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Fish Oil May Halt Memory Decline in Alzheimer's
Preliminary clinical trial shows delay in disease progression from early stages; findings support studies linking fish consumption to reduced risk of dementia
10/12/2006By Craig Weatherby
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Alzheimer’s disease is the most frequent form of dementia, and its economic cost in the US is estimated in excess of $100 billion. 

Given the rapid rise in numbers of aging baby boomers and the critical need for practical ways to prevent Alzheimer's disease, the positive research results reported this week from Sweden offer a rare ray of hope.

The results of prior epidemiological studies indicated that people who eat ample amounts of fish routinely enjoy reduced risks of Alzheimer's disease and other forms of senile dementia (see "New Findings Boost Brain-Protecting Power of Fish”).

Key Points
  • First-ever clinical trial reduces progression of the disease in mild, early-stage Alzheimer's cases.

  • Findings are supported by evidence of mechanisms by which omega-3s might work.

  • Results fit with the preventive effect of fish-heavy diets seen in population studies.
Now, in the first such study ever conducted, researchers at Stockholm’s Karolinska Institute and Uppsala University Hospital conducted a controlled clinical trial designed to test the effects of omega-3 fish oil supplements in people in various stage of Alzheimer’s disease.

The Swedish team, led by Yvonne Freund-Levi, MD, recruited 204 patients for a one-year placebo-controlled clinical trial that was divided into two six-month two phases:
  • During the first six months, the participants were assigned randomly to take either fish oil capsules containing omega-3 fatty acids (1720 mg of DHA and 600 mg of EPA) or placebo capsules containing corn oil.

  • During the second six-month period, the participants all received omega-3 capsules.
In accordance with standard medical practice, all the subjects were taking prescribed cholinesterase-inhibitor drugs (e.g., Aricept™), which prevent breakdown of the neurotransmitter acetylcholine and are typically given to patients in the early stages of the disease.

Thirty subjects dropped out during the study, leaving 174 at the end of the year-long trial.

The mental status of each participant was tracked by standard cognitive-performance assessment tests administered at the start of the study, after the first six months, and during the final six-month phase.

Omega-3s slow disease pace in patients with mild, early Alzheimer’s
At the end of the first six months, the assessment tests indicated that there had been significantly less decline in mental status among the 32 members of the omega-3 group who’d been diagnosed with very mild, early-stage Alzheimer’s, compared with their counterparts in the placebo group.

As Dr. Freund-Levi said, "… our study indicated that the omega-3 fatty acid preparation conferred a slower decline of cognition in those with the mildest impairment compared with placebo control subjects with a similar degree of cognitive dysfunction at the start of the study.”

And even the members of the placebo group with mild Alzheimer’s enjoyed similar therapeutic benefits during the second six months, when they, too, started taking omega-3 fatty supplements.

(The mental status of participants suffering from moderate or advanced stages of Alzheimer’s continued to decline, regardless of which group they started in.)

The improvements seen among the people in early-stage Alzheimer’s disease were most apparent in their short-term memory capacity, which ranks among the first and most crippling impacts of Alzheimer’s disease.

We should note that the study had two limitations: the trial was relatively small, the second six-month period was not placebo-controlled, and the improvements seen in the assessment scores could have been due in part to "practice effects”.

Consequently, the research team called for larger trials in patients with mild cognitive impairment, and in people at high risk of Alzheimer’s disease.

Prior studies hold clues to omega-3s’ preventive and therapeutic effects
The cause of Alzheimer’s is not clear, but most evidence points to the build-up of brain plaques consisting of beta-amyloid protein deposits.

The body’s immune system attacks these plaques by mounting an inflammatory response that includes generation of the unstable oxygen compounds called free radicals, which damage and kill brain cells.

Because omega-3 fatty acids exert anti-inflammatory effects, it’s been assumed that this might account for the reduction in Alzheimer’s risk seen among fish-lovers in population studies.

While the Swedish research team detected no decrease in standard markers of inflammation among the members of the omega-3 group, they proposed that the anti-inflammatory influence of omega-3s may be effective before the onset of dementia symptoms:
  • "It is possible that when the disease is clinically apparent, the neuropathological involvement [brain damage] is too advanced to be substantially attenuated by anti-inflammatory [effects]”.

  • "Those results [of epidemiological studies] and the results from the present study support the idea that omega-3 fatty acids have a role in primary prevention of AD but not in treatment of manifest disease.”
And with regard to the anti-inflammatory properties of omega-3s, the Swedes seem to have overlooked the implications of a finding made last year by scientists at Louisiana State University (LSU).

DHA’s unique brain-protecting powers: the LSU discovery

In 2005, the LSU team discovered neuroprotectin D1 (NPD1): an anti-inflammatory compound that the body makes from omega-3 DHA (See "Research Reveals How Fish Oil Deters Alzheimer’s Disease”), which doesn’t affect the standard medical measures of inflammation but plays a key role in protecting the brain from the brain-cell die-off induced by accumulation of the inflammatory brain plaques that characterize Alzheimer's disease.

The "pro-plastic” effects of omega-3s
The mouse study we summarized in our last issue points to another possible preventive mechanism, having nothing to do with the anti-inflammatory properties of omega-3s (see "New Insight into Anti-Aging Brain Benefits of Omega-3s”).

Human aging is usually accompanied by decreased "neuro-plasticity” in the brain, and this deficit is largely responsible for age-related losses of memory and mental flexibility. Neuro-plasticity is the brain’s ability to form new connections (synapses) among its cells (neurons), and thereby adapt to external environments and form new memories.

A neurotransmitter called glutamate is critical to learning and memory formation, in part through its role in regulating neuro-plasticity. And as we reported, researchers found recently that rats fed omega-3s display complete reversals in age-related deficits in the glutamate receptors of brain cells.

It seems likely that, together with the LSU finding from 2005, the Brits’ recent discovery in rodents may explain why omega-3s seemed to benefit early-stage Alzheimer’s patients, and prevent some people from developing Alzheimer’s and other, less common forms of dementia.

  • Freund-Levi Y, Eriksdotter-Jönhagen M, Cederholm T, Basun H, Faxén-Irving G, Garlind A, Vedin I, Vessby B, Wahlund L, Palmblad J. n-3 Fatty Acid Treatment in 174 Patients With Mild to Moderate Alzheimer Disease: OmegAD Study: A Randomized Double-blind Trial. Arch Neurol. 2006;63:1402-1408.
  • Morris MC, Evans DA, Bienias JL, et al. Consumption of fish and n-3 fatty acids and risk of incident Alzheimer disease. Arch Neurol. 2003;60:940-946.
  • Morris MC, Evans DA, Tangney CC, Bienias JL, Wilson RS. Fish consumption and cognitive decline with age in a large community study. Arch Neurol. 2005 Dec;62(12):1849-53. Epub 2005 Oct 10.

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