Table 2.

Clinical trials assessing the effect of long chain n-3 PUFAs dietary supplementation on cognition in healthy and unhealthy adult and aged subjects.

Subjects	Treatment/day and Duration	Primary Outcome	Results	Refs.
Healthy adult subjects
Healthy adults 18–35 years	1 g EPA+DHA 12 weeks	Cognition and mood	No improvement of memory or mood Improvement of cognitive fatigue	[282]
Young adult females	400 mg of DHA 50 days	Memory, mood, reaction times, vigilance or visual acuity	Improvement of memory	[283]
Healthy aged subjects with cognitive complaint or deficit
Subjects at risk for developing late age-related macular degeneration	1 g LC PUFAs and/or 10 mg lutein/2 mg zeaxanthin 5 years	Cognitive function	No effect	[284]
Healthy subjects 50-75 years	2.2 g/d of n-3 PUFA	Executive function MRI	Improvement of executive function and gray matter volume	[285]
Subjects with subjective memory impairment aged 62-80 years	Fish oil (EPA+DHA: 2.4 g/d) 24 weeks	Erythrocyte membrane EPA+DHA fMRI posterior cingulate cortex working memory task	Positive effect on all parameters	[286]
Healthy adults 50-70 years	240 mg EPA + 240 mg DHA or 480 mg EPA + 480 mg DHA with a multivitamin or 480 mg EPA + 480 mg DHA 6 weeks and 16 weeks	Cognitive and cardiovascular function Erythrocyte n-3 PUFAs	Increased n-3 PUFAs No effect on primary cognitive outcome Improvement in spatial memory	[287]
Postmenopausal women 60-84 years	1g DHA, 160 mg EPA, 240 mg Ginkgo biloba, 60 mg phosphatidylserine, 20mg d-α tocopherol, 1mg folic acid and 20 µg vitamin B12 6 months	Mobility Cognition	Partial improvement	[288]
Cognitively healthy individuals aged 50-75 years	n-3 LC-PUFAs 2,200 mg/day 26 weeks	Object location memory	Improvement of recall of object locations	[289]
Healthy older adults aged 50-70 years with subjective memory deficits	DHA or DHA plus Gingko biloba, phosphatidylserine and vitamins B6 and B12 6 months	Cerebral hemodynamics and cognitive functions	No improvement	[290]
Healthy middle aged to elderly subjects	3g Fish oil n-3 PUFA 5 weeks	Working memory	Improvement	[291]
Healthy elderly >55 years with subjective memory complaint	900 mg of algal DHA 24 weeks	Paired Associate Learning	Improvement	[292]
Non demented patients with cognitive complaints 70 years	800 mg DHA and 225 mg EPA and/or cognitive training and physical activity 36 months	Cognition	No improvement In a subset of patients with high EPA+DHA in erythrocytes, less cognitive decline	[293]
Unhealthy subjects with cognitive impairment
Elderly people (average 83 yr) with moderately severe dementia from thrombotic cerebrovascular disorder	4.32 g/day of DHA 3, 6, and 12 months	Cognition (MMSE) Erythrocyte n-3 PUFAs	Improvement of the dementia score Increase in DHA erythrocyte content	[294]
Subjects	Treatment/day and Duration	Primary Outcome	Results	Refs.
Unhealthy subjects with cognitive impairment
Patients with coronary artery disease	1.9 g/d n-3 PUFA 12 weeks	Vascular cognitive impairment	No effect on cognitive performance Verbal memory impairment in a subgroup of nondepressed patients	[295]
Individuals with cognitive impairment no dementia or Alzheimer’s disease	600 mg EPA and 625 mg DHA 4 months	Cognitive functions Mood	No improvement	[296]
Subjects with diagnosis of probable Alzheimer’s disease > 55 years	675 mg DHA and 975 mg EPA/day or 675 mg DHA and 975 mg EPA plus 600 mg lipoic acid (LA)/day 12 months	Urine lipid oxidation (F2-isoprostane) Cognition Functional impairment	No significant change of F2-is prostane Improvement of the cognitive decline in the DHA+EPA+LA group Improvement of functional impairment in all groups	[297]
Elderly patients with MCI	1.74 g/d of EPA/DHA 12 months	Memory, psychomotor speed, executive function and attention, and visual-constructive skills	Improvement in memory	[298]
Alzheimer’s disease patients
Drug-naıve patients with mild Alzheimer’s disease	DHA, EPA, phospholipids, choline, UMP, vitamin B12, B6, and folate, vitamins C and E, and selenium 24 weeks	Memory performance EEG	Improvement	[299]
Individuals with mild to moderate Alzheimer’s disease	2 g of algal DHA/d 18 months	Alzheimer’s disease assessment and dementia	No improvement of cognitive and functional decline	[280]
Alzheimer’s disease patients	2.3 g n-3 PUFAs 6 months	Cognitive performance	Positive correlation between n-3 PUFA rize and cognitive performance	[300]
Alzheimer’s disease patients, Vascular dementia, Dementia with Lewis Bodies, Parkinson disease dementia, Frontotemporal dementia	n-3 LC-PUFAs 6, 12 and 18 months	Mental health Dementia	No positive effects Moderate effect on instrumental activity	[301]
Alzheimer’s disease patients	1.7 g DHA and 0.6 g of EPA 6 months	Cognition (MMSE)	No improvement of cognition Positive effect in a small group of patients with very mild Alzheimer’s disease	[302]