Prospective Relations between Red Blood Cell n‐6 and n‐3 Fatty Acid Composition and Cognitive Function among Older Puerto Rican Adults
Authors: Bigornia Sherman J , Scott Tammy M , Harris William S , Tucker Katherine L 
Published: November 2023

ObjectivesTo examine the association between red blood cell (RBC) n‐6 and n‐3 fatty acid (FA) composition, their ratio, and 2‐y cognitive function and incidence of cognitive impairment among older U.S. mainland Puerto Ricans.MethodsData are from the Boston Puerto Rican Health Study. RBC membrane FA status was ascertained at baseline. Total n‐6 FA composition was defined as the sum total of FAs 18:3n‐6, 18:2n‐6, 20:3n‐6, 20:4n‐6, 22:5n‐6, 22:4n‐6, and 20:2n‐6 expressed as a percent of total FA content. Total n‐3 FAs included 18:3n‐3, 20:5n‐3, 22:5n‐3, and 22:6n‐3. General cognitive function was measured at baseline and at 2‐y (median, IQR: 2.0 y, 1.9–2.2) using the Mini‐Mental State Exam (MMSE). The MMSE is on a scale of 0–30 with a higher score indicating better function. We defined cognitive impairment as MMSE scores ≤21, ≤23, and ≤24 for those with less than a high school education, a high school degree, and some college education or higher, respectively. Relations between RBC FAs and 2‐y MMSE scores were examined in 946 participants and incidence of cognitive impairment among those considered to have normal baseline cognitive function (n=639).ResultsParticipants were predominantly female (74%) and 57±8 y of age. In multivariate models, total n‐6 FAs were associated with lower MMSE scores at 2‐y (Table, Model 2, P‐trend= 0.003), which remained significant after accounting for baseline MMSE score (Model 3, P‐trend=0.02). Total n‐3 FAs were positively (Model 2, P‐trend=0.04) and the n‐6:n‐3 ratio inversely (Model 2, P‐trend=0.007) related to 2‐y cognitive function, but these relationships attenuated with adjustment for baseline score (Model 3). The incidence of cognitive impairment at follow‐up was 22%. In multivariate models, a 1% increase in total n‐6 FAs was related to a 9% greater incidence of cognitive impairment [RR=1.09 (95% CI: 1.01, 1.18), P=0.03]. The n‐6:n‐3 ratio was positively associated with incident cognitive impairment [RR=1.13 (95% CI: 1.00, 1.27), P=0.05], whereas total n‐3 FAs were inversely related [RR=0.92 (0.81 to 1.04), P=0.16]. We did not find evidence of interaction between total n‐6 and n‐3 FAs and associations with 2‐y MMSE score or incident cognitive impairment.ConclusionsAn objective biomarker of n‐6 FA consumption and metabolism was consistently associated with poorer cognitive function and incidence of cognitive impairment over 2‐y follow‐up. Our data suggest that greater intakes of food sources of n‐6 FA may play a role in cognitive decline among older U.S. mainland Puerto Ricans.Support or Funding InformationThis research was supported by NIH grants P01‐AG023394, P50‐HL105185, and R01‐AG027087

Baseline composition of red blood cell total n‐6, n‐3, and n‐6:n‐3 fatty acid ratio and relations with 2‐y Mini‐Mental State Exam scores (n=946)1

Red Blood Cell Fatty Acid Composition (Quartiles)

Fatty acid
Model2
1
2
3
4
P‐trend

n=236
n=237
n=237
n=236

Total n‐6

33.2 ± 1.5%
35.4 ± 0.4%
36.6 ± 0.3%
38.2 ± 0.9%

1
23.8 (23.3, 24.2)
23.4 (23.0, 23.8)
23.4 (23.0, 23.7)
22.9 (22.5, 23.4)
0.007

2
23.7 (23.3, 24.2)
23.4 (22.9, 23.8)
23.4 (22.9, 23.8)
22.8 (22.3, 23.3)
0.003

3
23.5 (23.1, 23.8)
23.4 (23.2, 23.7)
23.3 (22.9, 23.7)
23.0 (22.6, 23.3)
0.02

Total n‐3

5.2 ± 0.5%
6.1 ± 0.2%
6.9 ± 0.2%
8.3 ± 0.9%

1
23.1 (22.7, 23.5)
23.2 (22.8, 23.6)
23.3 (22.9, 23.7)
23.8 (23.4, 24.2)
0.02

2
23.1 (22.7, 23.6)
23.2 (22.8, 23.7)
23.3 (22.8, 23.7)
23.7 (23.3, 24.2)
0.04

3
23.2 (22.8, 23.6)
23.2 (22.8, 23.6)
23.3 (22.9, 23.7)
23.4 (23.1, 23.8)
0.30

n‐6:n‐3 ratio

4.2 ± 0.5
5.2 ± 0.2
6.0 ± 0.2
7.2 ± 0.8

1
23.8 (23.4, 24.2)
23.5 (23.1, 23.9)
23.1 (22.7, 23.5)
23.1 (22.7, 23.5)
0.004

2
23.8 (23.3, 24.2)
23.5 (23.0, 23.9)
23.1 (22.6, 23.5)
23.1 (22.6, 23.5)
0.007

3
23.5 (23.1, 23.8)
23.4 (23.0, 23.7)
23.1 (22.8, 23.5)
23.2 (22.8, 23.5)
0.13

Data are adjusted means and 95% CIs for 2‐y Mini‐Mental State Exam scores.
Model 1: age, sex, BMI, high school education; Model 2: + physical activity score, smoking status, diabetes, heart disease, depression; Model 3: + baseline mini‐mental state exam score.