Relationship of Mediterranean Diet and Caloric Intake to Phenoconversion in Huntington Disease
←
→
Page content transcription
If your browser does not render page correctly, please read the page content below
Research
Original Investigation
Relationship of Mediterranean Diet and Caloric Intake
to Phenoconversion in Huntington Disease
Karen Marder, MD, MPH; Yian Gu, PhD; Shirley Eberly, MS; Caroline M. Tanner, MD, PhD;
Nikolaos Scarmeas, MD, MS; David Oakes, PhD; Ira Shoulson, MD; for the Huntington Study Group
PHAROS Investigators
IMPORTANCE Adherence to Mediterranean-type diet (MeDi) may delay onset of Alzheimer
and Parkinson diseases. Whether adherence to MeDi affects time to phenoconversion in
Huntington disease (HD), a highly penetrant, single-gene disorder, is unknown.
OBJECTIVES To determine if MeDi modifies the time to clinical onset of HD (phenocon-
version) in premanifest carriers participating in Prospective Huntington at Risk Observational
Study (PHAROS), and to examine the effects of body mass index and caloric intake on time to
phenoconversion.
DESIGN, SETTING, AND PARTICIPANTS A prospective cohort study of 41 Huntington study
group sites in the United States and Canada involving 1001 participants enrolled in PHAROS
between July 1999 and January 2004 who were followed up every 9 months until 2010. A
total of 211 participants aged 26 to 57 years had an expanded CAG repeat length (ⱖ37).
EXPOSURE A semiquantitative food frequency questionnaire was administered 33 months
after baseline. We calculated daily gram intake for dairy, meat, fruit, vegetables, legumes,
cereals, fish, monounsaturated and saturated fatty acids, and alcohol and constructed MeDi
scores (0-9); higher scores indicate higher adherence. Demographics, medical history, body
mass index, and Unified Huntington's Disease Rating Scale (UHDRS) score were collected.
MAIN OUTCOME AND MEASURE Cox proportional hazards regression models to determine the
association of MeDi and phenoconversion.
RESULTS Age, sex, caloric intake, education status, and UHDRS motor scores did not differ
among MeDi tertiles (0-3, 4-5, and 6-9). The highest body mass index was associated with
the lowest adherence to MeDi. Thirty-one participants phenoconverted. In a model adjusted
for age, CAG repeat length, and caloric intake, MeDi was not associated with
phenoconversion (P for trend = 0.14 for tertile of MeDi, and P = .22 for continuous MeDi).
When individual components of MeDi were analyzed, higher dairy consumption (hazard ratio,
2.36; 95% CI, 1.0-5.57; P = .05) and higher caloric intake (P = .04) were associated with risk of
phenoconversion.
CONCLUSIONS AND RELEVANCE MeDi was not associated with phenoconversion; however,
higher consumption of dairy products had a 2-fold increased risk and may be a surrogate for
lower urate levels (associated with faster progression in manifest HD). Studies of diet and
energy expenditure in premanifest HD may provide data for interventions to modify specific
Author Affiliations: Author
components of diet that may delay the onset of HD.
affiliations are listed at the end of this
article.
Group Information: The Huntington
Study Group PHAROS (Prospective
Huntington at Risk Observational
Study) Investigators are listed at the
end of the article.
Corresponding Author: Karen
Marder, MD, MPH, 630 W 168th St,
Unit 16, Columbia University College
of Physicians and Surgeons,
JAMA Neurol. 2013;70(11):1382-1388. doi:10.1001/jamaneurol.2013.3487 New York, NY 10032 (ksm1
Published online September 2, 2013. @cumc.columbia.edu).
1382 jamaneurology.com
Downloaded From: http://www.jamafacial.com/ on 02/03/2015MeDi, Caloric Intake, and Phenoconversion in HD Original Investigation Research
C
AG repeat length is the primary determinant of age of testing was performed at the baseline visit, and investigators
onset of Huntington disease (HD), but environmental and participants remained blinded to gene status for the du-
modifiers of age of onset may also act. Converging evi- ration of the trial. Details of the baseline assessment of these
dence from murine and human HD point to a procatabolic state 1001 individuals and blinding procedures have been
that may antedate overt motor manifestations of HD.1-3 Nu- published.13 At each assessment, an independent rater at each
merous studies have demonstrated that individuals with mani- site performed the motor component of the Unified Hunting-
fest HD have lower body mass index (BMI; calculated as weight ton's Disease Rating Scale (UHDRS) and assigned a level of di-
in kilograms divided by height in meters squared) than age- agnostic confidence of HD based solely on the results of this
matched control subjects.4-8 Weight loss is more prominent in motor examination. A rating of 4 indicated 99% or more con-
humans and mice with greater CAG repeat length9 and in- fidence of clinically definite HD based on the presence of an
creases with disease progression.4,6 unequivocal otherwise unexplained extrapyramidal move-
In a previous study,10 the relationship between BMI, diet, ment disorder.19 The first time a rating of 4 was given it was
and HD onset was examined by administering a semiquanti- considered motor phenoconversion. Only participants who had
tative food frequency questionnaire (FFQ)11,12 to participants an expanded CAG repeat length (≥37) and who did not have a
in the Prospective Huntington at Risk Observational Study diagnostic confidence rating of 4 at enrollment were in-
(PHAROS),13 who were at risk for HD but who had not under- cluded in these analyses. Subjects who phenoconverted at the
gone genetic testing at the time of enrollment. Because these visit when the FFQ was completed or for whom the visit was
participants did not know their genetic status, they were un- the last visit (n = 15) were excluded because we were inter-
likely to have altered their diets differentially. We found no ma- ested in phenoconversion.
jor differences in macronutrient consumption (protein, car-
bohydrates, and fat) between expanded and nonexpanded CAG Dietary Assessment
repeat length groups. Seven hundred thirty-eight individuals completed at least one
Humans eat meals with complex combinations of nutri- National Cancer Institute FFQ, which has been shown to be
ents or food items that are likely to be synergistic (or antago- reliable and valid.12 The initial FFQ was administered, on av-
nistic), so that the action of the food matrix is different in each erage, 33 months after baseline examination. Details of the di-
individual. One particular dietary pattern, Mediterranean- etary assessment have been previously reported.10 The analy-
type diet (MeDi), has been widely explored in relation to vari- sis cohort includes 211 subjects with an expanded CAG repeat
ous neurological disorders.14,15 MeDi, a diet high in plant foods length. MeDi is defined by high consumption of plant foods,
(eg, fruits, nuts, legumes, and cereals) and fish, with olive oil high intake of MUFA compared with saturated fatty acids (SFA),
as the primary source of monounsaturated fat (MUFA) and low high intake of fish, low intake of meat (including poultry) and
to moderate intake of wine, as well as low intake of red meat, dairy products, and moderate consumption of alcohol (wine).
poultry, and dairy products, is known to be beneficial for health We followed the most commonly described method16 to
owing to its protective effects in many chronic diseases.16,17 construct the MeDi score as described in previous reports14,20,21
Studies have found that higher adherence to MeDi may delay (http://onlinelibrary.wiley.com/doi/10.1002/ana.20854/full
the onset of Alzheimer disease14 and may be associated with -bib31). More specifically, we first regressed total daily energy
older age at onset of Parkinson disease.15 Nutritional supple- intake (measured in kilocalories) and calculated the derived re-
ments including coenzyme Q10, ethyl eicosapentaenoic acid, siduals of daily gram intake22 for each of the following 7 cat-
and creatine have been used in therapeutic trials in HD tar- egories: dairy, meat, fruits, vegetables, legumes, cereals, and
geted at improving bioenergetics in manifest HD.18 Double- fish. Individuals were assigned a value of 1 for each compo-
blind, placebo-controlled trials of specific dietary interven- nent presumed to be beneficial (fruits, vegetables, legumes, ce-
tions have not been conducted in premanifest HD. Our reals, and fish) if their caloric-adjusted consumption was at or
objectives in this prospective study are (1) to determine whether above the sex-specific median, and for each detrimental com-
adherence to a MeDi affects time to diagnosis of HD (pheno- ponent (meat and dairy products) if the caloric-adjusted con-
conversion) among participants in PHAROS and (2) to exam- sumption was below the sex-specific median. Individuals were
ine the effects of BMI and caloric intake on time to phenocon- assigned a value of 0 for each beneficial component if the ca-
version. loric-adjusted consumption was below the sex-specific me-
dian, and for each detrimental, at or above the sex-specific me-
dian. For the fat component, we used the ratio of daily
consumption (in grams) of MUFA to SFA, and a value of 1 was
Methods assigned if the intake was at or above the sex-specific median,
Subjects and 0 if below the sex-specific median. Finally, subjects were
All the participants were enrolled in PHAROS between July 1999 assigned a score of 0 for either less than 4 g/d (approximately
and January 2004.13 Institutional review boards at all partici- 1 glass of wine weekly) or more than moderate (≥30 g/d, ap-
pating sites approved the protocols and consent procedures. proximately 1 glass of wine daily) consumption, and a value of
At baseline, participants were aged between 26 and 57 years 1 for mild to moderate alcohol consumption (>0 toResearch Original Investigation MeDi, Caloric Intake, and Phenoconversion in HD
Table 1. Characteristics of 211 Participants With CAG≥37 at FFQ Completion Date by MeDi Tertiles
MeDi 0-3 MeDi 4-5 MeDi 6-9
Variable (n = 67)a (n = 94)a (n = 50)a P Valueb
Age (range), y 44.1 (35.9, 48.6) 44.0 (37.9, 48.6) 42.8 (36.3, 51.2) .66
CAG repeat length 42 (40, 43) 41.5 (40, 43) 42.5 (41, 44) .048
Caloric intake 1847 (1376, 2176) 1764 (1414, 2306) 1785 (1480, 2597) .68
BMI 27.1 (23.4, 31.6) 26.2 (23.6, 29.6) 25.8 (22.1, 28.8) .03
UHDRS motor score 4 (1, 10) 3 (0, 8) 2 (1, 6) .10
Chorea 0 (0, 3) 0 (0, 2) 0 (0, 2) .59
Education status, y 14 (13, 16) 16 (12, 17) 16 (14, 17) .09
Female sex 51 (76) 69 (73) 32 (64) .16
Abbreviations: BMI, body mass index (calculated as weight in kilograms divided (percent), as appropriate.
by height in meters squared); FFQ, frequency food questionnaire; b
P values shown are from trend tests from separate multiple regressions using
MeDi, Mediterranean-type diet; UHDRS, Unified Huntington's Disease Rating ranks or from a Cochran-Armitage trend test, as appropriate.
Scale.
a
Values shown are median (25th percentile, 75th percentile) or number
Table 2. Adjusted Hazard Ratios (HRs) From Models to Predict Phenoconversiona
Variable Full Model, HR (95% CI) P Value Small Model, HR (95% CI) P Value
Age 1.14 (1.07-1.22)MeDi, Caloric Intake, and Phenoconversion in HD Original Investigation Research
Table 3. Association Between Individual MeDi Components
Results and Phenoconversiona
Small Model,
Age, sex, caloric intake, education status, UHDRS motor score, Variable HR (95% CI) P Value
and the chorea subscore did not differ among the MeDi ter- Age 1.17 (1.10-1.25)Research Original Investigation MeDi, Caloric Intake, and Phenoconversion in HD
HD38,39 (P = .01). We concluded that increased caloric intake the study, reducing our sample size and potentially intro-
was necessary to maintain BMI in the premanifest state but ducing a survivorship bias.10 Post hoc power calculations
could not determine whether this was due to a hypermeta- suggest that the study had 50% to 85% power to detect haz-
bolic state, subtle involuntary movements, swallowing im- ard ratios in the range of 2.0 to 3.0, so that some moderate-
pairment, or malabsorption. In this study, we show that higher sized associations may have been undetected. Dietary
caloric intake, and not BMI, was marginally associated with risk assessments were self-reports, and there was no opportunity
for actual rather than estimated phenoconversion. to validate dietary intake. We cannot determine whether
Strengths of this study include the fact that participants presymptomatic HD carriers of an expanded CAG repeat
did not know whether they carried an expanded CAG repeat length changed their dietary preference as they approached
length and, therefore, did not differentially modify their phenoconversion. Exploration of individual food groups was
diets. Because they did not have HD at the time of adminis- in the form of dichotomous variables, while continuous
tration of the FFQ, caloric intake or BMI were unlikely to be scores could have provided additional power. Blood was col-
affected by extrapyramidal signs. All the participants were lected only for DNA, so urate, calcium, and other potential
evaluated annually by movement disorders specialists who covariates could not be examined.
were also blind to genetic status. A validated FFQ and stan- The fact that, in a highly penetrant single-gene disorder,
dard methods for caloric intake, MeDi calculation, and BMI there could be risk factors that modify disease onset is prom-
measurements were used. The analyses were adjusted for ising. Our results suggest that studies of diet and energy ex-
several potential covariates. Limitations of the study include penditure in premanifest HD may provide data for both
the administration of the diet survey at more than 30 nonpharmacological interventions and pharmacological in-
months after study initiation, at which time there were indi- terventions to modify specific components of diet that may de-
viduals who had already developed HD or dropped out of lay the onset of HD.
ARTICLE INFORMATION Group, CHDI Foundation Inc, and the Michael J. Fox that provide grant support to the University of
Accepted for Publication: May 10, 2013. Foundation. Ms Eberly has received research Rochester, New York, New York, or Georgetown
support from NIH, Department of Defense, Michael University, Washington, DC. US Government
Published Online: September 2, 2013. J. Fox Foundation, Parkinson Disease Foundation, Sponsors are the National Institutes of Health (2
doi:10.1001/jamaneurol.2013.3487. Cephalon, and Lundbeck. Dr Tanner served on the R01 HG002449-06), including support from the
Author Affiliations: Departments of Neurology Scientific Advisory Boards of the Michael J. Fox NHGRI and the NINDS or from Cure Huntington
and Psychiatry, Columbia University College of Foundation and the National Spasmodic Dystonia Disease Initiative, Huntington’s Disease Society of
Physicians and Surgeons, New York, New York Association; has received support from Agency for America, Hereditary Disease Foundation,
(Marder, Scarmeas); Taub Institute for Research on Healthcare and Research Quality, the Brin Huntington Society of Canada, and the Fox Family
Alzheimer’s Disease and the Aging Brain, Columbia Foundation, National Institute of Environmental Foundation.
University, New York, New York (Gu); Gertrude H. Health Sciences, National Institute of Neurological Group Information: The Huntington Study Group
Sergievsky Center, Columbia University Medical Disorders and Stroke (NINDS), Parkinson’s Disease PHAROS Investigators are Steering Committee: Ira
Center, New York, New York (Marder, Scarmeas); Foundation, Parkinson’s Institute and Clinical Shoulson, MD (principal investigator), Karl Kieburtz,
Department of Biostatistics and Computational Center, and US Army Medical Research Acquisition MD, MPH (director, Clinical Trials Coordination
Biology, University of Rochester, New York, New Activity (Telemedicine & Advanced Technology Center), David Oakes (chief biostatistician), Elise
York (Eberly); Parkinson’s Institute, Sunnyvale, Research Center managed through the Neurotoxin Kayson, MS, RNC (project coordinator), Hongwei
California (Tanner, Oakes); Department of Social Exposure Treatment Research program); is a Zhao, ScD, M. Aileen Shinaman, JD (Huntington
Medicine, Psychiatry, and Neurology, National and consultant for Adamas Pharmaceuticals with Study Group executive director), Megan Romer,
Kapodistrian University of Athens, Athens, Greece money to Parkinson’s Institute and Clinical Center MS, University of Rochester, Rochester, New York;
(Scarmeas); Department of Neurology, Georgetown and Impax Pharmaceuticals. Dr Oakes has received Anne Young, MD, PhD (co-principal investigator),
University, Washington, DC (Shoulson). research support from NINDS, the Department of Steven Hersch, MD, PhD, Jack Penney, MD
Author Contributions: Study concept and design: Defense, and the Michael J. Fox Foundation for (deceased), Massachusetts General Hospital,
Gu, Tanner, Scarmeas, Shoulson. studies in Parkinson disease and Huntington Charlestown; Kevin Biglan, MD (medical monitor),
Acquisition of data: Marder. disease; served as a consultant for Novo Nordisk Inc The Johns Hopkins University, Baltimore, Maryland;
Analysis and interpretation of data: Marder, Eberly, on an unrelated project. Dr Shoulson has consulting Karen Marder, MD, MPH, Columbia University
Tanner, Scarmeas, Oakes, Shoulson. and advisory board membership with honoraria Medical Center, New York, New York; Jane Paulsen,
Drafting of the manuscript: Marder, Oakes. from the following: Alkermes Inc, Auspex PhD, University of Iowa, Iowa City; Kimberly Quaid,
Critical revision of the manuscript for important Pharmaceuticals, AZTherapies, Biogen Idec, Clarion PhD, Indiana University School of Medicine,
intellectual content: Gu, Eberly, Tanner, Scarmeas, Healthcare Consulting LLC, Corporate Meeting Indianapolis; Eric Siemers, MD, Lilly Corporate
Shoulson. Solutions for Update in Neurology Conference, Center, Indianapolis, Indiana; Caroline Tanner, MD,
Statistical analysis: Gu, Eberly, Oakes. Edison Pharmaceuticals, Envoy, Impax, Ipsen, JAMA The Parkinson’s Institute, Sunnyvale, California.
Obtained funding: Shoulson. Neurology, Johns Hopkins University, Johnson & Participating Investigators and Coordinators:
Administrative, technical, or material support: Johnson, Knopp Biosciences LLC, Lundbeck, William Mallonee, MD, David Palmer, MD
Shoulson. Medtronic, Michael J. Fox Foundation, Omeros (deceased), Greg Suter, BA, Hereditary Neurological
Study supervision: Scarmeas. Corporation, Partners Health Care, Prana Disease Centre, Wichita, Kansas; Richard Dubinsky,
Biotechnology, Salamandra, Seneb Biosciences Inc, MD, Gary Gronseth, MD, R. Neil Schimke, MD,
Conflict of Interest Disclosures: Dr Marder served Shire HGT Inc, University of California, Irvine;
on the editorial board of Neurology; receives Carolyn Gray, RN, University of Kansas Medical
receives grants (to Georgetown University and the Center, Kansas City; Martha Nance, MD, Scott
research support from grants NS036630, 1UL1 University of Rochester)from the Food and Drug
RR024156-01, PO412196-G, and PO412196-G from Bundlie, MD, Dawn Radtke, RN, Hennepin County
Administration, The Johns Hopkins University, Medical Center/Minneapolis, Minnesota; Sandra
the National Institutes of Health (NIH). She received National Institutes of Health (National Human
compensation for participating on the steering Kostyk, MD, PhD, George W. Paulson, MD, Karen
Genome Research Institute [(NHGRI] and NINDS), Thomas, DO, Nonna Stepanov, MD, Corrine Baic,
committee for U01NS052592 and from the and the Parkinson Disease Foundation. Neither Dr
Parkinson Disease Foundation, Huntington's BS, Ohio State University, Columbus; James Caress,
Shoulson nor his immediate family received any MD, Francis Walker, MD, Vicki Hunt, RN, Wake
Disease Society of America, the Parkinson Study personal remuneration from any of the sponsors
1386 JAMA Neurology November 2013 Volume 70, Number 11 jamaneurology.com
Downloaded From: http://www.jamafacial.com/ on 02/03/2015MeDi, Caloric Intake, and Phenoconversion in HD Original Investigation Research
Forest University School of Medicine, MD, Donna Pendley, RN, Jane Lane, RN, BSN, Hospital. Independent Monitoring Committee:
Winston-Salem, North Carolina; Sylvain Chouinard, University of Alabama at Birmingham; Madaline Stanley Fahn, MD, Columbia University; Michael
MD, Guy Rouleau, MD, PhD, Hubert Poiffaut, RN, Harrison, MD, Elke Rost-Ruffner, RN, BSN, Conneally, PhD (deceased), Indiana University;
Brigitte Rioux (deceased), Hotel-Dieu University of Virginia, Charlottesville; William Weiu-Yann Tsai, PhD, Columbia University. Scientific
Hospital-Centre hospitalier de l’universite de Johnson, MD, University of Medicine and Dentistry Advisory Committee: Flint Beal, MD, New York
Montreal, Montreal, Quebec, Canada; Claudia Testa, of New Jersey Robert Wood Johnson Medical Hospital Department of Neurology, New York;
MD, PhD, Timothy Greenamyre, MD, PhD, Joan Center, Stratford; Amy Colcher, MD, Andrew David Housman, PhD, Massachusetts Institute of
Harrison, RN, Emory University School of Medicine, Siderowf, MD, Mary Matthews, RN, University of Technology, Boston; Christopher Ross, MD, PhD,
Atlanta, Georgia; Jody Corey-Bloom, MD, PhD, Pennsylvania, Philadelphia; Danna Jennings, MD, The Johns Hopkins University; Rudolph Tanzi, PhD,
David Song, MD, Guerry Peavy, PhD, Jody Kenneth Marek, MD, Karen Caplan, MSW, Institute Anne Young, MD, PhD, Massachusetts General
Goldstein, BS, University of California, San Diego, for Neurodegenerative Disorders, New Haven, Hospital; Claudia Kawas, MD, University of
LaJolla; Jane Paulsen, PhD, Henry Paulson, MD, Connecticut; Stewart Factor, DO, Donald Higgins, California, Irvine; Marie Francoise-Chesselet, MD,
Robert L. Rodnitzky, MD, Ania Mikos, BA, Becky MD, Eric Molho, MD, Constance Nickerson, LPN, PhD, University of California Los Angeles. DNA
Reese, BS, Laura Stierman, BS, Katie Williams, BA, Sharon Evans, LPN, Diane Brown, RN (deceased), Oversight Committee: Michael Conneally, PhD
Lynn Vining, RN, MSN, University of Iowa; Karen Albany Medical College, Albany, New York; Douglas (deceased), Indiana University Medical Center;
Marder, MD, MPH, Elan Louis, MD, MSc, Carol Hobson, MD, Paul Shelton, MD, Shaun Hobson, RN, Martha Nance, MD, University of Minnesota/
Moskowitz, RN, Columbia University Medical Winnipeg Clinic, Winnipeg, Manitoba, Canada; Minnesota VA Medical Center; Clifford Shults, MD
Center; Kimberly Quaid, PhD, Joanne Wojcieszek, Carlos Singer, MD, Nestor Galvez-Jimenez, MD, (deceased), University of California, San Diego;
MD, Melissa Wesson, MS, Indiana University School William Koller, MD (deceased), Doris Martin, DDS, Caroline Tanner, MD, The Parkinson’s Institute.
of Medicine; Ali Samii, MD, Thomas Bird, MD, Hillary Kelly Lyons, PhD, Dinorah Rodriguez, RN, University Independent Rater Video Committee: Penelope
Lipe, ARNP, University of Washington & VA Puget of Miami, Miami, Florida; Kathleen Shannon, MD, Hogarth, MD, Oregon Health & Science University;
Sound Health Care System, Seattle; Norman Cynthia Comella, MD, Jean Jaglin, RN, CCRC, Rush Diana Rosas, MD, Massachusetts General Hospital;
Reynolds, MD, Karen Blindauer, MD, Jeannine Petit, Presbyterian–St Luke’s Medical Center, Chicago, Hongwei Zhao, ScD, University of Rochester.
ANP, Medical College of Wisconsin, Milwaukee; Illinois; Karen Anderson, MD, William Weiner, MD Additional Contributions: A special thanks to all
Peter Como, PhD, Frederick Marshall, MD, Timothy (deceased), Kelly Dustin, RN, BSN, University of the PHAROS coordinators, without whom this
Counihan, MD, Kevin Biglan, MD, Carol Zimmerman, Maryland School of Medicine; Adam Rosenblatt, effort would have been impossible. We also thank
RN, University of Rochester; Penelope Hogarth, MD, Christopher Ross, MD, PhD, Deborah Pollard, all the participants for their tremendous dedication
MD, John Nutt, MD, Pamela Andrews, BS, CCRC, The Johns Hopkins University; Marie H. to this project.
Oregon Health & Science University, Portland; Saint-Hilaire, MD, Peter Novak, MD, J. Stephen Fink,
Steven Hersch, MD, PhD, Leslie Shinobu, MD, PhD, MD, PhD (deceased), Bonnie Hersh, MD, Melissa Correction: This article was corrected online
Diana Rosas, MD, Yoshio Kaneko, BA, Sona Diggin, MS, RN, Leslie Vickers, RN, MS, Boston September 6, 2013, for the inappropriate insertion
Gevorkian, MS, Paula Sexton, BA, CCRA, University, Botson; Wallace Deckel, PhD, James of an article (the) in the Importance section of the
Massachusetts General Hospital; John Caviness, Duffy, MD, Mary Jane Fitzpatrick, APRN, University Abstract.
MD, Charles Adler, MD, PhD, Mayo Clinic Scottsdale, of Connecticut, Hartford. Participating NIH Authors:
Scottsdale, Arizona; Vicki Wheelock, MD, David Elizabeth Thomson, PhD, National Human Genome REFERENCES
Richman, MD, Teresa Tempkin, RNC, MSN, Research Institute, Bethesda, Maryland; National 1. Petersén A, Björkqvist M. Hypothalamic-
University of California Davis, Sacramento; Institute of Neurological Disorders and Stroke, endocrine aspects in Huntington’s disease. Eur J
Chuang-Kuo Wu, MD, PhD, Hubert Fernandez, MD, Bethesda. Event Monitoring Committee: Steven Neurosci. 2006;24(4):961-967.
Joseph H. Friedman, MD, Margaret Lannon, RN, Hersch, MD, PhD (cochair), Massachusetts General 2. Sathasivam K, Hobbs C, Mangiarini L, et al.
MS, Brown University (Memorial Hospital of Rhode Hospital; Julie Stout, PhD (co-chair), James Transgenic models of Huntington’s disease. Philos
Island), Pawtucket; Lauren Seeberger, MD, Calhoun, Indiana University; William Coryell, MD, Trans R Soc Lond B Biol Sci. 1999;354(1386):
Christopher O’Brien, MD, Sherrie Montellano, MA, Cheryl Erwin, JD, PhD, University of Iowa; Vicki 963-969.
Colorado Neurological Institute, Englewood; Ninith Hunt, RN, Wake Forest University School of
Kartha, MD, Sharin Sakurai, MD, PhD, Susan Medicine; Christopher Ross, MD, PhD, The Johns 3. Underwood BR, Broadhurst D, Dunn WB, et al.
Hickenbottom, MD, PhD, Roger Albin, MD, PhD, Hopkins University; Dorothy Vawter, PhD, Huntington disease patients and transgenic mice
Kristine Wernette, RN, MS, University of Michigan, Minnesota Center for Health Care Ethics. Ethics have similar pro-catabolic serum metabolite
Ann Arbor; Brad Racette, MD, Joel S. Perlmutter, Committee: Lori Andrews, JD, Debbie Bury, James profiles. Brain. 2006;129(pt 4):877-886.
MD, Laura Good, BA, Washington University, St Calhoun, Chicago-Kent College of Law, Chicago, 4. Morales LM, Estévez J, Suárez H, Villalobos R,
Louis, Missouri; George Jackson, MD, PhD, Susan Illinois; Steven Hersch, MD, PhD (chair), Chacín de Bonilla L, Bonilla E. Nutritional evaluation
Perlman, MD, Shelley Segal, MD, Russell Carroll, Massachusetts General Hospital; Vicki Hunt, RN, of Huntington disease patients. Am J Clin Nutr.
MA, Laurie Carr, BS, UCLA Medical Center, Los Carl Leventhal, MD, Wake Forest University School 1989;50(1):145-150.
Angeles, California; Wayne Martin, MD, Ted of Medicine; Kimberly Quaid, PhD, Indiana 5. Hamilton JM, Wolfson T, Peavy GM, Jacobson
Roberts, MD, Marguerite Wieler, BSC, PT, University University School of Medicine; Aileen Shinaman, JD, MW, Corey-Bloom J; Huntington Study Group. Rate
of Alberta, Edmonton, Alberta, Canada; Blair University of Rochester; Dorothy Vawter, PhD, and correlates of weight change in Huntington’s
Leavitt, MD, Lorne Clarke, MD, CM, Lynn Raymond, Minnesota Center for Health Care Ethics; Nancy disease. J Neurol Neurosurg Psychiatry.
MD, PhD, Joji Decolongon, MSC, Vesna Popovska, Wexler, PhD, Columbia University, New York. 2004;75(2):209-212.
MD, Elisabeth Almqvist, RN, PhD, University of Biostatistics and Clinical Trials Coordination Center:
British Columbia, Vancouver, British Columbia, Alicia Brocht, BA, Susan Daigneault, Karen Gerwitz, 6. Robbins AO, Ho AK, Barker RA. Weight changes
Canada; William Ondo, MD, Madhavi Thomas, MD, BS, Connie Orme, BA, Ruth Nobel, Victoria Ross, in Huntington’s disease. Eur J Neurol.
Tetsuo Ashizawa, MD, Joseph Jankovic, MD, Baylor MA, Mary Slough, Arthur Watts, BS, Joe Weber, BS, 2006;13(8):e7.
College of Medicine, Houston, Texas; Robert Christine Weaver, Elaine Julian-Baros, University of 7. Djoussé L, Knowlton B, Cupples LA, Marder K,
Hauser, MD, Juan Sanchez-Ramos, MD, PhD, Karen Rochester. Genetic/ Environmental Modifiers Shoulson I, Myers RH. Weight loss in early stage of
Price, MA, Holly Delgado, RN, University of South Committee: Anne Young, MD, PhD (chair), Huntington’s disease. Neurology.
Florida, Tampa; Sarah Furtado, MD, PhD, Anne Massachusetts General Hospital; Karen Marder, MD 2002;59(9):1325-1330.
Louise LaFontaine, MD, Oksana Suchowersky, MD, (co-chair), Columbia University Medical Center; 8. Trejo A, Tarrats RM, Alonso ME, Boll MC, Ochoa
Mary Lou Klimek, RN, MA, University of Calgary, Tatiana Foroud, PhD, Indiana University School of A, Velásquez L. Assessment of the nutrition status
Calgary, Alberta, Canada; Rustom Sethna, MD, Mark Medicine; James Gusella, PhD, Massachusetts of patients with Huntington’s disease. Nutrition.
Guttman, MD, Sandra Russell, BSW, RSW, Sheryl General Hospital; David Housman, PhD, 2004;20(2):192-196.
Elliott, RN, Centre for Addiction and Mental Health, Massachusetts Institute of Technology, Boston;
Markham, Ontario, Canada; Marc Mentis, MB, CHB, Marcy MacDonald, PhD, Massachusetts General 9. Aziz NA, van der Burg JM, Landwehrmeyer GB,
Andrew Feigin, MD, Marie Cox, RN, BSN, Barbara Hospital; Richard Myers, PhD, Boston University; Brundin P, Stijnen T, Roos RA; EHDI Study Group.
Shannon, RN, North Shore University Hospital, Caroline Tanner, MD, The Parkinson’s Institute; Weight loss in Huntington disease increases with
Manhasset, New York; Alan Percy, MD, Leon Dure, Rudolph Tanzi, PhD, Massachusetts General higher CAG repeat number. Neurology.
2008;71(19):1506-1513.
jamaneurology.com JAMA Neurology November 2013 Volume 70, Number 11 1387
Downloaded From: http://www.jamafacial.com/ on 02/03/2015Research Original Investigation MeDi, Caloric Intake, and Phenoconversion in HD
10. Marder K, Zhao H, Eberly S, Tanner CM, Oakes 21. Gu Y, Luchsinger JA, Stern Y, Scarmeas N. with plasma urate, in a cross-sectional study. PLoS
D, Shoulson I; Huntington Study Group. Dietary Mediterranean diet, inflammatory and metabolic One. 2012;7(6):e38123.
intake in adults at risk for Huntington disease: biomarkers, and risk of Alzheimer’s disease. 31. Auinger P, Kieburtz K, McDermott MP. The
analysis of PHAROS research participants. J Alzheimers Dis. 2010;22(2):483-492. relationship between uric acid levels and
Neurology. 2009;73(5):385-392. 22. Willett W, Stampfer M. Implications of total Huntington’s disease progression. Mov Disord.
11. Block G, Hartman AM, Naughton D. A reduced energy intake for epidemiological analyses. In: 2010;25(2):224-228.
dietary questionnaire: development and validation. Willett W, ed. Nutritional Epidemiology. New York: 32. Chen H, Zhang SM, Hernán MA, Willett WC,
Epidemiology. 1990;1(1):58-64. Oxford University Press; 1998:273-301. Ascherio A. Diet and Parkinson’s disease: a potential
12. Block G, Woods M, Potosky A, Clifford C. 23. Scarmeas N, Stern Y, Mayeux R, Manly JJ, role of dairy products in men. Ann Neurol.
Validation of a self-administered diet history Schupf N, Luchsinger JA. Mediterranean diet and 2002;52(6):793-801.
questionnaire using multiple diet records. J Clin mild cognitive impairment. Arch Neurol. 33. Chen H, O’Reilly E, McCullough ML, et al.
Epidemiol. 1990;43(12):1327-1335. 2009;66(2):216-225. Consumption of dairy products and risk of
13. Huntington Study Group PHAROS 24. Scarmeas N, Luchsinger JA, Stern Y, et al. Parkinson’s disease. Am J Epidemiol.
Investigators. At risk for Huntington disease: the Mediterranean diet and magnetic resonance 2007;165(9):998-1006.
Huntington Study Group PHAROS (Prospective imaging-assessed cerebrovascular disease. Ann 34. Park M, Ross GW, Petrovitch H, et al.
Huntington At Risk Observational Study) cohort Neurol. 2011;69(2):257-268. Consumption of milk and calcium in midlife and the
enrolled. Arch Neurol. 2006;63(7):991-996. 25. Gardener H, Wright CB, Gu Y, et al. future risk of Parkinson disease. Neurology.
14. Scarmeas N, Stern Y, Tang MX, Mayeux R, Mediterranean-style diet and risk of ischemic 2005;64(6):1047-1051.
Luchsinger JA. Mediterranean diet and risk for stroke, myocardial infarction, and vascular death: 35. Gao X, Chen H, Choi HK, Curhan G,
Alzheimer’s disease. Ann Neurol. 2006;59(6): the Northern Manhattan Study. Am J Clin Nutr. Schwarzschild MA, Ascherio A. Diet, urate, and
912-921. 2011;94(6):1458-1464. Parkinson’s disease risk in men. Am J Epidemiol.
15. Alcalay RN, Gu Y, Mejia-Santana H, Cote L, 26. Scarmeas N, Louis ED. Mediterranean diet and 2008;167(7):831-838.
Marder KS, Scarmeas N. The association between essential tremor. A case-control study. 36. Mochel F, Charles P, Seguin F, et al. Early energy
Mediterranean diet adherence and Parkinson’s Neuroepidemiology. 2007;29(3-4):170-177. deficit in Huntington disease: identification of a
disease. Mov Disord. 2012;27(6):771-774. 27. Sánchez-Moreno C, Cano MP, de Ancos B, et al. plasma biomarker traceable during disease
16. Trichopoulou A, Costacou T, Bamia C, Mediterranean vegetable soup consumption progression. PLoS One. 2007;2(7):e647.
Trichopoulos D. Adherence to a Mediterranean diet increases plasma vitamin C and decreases 37. Tasset I, Pontes AJ, Hinojosa AJ, de la Torre R,
and survival in a Greek population. N Engl J Med. F2-isoprostanes, prostaglandin E2 and monocyte Túnez I. Olive oil reduces oxidative damage in a
2003;348(26):2599-2608. chemotactic protein-1 in healthy humans. J Nutr 3-nitropropionic acid-induced Huntington’s
17. Roman B, Carta L, Martínez-González MA, Biochem. 2006;17(3):183-189. disease-like rat model. Nutr Neurosci.
Serra-Majem L. Effectiveness of the Mediterranean 28. Esposito K, Marfella R, Ciotola M, et al. Effect of 2011;14(3):106-111.
diet in the elderly. Clin Interv Aging. a Mediterranean-style diet on endothelial 38. Langbehn DR, Brinkman RR, Falush D, Paulsen
2008;3(1):97-109. dysfunction and markers of vascular inflammation JS, Hayden MR; International Huntington’s Disease
18. Mochel F, Haller RG. Energy deficit in in the metabolic syndrome: a randomized trial. Collaborative Group. A new model for prediction of
Huntington disease: why it matters. J Clin Invest. JAMA. 2004;292(12):1440-1446. the age of onset and penetrance for Huntington’s
2011;121(2):493-499. 29. Buruma OJ, Van der Kamp W, Barendswaard disease based on CAG length. Clin Genet.
19. Hogarth P, Kayson E, Kieburtz K, et al. EC, Roos RA, Kromhout D, Van der Velde EA. Which 2004;65(4):267-277.
Interrater agreement in the assessment of motor factors influence age at onset and rate of 39. Paulsen JS, Langbehn DR, Stout JC, et al;
manifestations of Huntington’s disease. Mov Disord. progression in Huntington’s disease? J Neurol Sci. Predict-HD Investigators and Coordinators of the
2005;20(3):293-297. 1987;80(2-3):299-306. Huntington Study Group. Detection of Huntington’s
20. Scarmeas N, Luchsinger JA, Schupf N, et al. 30. Zgaga L, Theodoratou E, Kyle J, et al. The disease decades before diagnosis: the Predict-HD
Physical activity, diet, and risk of Alzheimer disease. association of dietary intake of purine-rich study. J Neurol Neurosurg Psychiatry.
JAMA. 2009;302(6):627-637. vegetables, sugar-sweetened beverages and dairy 2008;79(8):874-880.
1388 JAMA Neurology November 2013 Volume 70, Number 11 jamaneurology.com
Downloaded From: http://www.jamafacial.com/ on 02/03/2015You can also read
