Association of Docosahexaenoic Acid Supplementation With Alzheimer Disease Stage in Apolipoprotein E ε4 Carriers

Yassine, Hussein N.; Braskie, Meredith N.; Mack, Wendy J.; Castor, Katherine; Fonteh, Alfred N.; Schneider, Lon S.; Harrington, Michael G.; Chui, Helena C.

doi:10.1001/jamaneurol.2016.4899

Cited by 118 publications

(116 citation statements)

References 78 publications

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“…In recent years, polyunsaturated fatty acids like DHA have gained much attention due to promising results in a number of neurodegenerative conditions 20, 21. Moreover, polyunsaturated fatty acids are required for the normal development of the central nervous system and their deficiency can impair cerebral function in mice 22…”

Section: Discussionmentioning

confidence: 99%

Docosahexaenoic acid is a beneficial replacement treatment for spinocerebellar ataxia 38

Manes

Alberici

Gregorio

et al. 2017

Annals of Neurology

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ObjectiveSpinocerebellar ataxia 38 (SCA38) is caused by mutations in the ELOVL5 gene, which encodes an elongase involved in the synthesis of polyunsaturated fatty acids, including docosahexaenoic acid (DHA). As a consequence, DHA is significantly reduced in the serum of SCA38 subjects. In the present study, we evaluated the safety of DHA supplementation, its efficacy for clinical symptoms, and changes of brain functional imaging in SCA38 patients.MethodsWe enrolled 10 SCA38 patients, and carried out a double‐blind randomized placebo‐controlled study for 16 weeks, followed by an open‐label study with overall 40‐week DHA treatment. At baseline and at follow‐up visit, patients underwent standardized clinical assessment, brain 18‐fluorodeoxyglucose positron emission tomography, electroneurography, and ELOVL5 expression analysis.ResultsAfter 16 weeks, we showed a significant pre–post clinical improvement in the DHA group versus placebo, using the Scale for the Assessment and Rating of Ataxia (SARA; mean difference [MD] = +2.70, 95% confidence interval [CI] = +0.13 to + 5.27, p = 0.042). At 40‐week treatment, clinical improvement was found significant by both SARA (MD = +2.2, 95% CI = +0.93 to + 3.46, p = 0.008) and International Cooperative Ataxia Rating Scale (MD = +3.8, 95% CI = +1.39 to + 6.41, p = 0.02) scores; clinical data were corroborated by significant improvement of cerebellar hypometabolism (statistical parametric mapping analyses, false discovery rate corrected). We also showed a decreased expression of ELOVL5 in patients’ blood at 40 weeks as compared to baseline. No side effect was recorded.InterpretationDHA supplementation is a safe and effective treatment for SCA38, showing an improvement of clinical symptoms and cerebellar hypometabolism. Ann Neurol 2017;82:615–621

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Section: Discussionmentioning

confidence: 99%

Docosahexaenoic acid is a beneficial replacement treatment for spinocerebellar ataxia 38

Manes

Alberici

Gregorio

et al. 2017

Annals of Neurology

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“…58,63 Overall, the results are discordant, due to the heterogeneity of methods used to evaluate the depressive and/or cognitive symptoms, the form, dose and duration of the omega-3 PUFA supplementation, the lack of evaluation of nutritional intake and metabolism of PUFA prior to starting the supplementation, or the lack of evaluation of genotype-associated risk factors. 64 However, despite the discrepancies in the results, it is important to note that several RCTs performed in patients with depressive disorders revealed an additional effect of long chain omega-3 PUFA supplementation to antidepressant treatments. 65 Of note, a recent study identifies that depressive patients presenting a high level of inflammatory markers are more responsive to long chain omega-3 PUFA supplementation.…”

Section: Dietary Omega-3 Pufa Regulate Neuroinflammation and Ecbs: Romentioning

confidence: 99%

“…Concerning cognitive decline, despite poor positive results of PUFA dietary supplementation in Alzheimer's disease (AD) patients, RCTs using DHA supplementation in subjects carrying the apolipoprotein E ε4 (APOE4) allele, a risk factor for AD, reveal an improvement of pre-dementia. 64 Overall, discrepancies in clinical studies strongly support the need for preclinical studies aimed at depicting the mechanisms of omega-3 PUFA on brain dysfunctions, which should help to better target populations at risk of cognitive and mood disorders. In addition, the consideration of omega-3 PUFA levels in food to cover the physiological requirement of these PUFA for an optimal brain function is a challenge for the food industry.…”

Section: Dietary Omega-3 Pufa Regulate Neuroinflammation and Ecbs: Romentioning

confidence: 99%

Food for thought: how nutrition impacts cognition and emotion

et al. 2017

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More than one-third of American adults are obese and statistics are similar worldwide. Caloric intake and diet composition have large and lasting effects on cognition and emotion, especially during critical periods in development, but the neural mechanisms for these effects are not well understood. A clear understanding of the cognitive-emotional processes underpinning desires to over-consume foods can assist more effective prevention and treatments of obesity. This review addresses recent work linking dietary fat intake and omega-3 polyunsaturated fatty acid dietary imbalance with inflammation in developing, adult, and aged brains. Thus, early-life diet and exposure to stress can lead to cognitive dysfunction throughout life and there is potential for early nutritional interventions (e.g., with essential micronutrients) for preventing these deficits. Likewise, acute consumption of a high-fat diet primes the hippocampus to produce a potentiated neuroinflammatory response to a mild immune challenge, causing memory deficits. Low dietary intake of omega-3 polyunsaturated fatty acids can also contribute to depression through its effects on endocannabinoid and inflammatory pathways in specific brain regions leading to synaptic phagocytosis by microglia in the hippocampus, contributing to memory loss. However, encouragingly, consumption of fruits and vegetables high in polyphenolics can prevent and even reverse age-related cognitive deficits by lowering oxidative stress and inflammation. Understanding relationships between diet, cognition, and emotion is necessary to uncover mechanisms involved in and strategies to prevent or attenuate comorbid neurological conditions in obese individuals.

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“…While age is the greatest AD risk factor, genetic variants that may differentially metabolize and deliver PUFA into the brain are now known to contribute to AD pathology. For example, ApoE E4 allele carriers process DHA differently, so study participants with unrelated genotypes may not respond to the same intervention [2]. Serum levels of PUFAs are also controlled by the rate limiting enzyme, delta-6 desaturase.…”

Section: Short Communicationmentioning

confidence: 99%

Reasons Why Omega-3 Polyunsaturated Fatty Acids Produce Mixed Results in Alzheimer's Disease Prevention Studies

Fonteh¹

2018

J Glycomics Lipidomics

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Association of Docosahexaenoic Acid Supplementation With Alzheimer Disease Stage in Apolipoprotein E ε4 Carriers

Abstract: High-dose DHA supplementation in APOE4 carriers before the onset of AD dementia can be a promising approach to decrease the incidence of AD. Given the safety profile, availability, and affordability of DHA supplements, refining an ω-3 intervention in APOE4 carriers is warranted.

Cited by 118 publications

References 78 publications

Docosahexaenoic acid is a beneficial replacement treatment for spinocerebellar ataxia 38

Docosahexaenoic acid is a beneficial replacement treatment for spinocerebellar ataxia 38

Food for thought: how nutrition impacts cognition and emotion

Reasons Why Omega-3 Polyunsaturated Fatty Acids Produce Mixed Results in Alzheimer's Disease Prevention Studies

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