| 1. |
- Freund-Levi, Yvonne, 1956-, et al.
(author)
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Omega-3 fatty acid treatment in 174 patients with mild to moderate Alzheimer disease : OmegAD study - A randomized double-blind trial
- 2006
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In: Archives of Neurology. - : American Medical Association (AMA). - 0003-9942 .- 1538-3687. ; 63:10, s. 1402-1408
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Journal article (peer-reviewed)abstract
- Background: Epidemiologic and animal studies have suggested that dietary fish or fish oil rich in omega-3 fatty acids, for example, docosahexaenoic acid and eicosapentaenoic acid, may prevent Alzheimer disease (AD). Objective: To determine effects of dietary omega-3 fatty acid supplementation on cognitive functions in patients with mild to moderate AD. Design: Randomized, double-blind, placebo-controlled clinical trial. Participants: Two hundred four patients with AD (age range [mean +/- SD], 74 +/- 9 years) whose conditions were stable while receiving acetylcholine esterase inhibitor treatment and who had a Mini-Mental State Examination (MMSE) score of 15 points or more were randomized to daily intake of 1.7 g of docosahexaenoic acid and 0.6 g of eicosapentaenoic acid (omega-3 fatty acid-treated group) or placebo for 6 months, after which all received omega-3 fatty acid supplementation for 6 months more. Main Outcome Measures: The primary outcome was cognition measured with the MMSE and the cognitive portion of the Alzheimer Disease Assessment Scale. The secondary outcome was global function as assessed with the Clinical Dementia Rating Scale; safety and tolerability of omega-3 fatty acid supplementation; and blood pressure determinations. Results: One hundred seventy-four patients fulfilled the trial. At baseline, mean values for the Clinical Dementia Rating Scale, MMSE, and cognitive portion of the Alzheimer Disease Assessment Scale in the 2 randomized groups were similar. At 6 months, the decline in cognitive functions as assessed by the latter 2 scales did not differ between the groups. However, in a subgroup (n=32) with very mild cognitive dysfunction (MMSE > 27 points), a significant (P <.05) reduction in MMSE decline rate was observed in the omega-3 fatty acid-treated group compared with the placebo group. A similar arrest in decline rate was observed between 6 and 12 months in this placebo subgroup when receiving omega-3 fatty acid supplementation. The omega-3 fatty acid treatment was safe and well tolerated. Conclusions: Administration of omega-3 fatty acid in patients with mild to moderate AD did not delay the rate of cognitive decline according to the MMSE or the cognitive portion of the Alzheimer Disease Assessment Scale. However, positive effects were observed in a small group of patients with very mild AD (MMSE > 27 points).
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| 2. |
- Freund-Levi, Yvonne, 1956-, et al.
(author)
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Omega-3 supplementation in mild to moderate Alzheimer's disease : effects on neuropsychiatric symptoms
- 2008
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In: International Journal of Geriatric Psychiatry. - : Wiley. - 0885-6230 .- 1099-1166. ; 23:2, s. 161-169
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Journal article (peer-reviewed)abstract
- Background: Epidemiological and animal studies have suggested that dietary fish or fish oil rich in omega-3 fatty acids (ω3), docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), may have effects in psychiatric and behavioral symptoms in Alzheimer's disease (AD). An association with APOEω4 carriers and neuropsychiatric symptoms in AD has also been suggested. Objective: To determine effects of dietary ω3 supplementation to AD patients with mild to moderate disease on psychiatric and behavioral symptoms, daily functions and a possible relation to APOEgenotype. Methods: Randomized, double-blind, placebo-controlled clinical trial where 204 AD patients (74 ± 9 years) with acetylcholine esterase inhibitor treatment and a MMSE >15 points were randomized to daily intake of 1.7 g DHA and 0.6 g EPA (ω3 group) or placebo for 6 months. Then, all received the ω3 supplementation for 6 more months. Neuropsychiatric symptoms were measured with Neuropsychiatric Inventory (NPI) and Montgomery Åsberg Depression Scale (MADRS). Caregivers burden and activities of daily living (Disability Assessment for Dementia, DAD) were also assessed. Results: One hundred and seventy-four patients fulfilled the trial. 72% were APOEω4 carriers. No significant overall treatment effects on neuropsychiatric symptoms, on activities of daily living or on caregiver's burden were found. However, significant positive treatment effects on the scores in the NPI agitation domain in APOEω4 carriers (p = 0.006) and in MADRS scores in non-APOEω4 carriers (p = 0.005) were found. Conclusions: Supplementation with ω3 in patients with mild to moderate AD did not result in marked effects on neuropsychiatric symptoms except for possible positive effects on depressive symptoms (assessed by MADRS) in non-APOEω4 carriers and agitation symptoms (assessed by NPI) in APOEω4 carriers. ClinicalTrials.gov identifier: NCT00211159.
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| 3. |
- Johansson, Ann-Sofi, et al.
(author)
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Docosahexaenoic acid stabilizes soluble amyloid-β protofibrils and sustains amyloid-β induced neurotoxicity in vitro
- 2007
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In: The FEBS Journal. - : Wiley. - 1742-464X .- 1742-4658. ; 274:4, s. 990-1000
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Journal article (peer-reviewed)abstract
- Enrichment of diet and culture media with the polyunsaturated fatty acid docosahexaenoic acid has been found to reduce the amyloid burden in mice and lower amyloid-β (Aβ) levels in both mice and cultured cells. However, the direct interaction of polyunsaturated fatty acids, such as docosahexaenoic acid, with Aβ, and their effect on Aβ aggregation has not been explored in detail. Therefore, we have investigated the effect of docosahexaenoic acid, arachidonic acid and the saturated fatty acid arachidic acid on monomer oligomerization into protofibrils and protofibril fibrillization into fibrils in vitro, using size exclusion chromatography. The polyunsaturated fatty acids docosahexaenoic acid and arachidonic acid at micellar concentrations stabilized soluble Aβ42 wild-type protofibrils, thereby hindering their conversion to insoluble fibrils. As a consequence, docosahexaenoic acid sustained amyloid-β-induced toxicity in PC12 cells over time, whereas Aβ without docosahexaenoic acid stabilization resulted in reduced toxicity, as Aβ formed fibrils. Arachidic acid had no effect on Aβ aggregation, and neither of the fatty acids had any protofibril-stabilizing effect on Aβ42 harboring the Arctic mutation (AβE22G). Consequently, AβArctic-induced toxicity could not be sustained using docosahexaenoic acid. These results provide new insights into the toxicity of different Aβ aggregates and how endogenous lipids can affect Aβ aggregation.
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| 4. |
- Lekander, Mats, et al.
(author)
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Cytokines and memory across the mature life span of women
- 2011
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In: Scandinavian Journal of Psychology. - : Wiley. - 0036-5564 .- 1467-9450. ; 52:3, s. 229-235
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Journal article (peer-reviewed)abstract
- Increasing evidence suggests a role of the immune system in modulation of cognition, but details on affected memory systems are largely lacking. We therefore aimed to study the relation between selected cytokines and subsets of memory, and the impact of age in these relations. From a random population-based sample (the Betula Prospective Cohort Study), 298 women (age 45-90) were studied in terms of episodic recall and recognition, semantic fluency and knowledge, and prospective memory. Circulating cytokines of relevance for cognition and aging were measured with ELISA. Levels of interleukin (IL)-6 and sIL-2R were significantly and negatively associated with most cognitive variables, while the opposite was true for IL-1 beta. Age shared substantial variance with both cytokines and memory, and turned most correlations non-significant when controlled for together with education, BMI and presence of disease. Interactions between age and cytokines were further analyzed in multiple regressions. For IL-6, significant negative interactions with age were found for semantic fluency (p < 0.05) and prospective memory (p < 0.01), and for sIL-2R in predicting semantic knowledge (p < 0.05), indicating an increased negative impact of these cytokines on memory with increasing age. In conclusion, the study indicates a relation between cytokines and memory that appears to be largely mediated by age, and supports the suggestion that cytokine dysregulation with higher age may interact with cognitive aging.
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| 6. |
- Vedin, Inger, et al.
(author)
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Effects of DHA-rich n-3 fatty acid supplementation on gene expression in blood mononuclear leukocytes : the OmegAD study
- 2012
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In: PLOS ONE. - : PLOS. - 1932-6203. ; 7:4
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Journal article (peer-reviewed)abstract
- BACKGROUND: Dietary fish oil, rich in n-3 fatty acids (n-3 FAs), e.g. docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), regulate inflammatory reactions by various mechanisms, e.g. gene activation. However, the effects of long-term treatment with DHA and EPA in humans, using genome wide techniques, are poorly described. Hence, our aim was to determine the effects of 6 mo of dietary supplementation with an n-3 FA preparation rich in DHA on global gene expression in peripheral blood mononuclear cells.METHODS AND FINDINGS: In the present study, blood samples were obtained from a subgroup of 16 patients originating from the randomized double-blind, placebo-controlled OmegAD study, where 174 Alzheimer disease (AD) patients received daily either 1.7 g of DHA and 0.6 g EPA or placebo for 6 months. In blood samples obtained from 11 patients receiving n-3 FA and five placebo, expressions of approximately 8000 genes were assessed by gene array. Significant changes were confirmed by real-time PCR. At 6 months, the n-3 FAs group displayed significant rises of DHA and EPA plasma concentrations, as well as up- and down-regulation of nine and ten genes, respectively, was noticed. Many of these genes are involved in inflammation regulation and neurodegeneration, e.g. CD63, MAN2A1, CASP4, LOC399491, NAIP, and SORL1 and in ubiqutination processes, e.g. ANAPC5 and UBE2V1. Down-regulations of ANAPC5 and RHOB correlated to increases of plasma DHA and EPA levels.CONCLUSIONS: We suggest that 6 months of dietary n-3 FA supplementation affected expression of genes that might influence inflammatory processes and could be of significance for AD.TRIAL REGISTRATION: ClinicalTrials.gov NCT00211159.
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| 7. |
- Vedin, Inger, et al.
(author)
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Effects of docosahexaenoic acid-rich n-3 fatty acid supplementation on cytokine release from blood mononuclear leukocytes : the OmegAD study
- 2008
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In: American Journal of Clinical Nutrition. - : HighWire Press. - 0002-9165 .- 1938-3207. ; 87:6, s. 1616-1622
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Journal article (peer-reviewed)abstract
- BACKGROUND: Dietary fish or fish oil rich in n-3 fatty acids (n-3 FAs), eg, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), ameliorate inflammatory reactions by various mechanisms. Whereas most studies have explored the effects of predominantly EPA-based n-3 FAs preparations, few have addressed the effects of n-3 FAs preparations with DHA as the main FA.OBJECTIVE: The objective was to determine the effects of 6 mo of dietary supplementation with an n-3 FAs preparation rich in DHA on release of cytokines and growth factors from peripheral blood mononuclear cells (PBMCs).DESIGN: In a randomized, double-blind, placebo-controlled trial, 174 Alzheimer disease (AD) patients received daily either 1.7 g DHA and 0.6 g EPA (n-3 FAs group) or placebo for 6 mo. In the present study blood samples were obtained from the 23 first randomized patients, and PBMCs were isolated before and after 6 mo of treatment.RESULTS: Plasma concentrations of DHA and EPA were significantly increased at 6 mo in the n-3 FAs group. This group also showed significant decreases of interleukin (IL)-6, IL-1beta, and granulocyte colony-stimulating factor secretion after stimulation of PBMCs with lipopolysaccharide. Changes in the DHA and EPA concentrations were negatively associated with changes in IL-1beta and IL-6 release for all subjects. Reductions of IL-1beta and IL-6 were also significantly correlated with each other. In contrast, this n-3 FA treatment for 6 mo did not decrease tumor necrosis factor-alpha, IotaL-8, IL-10, and granulocyte-macrophage colony-stimulating factor secretion.CONCLUSION: AD patients treated with DHA-rich n-3 FAs supplementation increased their plasma concentrations of DHA (and EPA), which were associated with reduced release of IL-1beta, IL-6, and granulocyte colony-stimulating factor from PBMCs. This trial was registered at clinicaltrials.gov as NCT00211159.
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