| 1. |
- Freund-Levi, Yvonne, 1956-, et al.
(författare)
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Effects of omega-3 fatty acids on inflammatory markers in cerebrospinal fluid and plasma in Alzheimer's disease : the OmegAD study
- 2009
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Ingår i: Dementia and Geriatric Cognitive Disorders. - : S. Karger. - 1420-8008 .- 1421-9824. ; 27:5, s. 481-490
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: omega-3 fatty acids (omega-3 FAs) found in dietary fish or fish oils are anti-inflammatory agents that may influence Alzheimer's disease (AD).OBJECTIVE: To study the effects of dietary omega-3 FA supplementation on inflammatory markers in cerebrospinal fluid (CSF) and plasma from patients with mild to moderate AD.METHODS: Thirty-five patients (70.3 +/- 8.2 years) were randomized to a daily intake of 2.3 g omega-3 FAs or placebo for 6 months. The inflammatory markers interleukin (IL)-6, tumour necrosis factor-alpha and soluble interleukin-1 receptor type II (sIL-1RII) were analysed in CSF and plasma at baseline and at 6 months. The AD markers tau-protein, hyperphosphorylated tau-protein and beta-amyloid (Abeta(1-42)) were assessed in CSF. High-sensitivity C-reactive protein was assessed in plasma. A possible relation to the APOE genotype was investigated.RESULTS: There was no significant treatment effect of omega-3 FAs on inflammatory and AD biomarkers in CSF or on inflammatory markers in plasma, nor was there any relation with APOE. A significant correlation was observed at baseline between sIL-1RII and Abeta(1-42) levels in CSF.CONCLUSIONS: Treatment of AD patients with omega-3 FAs for 6 months did not influence inflammatory or biomarkers in CSF or plasma. The correlation between sIL-1RII and Abeta(1-42) may reflect the reciprocal interactions between IL-1 and Abeta peptides.
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| 2. |
- Freund-Levi, Yvonne, 1956-, et al.
(författare)
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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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Ingår i: Archives of Neurology. - : American Medical Association (AMA). - 0003-9942 .- 1538-3687. ; 63:10, s. 1402-1408
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Tidskriftsartikel (refereegranskat)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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| 3. |
- Freund-Levi, Yvonne
(författare)
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Omega-3 fatty acid treatment in mild to moderate Alzheimer's disease : results from the OmegAD study
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Alzheimer's disease (AD) is a major public health concern in all countries with an increasing prevalence. It is expected to quadruple by the year 2047. AD is a progressive neurodegenerative disease with a multifactorial origin, where a body of genetic and biochemical evidence, inflammatory aspects as well as the pivotal role of soluble amyloid β peptide (Aβ) may be the proximate cause of synaptic injuries and neuronal death leading to cognitive and neuropsychiatric decline leading to suffering in both the patient and the caregiver. Today there is no cure for AD, albeit we have access to pharmacotherapy that might improve cognitive and neuropsychiatric symptoms initially in the course of the disease. However, AD continues to progress despite treatment. It is therefore of utter importance to find other pharmacological strategies that might postpone the development of AD and also slow down the cognitive and neuropsychiatric decline in manifest AD. AD patients display lower levels of the omega-3 fatty acid (n-3 FA) docosahexaenoic acid (DHA) in both plasma and brain tissues as compared to age matched controls. Furthermore, epidemiological and animal studies suggest that high intake of DHA might have preventive properties against AD. Little is known, however, of the effects of n-3 FA on AD. Therefore we have conducted the first one year long randomised placebo controlled double-blind trial with six months administration of 2.3 g/day n-3 FA (1.7 g DHA + 0.6 g EPA) or placebo (linoleic acid, LA) followed by six months administration of n-3 FA to patients with mild to moderate AD. In total 204 patients with mild to moderate AD already on stable medication with acetylcholinesterase inhibitors (AChEI) were included. One hundred and seventy four patients fulfilled the trial and the Papers I, II and IV are based on these patients. In a subgroup of these patients lumbar puncture was performed (Paper III). All patients were followed for one year with cognitive, neuropsychiatric and functional evaluations as well as blood tests. In Paper I we conclude that n-3 FA treatment did not delay the rate of cognition as measured with the Mini Mental State Examination (MMSE) and the cognitive subscale of the Alzheimer's disease Assessment Scale (ADAS-cog) nor global status measured with the Clinical Dementia Rating scale (CDR). However, positive effects on cognition were observed in a small group of patients with very mild AD (MMSE >27). Safety and tolerability was good as was compliance measured with plasma levels of DHA, EPA and LA. In Paper II we addressed the effects of supplementation of n-3 FA on the neuropsychiatric, behavioural and functional symptoms using the Neuropsychiatric Inventory (NPI) and the Montgomery Åsberg Depression Rating scale (MADRS). Disability Assessment for Dementia (DAD) and Care givers burden (CGB). The relationship with APOE genotype was assessed. There was no overall treatment effect on neuropsychiatric, behavioural and functional symptoms, but n-3 FA appeared to have positive treatment effects on depression in non-APOEε4 carriers and in agitation in APOE ε4 carriers. In Paper III inflammatory markers in plasma (hs-CRP, IL-6, TNF-α and sIL-RII) and cerebrospinal fluid (CSF, IL-6, TNF-α and sIL-RII) and biological AD markers in CSF (Aβ42, T-tau and P-tau) were analyzed in a subgroup of 35 patients. A correlation at baseline between Aβ42 and sIL-RII was detected albeit no n-3 FA treatment effects were found in neither inflammatory nor biological AD markers. In Paper IV we investigated the hypothesis that supplementation with n-3 FA would affect appetite and weight in relation to inflammatory biomarkers and to APOE ε4 carrier ship. Mean weight and Body Mass Index (BMI) increased at 6 and 12 months in the n-3 FA group. When the placebo group was administered n-3 FA for six months, the weight and BMI also increased significantly within the group. However, there was no significant treatment effect on weight and BMI between the groups. Not carrying the APOEε4 allele and increased DHA were independently associated with weight gain. Caregiver s assessed appetite improved in the n-3 FA treatment group over the treatment period. In conclusion, our study gives some evidence that supplementation with 2.3 g/day n-3 FA to patients with mild to moderate AD may have effects on cognition in the early phases of AD, may reduce depression and agitation depending on APOE ε4 status and increase body weight loss in patients with mild to moderate AD. No effect on possible neuroinflammation in subjects with AD was observed. Supplementation with n-3 FA may be a strategy to add to lifestyle prevention for postponing early cognitive symptoms in AD but more research is needed.
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| 4. |
- Freund-Levi, Yvonne, 1956-, et al.
(författare)
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Omega-3 supplementation in mild to moderate Alzheimer's disease : effects on neuropsychiatric symptoms
- 2008
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Ingår i: International Journal of Geriatric Psychiatry. - : Wiley. - 0885-6230 .- 1099-1166. ; 23:2, s. 161-169
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Tidskriftsartikel (refereegranskat)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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| 5. |
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| 6. |
- Irving, Gerd Faxén, et al.
(författare)
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Omega-3 fatty acid supplementation effects on weight and appetite in patients with Alzheimer's disease : the omega-3 Alzheimer's disease study
- 2009
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Ingår i: Journal of The American Geriatrics Society. - : Wiley. - 0002-8614 .- 1532-5415. ; 57:1, s. 11-17
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To study the effects of omega (Omega)-3 fatty acid (FA) supplements on weight and appetite in patients with mild to moderate Alzheimer's disease (AD) in relation to inflammatory biomarkers and apolipoprotein E epsilon4 (APOEepsilon4). DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: Specialist memory clinics in the Stockholm catchment area. PARTICIPANTS: Two hundred four patients (aged 73+/-9, 52% women) with mild to moderate AD. INTERVENTION: Patients with AD received 1.7 g of docosahexaenoic acid (DHA) and 0.6 g of eicosapentaenoic acid (EPA) (Omega-3/Omega-3 group; n=89, aged 73+/-9, 57% women) or placebo 0.6 g of linoleic acid per day (placebo/Omega-3 group; n=85, aged 73+/-9, 46% women) for 6 months. After 6 months, all patients received DHA and EPA for another 6 months. MEASUREMENTS: Anthropometry, biochemical nutritional and inflammatory markers, and appetite assessed by caregiver. RESULTS: Mean weight and body mass index (kg/m(2)) at baseline were 70.0+/-11.8 kg and 24.3+/-3.0 kg/m(2), respectively. At 6- and 12-month follow-up, weight had increased 0.7+/-2.5 kg (P=.02) and 1.4+/-2.9 kg (P<.001) in the Omega-3/Omega-3 group. In the placebo group, weight was unchanged at 6 months but had increased (P=.01) at 12 months follow-up after Omega-3 supplementation was initiated. Appetite improved in the Omega-3/Omega-3 group over the treatment period (P=.01). In logistic regression analyses, not carrying the APOEepsilon4 allele and high plasma DHA concentrations were independently related to weight gain in the combined group of patients at 6 months follow-up. CONCLUSION: A DHA-enriched Omega-3 FA supplement may positively affect weight and appetite in patients with mild to moderate AD. Not carrying the APOEepsilon4 allele and high DHA were independently associated with weight gain.
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| 7. |
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| 8. |
- Nyberg, Svante, et al.
(författare)
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Detection of amyloid in Alzheimer's disease with positron emission tomography using [11C]AZD2184
- 2009
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Ingår i: European Journal of Nuclear Medicine and Molecular Imaging. - : Springer. - 1619-7070 .- 1619-7089. ; 36:11, s. 1859-1863
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Current positron emission tomography (PET) radioligands for detection of Aβ amyloid in Alzheimer's disease (AD) are not ideal for quantification. To improve the signal to noise ratio we have developed the radioligand [11C]AZD2184 and report here the first clinical evaluation.METHODS: Eight AD patients and four younger control subjects underwent 93-min PET measurements with [11C]AZD2184. A ratio approach using the cerebellum as reference region was applied to determine binding parameters.RESULTS: Brain uptake of [11C]AZD2184 peaked within 1 min at 3-4% of injected radioactivity. AD patients had high radioactivity in cortical regions while controls had uniformly low radioactivity uptake. Specific binding peaked within 30 min at which time standardized uptake value ratios (SUVR) ranged between 1.19 and 2.57.CONCLUSION: [11C]AZD2184 is a promising radioligand for detailed mapping of Aβ amyloid depositions in Alzheimer's disease, due to low non-specific binding, high signal to background ratio and reversible binding as evident from early peak equilibrium.
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| 9. |
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| 10. |
- Vedin, Inger, et al.
(författare)
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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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Ingår i: American Journal of Clinical Nutrition. - : HighWire Press. - 0002-9165 .- 1938-3207. ; 87:6, s. 1616-1622
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Tidskriftsartikel (refereegranskat)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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