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Articles
December 28, 2011
Letter to the Editor

Nutrient biomarker patterns, cognitive function, and MRI measures of brain aging

January 24, 2012 issue
78 (4) 241-249

Abstract

Objective:

To examine the cross-sectional relationship between nutrient status and psychometric and imaging indices of brain health in dementia-free elders.

Methods:

Thirty plasma biomarkers of diet were assayed in the Oregon Brain Aging Study cohort (n = 104). Principal component analysis constructed nutrient biomarker patterns (NBPs) and regression models assessed the relationship of these with cognitive and MRI outcomes.

Results:

Mean age was 87 ± 10 years and 62% of subjects were female. Two NBPs associated with more favorable cognitive and MRI measures: one high in plasma vitamins B (B1, B2, B6, folate, and B12), C, D, and E, and another high in plasma marine ω-3 fatty acids. A third pattern characterized by high trans fat was associated with less favorable cognitive function and less total cerebral brain volume. Depression attenuated the relationship between the marine ω-3 pattern and white matter hyperintensity volume.

Conclusion:

Distinct nutrient biomarker patterns detected in plasma are interpretable and account for a significant degree of variance in both cognitive function and brain volume. Objective and multivariate approaches to the study of nutrition in brain health warrant further study. These findings should be confirmed in a separate population. Neurology® 2012;78:241–249

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Letters to the Editor
17 February 2012
Re:Nutrients and brain: regional volume changes should be considered in future research
Gene L. Bowman
Lisa Silbert, Hiroko Dodge, Joseph Quinn, Jeffrey Kaye

We thank Annweiler et al. for their comments. In this first analysis investigating nutrient biomarker profiles in relation to brain health, [1] we started from the generalizable premise that there would be a distinct nutrient combination associated with brain health marked by well-established global volumetric indices. There are data demonstrating that overall brain atrophy is a measure of age-related brain health, risk for disease, or reserve. [2-3] Essentially all regions of the brain atrophy with healthy aging [3]; total brain volume is a global index of the magnitude of this phenomenon. Similarly, white matter change has been associated with vascular disease and thus this MRI marker (total white matter hyperintensity volume) would suggest nutrient profiles associated with protection from global vascular disease.

We felt it was premature to generate a hypothesis related to specific subregions; there is no a priori reason to expect that the left dorsal medial fasciculus Y is associated with vitamin Z. Practically speaking, we had to resist the temptation to parcel the brain into potentially hundreds and subregions to avoid type II errors. We have subsequently evaluated total ventricular volume (another marker of overall atrophy) and the result is consistent with the use of total brain volume as a marker.

Future studies will address more specific regions guided by this preliminary data. We appreciate the value of using ventricular subregions as ready surrogates for more targeted studies such as of the medial temporal lobe. [4]

1. Bowman GL, Silbert LC, Howieson D, et al. Nutrient biomarker patterns, cognitive function, and MRI measures of brain aging. Neurology 2012;78:241 -249.

2. Jack CR, Shiung MM, Gunter JL, et al. Comparison of Different MRI Brain Atrophy Rate Measures with Clinical Disease Progression in AD. Neurology 2004; 62: 591-600.

3. Fjell AM, Walhovd KB, Fennema-Notestine C, et al. One-year brain atrophy evident in healthy aging. Journal of Neuroscience 2009; 29: 15233-15231.

4. Erten-Lyons D, Howieson D, Moore MM, et al. Brain volume loss in MCI predicts dementia. Neurology; 66;233-235:2006.

For disclosures contact [email protected].

10 February 2012
Nutrients and brain: regional volume changes should be considered in future research
Cedric Annweiler, Physician
Manuel Montero-Odasso, Robert Bartha, and Olivier Beauchet

Recently, Bowman et al. [1] reported in older community-dwellers that a plasma nutrient pattern rich in vitamin D was associated with better cognition and larger brain volume on MRI. Despite comprehensively estimating nutrients, such studies could be enhanced by measuring regional volumes rather than whole-brain volume to identify specific brain areas protected by vitamins. Since structural brain changes manifest long before cognitive symptoms, accurate morphometric approaches are crucial. [2] Current automated segmentation algorithms can determine the volume of different 'regions of interest', [3] which may help to clarify vitamins' effects. However, restricting the scope of investigations limits the relevance of findings. An attractive alternative is the measurement of lateral ventricle volume, which is an indirect measure of multi-point atrophy because cerebrospinal fluid is under pressure and any parenchymal loss results in passive ventricle expansion. [4] Modern software can segment ventricles in sub-volumes providing insight into the volume of adjacent brain structures. For instance, atrophy of medial temporal lobe leads to ventricle temporal horn enlargement, and expansion of ventricle frontal horn reflects frontal lobe shrinkage. [5] Future studies should describe regional changes in brain, ventricles, or both to better understand the neurobiological basis of cognitive changes associated with diet, and specifically with the remarkable neurosteroid vitamin D.

1. Bowman GL, Silbert LC, Howieson D, et al. Nutrient biomarker patterns, cognitive function, and MRI measures of brain aging. Neurology 2012;78:241 -249.

2. Dickerson BC, Stoub TR, Shah RC, et al. Alzheimer-signature MRI biomarkers predicts AD dementia in cognitively normal adults. Neurology 2011;76:1395-1402.

3. Pham DL, Xu C, Prince JL. Current methods in medical image segmentation. Annu Rev Biomed Eng 2000;2:315-337.

4. Bradley WG, Orrison WW. Hydrocephalus and cerebrospinal fluid flow. In: Orrison WW, editor. Neuroimaging. Philadelphia: Saunders WB; 2000: 704- 1716.

5. Chance SA, Esiri MM, Crow TJ. Ventricular enlargement in schizophrenia: a primary change in the temporal lobe? Schizophr Res 2003;62:123-131.

For disclosures, contact the editorial office.

Information & Authors

Information

Published In

Neurology®
Volume 78Number 4January 24, 2012
Pages: 241-249
PubMed: 22205763

Publication History

Received: April 10, 2011
Accepted: July 18, 2011
Published online: December 28, 2011
Published in print: January 24, 2012

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Disclosure

Dr. Bowman serves on the editorial board of the Journal of Alzheimer's Disease, receives salary and research support from the NIH, and insurance reimbursement for patient care. Dr. Silbert receives research support from the NIH; receives reimbursement through Medicare or commercial insurance plans for providing clinical assessment and care for patients and for intraoperative neurophysiological monitoring; and is salaried to see patients at the Portland VA Medical Center. Dr. Howieson receives salary support from the NIH/NIA and insurance reimbursement from Medicare and other sources for providing patient care. Dr. Dodge receives research support from the NIH and serves on the Scientific Review Board of the National Alzheimer's Coordinating Center. Dr. Traber receives research support from the NIH and USDA National Institute for Food and Agriculture. Dr. Frei currently serves on the Scientific Advisory Board for Unilever, Englewood Cliffs, NJ; the Almond Board Nutrition & Health Advisory Council of the Almond Board of California, Modesto, CA; the Neutrogena Naturals Advisory Board, Los Angeles, CA; and is a consultant for Bayer Consumer Care Ltd., Basel, Switzerland. He receives research funding from NIH grants P01 AT002034 and T32 AT002688, and USANA Health Sciences, Inc., Salt Lake City, UT. Dr. Kaye receives research support from the Department of Veterans Affairs (Merit Review grant) and the NIH; directs a center that receives research support from the NIH, Elan Corporation, Intel Corporation; receives reimbursement through Medicare and commercial insurance plans for providing patient care; is salaried to see patients at the Portland VA Medical Center; serves as an unpaid Chair for the Work Group on Technology and for the National Alzheimer's Association and as an unpaid Commissioner for the Center for Aging Services and Technologies; receives an annual royalty from sales of the book, Evidence-based Dementia Practice; and serves on the editorial advisory board of Alzheimer's & Dementia. Dr. Shannon reports no disclosures. Dr. Quinn has received honoraria for speaking from Pfizer Inc, Novartis, and Forest Laboratories, Inc. and for consulting from Phylogeny, Inc.; is a co-inventor on a patent for the use of DHA for the treatment of Alzheimer's disease; receives compensation for conducting clinical trials from Elan Corporation, Bristol-Myers Squibb, and Baxter International Inc.; and receives funding from the NIH and Department of Veterans Affairs.

Authors

Affiliations & Disclosures

G.L. Bowman, ND, MPH
From the Departments of Neurology (G.L.B., L.C.S., D.H., H.H.D., J.A.K., J.F.Q.) and Public Health and Preventive Medicine (G.L.B., J.S.), and Center for Research in Occupational and Environmental Toxicology (J.S.), Oregon Health & Science University, Portland; Portland VA Medical Center (J.A.K., J.S., J.F.Q.); and the Linus Pauling Institute (M.G.T., B.F.), Oregon State University, Corvallis.
L.C. Silbert, MD, MCR
From the Departments of Neurology (G.L.B., L.C.S., D.H., H.H.D., J.A.K., J.F.Q.) and Public Health and Preventive Medicine (G.L.B., J.S.), and Center for Research in Occupational and Environmental Toxicology (J.S.), Oregon Health & Science University, Portland; Portland VA Medical Center (J.A.K., J.S., J.F.Q.); and the Linus Pauling Institute (M.G.T., B.F.), Oregon State University, Corvallis.
D. Howieson, PhD
From the Departments of Neurology (G.L.B., L.C.S., D.H., H.H.D., J.A.K., J.F.Q.) and Public Health and Preventive Medicine (G.L.B., J.S.), and Center for Research in Occupational and Environmental Toxicology (J.S.), Oregon Health & Science University, Portland; Portland VA Medical Center (J.A.K., J.S., J.F.Q.); and the Linus Pauling Institute (M.G.T., B.F.), Oregon State University, Corvallis.
H.H. Dodge, PhD
From the Departments of Neurology (G.L.B., L.C.S., D.H., H.H.D., J.A.K., J.F.Q.) and Public Health and Preventive Medicine (G.L.B., J.S.), and Center for Research in Occupational and Environmental Toxicology (J.S.), Oregon Health & Science University, Portland; Portland VA Medical Center (J.A.K., J.S., J.F.Q.); and the Linus Pauling Institute (M.G.T., B.F.), Oregon State University, Corvallis.
M.G. Traber, PhD
From the Departments of Neurology (G.L.B., L.C.S., D.H., H.H.D., J.A.K., J.F.Q.) and Public Health and Preventive Medicine (G.L.B., J.S.), and Center for Research in Occupational and Environmental Toxicology (J.S.), Oregon Health & Science University, Portland; Portland VA Medical Center (J.A.K., J.S., J.F.Q.); and the Linus Pauling Institute (M.G.T., B.F.), Oregon State University, Corvallis.
B. Frei, PhD
From the Departments of Neurology (G.L.B., L.C.S., D.H., H.H.D., J.A.K., J.F.Q.) and Public Health and Preventive Medicine (G.L.B., J.S.), and Center for Research in Occupational and Environmental Toxicology (J.S.), Oregon Health & Science University, Portland; Portland VA Medical Center (J.A.K., J.S., J.F.Q.); and the Linus Pauling Institute (M.G.T., B.F.), Oregon State University, Corvallis.
J.A. Kaye, MD
From the Departments of Neurology (G.L.B., L.C.S., D.H., H.H.D., J.A.K., J.F.Q.) and Public Health and Preventive Medicine (G.L.B., J.S.), and Center for Research in Occupational and Environmental Toxicology (J.S.), Oregon Health & Science University, Portland; Portland VA Medical Center (J.A.K., J.S., J.F.Q.); and the Linus Pauling Institute (M.G.T., B.F.), Oregon State University, Corvallis.
J. Shannon, PhD, MPH
From the Departments of Neurology (G.L.B., L.C.S., D.H., H.H.D., J.A.K., J.F.Q.) and Public Health and Preventive Medicine (G.L.B., J.S.), and Center for Research in Occupational and Environmental Toxicology (J.S.), Oregon Health & Science University, Portland; Portland VA Medical Center (J.A.K., J.S., J.F.Q.); and the Linus Pauling Institute (M.G.T., B.F.), Oregon State University, Corvallis.
J.F. Quinn, MD
From the Departments of Neurology (G.L.B., L.C.S., D.H., H.H.D., J.A.K., J.F.Q.) and Public Health and Preventive Medicine (G.L.B., J.S.), and Center for Research in Occupational and Environmental Toxicology (J.S.), Oregon Health & Science University, Portland; Portland VA Medical Center (J.A.K., J.S., J.F.Q.); and the Linus Pauling Institute (M.G.T., B.F.), Oregon State University, Corvallis.

Notes

Correspondence & reprint requests to Dr. Bowman: [email protected].
References e1–e13 are available on the Neurology® Website at www.neurology.org
Study funding: Supported by NIH/NCCAM AT004777 (G.L.B.), NIH/NIA P30 AG008017 (J.A.K.), NIH/NCRR UL1 RR024140 Oregon Clinical and Translational Research Institute, and Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development.

Author Contributions

Dr. Bowman conceptualized the study, led the study procedures, the analysis, interpretation, and drafting of the manuscript. Dr. Silbert contributed to the interpretation of the neuroimaging studies and made substantive contribution to revising the manuscript for intellectual content. Dr. Howieson consulted in the interpretation of neuropsychological evaluations and made a substantive contribution in revising the manuscript for intellectual content. Dr. Dodge assisted in the data analysis for this manuscript and made a substantive contribution in revising the manuscript for intellectual content. Dr. Traber assisted in the interpretation of the data and made a substantive contribution in revising the manuscript for intellectual content. Dr. Frei assisted in the interpretation of the data and made a substantive contribution in revising the manuscript for intellectual content. Dr. Kaye made a substantive contribution in revising the manuscript for intellectual content. Dr. Shannon assisted with the conceptualization and interpretation of the results. She also made a substantive contribution in revising the manuscript for intellectual content. Dr. Quinn assisted with the conceptualization and interpretation of the results. He also made a substantive contribution in revising the manuscript for intellectual content.

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