Omega-3 fatty acids: potential role in the management of early Alzheimer’s disease

Abstract

Omega-3 fatty acids are essential for brain growth and development. They play an important role throughout life, as critical modulators of neuronal function and regulation of oxidative stress mechanisms, in brain health and disease. Docosahexanoic acid (DHA), the major omega-3 fatty acid found in neurons, has taken on a central role as a target for therapeutic intervention in Alzheimer’s disease (AD). A plethora of in vitro, animal model, and human data, gathered over the past decade, highlight the important role DHA may play in the development of a variety of neurological and psychiatric disorders, including AD. Cross sectional and prospective cohort data have demonstrated that reduced dietary intake or low brain levels of DHA are associated with accelerated cognitive decline or the development of incipient dementia, including AD. Several clinical trials investigating the effects of omega-3 fatty acid supplementation in AD have been completed and all failed to demonstrate its efficacy in the treatment of AD. However, these trials produced intriguing data suggesting that the beneficial effects of omega-3 fatty acid supplementation may depend on the stage of disease, other dietary mediators, and apolipoprotein E status.

Keywords:

• Alzheimer’s disease
• omega-3 fatty acids
• oxidative stress
• clinical studies
• treatment

Acknowledgements

We gratefully acknowledge the many subjects, caregivers, friends, and families of persons with AD that have engaged in clinical research activities that allow discoveries to be made. We also thank Paula Thomason for critical review and editing of the manuscript.

Disclosures

Dr Jicha is supported by funding from the NIH/NIA 1 P30 AG028383 and 2R01AG019241, NIH LRP 1 L30 AG032934, and the Sanders-Brown Foundation. Dr Jicha has also received research support for clinical trial activities from NIH/NIA ADCS U01AG010483, Pfizer Inc., Elan Pharmaceuticals, Medivation Inc., and Baxter Inc., and has served as a consultant for Medivation and Martek Inc. in clinical trial development. Dr Markesbery was supported by NIA grants P30 AG028383 (PI), P01 AG05119 (PI), and R01 AG19241 (PI); and by the Healy Family Foundation, and Kleberg Foundation.

In memoriam

William R Markesbery, MD, internationally known Alzheimer’s disease (AD) researcher, died on January 30, 2010, from complications of mycobacterium avium complex at the University of Kentucky (UK) Chandler Medical Center, shortly after co-authoring the present review on omega-3 fatty acids in Alzheimer’s disease for the journal, Clinical Interventions in Aging.

Among Dr Markesbery’s many achievements, the establishment of the UK Sanders-Brown Center on Aging in 1979 and its continued success over the last 30 years marks his legacy. Soon after the establishment of the Center, Dr Markesbery was awarded one of the first of ten federally funded AD Research Centers (ADCs) with a primary focus on neuropathology. He received 30 years of continuous NIH peer reviewed funding for his research and had over 415 peer reviewed scientific publications. He served as the Chairman of the Medical and Scientific and Advisory Board of the Alzheimer’s Association and on the National Advisory Council at NIA. In the early 1980s, Dr Markesbery and collaborators published the first of several studies that disproved the prevailing theory that AD was caused by an accumulation of aluminum and other toxic metals in the brain. Subsequently he and his colleagues were among the first to show that oxidative stress is present early in AD. He later described the neuropathological manifestations in mild cognitive impairment -the earliest detectable clinical phase of AD.

He received numerous awards for his work including the Award for Meritorious Contributions to Neuropathology, the Irving H Shaw Award for Distinguished Service in the Field of Health Care, the Medallion for Intellectual Achievement, UK Library Associates, and recognition by the Alltech Lecture Series, University College, Dublin. In 2009, Dr Markesbery received the prestigious Khachaturian Award from the National Alzheimer’s Association for advancing the field of Alzheimer’s disease. Bill said “I am grateful to have the opportunity to take part in the investigation of the most devastating disease that affects humanity. It has been a privilege to care for individuals with the disease, support the families and through research, strive to gain a better understanding of Alzheimer’s disease so that one day soon we will learn how to prevent the disease in those at risk and stop the progression of those with the disease.”

Despite all his accomplishments and his illnesses in the past 15 years, Dr Markesbery remained a tireless researcher and compassionate clinician. He epitomized the meaning of a Southern gentleman and was proud to refer to himself as a 7th generation Kentuckian. He was admired and respected by all for his humility, kindness, generosity, high standards in all he undertook, and patience. He always had the time to listen to and counsel anyone at any level. He will be greatly missed by family, colleagues, patients and students, but his love of learning, high standards, kindness, and desire to teach will never be forgotten.