Summary:
Mild cognitive impairment is a clinical diagnosis for a condition characterized by cognitive decline that does not (yet) meet criteria for dementia. Inflammation in the brain is a common characteristic of (and suspected contributor to) mild cognitive impairment and dementias; studies have correspondingly found positive effects of DHA in the context of mild cognitive impairment.
 
Introduction:
Mild cognitive impairment is a condition wherein a person’s cognitive abilities (such as memory, problem solving, attention) show a decline that is greater than expected for that person’s age, yet is nonetheless not severe enough for meeting dementia criteria. People with mild cognitive impairment may have difficulty remembering recent events, solving problems, or processing information quickly. Depression is another common symptom experienced by people with mild cognitive impairment. However, these symptoms are typically not severe enough to significantly disrupt their ability to perform everyday tasks. Mild cognitive impairment represents an intermediate state between normal age-related cognitive decline and more serious conditions like Alzheimer’s disease or other forms of dementia. Two sub-forms are recognized: amnestic and non-amnestic mild cognitive impairment. The former is primarily characterized by memory problems, whereas the latter typically involves difficulties with language, attention or problem solving, rather than memory. Crucially, mild cognitive impairment is recognized as a good target for interventionist approaches that aim to counter cognitive symptoms associated with dementias. Namely, this condition may represent a precursor stage of many dementias that still allows for treatment. The efficacy of many treatments may be lost as cognitive symptoms worsen and mild cognitive impairment transitions into a type of dementia, coupled with irreversible impairment of cognitive functions. Chronic inflammation and oxidative stress in the brain are recognized characteristics of many dementias and even thought to be a major contributor to their pathophysiology. Therefore, many studies have focused on reducing inflammation in pre-dementia stages to counter cognitive decline. A well-known anti-inflammatory antioxidant is DHA, which studies have found to be causally relevant in the face of (protection against) cognitive decline, described below. Notably, DHA is the most common fatty acid in the brain, highlighting its importance in supporting healthy cognition.
 
Research findings:
Yurko-Mauro and fellow scientists set up a double-blind clinical trial to establish the effects of DHA supplementation on cognitive performance in tests commonly used to assess mild cognitive impairment (Yurko-Mauro et al. 2010). The researchers selected a group of 485 cognitively healthy participants aged 55 and over. The participants were randomly divided to receive either 900mg DHA per day or a placebo for a period of 24 weeks. At the start of the study and after this supplementation period, a Paired Associate Learning (PAL) test was conducted, which assesses learning and episodic memory. This test was chosen because the cognitive functions used in the test are one of the first to be negatively affected by age and pre-dementia conditions such as mild cognitive impairment. The authors reported that compared to the placebo group, the DHA supplementation group showed a greater improvement in test components assessing visuospatial learning and episodic memory. Moreover, these improvements in cognitive scores in the supplementation group correlated with their plasma DHA levels. Although the placebo group also showed a slight improvement in the Paired Associate Learning test, this is to be expected as participants are more likely to perform better in a test they have completed once before. Strikingly, when the authors plotted the test performance of study participants to normative data of performance related to age provided by the creators of the test (Cambridge University), the positive effect of DHA on cognition was emphasized. Namely, whereas the increased test performance of the placebo group corresponded to a 3.6-year improvement of cognitive age (test familiarity effect), the DHA group had a 7-year cognitive age rejuvenation in this test.  
 
In a double-blind randomized clinical trial, Lee and colleagues investigated the effects of DHA and EPA on cognitive test performance in adults with mild cognitive impairment (Lee, Shahar, Chin, et al. 2013). For a period of 12 months, 36 elderly individuals with mild cognitive impairment were evenly divided into two groups: one receiving 450mg DHA and 150mg EPA per day, the other group a daily placebo. Cognitive tests were conducted at the 6- and 12-month timepoint. After 12 months, the supplementation group showed an increase in plasma levels of 83.7% for DHA and 121.6% for EPA, whereas the placebo group showed no differences. It was found that the group receiving DHA and EPA supplementation showed improvements in short term memory, working memory, immediate verbal memory and delayed recall capability. This points toward a positive role of DHA and EPA on memory functions in mild cognitive impairment.
 
In a study by the same research group, Lee and fellow investigators examined the levels of plasma lipid hydroperoxide in relation to Omega-3 fatty acid intake in mild cognitive impairment patients (Lee, Shahar, Rajab, et al. 2013). Blood plasma lipid hydroperoxide is a protein that can be used as an indicator of oxidative stress; this stress is thought to be a major contributor to mild cognitive impairment pathophysiology. The researchers examined plasma lipid hydroperoxide levels and Omega-3 fatty acid intake in 67 mild cognitive impairment patients and 134 cognitively healthy elderly controls. These results were then examined in the context of performance in cognitive tests. Their first finding was that lipid hydroperoxide levels were higher in the mild cognitive impairment group compared to the cognitively healthy control group, indicative of oxidative stress in the former group. Crucially, the levels of this oxidative stress indicator were negatively associated with dietary intake of Omega-3 fatty acids DHA and EPA. Correspondingly, dietary intake of EPA and DHA was associated with better performance in cognitive tests used to assess mild cognitive impairment. The authors concluded that DHA and EPA improve cognitive function in mild cognitive impairment by reducing oxidative stress.
 
Sinn and colleagues set up a randomised controlled clinical trial to investigate the effects of DHA and EPA on depressive symptoms, quality of life and cognitive function in persons with mild cognitive impairment (Sinn et al. 2012). As depression is prevalent amongst persons affected by mild cognitive impairment, targeting depression would be a good way to improve the quality of life in this condition. Fifty study participants with mild cognitive impairment aged 65 and over were given a daily supplement for a period of 6 months. This contained either 1.67g EPA and 0.16g DHA (“EPA group”, 17 participants), 1.55g DHA and 0.4g EPA (“DHA group”, 18 participants), or Linoleic acid (“Placebo group”, 15 participants).  At the beginning and end of the supplementation period, depressive symptoms were assessed using the Geriatric Depression Scale, self-reported quality of life was assessed, as well as performance in an array of cognitive tests. In comparison to the placebo group, both the EPA and DHA group showed improvements in scores on the Geriatric Depression Scale. Moreover, for the verbal fluency component of the cognitive tests, the DHA group showed an improvement compared to the placebo group. Finally, participants in the DHA group reported an improvement in their physical health, this difference was not observed in the EPA group.  
 
Conclusion
Mild cognitive impairment is a condition wherein affected individuals show a decline in cognitive function that surpasses the expected decrease for their age, yet is nevertheless not severe enough to meet dementia criteria. This condition is associated with decreased quality of life and is often considered as a precursor stage for many types of dementias. Therefore, it has accrued interest as a crucial target stage to counter further cognitive decline into severity levels associated with dementias. As many dementias are characterized by the presence of oxidative stress and inflammation in the brain, anti-oxidative anti-inflammatory compounds such as DHA have been proposed as potential protective agents against cognitive decline. The studies outlined above show that in both cognitively healthy persons and those with mild cognitive impairment, DHA supplementation induces a positive effect on cognitive functions that are negatively affected in mild cognitive impairment. Supplementation with DHA is also shown to improve depression symptoms and self-reported quality of life. Moreover, in this condition, higher relative DHA and EPA plasma levels are associated with decreased oxidative stress, which correlates with improved performance in cognitive tests. Taken together, DHA plays important roles in supporting cognition; it counters oxidative stress and supports cognitive function, as well as quality of life and geriatric depression symptoms.
 
References:
Lee, Lai Kuan, Suzana Shahar, Ai-Vyrn Chin, and Noor Aini Mohd Yusoff. 2013. ‘Docosahexaenoic Acid-Concentrated Fish Oil Supplementation in Subjects with Mild Cognitive Impairment (MCI): A 12-Month Randomised, Double-Blind, Placebo-Controlled Trial’. Psychopharmacology 225(3):605–12. doi: 10.1007/s00213-012-2848-0.

Lee, Lai Kuan, Suzana Shahar, NorFadilah Rajab, Noor Aini Mohd Yusoff, Rahman A. Jamal, and Sue Mian Then. 2013. ‘The Role of Long Chain Omega-3 Polyunsaturated Fatty Acids in Reducing Lipid Peroxidation among Elderly Patients with Mild Cognitive Impairment: A Case-Control Study’. The Journal of Nutritional Biochemistry 24(5):803–8. doi: 10.1016/j.jnutbio.2012.04.014.

Sinn, Natalie, Catherine M. Milte, Steven J. Street, Jonathan D. Buckley, Alison M. Coates, John Petkov, and Peter R. C. Howe. 2012. ‘Effects of N-3 Fatty Acids, EPA v. DHA, on Depressive Symptoms, Quality of Life, Memory and Executive Function in Older Adults with Mild Cognitive Impairment: A 6-Month Randomised Controlled Trial’. British Journal of Nutrition 107(11):1682–93. doi: 10.1017/S0007114511004788.