Table 2.
Influence of bioactive lipids on cognition: Human studies
| Study | Study aims and design | Sample | Variables | Results |
|---|---|---|---|---|
| M. A. Beydoun et al. (111) |
Association between plasma n-3 FAs and cognitive decline in older adults. Prospective cohort design. |
2251 individuals (aged 50 – 65 yrs) residing in Minneapolis, MN during 1990-1992 and 1996-1998. |
DV: (1) Cognition assessed at 2 time points (3-yr interval): (a) verbal learning and memory (b) psychomotor (c) verbal fluency (d) global cognitive decline (composite score based on change scores for tests a- c) (2) Plasma FAs at study entry (saturated, monounsaturated, linoleic acid, α- linolenic acid, n-3 and n-6 FAs) |
Association between FAs and cognitive decline from baseline to 3 years: (1) ↑ global cognitive decline associated with: ↑ palmitic acid ↑ AA ↓ linoleic acid (2) ↓ decline in verbal fluency associated with: ↑ DHA + EPA |
| J. Colombo et al. (108) |
Association between levels of phospholipid DHA in mothers and infants at delivery, and the development of attention during infancy and toddlerhood. Longitudinal (prospective) follow- up design. |
70 infants recruited for follow-up from among 350 infants and mothers enrolled in study of effects of DHA supplementation on pregnancy outcomes (randomized, double-blind, controlled clinical trial). |
IV: (1) Supplemented mothers’ diet during last trimester of pregnancy by providing eggs with high- vs. standard-levels of DHA (135 mg vs. 35 mg DHA/egg, respectively). (2) Group membership (high- vs. low- DHA) determined by levels of DHA in RBC for mother and infant at delivery. DV: Laboratory measures (gaze duration, heart rate) of attention in children during: (a) Visual habituation task in infants at ages 4, 6, and 8 mos. (b) Single-object exploration and distractibility tasks in toddlers at ages 12 and 18 mos. |
Compared to children of mothers with low-DHA levels at delivery: (1) Infants of mothers with high-DHA levels at delivery showed accelerated development for visual attention at ages 4 and 6 mos. (shorter gaze duration during visual habituation task). (2) Toddlers of mothers with high-DHA levels at delivery showed more mature development of attention (longer single-object exploration; reduced distractibility). |
| E. Cyhlarova et al. (123) |
Association between literacy skills and n-3 and n-6 FAs in dyslexia. |
32 dyslexic adults, 20 non- dyslexic controls (mean ages = 32 and 34 yrs, respectively) |
DV: RBC levels of n-3 and n-6 FAs (venous blood draw after overnight fast) Literacy skills and intelligence: WRAT word reading, spelling; WAIS subtests (similarities, vocabulary, block design, picture arrangement, digit span, digit symbol) |
A. Dyslexic individuals and non-dyslexic controls did not differ for mean levels of RBC FAs. B. Both dyslexic and control groups: Word reading and total n-3 FAs positively correlated: ↑ total n-3 FAs ↑ reading score C. Dyslexic individuals only: (1) Word reading positively correlated with n-3 FAs: ↑ α-linolenic acid ↑ reading score (2) Word reading negatively correlated with n-6 FAs: ↑ adrenic acid ↓ reading score D. Control individuals only: Word reading positively correlated with n-3 FAs: ↑ DHA ↑ reading score |
| C. Dullemeijer et al. (112) |
Association between n-3 PUFAs and change in cognition over 3 years in older adults. Parent protocol: Randomized, placebo-controlled trial to determine effect of folic acid on cognitive performance, carotid intima-media thickness, hearing. Baseline assessments occurred during 2000 and 2001. |
819 male and female adults at baseline (ages 50-70 yrs) |
IV: Random assignment to folic acid supplementation (n=406) vs. placebo (n=413) DV: Data reported for individuals in placebo-arm only (n=404): (1) Change in performance from baseline to 3 yrs in 5 domains: (a) Memory (Word Learning Test) (b) Sensorimotor speed (Stroop Color-Word-Subtest I; Concept Shifting-Subtests O, A, B) (c) Complex speed (Stroop Color-Word- III; Concept Shifting- C) (d) Information-processing speed (Letter Digit Substitution) (e) Word fluency (Verbal Fluency Test) (2) Plasma n-3 PUFAs at baseline (venous blood after overnight fast): EPA, docosapentaeoic acid, DHA |
A. Cognitive performance declined from baseline to 3 yrs for speed-related responding: sensorimotor speed, complex speed, information-processing speed. B. n-3 PUFA concentrations at baseline were associated with decline in speed-related responding at 3 yrs: ↑ n-3 PUFAs at baseline ↓ decline over 3 yrs for sensorimotor speed and complex speed. |
| J. A. Dunstan et al. (109) |
Effects of antenatal n-3 PUFA supplementation on cognitive development in children at age 2.5 yrs. Randomized, double-blind placebo-controlled trial conducted between January 2000 and September 2001. |
72 infants of 98 women enrolled during pregnancy |
IV: From 20 weeks gestation to delivery, pregnant Caucasian women with allergic disease randomly assigned to receive: (1) n-3 FA supplementation (n=52; 4 g/day fish oil with 2.2 g/day DHA and 1.1 g/day EPA) vs. (2) placebo (n=46; 4 g/day olive oil with 2.7 g/day n-9 oleic acid). Both n-3 FA supplement and placebo included 3-4 mg/g oil α-tocopherol. DV: (1) n-3 and n-6 PUFAs in phospholipids of erythrocyte membranes in umbilical cord blood (2) Assessments of children at age 2.5 yrs on measures of infant growth and development (GMDS), receptive language (PPVT), and behavior (CBCL) |
A. Effect of antenatal supplementation with n-3 PUFA on FA composition of erythrocyte membranes in umbilical cord blood of neonates: ↑ n-3 PUFAs ↓ n-6 PUFAs B. Effects of antenatal supplementation with n-3 PUFA on child’s cognitive development at age 2.5 yrs: ↑ eye–hand coordination C. Association between cognition at age 2.5 yrs and PUFA levels in cord–blood erythrocytes: (1) Eye–hand coordination positively correlated with n-3 PUFA levels (EPA, DHA): ↑ n-3 PUFA levels ↑ eye–hand coordination. (2) Eye–hand coordination and performance scores negatively correlated with n-6 PUFA levels: ↑ AA levels ↓ eye–hand coordination and performance. |
| Y. Ishikura et al. (124) |
Effect of dietary supplementation with AA on auditory P300 in healthy older men. Double-blind crossover design |
25 healthy men (ages 57-68 yrs) |
IV: 3-month crossover protocol (1 mo/phase): Group A (n=13): AA, washout, placebo Group B (n=12): placebo, washout, AA AA supplement: 600 mg/day of AA-enriched triglyceride (240 mg AA); Placebo: olive oil (600 mg/day) DV: (1) EEG recorded from midline parietal electrode (Pz) to evaluate amplitude and latency of auditory P300 component of event-related potential elicited using an oddball paradigm. (2) Serum phospholipids measured before and after supplement and placebo periods. |
A. Significant effect of AA- supplementation on P300 response: ↓ P300 latency (mean Δ = −10.1 ms ± 15.9) ↑ P300 amplitude (mean Δ = 0.8 μV ± 1.7). B. Significant effect of AA- supplementation on serum phospholipids: ↑ serum AA (mean Δ = 37.7 μg/ml ± 26.2) ↓ serum EPA (mean Δ = −13.0 μg/ml ± 20.3). |
| J. L. Jacobson et al. (110) |
Relationship of cord-plasma DHA concentration to physical growth and cognitive development at ages 6 and 11 mos for Inuit infants living in Arctic Quebec. Developmental outcomes associated with PUFA intake from breast feeding were also evaluated. Prospective longitudinal cohort study, November 1995 to March 2001 |
109 Inuit infants and their mothers |
DV: (1) Biological samples: (a) Blood collected from severed umbilical cord and from mothers after delivery. Milk collected from breast- feeding mothers at 1-mo postnatal interview. (b) FA compositions of plasma phospholipids and total maternal milk lipids. (2) Perceptual, cognitive, and motor development assessed at ages 6 mos (Teller; FTII) and 11 mos (Teller; FTII; BSID-II) |
A. ↑ DHA concentration in umbilical cord positively associated with development: ↑ gestation length ↑ visual acuity (6 mos) ↑ novelty preference (6 mos) ↑ Mental development score (11 mos) ↑ Psychomotor development score (11 mos) B. Post-natal DHA intake from breast-feeding was not correlated with developmental outcome. |
| O. van de Rest et al. (114) |
Association between dietary intake of fatty fish and change in cognition over 6 years in elderly men. Prospective cohort study, the Veterans Affairs Normative Aging Study. Recruitment initiated in 1963 in Boston, MA area. |
451 men for whom complete set of measures available (mean age at baseline cognitive assessment = 68 yrs). |
DV: (1) Estimates of n-3 PUFA intake from dietary questionnaire (g of n-3 FAs per portion/day): dark-meat fish (1.37 g); canned tuna (0.69 g); shellfish (0.46 g); other fish (0.17 g) (2) Cognitive domains assessed at baseline and over 6 yrs followup: language, speed, attention, memory, and spatial copying |
A. Cross-sectional (baseline) analyses: Cognitive performance was not associated with dietary fatty fish or n-3 PUFA intake. B. Longitudinal analyses: Cognitive change over 6 yrs was not associated with dietary fatty fish or n-3 PUFA intake. |
| L. J. Whalley et al. (120) |
Influence of erythrocyte n-3 PUFA concentration on age- related cognitive decline in the presence or absence of the APOE ε4 allele. Prospective study of population- based sample (1936 birth cohort). Recruitment from November 1999 to February 2002. |
Original sample = 478 healthy volunteers (ages 63-66 yrs); Subsample = 120 individuals for whom cognitive assessments and FA data were available. |
DV: (1) Intelligence score at 11 yrs available from national database (2) At baseline, venous blood collected for (a) APOE genotyping and (b) FA composition of erythrocyte membranes (total n-3 PUFAs, EPA, DHA, n-6:n-3 ratio) (3) Cognition evaluated at ages 64 (baseline), 66, and 68 yrs: nonverbal reasoning (RPM), verbal declarative memory (AVLT), executive function (Uses of Common Objects), information processing speed and psychomotor performance (WAIS-R Digit Symbol), constructional ability (WAIS Block Design) |
A. Relationship between PUFA concentrations and intelligence: (1) For APOE ε4 noncarriers (absent), total n-3 PUFA at baseline (≈ 63 yrs) was positively correlated with general intelligence at ages 11 yrs and 63-65 yrs: ↑ n-3 PUFA at 63 yrs ↑ Intelligence score at ages 11 and 63 yrs. (2) Relationship between PUFA concentrations and intelligence was not significant for APOE ε4 carriers (present). B. Erythrocyte membrane PUFA content did not differ between groups based on APOE ε4 status. C. Verbal declarative memory (AVLT) score differed significantly between APOE ε4 allele groups at all time points: APOE ε4 allele noncarriers > carriers. |
Abbreviations for Table 2: ↑, increase; ↓, decrease; Δ, change; AA, Arachidonic acid; AVLT, Rey’s Auditory Verbal Learning Test; BSID-II, Bayley Scales of Infant Development, 2nd edition; CBCL, Child Behavior Checklist; CGI, Clinical Global Impression scale; DHA, Docosahexaenoic acid; DV, Dependent variable; EEG, Electroencephalogram; EPA, Eicosapentaenoic acid; FA, Fatty Acid; FTII, Fagan Test of Infant Intelligence; GMDS, Griffiths Mental Development Scales; IV, Independent variable; PPVT, Peabody Picture Vocabulary Test; PUFA, Polyunsaturated fatty acid; RBC, Red Blood Cell; RPM, Raven’s Progressive Matrices; Teller, Teller Visual Acuity Card Test; WAIS-R, Wechsler Adult Intelligence Scale–revised.