(17-11-07) Long-Chain Omega-3s of Little Clinical Benefit in Alzheimer?s Symptoms

Increasing longevity has resulted in a dramatic increase in the number of elderly patients with impaired cognition and inability to function independently. The worldwide prevalence of dementia has been estimated at nearly 28 million, with someone (in the U.S.) developing Alzheimer?s disease every 72 seconds. Secrets for preventing this most common type of dementia remain undiscovered, although some lifestyle habits may be useful. These include being socially active, attaining higher education levels, engaging the mind and, from a dietary point of view, consuming fish regularly. Factors beyond one?s control, such as age, genetic susceptibility and carrying the APOE-ε4 gene increase the chance of developing the condition later in life.

Long-chain polyunsaturated fatty acids (LC-PUFAs), especially docosahexaenoic acid (DHA) and arachidonic acid are significantly decreased in the brains of Alzheimer?s patients, but there is scant evidence that treatment with omega-3 (n-3) LC-PUFAs affect the course of the disease. In the early phase of the disease, increased consumption of DHA-rich n-3 LC-PUFAs may slow its insidious progress. In this second report from a randomized, double-blind, placebo-controlled trial of the effects of n-3 LC-PUFAs in early Alzheimer?s disease, Yvonne Freund-Levi and colleagues at the Karolinska University Hospital in Sweden describe the neuropsychiatric effects of 6 and 12 months of supplementation. Of the original 204 participants, 174 completed the study. Patients averaged 73 years of age.

The study protocol called for supplementation with n-3 LC-PUFAs (600 mg eicosapentaenoic acid (EPA) + 1,720 mg DHA) or corn oil for 6 months, followed by open treatment of all participants with n-3 LC-PUFAs. Several outcomes were assessed at baseline, 6 and 12 months. These included the Neuropsychiatric Inventory of 12 behavioral domains, Montgomery ?sborg Depression rating scale, caregivers burden scale (3 items) and the Disability Assessment for Dementia scale, which assesses daily living activities.

Less than 10% of participants exhibited psychotic symptoms and scores for neuropsychiatric symptoms were low in both groups. Total neuropsychiatric, depression, caregivers burden and daily living scores did not differ between the two groups at 6 or 12 months. Within the neuropsychiatric domains, however, there were significant improvements in hallucinations with the consumption of n-3 LC-PUFAs and in irritation scores with the placebo. When scores were adjusted for age, APOE genotype and gender, these differences were not significant. Interestingly, in the adjusted analysis, agitation was significantly improved in participants carrying the APOE-ε4 gene. There was a significant interaction between treatment and APOE genotype with agitation and total depression score. No other outcomes were affected by treatment.

Overall, these findings suggest that consuming modest amounts of n-3 LC-PUFAs in early Alzheimer?s disease has only a slim benefit, which is related to the APOE genotype. Agitation improved in carriers of the APOE-ε4 gene and overall depression score improved in non-carriers. The latter observation is consistent with improved depression scores in non-Alzheimer?s patients consuming n-3 LC-PUFAs.

Several factors may have clouded the possible benefits from n-3 LC-PUFAs. One is the dose of 2.3 g n-3 LC-PUFAs/day. Late in life, even higher doses may be needed to reach effectiveness.

Another consideration is the effect of Alzheimer?s medications and anti-depressants. These may have shadowed the treatment effects of n-3 LC-PUFAs. Of course, it is also possible that brain function at this stage of the condition is relatively impervious to an additional supply of n-3 LC-PUFAs. DHA has been effective in suppressing the production of the abnormal beta-amyloid proteins in animal models of the disease and in human neural cells, but whether and at what stage it may be effective in people is unknown. This randomized trial is contributing useful information to the field, but shows the large gap between animal studies and what may be occurring in the seventh stage of man.

Source: Mental Health, Freund-Levi Y, Basun H, Cederholm T, Faxen-Irving G, Garlind A, Grut M, Vedin I, Palmblad J, Wahlund LO, Eriksdotter-Jonhagen M. Omega-3 supplementation in mild to moderate Alzheimer?s disease: effects on neuropsychiatric symptoms. Int J Geriatr Psychiatry 2007; doi:10.1002/gps.1857

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