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Omega-3 Fatty Acid Status Enhances the Prevention of Cognitive Decline by B Vitamins in Mild Cognitive Impairment.
Oulhaj, A, Jernerén, F, Refsum, H, Smith, AD, de Jager, CA
Journal of Alzheimer's disease : JAD. 2016;50(2):547-57
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Plain language summary
Many studies are exploring preventative measures to delay or prevent mild cognitive impairment (MCI) and Alzheimer’s disease. A recent trial (VITACOG) demonstrated that omega-3 fatty acid status enhances the protective effects of B-vitamins on brain atrophy. The present study uses the VITACOG data to investigate whether there is an association on cognitive function. This study revealed that a higher baseline omega-3 fatty acid status enhances the beneficial effects of B vitamins on both brain atrophy and cognitive decline. The authors conclude that this interaction may slow down the disease process in MCI and warrants further clinical trials investigating this relationship.
Abstract
A randomized trial (VITACOG) in people with mild cognitive impairment (MCI) found that B vitamin treatment to lower homocysteine slowed the rate of cognitive and clinical decline. We have used data from this trial to see whether baseline omega-3 fatty acid status interacts with the effects of B vitamin treatment. 266 participants with MCI aged ≥70 years were randomized to B vitamins (folic acid, vitamins B6 and B12) or placebo for 2 years. Baseline cognitive test performance, clinical dementia rating (CDR) scale, and plasma concentrations of total homocysteine, total docosahexaenoic and eicosapentaenoic acids (omega-3 fatty acids) were measured. Final scores for verbal delayed recall, global cognition, and CDR sum-of-boxes were better in the B vitamin-treated group according to increasing baseline concentrations of omega-3 fatty acids, whereas scores in the placebo group were similar across these concentrations. Among those with good omega-3 status, 33% of those on B vitamin treatment had global CDR scores >0 compared with 59% among those on placebo. For all three outcome measures, higher concentrations of docosahexaenoic acid alone significantly enhanced the cognitive effects of B vitamins, while eicosapentaenoic acid appeared less effective. When omega-3 fatty acid concentrations are low, B vitamin treatment has no effect on cognitive decline in MCI, but when omega-3 levels are in the upper normal range, B vitamins interact to slow cognitive decline. A clinical trial of B vitamins combined with omega-3 fatty acids is needed to see whether it is possible to slow the conversion from MCI to AD.
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Cognitive Effects of Intentional Weight Loss in Elderly Obese Individuals With Mild Cognitive Impairment.
Horie, NC, Serrao, VT, Simon, SS, Gascon, MR, Dos Santos, AX, Zambone, MA, Del Bigio de Freitas, MM, Cunha-Neto, E, Marques, EL, Halpern, A, et al
The Journal of clinical endocrinology and metabolism. 2016;101(3):1104-12
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Several studies have elucidated that midlife obesity increases the risk of dementia later in life. While the neuroprotective effects of caloric restriction have been widely demonstrated, they have not yet been investigated in patients with mild cognitive impairment (MCI). The aim of this trial was to evaluate the effect of intentional weight loss in elderly adults with mild cognitive impairment (MCI). Eighty participants aged over 60 were randomly allocated to receive either nutritional counselling or medical care alone for 12 months. The findings of this study indicated that intentional weight loss through diet was associated with cognitive improvement in patients with MCI, and this association was strongest in younger adults and APOE4 carriers. As this was the first clinical trial exploring these effects in patients with MCI further research is warranted.
Abstract
CONTEXT Obesity in midlife is a risk factor for dementia, but it is unknown if caloric restriction-induced weight loss could prevent cognitive decline and therefore dementia in elderly patients with cognitive impairment. OBJECTIVE To evaluate the cognitive effect of intentional weight loss in obese elderly patients with mild cognitive impairment (MCI), considering the influence of age, apolipoprotein E (APOE) genotype, physical activity, biochemical markers, and diet. DESIGN Single-center, prospective controlled trial. SETTING Academic medical center. PARTICIPANTS Eighty obese patients with MCI, aged 60 or older (68.1 ± 4.9 y, body mass index [BMI] 35.5 ± 4.4 kg/m(2), 83.7% women, 26.3% APOE allele ϵ4 carriers). INTERVENTION Random allocation to conventional medical care alone (n = 40) or together with nutritional counselling (n = 40) in group meetings aiming to promote weight loss through caloric restriction for 12 months. OUTCOME MEASUREMENTS clinical data, body composition, neuropsychological tests (main outcome), serum biomarkers, APOE genotype, physical performance, dietary recalls. RESULTS Seventy-five patients completed the follow-up. BMI, on average, decreased 1.7 ± 1.8 kg/m(2) (P = .021), and most of the cognitive tests improved, without difference between the groups. In analysis with linear generalized models, the BMI decrease was associated with improvements in verbal memory, verbal fluency, executive function, and global cognition, after adjustment for education, gender, physical activity, and baseline tests. This association was strongest in younger seniors (for memory and fluency) and in APOE allele ϵ4 carriers (for executive function). Changes in homeostasis model assessment-estimated insulin resistance, C-reactive protein, leptin and intake of energy, carbohydrates, and fats were associated with improvement in cognitive tests. CONCLUSIONS Intentional weight loss through diet was associated with cognitive improvement in patients with MCI.
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Brain atrophy in cognitively impaired elderly: the importance of long-chain ω-3 fatty acids and B vitamin status in a randomized controlled trial.
Jernerén, F, Elshorbagy, AK, Oulhaj, A, Smith, SM, Refsum, H, Smith, AD
The American journal of clinical nutrition. 2015;102(1):215-21
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Mild cognitive impairment (MCI) is a characterised by a decline in cognitive function between normal aging and the development of dementia. While brain atrophy occurs in normal aging, patients with MCI or dementia exhibit much higher rates of atrophy. Results from a recent trial demonstrated that homocysteine-lowering B vitamins resulted in a significant reduction in brain atrophy rates, and links between omega-3 fatty acids and homocysteine have been suggested. The purpose of this study was to investigate whether plasma omega-3 fatty acid concentrations modify the treatment effect of B vitamins on brain atrophy rates among 168 elderly adults with MCI. Participants were randomly assigned to receive placebo or high-dose vitamin B supplementation and both brain scans and plasma concentrations were done at baseline and 2 years. The findings of this study demonstrated that, in patients with high omega-3 plasma concentrations, B vitamin supplementation slowed brain atrophy by 40% compared with those in the placebo group. This indicates that the effect of B vitamin supplementation on brain atrophy rates depend on plasma omega-3 fatty acid concentrations.
Abstract
BACKGROUND Increased brain atrophy rates are common in older people with cognitive impairment, particularly in those who eventually convert to Alzheimer disease. Plasma concentrations of omega-3 (ω-3) fatty acids and homocysteine are associated with the development of brain atrophy and dementia. OBJECTIVE We investigated whether plasma ω-3 fatty acid concentrations (eicosapentaenoic acid and docosahexaenoic acid) modify the treatment effect of homocysteine-lowering B vitamins on brain atrophy rates in a placebo-controlled trial (VITACOG). DESIGN This retrospective analysis included 168 elderly people (≥70 y) with mild cognitive impairment, randomly assigned either to placebo (n = 83) or to daily high-dose B vitamin supplementation (folic acid, 0.8 mg; vitamin B-6, 20 mg; vitamin B-12, 0.5 mg) (n = 85). The subjects underwent cranial magnetic resonance imaging scans at baseline and 2 y later. The effect of the intervention was analyzed according to tertiles of baseline ω-3 fatty acid concentrations. RESULTS There was a significant interaction (P = 0.024) between B vitamin treatment and plasma combined ω-3 fatty acids (eicosapentaenoic acid and docosahexaenoic acid) on brain atrophy rates. In subjects with high baseline ω-3 fatty acids (>590 μmol/L), B vitamin treatment slowed the mean atrophy rate by 40.0% compared with placebo (P = 0.023). B vitamin treatment had no significant effect on the rate of atrophy among subjects with low baseline ω-3 fatty acids (<390 μmol/L). High baseline ω-3 fatty acids were associated with a slower rate of brain atrophy in the B vitamin group but not in the placebo group. CONCLUSIONS The beneficial effect of B vitamin treatment on brain atrophy was observed only in subjects with high plasma ω-3 fatty acids. It is also suggested that the beneficial effect of ω-3 fatty acids on brain atrophy may be confined to subjects with good B vitamin status. The results highlight the importance of identifying subgroups likely to benefit in clinical trials. This trial was registered at www.controlled-trials.com as ISRCTN94410159.