What was lost in translation in the DHA trial is whom you should intend to treat.
The results of a randomized double-blind placebocontrolled trial with docosahexaenoic acid (DHA) supplementation in mild to moderate Alzheimer's disease (AD) published by Quinn and colleagues in JAMA argues against overall efficacy of DHA in slowing progression. However, certain caveats in the results caution against discarding DHA altogether, raising questions about oxidation, dosage, pharmacogenomics and stage of intervention.One potential misconception is that what works for prevention will slow progression in AD subjects.Preclinical studies with DHA supported the rationale for early stage intervention; and three epidemiological studies indicated DHA intake was associated with reduced risk in non-apolipoprotein E4 (ApoE4) carriers. Putative drugs are initially tested for impact on progression because prevention approaches are problematic. However, should a drug be discarded for prevention if it fails to modify progression? Consistent with epidemiology, DHA significantly benefited two measures of cognition in mild to moderate non-ApoE4 carriers. Although the results of this trial were overall negative, failing to modify other outcomes, this commentary discusses important questions raised by them. Should future trials pursue DHA in non-ApoE4 carriers for slowing progression? Since in vivo oxidation of DHA may have adverse effects, particularly in ApoE4 patients, should preclinical and clinical studies be performed to optimize dose and mitigate oxidation before pursuing intervention or prevention trials with DHA? And finally, should DHA be tested now for mild cognitive impairment or prevention?
Veterans Greater Los Angeles Healthcare System, Geriatric Research Education and Clinical Center, 16111 Plummer St, North Hills, CA 91343, USA. frautsch@ucla.edu.
Sally A
SA
Frautschy
Greg M
GM
Cole
Alzheimers Dement. 2010 Nov;6(6):456-64
20434961
Am J Clin Nutr. 2010 Jun;91(6):1725-32
20410089
J Neurosci. 2007 Apr 18;27(16):4385-95
17442823
Lipids. 1997 May;32(5):535-41
9168460
J Nutr. 1992 Nov;122(11):2190-5
1432259
Am J Clin Nutr. 1996 Sep;64(3):297-304
8780337
JAMA. 2010 Nov 3;304(17):1903-11
21045096
Prog Neuropsychopharmacol Biol Psychiatry. 2008 Aug 1;32(6):1538-44
18573585
J Alzheimers Dis. 2008 Apr;13(3):323-31
18430999
Neuron. 2004 Sep 2;43(5):633-45
15339646
Nutr Neurosci. 2008 Apr;11(2):75-83
18510807
Neurosci Res. 2006 Oct;56(2):159-64
16905216
J Neuropathol Exp Neurol. 2006 Jun;65(6):592-601
16783169
Arch Neurol. 2006 Oct;63(10):1402-8
17030655
J Neurosci. 2009 Jul 15;29(28):9078-89
19605645
J Neurosci. 2005 Mar 23;25(12):3032-40
15788759
Neurology. 2008 Aug 5;71(6):430-8
18678826
J Nutr. 2010 Apr;140(4):869-74
20181786