Fatty Acid Status and Its Relationship to Cognitive Decline and Homocysteine Levels in the Elderly

Abstract: Polyunsaturated fatty acids (PUFAs), especially the n-3 series, are known for their protective effects. Considering that cardiovascular diseases are risk factors for dementia, which is common at aging, the aim of this study was to evaluate whether fatty acid status in the elderly was associated with cognitive function and cardiovascular risk. Forty-five elderly persons (age ≥60 years) were included and divided into two groups based on their Mini-Mental Status Examination score adjusted for educational level: the case group (n = 12) and the control group (n = 33). Serum fatty acid composition, homocysteine (Hcy), hs-CRP, lipid profile and different cognitive domains were evaluated. The case group, characterized by reduced cognitive performance, showed higher levels of 14:0, 16:0, 16:1n-7 fatty acids and lower levels of 22:0, 24:1n-9, 22:6n-3 (DHA) and total PUFAs compared to the control group (p < 0.05). The n-6/n-3 ratio was elevated in both study groups, whereas alterations in Hcy, hs-CRP and lipid profile were observed in the case group. Cognitive function was positively associated with the 24:1n-9, DHA and total n-3 PUFAs, while 14:0, 16:0 and 16:1n-7 fatty acids, the n-6/n-3 ratio and Hcy were inversely associated. In addition, n-3 PUFAs, particularly DHA, were inversely associated with cardiovascular risk, assessed by Hcy levels in the elderly.

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Alex’s Notes: Fats are always an interesting topic. Fish oil and the omega-3 fatty acids have received unprecedented attention for their purported benefits on a range of health markers. Similarly, excessive consumption of omega-6 fatty acids may be an implication in many diseases. Monounsaturated fats are touted as heart healthy, even by the mainstream. Saturated fats are the scapegoats of conventional wisdom and the highlight of high-fat dieters. The current study aimed to see if there is an association between these fatty acids and cognitive decline in the elderly, as well as if there is an association to homocysteine – a marker of cardiovascular disease risk.

The study recruited 45 men and women over the age of 60 and had them complete the Mini-Mental Status Examination (MMSE) to determine if they had cognitive impairment or not. According to these results, 12 subjects comprised the “case group” (with impairment) and 33 comprised the “control group” (without impairment). In addition to the MMSE,

“Global cognitive function was assessed by a psychologist in individual interviews through the following tests adapted from the CERAD battery (Consortium to Establish a Registry for Alzheimer’s Disease): Verbal Fluency, Animal Category, Boston’s Naming Test (short version), Word List Memory, Delay Recall of Word List, Recognition Word List, Constructional Praxis, Delay Visual Memory, Trail Making Test (TMT) and Wechsler Adult Intelligence Scale 3rd Edition, Digit Subtest (WAIS-III).”

Before getting to the main outcomes, an interesting note was that the case subjects had significantly greater total cholesterol (243 vs 201 mg/dL), LDL-C (154 vs 122 mg/dL), and triglycerides (212 vs 124 mg/dL). This becomes more interesting when we consider that 24% of the control subjects had diabetes while only 8% of the case subject did (but it wasn’t statistically significant). Moreover, MMSE scores for the case group ranged from eight to 22, while they ranged from 22-30 in the control group, clearly demonstrating a level of lower cognitive functioning. This is confirmed by the CERAD battery, which found that of the 11 cognitive function tests, only two (recognition word list & trails test B time) were not significantly different. All others were an average of 45% lower in the case group.

As for the fatty acid profiles, I summarized the significant differences in the table below expressed as the percentage (%) of total fatty acid levels unless otherwise stated.

Fatty Acid

Common Name




Difference relative to Control


Myristic acid






Palmitic acid






Behenic acid






Palmitoleic acid






Nervonic acid











Total PUFA






It was surprising that the n-6:n-3 ratio wasn’t significantly different between groups, although it was above 11 in both. The authors note that these results were corroborated by the dietary intake data they received, but unfortunately they chose not to show it. When comparing the serum fatty acid profiles with the cognitive exams,

“Positive associations were found between different instruments for the evaluation of cognitive performance and the 24:1n-9, 22:6n-3 fatty acids and the total n-3 PUFAs, while saturated fatty acids (14:0; 16:0), 16:1n-7 and the n-6/n-3 ratio were inversely associated. However, no association was observed with 20:4n-6.”

Finally, homocysteine levels were about 36% greater in the case group, and greater homocysteine levels were associated with a decrease in total omega-3 PUFAs, especially DHA and EPA, as well as an increase in the omega-6 to omega-3 ratio. However, I am willing to bet this is reverse casualty. I highly doubt that elevated homocysteine depletes serum omega-3s, but it is more reasonable to believe that low serum omega-3s may elevate homocysteine, although the mechanisms of action are not well understood.

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