Epidemiological and animal studies have suggested that dietary fish or fish oil rich in omega-3 fatty acids (omega3), docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), may have effects in psychiatric and behavioral symptoms in Alzheimer's disease (AD). An association with APOEomega4 carriers and neuropsychiatric symptoms in AD has also been suggested.
To determine effects of dietary omega3 supplementation to AD patients with mild to moderate disease on psychiatric and behavioral symptoms, daily functions and a possible relation to APOEgenotype.
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 (omega3 group) or placebo for 6 months. Then, all received the omega3 supplementation for 6 more months. Neuropsychiatric symptoms were measured with Neuropsychiatric Inventory (NPI) and Montgomery Asberg Depression Scale (MADRS). Caregivers burden and activities of daily living (Disability Assessment for Dementia, DAD) were also assessed.
One hundred and seventy-four patients fulfilled the trial. 72% were APOEomega4 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 APOEomega4 carriers (p=0.006) and in MADRS scores in non-APOEomega4 carriers (p=0.005) were found.
Supplementation with omega3 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-APOEomega4 carriers and agitation symptoms (assessed by NPI) in APOEomega4 carriers. ClinicalTrials.gov identifier: NCT00211159
"Another clinical trial by the same group using the same treatment regimen in AD patients on AChE inhibitor medication investigated the effects of ω-3 PUFA supplementation on neuropsychiatric symptoms and was unable to find any overall treatment effects. However, potential positive effects were observed for depressive symptoms in non-carriers of the ApoE ε4 allele, and for agitation symptoms in patients with this allele . Finally, a systemic review of literature addressing the effects of fish consumption or ω-3 PUFA supplementation on AD risk and cognitive decline found that in patients without AD ω-3 PUFAs may yield positive effects on cognitive decline, whereas they did not seem to prevent or treat AD, reflected by the results of studies reporting cognitive decline or AD incidence as primary outcome . "
[Show abstract][Hide abstract] ABSTRACT: Alzheimer's disease (AD) is a progressive neurodegenerative disorder, characterized by deposition of amyloid beta, neurofibrillary tangles, astrogliosis and microgliosis, leading to neuronal dysfunction and loss in the brain. Bio- and histochemical evidence suggests a pivotal role of central and peripheral inflammation in its aetiopathology, linked to the production of free radicals. Numerous epidemiological studies support that the long-term use of non-steroidal anti-inflammatory drugs is preventive against AD, but these medications do not slow down the progression of the disease in already diagnosed patients. There are a number of studies focusing on traditional herbal medicines and small molecules (usually plant secondary metabolites) as potential anti-inflammatory drugs, particulary in respect to cytokine suppression. For instance, ω-3 polyunsaturated fatty acids and a number of polyphenolic phytochemicals have been shown to be effective against inflammation in animal and cell models. Some of these plant secondary metabolites have also been shown to possess antioxidant, anti-inflammatory, anti-amyloidogenic, neuroprotective, and cognition-enhancing effects. This review will overview the the effects of catechins/proanthocyanidins from green tea, curcumin from turmeric, extracts enriched in bacosides from Brahmi, Ginkgo flavone glycosides, and ω-3 polyunsaturated fatty acids not only counteract one pathophysiological aspect of AD in numerous in vitro and in vivo studies of models of AD, but also ameliorate several of the above mentioned pathologies. The evidence suggests that increased consumption of these compounds might lead to a safe strategy to delay the onset of AD. The continuing investigation of the potential of these substances is necessary as they are promising to yield a possible remedy for this pervasive disease.
CNS & Neurological Disorders - Drug Targets (Formerly Current Drug Targets - CNS & Neurological Disorders) 09/2014; 13(7). DOI:10.2174/1871527313666140917110635 · 2.63 Impact Factor
"Among selected RCTs lacking in data, such as means and/or standard deviations (SDs), the data of one study  were provided by authors; SDs and 95% confidence intervals (CIs) of five studies – were retrieved from graphs; data of one study  were medians; and data of three studies – were imputed from data from all other trials using the same measure for depression as described elsewhere . Eight studies – were finally excluded from the meta-analysis due to lacking data, resulting in a total number of 39 studies to be included in the analysis. "
[Show abstract][Hide abstract] ABSTRACT: Despite omega-3 polyunsaturated fatty acids (PUFA) supplementation in depressed patients have been suggested to improve depressive symptomatology, previous findings are not univocal.
To conduct an updated meta-analysis of randomized controlled trials (RCTs) of omega-3 PUFA treatment of depressive disorders, taking into account the clinical differences among patients included in the studies.
A search on MEDLINE, EMBASE, PsycInfo, and the Cochrane Database of RCTs using omega-3 PUFA on patients with depressive symptoms published up to August 2013 was performed. Standardized mean difference in clinical measure of depression severity was primary outcome. Type of omega-3 used (particularly eicosapentaenoic acid [EPA] and docosahexaenoic acid [DHA]) and omega-3 as mono- or adjuvant therapy was also examined. Meta-regression analyses assessed the effects of study size, baseline depression severity, trial duration, dose of omega-3, and age of patients.
Meta-analysis of 11 and 8 trials conducted respectively on patients with a DSM-defined diagnosis of major depressive disorder (MDD) and patients with depressive symptomatology but no diagnosis of MDD demonstrated significant clinical benefit of omega-3 PUFA treatment compared to placebo (standardized difference in random-effects model 0.56 SD [95% CI: 0.20, 0.92] and 0.22 SD [95% CI: 0.01, 0.43], respectively; pooled analysis was 0.38 SD [95% CI: 0.18, 0.59]). Use of mainly EPA within the preparation, rather than DHA, influenced final clinical efficacy. Significant clinical efficacy had the use of omega-3 PUFA as adjuvant rather than mono-therapy. No relation between efficacy and study size, baseline depression severity, trial duration, age of patients, and study quality was found. Omega-3 PUFA resulted effective in RCTs on patients with bipolar disorder, whereas no evidence was found for those exploring their efficacy on depressive symptoms in young populations, perinatal depression, primary disease other than depression and healthy subjects.
The use of omega-3 PUFA is effective in patients with diagnosis of MDD and on depressive patients without diagnosis of MDD.
PLoS ONE 05/2014; 9(5):e96905. DOI:10.1371/journal.pone.0096905 · 3.23 Impact Factor
"The common factor between these diets is that they are low in saturated fats and refined grains. Over the years, the importance of LCPUFA in neural development , aging, and neurodegeneration has been shown in both clinical and animal studies        . Supplementation with LCPUFA has shown to be beneficial in the development of both children and (young) rodents. "
[Show abstract][Hide abstract] ABSTRACT: Many clinical and animal studies demonstrate the importance of long-chain polyunsaturated fatty
acids (LCPUFA) in neural development and neurodegeneration. This review will focus on involvement
of LCPUFA from genesis to senescence. The LCPUFA docosahexaenoic acid and arachidonic acid are
important components of neuronal membranes, while eicosapentaenoic acid, docosahexaenoic acid,
and arachidonic acid also affect cardiovascular health and inflammation. In neural development, LCPUFA deficiency can lead to severe disorders like schizophrenia
and attention deficit hyperactivity disorder. Perinatal LCPUFA supplementation demonstrated
beneficial effects in neural development in humans and rodents resulting in improved cognition and
sensorimotor integration. In normal aging, the effect of LCPUFA on prevention of cognitive impairment will be
discussed. LCPUFA are important for neuronal membrane integrity and function, and also contribute
in prevention of brain hypoperfusion. Cerebral perfusion can be compromised as result of obesity,
cerebrovascular disease, hypertension, or diabetes mellitus type 2. Last, we will focus on the role of LCPUFA in most common neurodegenerative diseases like
Alzheimer’s disease and Parkinson’s Disease. These disorders are characterized by impaired cognition
and connectivity and both clinical and animal supplementation studies have shown the potential of
LCPUFA to decrease neurodegeneration and inflammation. This review shows that LCPUFA are
essential throughout life.
Progress in Lipid Research 02/2014; 53:1-17. DOI:10.1016/j.plipres.2013.10.002 · 10.02 Impact Factor
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