03461nas a2200445 4500008004100000022001400041245012500055210006900180260001500249300001200264490000800276520219900284653000902483653002102492653001502513653001902528653002102547653002502568653002502593653002902618653001102647653002202658653001102680653001802691653000902709653002402718653002402742653001702766653001102783653001802794653001802812100001802830700002402848700001902872700001902891700002002910700002402930700002502954856003602979 2014 eng d a1524-453900aCirculating omega-6 polyunsaturated fatty acids and total and cause-specific mortality: the Cardiovascular Health Study.0 aCirculating omega6 polyunsaturated fatty acids and total and cau c2014 Oct 7 a1245-530 v1303 a

BACKGROUND: Although omega-6 polyunsaturated fatty acids (n-6 PUFA) have been recommended to reduce coronary heart disease (CHD), controversy remains about benefits versus harms, including concerns over theorized proinflammatory effects of n-6 PUFA. We investigated associations of circulating n-6 PUFA including linoleic acid (the major dietary PUFA), γ-linolenic acid, dihomo-γ-linolenic acid, and arachidonic acid, with total and cause-specific mortality in the Cardiovascular Health Study, a community-based U.S. cohort.

METHODS AND RESULTS: Among 2792 participants(aged ≥65 years) free of cardiovascular disease at baseline, plasma phospholipid n-6 PUFA were measured at baseline using standardized methods. All-cause and cause-specific mortality, and total incident CHD and stroke, were assessed and adjudicated centrally. Associations of PUFA with risk were assessed by Cox regression. During 34 291 person-years of follow-up (1992-2010), 1994 deaths occurred (678 cardiovascular deaths), with 427 fatal and 418 nonfatal CHD, and 154 fatal and 399 nonfatal strokes. In multivariable models, higher linoleic acid was associated with lower total mortality, with extreme-quintile hazard ratio =0.87 (P trend=0.005). Lower death was largely attributable to cardiovascular disease causes, especially nonarrhythmic CHD mortality (hazard ratio, 0.51; 95% confidence interval, 0.32-0.82; P trend=0.001). Circulating γ-linolenic acid, dihomo-γ-linolenic acid, and arachidonic acid were not significantly associated with total or cause-specific mortality (eg, for arachidonic acid and CHD death, the extreme-quintile hazard ratio was 0.97; 95% confidence interval, 0.70-1.34; P trend=0.87). Evaluated semiparametrically, linoleic acid showed graded inverse associations with total mortality (P=0.005). There was little evidence that associations of n-6 PUFA with total mortality varied by age, sex, race, or plasma n-3 PUFA. Evaluating both n-6 and n-3 PUFA, lowest risk was evident with highest levels of both.

CONCLUSIONS: High circulating linoleic acid, but not other n-6 PUFA, was inversely associated with total and CHD mortality in older adults.

10aAged10aArachidonic Acid10aBiomarkers10aCohort Studies10aCoronary Disease10aFatty Acids, Omega-310aFatty Acids, Omega-610aFatty Acids, Unsaturated10aFemale10aFollow-Up Studies10aHumans10aLinoleic Acid10aMale10aProspective Studies10aRegression Analysis10aRisk Factors10aStroke10aSurvival Rate10aUnited States1 aH Y Wu, Jason1 aLemaitre, Rozenn, N1 aKing, Irena, B1 aSong, Xiaoling1 aPsaty, Bruce, M1 aSiscovick, David, S1 aMozaffarian, Dariush uhttps://chs-nhlbi.org/node/661302761nas a2200241 4500008004100000022001400041245009800055210006900153260001600222520200500238100002902243700001802272700002102290700002502311700002402336700001902360700001902379700001902398700001702417700002402434700002502458856003602483 2023 eng d a1875-890800aCirculating Omega-3 and Omega-6 Fatty Acids, Cognitive Decline, and Dementia in Older Adults.0 aCirculating Omega3 and Omega6 Fatty Acids Cognitive Decline and  c2023 Aug 233 a

BACKGROUND: Comprising nearly 35% of brain lipids, polyunsaturated fatty acids (PUFA) are essential for optimal brain function. However, the role of PUFA on cognitive health outcomes later in life is largely unknown.

OBJECTIVE: We investigated prospective associations of plasma phospholipid omega-3 (ALA [18 : 3], EPA [20 : 5], DPA [22 : 5], DHA [22 : 6]) and omega-6 (LA [18 : 2], AA [20 : 4]) PUFA with cognitive decline, risk of cognitive impairment and dementia among adults aged≥65 years in the Cardiovascular Health Study.

METHODS: Circulating fatty acid concentrations were measured serially at baseline (1992/1993), 6 years, and 13 years later. Cognitive decline and impairment were assessed using the 100-point Modified Mini-Mental State Examination (3MSE) up to 7 times. Clinical dementia was identified using adjudicated neuropsychological tests, and ICD-9 codes.

RESULTS: Among 3,564 older adults free of stroke and dementia at baseline, cognitive function declined annually by approximately -0.5 3MSE points; 507 participants developed cognitive impairment and 499 dementia over up to 23 years of follow-up. In multivariable models, higher circulating arachidonic acid (AA) concentrations were associated with slower cognitive decline and lower dementia risk, with associations growing stronger with greater length of follow-up (hazard ratio [HR,95% CI] of dementia per interquintile range, 0.74 [0.56-0.97] at 5 years, and 0.53 [0.37-0.77] at 15 years). Circulating docosapentaenoic (DPA) concentrations were associated with slower cognitive decline and lower risk of cognitive impairment (extreme-quintile HR, 0.72 [95% CI: 0.55, 0.95]). Findings were generally null or inconsistent for other omega-3 or omega-6 PUFA.

CONCLUSION: Circulating AA and DPA, but not other PUFA, are associated with slower rate of cognitive decline and lower risk of dementia or cognitive impairment later in life.

1 aOtto, Marcia, C de Olive1 aH Y Wu, Jason1 aThacker, Evan, L1 aLai, Heidi, Tsz Mung1 aLemaitre, Rozenn, N1 aPadhye, Nikhil1 aSong, Xiaoling1 aKing, Irena, B1 aLopez, Oscar1 aSiscovick, David, S1 aMozaffarian, Dariush uhttps://chs-nhlbi.org/node/9477