Table 3.
Studies investigating interaction between APOE4 and omega 3 fatty acids or fish consumption in cognitive decline
| Study | Study type | Number of patients | Avg Age | Diagnosis | Form of ω-3 fatty acid or fish consumption | Cognitive test | Benefit observed in primary outcome | Benefit in APOE subgroup analysis |
|---|---|---|---|---|---|---|---|---|
| Stonehouse 2013 | RCT | n=176 | 33 | Cognitively healthy | DHA supplementation | Computerized mental performance assessment system | Yes | Greater effect in APOE4 males |
| Quinn 2010 | RCT | n=295 | 76 | AD | DHA supplementation | ADAS-Cog, CDR sum of boxes | No | Non-carriers |
| van de Rest 2008 | RCT | n=302 | 70 | Cognitively healthy | EPA-DHA supplementation | 5-test battery | No | APOE4-attention |
| Yasuno, 2012 | Trial | n=663 | 72.7, 73 | Dementia-free | ω-3 fatty acid supplementation | Set- dependent activity; CCR; category fluency test; WAIS-R | Yes | APOE4>non-carriers |
| Ronnemaa 2012 | Prospective cohort | n=2009 | 50 | Longitudinal (various) | PUFA levels | Demenita diagnosis | No | No interaction |
| Samieri 2011 | Prospective cohort | n=1228 | 74 | Non-institutionalized | EPA and DHA plasma levels | Test battery including MMSE | No | APOE4 |
| Kroger 2009 | Prospective cohort | n=633 | 81 | Dementia-free | DHA levels, Mercury levels | MMSE, dementia diagnosis | No* | No interaction |
| Whalley 2008 | Prospective longitudinal** | n=120 | 64 | Dementia-free | Erythrocyte membrane ω-3 fatty acid levels | MMSE, RPM, AVLT, UCOT, DSST | Yes | Non-carriers |
| Kivipelto 2008 | Longitudinal retrospective | n=1449 | 57 | Longitudinal (various) | PUFA consumption from spreads | DWRT, DSST/WAIS, WFT | Yes | APOE4>non-carriers |
| Laitinen 2006 | Longitudinal retrospective | n=1449 | 50 | Longitudinal (various) | PUFA consumption from spreads | MMSE, dementia diagnosis | Yes | APOE4 |
| Beydoun 2007 | Prospective cohort | n=2251 | 57 | Longitudinal (various) | Plasma ω-3 fatty acid levels | DWRT, DSST, WFT | Yes | No interaction |
| Laurin 2003 | Cross sectional and prospective | n=65 | 76 | Cross sectional (various) and prospective (unimpaired at start of study) | ω-3 fatty acid levels | MMMSE, dementia diagnosis | No*** | No**** |
| Huang 2005 | Prospective Cohort | n=2233 | 71 | Cognitively healthy | Fatty fish 2x/week | MMSE, TICS, IQcode, dementia diagnosis |
Yes | Non-carriers |
| Barberger-Gateau 2007 | Prospective cohort | n=8085 | >65 | Non-demented | Weekly fish, ω-3 fatty acid | Dementia diagnosis | Yes | Non-carriers |
| Daiello 2015 | Retrospective Cohort | n=819 | 75 | Cognitively healthy, MCI, AD | Fish oil supplements | ADAS-Cog, MMSE | Yes | Cognitively healthy non-carriers |
| van de Rest, 2016 | Longitudinal retrospective | n=915 | 81 | Longitudinal (various) | Fish in diet, fish oil supplements | 21-test battery | Yes | APOE4 |
| Samieri 2018 | Retrospective cohort meta-analysis | n=23,688 | 74 | Various | Fish consumption | In person interviews, telephone battery | Yes | No interaction |
| Danthiir 2014 | Cross-sectional | n=390 | 73 | Cognitively healthy | Current and childhood fish consumption | Cognitive test battery | No | No interaction |
Abbreviations: Obs; observational study, RCT; randomized controlled trial, AD; Alzheimer’s disease, MMSE; mini-mental status examination, CCR; category cued recall, WAISR; Wechsler Adult Intelligence Scale-Revised, WAIS; Wechsler Adult Intelligence Scale, DSST; Digit Symbol Substitution Test, WFT; Word Fluency Test, MMMSE; modified mini mental status examination; RPM; Raven’s Progressive Matrices, AVLT; Auditory-Verbal Learning Test, UCOT; Universal Cognitive Aptitude Test, TICS; Telephone Interview for Cognitive Status, IQcode; Informant Questionnaire on Cognitive Decline in the Elderly, ADAS-Cog; Alzheimer’s Disease Assessment Scale-Cognitive Subscale, CDR; Clinical Dementia Rating.
However, dementia risk reduction was observed in individuals in the highest quartile of mercury concentration and also had high DHA, suggesting high fish consumption.
Cognition was assessed both at age 11, 64, 66, 68.
In prospective analysis, higher levels of EPA, DHA, omega 3 and PUFAs were found in patients with dementia or cognitive impairment.
APOE4 carriers with dementia had lower levels of n-6 and total PUFAs than controls. Non-carriers with dementia had higher levels of DHA. Subgroup analysis performed only in the cross-sectional analysis, not prospective.