TY - JOUR
T1 - Association of Red Blood Cell Omega-3 Fatty Acids with MRI Markers and Cognitive Function in Midlife
T2 - The Framingham Heart Study
AU - Satizabal, Claudia L.
AU - Himali, Jayandra Jung
AU - Beiser, Alexa S.
AU - Ramachandran, Vasan
AU - Melo Van Lent, Debora
AU - Himali, Dibya
AU - Aparicio, Hugo J.
AU - Maillard, Pauline
AU - Decarli, Charles S.
AU - Harris, William S.
AU - Seshadri, Sudha
N1 - Funding Information:
This study was supported by grants from the National Heart, Lung, and Blood Institute contract for the Framingham Heart Study (Contract No. N01-HC-25195, No. HHSN268201500001I, and No. 75N92019D00031), the National Institute on Aging (R01 AG054076, R01 AG049607, U01 AG052409, R01 AG059421, RF1 AG063507, RF1 AG066524, and U01 AG058589) and the National Institute of Neurologic Disorders and Stroke (R01 NS017950 and UH2 NS100605). Dr. Satizabal was supported by a New Investigator Research Grant to promote Diversity from the Alzheimer's Association (AARGD-16-443384) and also receives support from R01 AG059727, and UF1 NS125513. Dr. Himali is partly supported by AG062531 and by an endowment from the William Castella family as William Castella Distinguished University Chair for Alzheimer's Disease Research. Dr. Melo van Lent reports funding from R03 AG067062, the C. Richard Fleming grant and the Daniel H. Teitelbaum grant. Dr. Aparicio was supported by an American Academy of Neurology Career Development Award, Alzheimer's Association Research Grant (AARGD-20-685362), and Boston University's Aram V. Chobanian Assistant Professorship. Dr. DeCarli reports funding from P30 AG0101029. Drs. Satizabal, Himali, and Seshadri report funding from P30 AG066546. Drs. Seshadri and Himali are partially supported by the Bill and Rebecca Reed Endowment for Precision Therapies and Palliative Care. Dr. Seshadri is also supported by an endowment from the Barker Foundation as the Robert R. Barker Distinguished University Professor of Neurology, Psychiatry and Cellular and Integrative Physiology.
Publisher Copyright:
© 2022 American Academy of Neurology.
PY - 2022/12/6
Y1 - 2022/12/6
N2 - Background and ObjectivesDiet may be a key contributor to brain health in midlife. In particular, omega-3 fatty acids have been related to better neurologic outcomes in older adults. However, studies focusing on midlife are lacking. We investigated the cross-sectional association of red blood cell (RBC) omega-3 fatty acid concentrations with MRI and cognitive markers of brain aging in a community-based sample of predominantly middle-aged adults and further explore effect modification by APOE genotype.MethodsWe included participants from the Third-Generation and Omni 2 cohorts of the Framingham Heart Study attending their second examination. Docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) concentrations were measured from RBC using gas chromatography, and the Omega-3 index was calculated as EPA + DHA. We used linear regression models to relate omega-3 fatty acid concentrations to brain MRI measures (i.e., total brain, total gray matter, hippocampal, and white matter hyperintensity volumes) and cognitive function (i.e., episodic memory, processing speed, executive function, and abstract reasoning) adjusting for potential confounders. We further tested for interactions between omega-3 fatty acid levels and APOE genotype (e4 carrier vs noncarrier) on MRI and cognitive outcomes.ResultsWe included 2,183 dementia-free and stroke-free participants (mean age of 46 years, 53% women, 22% APOE-e4 carriers). In multivariable models, higher Omega-3 index was associated with larger hippocampal volumes (standard deviation unit beta ±standard error; 0.003 ± 0.001, p = 0.013) and better abstract reasoning (0.17 ± 0.07, p = 0.013). Similar results were obtained for DHA or EPA concentrations individually. Stratification by APOE-e4 status showed associations between higher DHA concentrations or Omega-3 index and larger hippocampal volumes in APOE-e4 noncarriers, whereas higher EPA concentrations were related to better abstract reasoning in APOE-e4 carriers. Finally, higher levels of all omega-3 predictors were related to lower white matter hyperintensity burden but only in APOE-e4 carriers.DiscussionOur results, albeit exploratory, suggest that higher omega-3 fatty acid concentrations are related to better brain structure and cognitive function in a predominantly middle-aged cohort free of clinical dementia. These associations differed by APOE genotype, suggesting potentially different metabolic patterns by APOE status. Additional studies in middle-aged populations are warranted to confirm these findings.
AB - Background and ObjectivesDiet may be a key contributor to brain health in midlife. In particular, omega-3 fatty acids have been related to better neurologic outcomes in older adults. However, studies focusing on midlife are lacking. We investigated the cross-sectional association of red blood cell (RBC) omega-3 fatty acid concentrations with MRI and cognitive markers of brain aging in a community-based sample of predominantly middle-aged adults and further explore effect modification by APOE genotype.MethodsWe included participants from the Third-Generation and Omni 2 cohorts of the Framingham Heart Study attending their second examination. Docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) concentrations were measured from RBC using gas chromatography, and the Omega-3 index was calculated as EPA + DHA. We used linear regression models to relate omega-3 fatty acid concentrations to brain MRI measures (i.e., total brain, total gray matter, hippocampal, and white matter hyperintensity volumes) and cognitive function (i.e., episodic memory, processing speed, executive function, and abstract reasoning) adjusting for potential confounders. We further tested for interactions between omega-3 fatty acid levels and APOE genotype (e4 carrier vs noncarrier) on MRI and cognitive outcomes.ResultsWe included 2,183 dementia-free and stroke-free participants (mean age of 46 years, 53% women, 22% APOE-e4 carriers). In multivariable models, higher Omega-3 index was associated with larger hippocampal volumes (standard deviation unit beta ±standard error; 0.003 ± 0.001, p = 0.013) and better abstract reasoning (0.17 ± 0.07, p = 0.013). Similar results were obtained for DHA or EPA concentrations individually. Stratification by APOE-e4 status showed associations between higher DHA concentrations or Omega-3 index and larger hippocampal volumes in APOE-e4 noncarriers, whereas higher EPA concentrations were related to better abstract reasoning in APOE-e4 carriers. Finally, higher levels of all omega-3 predictors were related to lower white matter hyperintensity burden but only in APOE-e4 carriers.DiscussionOur results, albeit exploratory, suggest that higher omega-3 fatty acid concentrations are related to better brain structure and cognitive function in a predominantly middle-aged cohort free of clinical dementia. These associations differed by APOE genotype, suggesting potentially different metabolic patterns by APOE status. Additional studies in middle-aged populations are warranted to confirm these findings.
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U2 - 10.1212/WNL.0000000000201296
DO - 10.1212/WNL.0000000000201296
M3 - Article
C2 - 36198518
AN - SCOPUS:85146018488
SN - 0028-3878
VL - 99
SP - E2572-E2582
JO - Neurology
JF - Neurology
IS - 23
ER -