TERRELL HARRINGTON BAPTIST HEALTH SYSTEM JOURNAL CLUB NOVEMBER 2014 Regular Fish Consumption and Age-Related Brain Gray Matter Loss.

TERRELL HARRINGTON

BAPTIST HEALTH SYSTEM

JOURNAL CLUB

NOVEMBER 2014

Regular Fish Consumption and Age-Related Brain Gray Matter Loss

Purpose

To investigate the relationship between dietary consumption of fishand brain structure among 260 cognitively normal elderly participants.

Hypotheses:1) Frequency of fish consumption correlates with higher grey matter

volumes in the brain areas responsible for memory and cognition in an elderly population.

2) Omega-3 fatty acid (FA) content of the consumed fish is related to specific increases in the volume of brain regions frequently targeted by Alzheimer’s disease in frontal, temporal, and parietal areas.

Relevance

• Approximately 24.3 million cases of dementia worldwide• Without effective prevention and treatment, this number is

projected to double every 20 years to more than 80 million by 20401

• Often incorrectly thought of as “senility” or “senile dementia”• Recent estimates suggest dementia has become the third leading

cause of death in the United States behind CVD and cancer2

Cognitive Decline

• Dementia – progressive decline in at least 2 cognitive domains of the brain severe enough to interfere with daily life• Memory• Communication and language• Ability to focus and pay attention• Reasoning and judgment• Visual perception

• Alzheimer’s disease is the most common form of dementia and accounts for more than half of cases• Vascular dementia• Parkinson’s disease• Frontotemporal dementia• Mixed dementia3

Grey Matter

• Composed of brownish-grey neurons and dendrites found at the surface of the cerebral hemispheres of the brain and spinal cord• Major component of the central nervous system (CNS)• More energy consuming than white matter and uses 95% of the oxygen

supplied to the brain4

• Responsible for: muscle control, sensory perception, memory, emotions, speech, decision making, and self-control• The more intelligent or skilled an individual is at any given task, the more

grey matter they will have in that corresponding region of the brain5

• A skilled musician will have more grey matter in Broca’s Area

Review of Literature

Obesity• 3 studies in 2010 associated obesity with cardiovascular health problems

which increase risk for cognitive decline and dementia4,6,7

• Higher BMI was associated with lower brain volumes in overweight and obese elderly subjects

Exercise• 2 studies between 2011 and 2012 showed increases in prefrontal and

hippocampal brain size and improved memory8,9

Review of Literature

Diet• 3 studies between 2007 and 2011 show the Mediterranean diet, folate, and

specific nutrient biomarkers are associated with a reduced risk of developing cognitive impairment and dementia10,11,12

• High trans fat biomarkers are associated with diminished cognitive function and less total brain volume

Omega 3 fatty acids• 6 studies between 2008 and 2013 show improved neuronal health, brain

function, and grey matter structure12,13,14,15,16,17

• However, many studies cannot show statistically significant associations between omega 3 intake and cognitive health18

Methodology• Study sample drawn from the Cardiovascular Health Study Cognition Study, a subset of

the parent study, the Cardiovascular Health Study• Fish consumption data collected in 1989-1990

• National Cancer Institute food frequency questionnaire• Focused on broiled or baked fish• Excluded fried fish because of low omega 3 content

• Brain structure MRIs collected in 1998-1999• Participant eligibility:

• Live in Pittsburgh area• Older than 65• Diagnosed as cognitively normal between 1992-1998 • Had high resolution MRI scan taken in 1998-1999• Had data on dietary intake

Methodology

• Relationship between fish consumption and brain structural MRIs for 260 participants modeled• 1.5-Tesla General Electric scanner

• Data evaluated by Voxel-based morphometry in multiple regression analysis to relate daily to weekly baked or broiled fish consumption to grey matter volume• Independent variable: fish consumption• Dependent variable: grey matter volume• Covariates

Results

Results

Results

Results

Results

• Two large significant clusters related to fish consumption1. Cluster 1 – Right frontal lobe, right orbital frontal cortex, right anterior cingulate gyrus2. Cluster 2 – Right and left posterior cingulate gyrus and bilateral hippocampus

• Effects of fish consumption were then used to estimate regional volume increases at the mean of each cluster• Cluster 1 = 4.3% increase in size• Cluster 2 = 14% increase in size

Results

Discussion

• 2 Main Findings1. Consuming baked or broiled fish is related to larger grey matter volumes

(cluster 1 and 2)2. These findings were not significantly related to plasma omega-3 FAs

• Brain Cluster Functions• Cluster 1 – 4.3% increase = Retaining long-term memories, judgment,

decision-making skills, attention span, social inhibition, and executive functions such as planning for the future• Cluster 2 – 14% increase = Retaining visual memories, comprehending

language, storing new memories, and deriving meaning from sensory output and emotions

Discussion

• Findings suggest lifestyle factors such as eating fish, not simply biological factors, can affect the structural integrity of the brain.

• Effects of fish consumption on brain structure are independent of any omega-3 FA effects which is consistent with other studies that show omega-3 supplementation has little effect on the prevention of dementia and does not improve cognition in Alzheimer’s patients.

Conclusion

• Instead of focusing on individual approaches to neuroprotective health (monotherapeutics), a wide emphasis on lifestyle choices and diet is essential.• Supplementation of omega-3 FAs without considering other aspects of diet

may not give an individual significant or noticeable neuroprotective affects. However, making healthy lifestyle choices while supplementing fish oil could promote positive affects.• Moving towards a Mediterranean-style diet with fish can help improve brain

function and prevent diseases such as dementia, obesity, and heart disease.• More long-term research is needed to determine the protective effects of

omega-3 FAs.

Strengths & Weaknesses

Strengths Weaknesses• Extensive availability of demographic,

clinical, and lifestyle factors in study participants

• Used MRIs to physically show effects of fish consumption on brain structure

• Duration of expirament

• Generalized all fish consumers into one category

• Gathered one year worth of diet data with FFQs

• Did not list plasma omega-3 FA concentrations

• Did not show non-fish consumer MRIs• Did not account for medications

EAL Elements

Elements Grade

Quality Fair (II)Consistency Good (I)Quantity Good (I)Clinical impact Fair (II)Generalizability Good (I)

Discussion Questions

1. This study further validates the need for diet and lifestyle changes to prevent diseases that impact the development of dementia. Discuss the methods that might be used for various age groups to improve prevention and ways of introducing such changes in the US today.

2. Frequent fish consumption is associated with higher education levels. How can less informed or less educated people know to include fish in their diet?

3. Frequent fish consumption is associated with higher income levels. How can financially burdened people include fish in their diet?

4. Is eating more fish something you would recommend to your patients? Why or why not?

References1. Raji CA, Erickson KI, Lopez OL, Kuller LH, Gach HM, Thompson PM, Riverol M, Becker JT. Regular Fish Consumption and Age-Related Brain Gray Matter Loss. Am J Prev Med.

2014;47(4):444-51.2. Bredesen DE. Reveral of cognitive decline: A novel therapeutic program. Aging. 2014;16(9):707-17.3. Fisher Center for Alzheimer’s. Alzheimer’s and Dementia. Fisher Center for Alzheimer’s. Available at: http://www.alzinfo.org/about-alzheimers. Accessed November 3, 2014.4. CNS Clinic. Cereberal Blood Flow and Oxygen Consumption. CNS Clinic. Available at: http://www.humanneurophysiology.com/cbfo2consumption.htm. Accessed November 4, 2014.5. Jancke L. Music drives brain plasticity. F1000 Biol Rep. 2009;1:78.6. Ho AJ, Raji CA, Becker JT, Lopez OL, Kuller LH, Hua X, Lee S, Hibar D, Dinov ID, Stein JL, Jack CR, Weiner MW, Toga AW, Thompson PM. Obesity is linked with lower brain volume in

700 AD and MCI patients. Neurobiol Aging. 2010;31(8): 1326-39.7. Ho AJ, Stein JL, Hua X, Lee S, Hibar DP, Leow AD, Dinov ID, Toga AW, Saykin AJ, Shen L, Foroud T, Pankratz N, Huentelman MJ, Craig DW, Gerber JD, Allen AN, Corneveaux JJ, Stephan

DA, DeCarli CS, DeChairo BM, Potkin SG, Jack CR, Weiner MW, Raji CA, Lopez OL, Becker JT, Carmichael OT, Thompson PM. A commonly carried allele of the obesityrelated FTO gene is associated with reduced brain volume in the healthy elderly. Proc Natl Acad Sci U S A. 2010;107(18):8404-9.

8. Erickson KI, Voss MW, Prakash RS, Basak C, Szabo A, Chaddock L, Kim JS, Heo S, Alves H, White SM, Wojcicki TR, Mailey E, Vieira VJ, Martin SA, Pence BD, Woods JA, McAuley E, Kramer AF. Exercise training increases size of hippocampus and improves memory. Proc Natl Acad Sci U S A. 2011;108(7):3017-22.

9. Erickson KI, Weinstein AM, Lopez OL. Physical activity, brain plasticity, and Alzheimerʼs disease. Arch Med Res 2012;43(8):615–21.10. Luchsinger JA, Tang MX, Miller J, Green R, Mayeux R. Relation of higher folate intake to lower risk of Alzheimer disease in the elderly. Arch Neurol. 2007;64(1):86-92.11. Panza F, Capurso C, DʼIntrono A, et al. Mediterranean diet, mild cognitive impairment, and Alzheimerʼs disease. Exp Gerontol. 2007; 42(1–2):6–7.12. Bowman GL, Silbert LC, Howieson D, et al. Nutrient biomarker patterns, cognitive function, and MRI measures of brain aging. Neurology 2012;78(4):241-9.13. Sinn N, Milte CM, Street SJ, et al. 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. Br J Nutr. 2012;107(11):1682-93.14. Gomez-Pinilla F. Brain foods: the effects of nutrients on brain function. Nat Rev Neurosci. 2008;9(7):568-78.15. Witte AV, Kerti L, Hermannstadter HM, et al. Long- chain omega-3 fatty acids improve brain function and structure in older adults. Cereb Cortex. 2014;24(11):3059-68.16. Samieri C, Maillard P, Crivello F, et al. Plasma long-chain omega-3 fatty acids and atrophy of the medial temporal lobe. Neurology. 2012; 79(7):642-50.17. Tan ZS, Harris WS, Beiser AS, et al. Red blood cell omega-3 fatty acid levels and markers of accelerated brain aging. Neurology. 2012;78(9):658-64.18. Virtanen JK, Siscovick DS, Lemaitre RN, et al. Circulating omega-3 polyunsaturated fatty acids and subclinical brain abnormalities on MRI in older adults: the cardiovascular health

study. J Am Heart Assoc. 2013;2(5):e000305.