Cross-Sectional Associations of Total Plasma Homocysteine with Cortical β-Amyloid Independently and as a Function of Omega 3 Polyunsaturated Fatty Acid Status in Older Adults at Risk of Dementia.

OBJECTIVES

Elevated total plasma homocysteine is a risk factor for Alzheimer's disease (AD) and there is some evidence that omega-3 polyunsaturated fatty acids (n-3 PUFAs) can modulate the effects of homocysteine-lowering B vitamins on AD related pathologies. Hence we investigated the relationship between total plasma homocysteine and cortical β-amyloid (Aβ) in older adults at risk of dementia. The role of erythrocyte membrane n-3 PUFAs (omega 3 index) on this relationship was also explored.

DESIGN

This is a cross-sectional study using data from the Multidomain Alzheimer Preventive Trial (MAPT); a randomised controlled trial.

SETTING

French community dwellers aged 70 or over reporting subjective memory complaints, but free from a diagnosis of clinical dementia.

PARTICIPANTS

Individuals were from the MAPT trial (n = 177) with data on total plasma homocysteine at baseline and cortical Aβ load.

MEASUREMENTS: Cortical-to-cerebellar standard uptake value ratios were assessed using [18F] florbetapir positron emission tomography (PET). Total baseline plasma homocysteine was measured using an enzymatic cycling assay. Baseline omega 3 index was measured using gas chromatography. Cross-sectional associations were explored using adjusted multiple linear regression models.

RESULTS

We found that total baseline plasma homocysteine was not significantly associated with cortical Aβ as demonstrated using multiple linear regression models adjusted for age, sex, education, cognitive status, time interval between baseline and PET-scan, omega-3 index, MAPT group allocation and Apolipoprotein E ε4 status (B-coefficient -0.001, 95 % CI: -0.008,0.006, p = 0.838). Exploratory analysis showed that homocysteine was however significantly associated with cortical Aβ in subjects with low baseline omega-3 index (< 4.72 %) after adjustment for Apolipoprotein E ε4 status (B-coefficient 0.041, 95 % CI: 0.017,0.066, p = 0.005, n = 10), but not in subjects with a high baseline omega-3 index (B-coefficient -0.010, 95 % CI: -0.023,0.003, p = 0.132, n = 66).

CONCLUSIONS

The role of n-3 PUFAs on the relationship between homocysteine and cerebral Aβ warrants further investigation.