floating around for a while, that over-sanitized environments reduce exposure to a diverse range of microorganisms, perhaps impairing proper development of the immune system. Hence, the rising incidence of allergies and auto-immune diseases in developed countries.

The study compared data from 192 countries. Higher rates of Alzheimer's were seen in countries with higher levels of sanitation, countries with much lower rates of infectious disease, and more urbanized countries. For example, UK and France have 9% higher Alzheimer's rates than Kenya and Cambodia; Switzerland and Iceland have 12% higher rates of Alzheimer's than China and Ghana; UK and Australia have 10% higher rates than Bangladesh and Nepal.

Differences in levels of sanitation, infectious disease and urbanization accounted respectively for 33%, 36% and 28% of the discrepancy in Alzheimer's rates between countries.

Previous research has shown that in the developed world, dementia rates doubled every 5.8 years compared with 6.7 years in low income, developing countries, and that Alzheimer's prevalence in Latin America, China and India are all lower than in Europe, and, within those regions, lower in rural compared with urban settings.

Having said all that, I would query the reliability of Alzheimer’s statistics from less developed countries. A recent study from China, for example, found dramatic under-reporting of Alzheimer’s. While this is certainly a plausible hypothesis, I think the wide variability in diagnosing Alzheimer’s stands in the way of this sort of comparison.

http://www.eurekalert.org/pub_releases/2013-09/uoc-bhi090413.php

http://www.theguardian.com/society/2013/sep/04/alzheimers-disease-link-hygiene

Full text freely available at http://emph.oxfordjournals.org/content/2013/1/173.full

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Gum disease may have ties to Alzheimer’s

Analysis of post-mortem with and without dementia has found lipopolysaccharide, a component of an oral bacterium (Porphyromonas gingivalis), in four out of 10 Alzheimer’s disease brain samples, but not in any of the 10 brains of people who didn’t have Alzheimer’s.

Gingivitis is extremely common, and about 64% of American seniors (65+) have moderate or severe periodontal disease.

The finding adds to evidence linking gum disease and Alzheimer’s.

http://www.futurity.org/alzheimers-may-ties-gum-disease/

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Pesticide DDT linked to higher Alzheimer’s risk

A study comparing blood serum levels of the DDT metabolite, DDE, in 86 patients with Alzheimer's disease (average age 74) and 79 controls (average age 70), has found that levels of DDE were 3.8 times higher in 74 of the 86 Alzheimer’s patients (86%). Having the Alzheimer’s gene, APOe4, plus high levels of the pesticide, produced more severe cognitive impairment.

Brain cell studies found that DDE increased production of the amyloid precursor protein (APP).

DDT was banned in the U.S. in 1972, but is still used elsewhere. It also takes a long time to break down in the environment. DDE was found in 75-80% of blood samples collected from the Centers for Disease Control and Prevention for a national health and nutrition survey.

http://www.eurekalert.org/pub_releases/2014-01/usmc-rfe012914.php

http://www.futurity.org/ddt-exposure-linked-higher-alzheimers-risk/

Reference: 

[3602] Richardson, J. R., Roy A., SL S., & et al
(2014).  ELevated serum pesticide levels and risk for alzheimer disease.
JAMA Neurology. 71(3), 284 - 290.

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Chronic sleep disturbance could trigger onset of Alzheimer's

A mouse study has found that mice (genetically engineered for Alzheimer’s) who were sleep deprived for eight weeks, not only showed significant cognitive impairment, but also showed a significant increase in the amount of tau protein that became phosphorylated and formed tangles. The other main characteristic of Alzheimer’s, amyloid-beta plaques, was not affected.

The findings are consistent with growing evidence of a link between sleep disturbance and Alzheimer’s, and suggests that chronic sleep disturbance accelerates Alzheimer’s pathology, and should be treated.

The sleep-deprived mice were given 20 hours of light each day, while the control mice were kept on a schedule of 12 hours of light and 12 hours of darkness.

http://www.eurekalert.org/pub_releases/2014-03/tu-csd031714.php

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Lower IQ & fitness in teen years increases risk of early-onset dementia

Data from 1.1 million young Swedish men (conscription information taken at age 18) has shown that those with poorer cardiovascular fitness were 2.5 times more likely to develop early-onset dementia later in life and 3.5 times more likely to develop mild cognitive impairment, while those with a lower IQ had a 4 times greater risk of early dementia and a threefold greater risk of MCI. A combination of both poor cardiovascular fitness and low IQ entailed a more than 7 times greater risk of early-onset dementia, and more than 8 times greater risk of MCI.

The increased risk remained even when controlled for other risk factors, such as heredity, medical history, and social-economic circumstances.

The development of early-onset dementia was taken from national disease registries. During the study period, a total of 660 men were diagnosed with early-onset dementia.

A further study of this database, taken from 488,484 men, of whom 487 developed early-onset dementia (at a median age of 54), found nine risk factors for early-onset dementia that together accounted for 68% of the attributable risk. These factors were alcohol intoxication, stroke, use of antipsychotics, depression, father's dementia, drug intoxication other than alcohol, low cognitive function at age 18, low stature at age 18, and high blood pressure at age 18.

http://brain.oxfordjournals.org/content/early/2014/03/06/brain.awu041.abstract

http://www.eurekalert.org/pub_releases/2014-03/uog-lii031014.php

http://www.jwatch.org/content/2013/NA32051?query=etoc_jwneuro

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