DFA: EPA/DHA and Cognitive Health (2011)
Samieri C, Feart C, Proust-Lima C, et al. Omega-3 acids and cognitive decline: Modulation by ApoEepsilon4 allele and depression. Neurobiol Aging. 2010 June. PMID 20570406
PubMed ID: 20570406
The goal of this study was to examine the relationship between EPA and DHA plasma levels and cognitive decline over seven years in a cohort of elderly community dwellers. Cognitive decline was assessed by performance on tests of global cognition, verbal fluency, working memory and executive function, while considering depressive symptoms and ApoE-ε4 status.
- Non-institutionalized
- Aged 65 years and older
- Lived in the French city of Bordeaux
- All participants signed informed consent.
Not described
Recruitment
Not described
Design
This study was part of the three-city study, a prospective cohort study following vascular risk factors for dementia in 9,294 community dwellers in three French cities. The present study examines the Bordeaux sample of the three-city study (N=2,104). Baseline and two, four, and seven year follow-up assessments were completed on this cohort. Participants were administered a variety of tests as a measure of cognitive decline over seven years. Associations between EPA and DHA levels and cognitive decline were examined, taking into account depressive symptoms and ApoE-ε4 carrier status.
Statistical Analysis
- Two-sided Student's tests: Compared mean plasma EPA and DHA and change in cognitive scores (by ApoE-ε4 carrier status and depressive symptoms)
- Linear mixed models: Used to analyze changes in cognition over time from baseline
- Associations of covariates with cognitive evolution from baseline were evaluated for each cognitive test both on the baseline mean score level and slope of cognitive change over time.
Covariates
- Plasma EPA or DHA proportions transformed into Z scored
- Depressive symptoms (high vs. low).
Adjustment factors
- Age at baseline
- Gender
- Educational level
- Marital status
- ApoE-ε4
- BMI
- Weight loss more than 3kg
- Smoking
- Alcohol consumption
- History of cardiovascular disease
- Diabetes
- Medication use
- Anti-depressant use
- Plasma triglycerides
- Plasma vitamin E.
Timing of Measurements
- Baseline: 1999-2000
- Follow-up examinations were performed two, four and seven years after baseline
- At baseline, sociodemographic information, lifestyle characteristics, medical symptoms, complaints, and conditions, neuropsychological testing, physical examination and blood sampling were performed
- Cognitive assessments (MMSE, IST, BVRT, and TMT-A and TMT-b) were performed at baseline and at least two follow-up visits
- Depressive symptoms measured at baseline
- Plasma fatty acids assessed at baseline.
Dependent Variables
- Cognitive assessments:
- MMSE (index of global cognitive performance)
- Isaacs Set Test (IST; assessment of semantic verbal fluency)
- Benton Visual Retention Test (BVRT; assessment of working memory)
- Trail-Making Test A and B (TMT-A and TMT-B; evaluation of executive functioning)
- Assessment of depressive symptoms: CES-D (20-item scale to measure depressive symptoms in elderly; scores zero to 60; score of 17 or more in men and 23 or more in women was considered high depressive symptoms).
- Other variables:
- ApoE-ε4 allelle carrier status:
- Measured genetic risk for dementia;
- Carrier: Presence of at least one allele
- Non-carrier: No allele
- Measured genetic risk for dementia;
- ApoE-ε4 allelle carrier status:
- Visual impairment: Assessed at baseline with Parinaud test
- Plasma vitamin E concentration: Measured by HPLC; marker for oxidative stress
- Plasma triglycerides: Used as a proxy for overall lipidic status.
Independent Variables
- Assessment of plasma fatty acids:
- Percent EPA and percent DHA: Calculated as percentage of total fatty acids
- Fasting blood samples collected at baseline visits.
Control Variables
- Age at baseline
- Gender
- Educational level
- Marital status
- ApoE-ε4 status
- BMI
- Weight loss more than 3kg
- Smoking
- Alcohol consumption
- History of cardiovascular disease
- Diabetes
- Medication use
- Anti-depressant use (yes vs. no)
- Plasma triglycerides
- Plasma vitamin E.
- Initial N: 1,343
- Attrition (final N): 1,228 (those non-demented at baseline and completed the MMSE at least once at follow-up; percent men=38.7%
- Age: Mean age: 74.7 years (4.9 SD)
- Ethnicity: French residents of Bordeaux
- Other relevant demographics: Non-demented subjects
- ApoE-ε4 carriers: N=235, 19.3%
- Anthropometrics: Mean BMI=26.4kg/m2 (4.2 SD)
- Location: Bordeaux, France.
Key Findings
Annual change in cognitive scores according to baseline depressive symptoms and ApoE-ε4 status:
- MMSE:
- High depressive symptoms were significantly associated with lower baseline mean MMSE scores; high depressive symptoms: MMSE score=26.80 (SD=2.00); low depressive symptoms: MMSE score=27.60 (SD=2.00) (P<0.001)
- High depressive symptoms were significantly associated with higher average annual decline in MMSE; high depressive symptoms: MMSE average annual change = -0.41 (SD=1.07); low depressive symptoms: MMSE average annual change = -0.12 (SD=0.55) (P<0.001)
- MMSE scores did not differ significantly by ApoE-ε4 status at baseline
- Higher annual declines in MMSE scores were observed in ApoE-ε4 carriers than non-carriers; high depressive: Average decline = -0.21 (SD=0.64); low depressive = -0.12 (SD=0.60) P<0.05
- IST:
- High depressive symptoms were significantly associated with lower mean IST scores at baseline; high depressive: IST score=28.10 (SD=6.90); low depressive IST score=29.90 (SD=6.20) (P<0.05)
- Depressive status was not associated with average annual change in IST
- IST scores were not associated with ApoE-ε4 status
- BVRT:
- High depressive symptoms were significantly associated with lower mean BVRT scores at baseline; high depressive BVRT score=10.80 (SD=2.5); low depressive BVRT score=11.40 (SD=2.10) (P<0.05)
- Depressive status was not associated with average annual change in BVRT scores
- BVRT scores were not associated with ApoE-ε4 status
- TMT-A and TMT-B:
- High depressive symptoms were significantly associated with higher mean performance times on TMT-A and TMT-B scores
- TMT-A: High depressive score=65.63 (SD=27.36); low depressive score=59.83 (SD=23.66); P<0.05
- TMT-B: High depressive score=136.46 (SD=65.64); low depressive score=120.89 (SD=53.37); P<0.05
- Depressive symptoms were not found to be associated with average annual changes in TMT-A and TMT-B scores
- Scores were not associated with ApoE-ε4 status.
- High depressive symptoms were significantly associated with higher mean performance times on TMT-A and TMT-B scores
Effects of plasma DHA on cognitive decline:
- Plasma DHA not significantly associated with evolution of any cognitive test scores over time (adjusted for age, gender and education)
- Plasma DHA not significantly associated with MMSE errors at baseline or decline in MMSE with time
- IST performance: Scores were significantly associated with plasma DHA at baseline; but IST evolution was not found to be associated with DHA
- TMT-A and TMT-B: Not associated with plasma DHA at baseline or over time
- Relationship between plasma DHA and BVRT scores:
- Significant interaction found between DHA proportion and ApoE-ε4 on the change of BVRT scores over time (P=0.02)
- In non-carriers of ApoE-ε4, an increase in plasma DHA was not associated with BVRT performances over time
- In ApoE-ε4 carriers, a one-SD increase in plasma DHA was related to a slower decline in BVRT performances (β=0.061; SD=0.024; P=0.01); However, after exclusion of incident dementia cases, there was no longer a relationship between ApoE-ε4 status and BVRT change over time. (In elderly that remained dementia-free over the follow-up period, DHA was not associated with BVRT performance over time).
Effects of plasma EPA on cognitive decline:
- Plasma EPA not associated with change in cognitive tests when adjusted for age, gender and education
- Fully adjusted models: Plasma EPA was not associated with MMSE errors at baseline or decline in MMSE over time
- IST scores: Higher plasma significantly associated with higher IST scores at baseline, but not evolution of IST scores
- TMT-A and TMT-B: plasma EPA not associated with these scores
- Relationship between plasma EPA and BVRT scores:
- Independent interactions between plasma EPA and both depressive symptoms (P=0.05) and ApoE- ε4 (P=0.006) on the change of BVRT score over time were observed
- In non-carriers with low depressive symptoms, plasma EPA was not related to evolution of BVRT scores (β=0.001; SD=0.012; P=0.93)
- In ApoE- ε4 carriers with low depressive symptoms, higher EPA was associated with slower change in BVRT scores (β=0.076; SD=0.025; P=0.003)
- In ApoE- ε4 non-carriers with high depressive symptoms, higher plasma EPA was associated with slower evolution of BVRT scores (β=0.096; SD=0.048; P<0.04)
- In ApoE- ε4 carriers with high depressive symptoms, higher plasma EPA was associated with slower evolution of BVRT scores (β=0.171; SD=0.049; P<0.001
- Exclusion of incident dementia cases and adjustment for visual impairment and total energy intake did not change results substantially for the relationship between plasma EPA and BVRT.
Other Findings
- 7.8% of sample were found to have high depressive symptoms (CES-D score ≥17 in men and ≥23 in women
- Lower baseline plasma EPA was significantly associated with higher depressive symptoms (P=0.02)
- Lower baseline plasma DHA was not associated with higher depressive symptoms (P=0.95)
- ApoE-ε4 carrier status:
- Plasma EPA and DHA were not significantly different in the whole sample between ApoE-ε4 carriers and not carriers
- Among those with high depressive symptoms, plasma EPA was lower, but not DHA, in carriers (borderline significance P=0.06)
- Among participants with low depressive symptoms, plasma EPA did not differ by ApoE-ε4 status.
The decline in visual working memory may be delayed in ApoE- ε4 carriers by EPA and DHA. EPA, but not DHA may impact the slowing of cognitive decline in depressed, older people.
Government: | The French National Research Agency; conseil Regional d'Aquitaine | |
Not-for-profit |
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Plasma EPA and DHA levels were only measured at baseline. It is possible that these levels could have changed over the course of the seven-year study.
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