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Alzheimer's disease consists of 3 distinct subtypes

  • A very small study points to three subtypes of Alzheimer's disease, each of which seems to be associated with:
    • different physiological abnormalities
    • different causes and risk factors
    • different symptoms / progression
    • different age-onsets.
  • This suggests that effective treatments need to be tailored to the subtype.

A two-year study which involved metabolic testing of 50 people, suggests that Alzheimer's disease consists of three distinct subtypes, each one of which may need to be treated differently. The finding may help explain why it has been so hard to find effective treatments for the disease.

The subtypes are:

  • Inflammatory, in which markers such as C-reactive protein and serum albumin to globulin ratios are increased.
  • Non-inflammatory, in which these markers are not increased but other metabolic abnormalities (such as insulin resistance, hypovitaminosis D, and hyper-homocysteinemia) are present. This tends to affect slightly older individuals than the first subtype: 80s rather than 70s.
  • Cortical, which affects relatively young individuals (typically 50s- early 70s) and appears more widely distributed across the brain than the other subtypes, showing widespread cortical atrophy rather than marked hippocampal atrophy. It typically presents with language and number difficulties first, rather than memory loss. Typically, there is an impaired ability to hold onto a train of thought. It is often misdiagnosed, typically affects people without a family history of Alzheimer's, who do not have an Alzheimer's-related gene, and is associated with a significant zinc deficiency (Zinc is implicated in multiple Alzheimer's-related metabolic processes, such as insulin resistance, chronic inflammation, ADAM10 proteolytic activity, and hormonal signaling. Zinc deficiency is relatively common, and associated with increasing age.).

The cortical subtype appears to be fundamentally a different condition than the other two.

I note a study I reported on last year, that found different molecular structures of amyloid-beta fibrils in the brains of Alzheimer's patients with different clinical histories and degrees of brain damage. That was a very small study, indicative only. However, I do wonder if there's any connection between these two findings. At the least, I think this approach a promising one.

The idea that there are different types of Alzheimer's disease is of course consistent with the research showing a variety of genetic risk factors, and an earlier study indicating at least two pathways to Alzheimer's.

It's also worth noting that the present study built on an earlier study, which showed that a program of lifestyle, exercise and diet changes designed to improve the body's metabolism reversed cognitive decline within 3-6 months in nine out of 10 patients with early Alzheimer's disease or its precursors. Note that this was a very small pilot program, and needs a proper clinical trial. Nevertheless, it is certainly very interesting.

http://www.eurekalert.org/pub_releases/2015-09/uoc--adc091615.php

Reference: 

Bredesen, D.E. 2015. Metabolic profiling distinguishes three subtypes of Alzheimer's disease. AGING, 7 (8), 595-600. Full text at http://www.impactaging.com/papers/v7/n8/full/100801.html

Bredesen, D.E. 2014. Reversal of cognitive decline: A novel therapeutic program. AGING, Vol 6, No 9 , pp 707-717. Full text at http://www.impactaging.com/papers/v6/n9/full/100690.html

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These 5 healthy habits reduce dementia risk

There are five healthy behaviors that appear to significantly reduce the risk of dementia,

A 35-year study that monitored the healthy behaviors of 2,235 Welsh men aged 45 to 59 at the beginning of the study has found that those who consistently followed at least four of these five healthy behaviors — regular exercise, no smoking, acceptable BMI, high fruit and vegetable intake, and low/moderate alcohol intake — experienced a 60% reduction in dementia and cognitive decline compared with people who followed none. They also had 70% fewer instances of diabetes, heart disease, and stroke,.

Exercise was the most important of these factors.

Only 5% of the men were living a healthy lifestyle (i.e., following at least 4 of these healthy behaviors). Just under half of the 2235 men were non-smokers (46%), and around a third (35%) had an acceptable BMI. Only 15 men ate their “5+” daily (!!), so the requirement was reduced to only three or more portions of fruit and vegetables, enabling 18% to reach it. 39% exercised regularly and 59% reported alcohol intake within the guidelines. Only two men managed five healthy behaviors, and 109 managed four; 19% managed three; 36% two; 31% one; 8% couldn’t manage any.

http://www.futurity.org/five-healthy-behaviors-can-reduce-dementia-risk/

http://www.eurekalert.org/pub_releases/2013-12/cu-3ys120913.php

Reference: 

Elwood, P., Galante, J., Pickering, J., Palmer, S., Bayer, A., Ben-Shlomo, Y., … Gallacher, J. (2013). Healthy Lifestyles Reduce the Incidence of Chronic Diseases and Dementia: Evidence from the Caerphilly Cohort Study. PLoS ONE, 8(12), e81877. doi:10.1371/journal.pone.0081877

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Supplements don’t reduce risk of cardiovascular disease in elderly

Data from AREDS2, involving 4,203 older adults with age-related macular degeneration, has found that daily dietary supplements of either omega-3 polyunsaturated fatty acids (also found in fish) or lutein and zeaxanthin (nutrients found in green leafy vegetables) were not associated with reduced risk for cardiovascular disease (CVD).

http://www.eurekalert.org/pub_releases/2014-03/tjnj-sna031414.php

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Mediterranean diet may lower risk of diabetes

A review of 19 studies involving over 162,000 people has found that adherence to the Mediterranean diet was associated with a 21% reduced risk of diabetes, with a greater effect (27%) for those at high risk for cardiovascular disease. The association was found in both European and non-European groups.

The research was presented at the American College of Cardiology's 63rd Annual Scientific Session.

http://www.eurekalert.org/pub_releases/2014-03/acoc-mdm032614.php

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