Predictors of memory in healthy aging – long-chain omega-3 levels important in helping to maintain memory health in older adults, new study suggests

A new study from the University of Illinois in the USA has looked at the effect of the LC-PUFA (long chain polyunsaturated fatty acid) balance in blood plasma in relation to memory function and brain white matter microstructure in a healthy elderly population (1). In recent years, a large number of studies have shown the omega-3 LC-PUFA DHA (docosahexaenoic acid) exerts protective effects on the aging brain through maintenance of neuronal cell membrane structural integrity, attenuation of inflammation and promotion of energy generating glucose metabolism (2). These effects were seen mainly in the brain grey matter, particularly in the frontal cortex and hippocampal regions. However, a very sensitive Magnetic Resonance Imaging (MRI) technique known as Diffusion Tensor Imaging (DTI) now allows the probing of brain white matter microstructure through measurement of fractional anisotropy (FA) (3,4).

The University Illinois study (1) was carried out with 94 healthy participants, average age 69 years (SD=3) who exhibited no signs of cognitive decline – they achieved a score of greater than 26 when assessed by the Mini-Mental State Examination (MMSE). The key result was that higher plasma LC-PUFA levels were associated with higher FA values in the fornix (a white brain matter structure) and higher memory scores. Further the complex statistical model used in the study demonstrated that increase fornix FA values fully mediated the relationship between plasma LC-PUFA levels at memory. 

FA values have been characterised as an efficient measure of the microstructure of the fornix. Restricted diffusion values are indicative of superior myelination and indeed, total number of myelinated nerve fibres (5). Deterioration of the microstructure of the fornix has previously been linked with the development of cognitive impairment in the elderly (6). The fornix consists of bilateral white matter bundles that originate from the DHA rich hippocampus. While grey matter is generally rich in DHA, it is not found at similar levels in white matter where the mono-enoic (single double bond) fatty acids tend to lead (7). However, it has been suggested that one of the roles of enhanced levels of DHA in brain grey matter is to stimulate the production of white matter.

Interestingly, the authors of the Illinois study (1) point out that LC-PUFAs are not the only micronutrients that preserve brain white matter integrity, but they also point to the beneficial effect of vitamins B1, B12, D and E in this respect.  The study does not clarify the effect of the balance of omega-3 to omega-6 fatty acids on the white matter of the brain. 

1. Zamroziewicz MK, Paul EJ, Zwilling CE & Barbey AK; “Predictors of Memory in Healthy Aging: Polyunsaturated Fatty Acid Balance and Fornix White Matter Integrity!; Aging and Disease 2018 (February); 9(1). Published online ahead of print: http://www.aginganddisease.org/EN/10.14336/AD.2017.0501 
2. Cunnane SC, Plourde M, Pifferi F et al.; “Fish, docosahexaenoic acid and Alzheimer’s Disease”; Prog Lipid Res, 48:239-56.
3. Carlesimo GA, Cherubini A, Caltagirone C et al.; “Hippocampal mean diffusivity and memory in healthy elderly individuals; A cross-sectional study”; Neurology 2010; 74(3); 194-200.
4. Pagani E, Agosta F, Rocca MA et al.; “Voxel-based analysis derived from fractional anisotropy images of white matter volume changes with ages”; Neuroimage 2008; 41(3); 657-67.
5. Salat DH, Tuch DS, Greve DN et al.; “Age-related alterations in white matter microstructure measured by diffusion tensor imaging”; Neurobiol Aging 2005; 26(8): 1215-27.
6. Fletcher E, Raman M, Heubner P et al.; “Loss of Fornix white matter volume as a predictor of cognitive impairment in cognitively normal elderly individuals”; JAMA Neurol 2013; 70 (11): 1389-95.
7. Salem N, Abood LJ & Hoss W; “Separation of brain phosphatidylserine according to degree of unsaturation by thin layer chromatography”; Analytical Biochemistry 1976; 76: 407-15.