Unrecognized vitamin D3 deficiency is common in Parkinson disease: Harvard Biomarker Study
Identifieur interne : 000064 ( PascalFrancis/Corpus ); précédent : 000063; suivant : 000065Unrecognized vitamin D3 deficiency is common in Parkinson disease: Harvard Biomarker Study
Auteurs : HONGLIU DING ; Kaltra Dhima ; Kaitlin C. Lockhart ; Joseph J. Locascio ; Ashley N. Hoesing ; Karen Duong ; Ana Trisini-Lipsanopoulos ; Michael T. Hayes ; U. Shivraj Sohur ; Anne-Marie Wills ; Brit Mollenhauer ; Alice W. Flaherty ; Albert Y. Hung ; Nicte Mejia ; Vikram Khurana ; Stephen N. Gomperts ; Dennis J. Selkoe ; Michael A. Schwarzschild ; Michael G. Schlossmacher ; Bradley T. Hyman ; Lewis R. Sudarsky ; John H. Growdon ; Clemens R. ScherzerSource :
- Neurology [ 0028-3878 ] ; 2013.
Descripteurs français
- Pascal (Inist)
English descriptors
Abstract
Objective: To conclusively test for a specific association between the biological marker 25-hydroxy-vitamin D3, a transcriptionally active hormone produced in human skin and liver, and the prevalence and severity of Parkinson disease (PD). Methods: We used liquid chromatography/tandem mass spectrometry to establish an association specifically between deficiency of 25-hydroxy-vitamin D3 and PD in a cross-sectional and longitudinal case-control study of 388 patients (mean Hoehn and Yahr stage of 2.1 ± 0.6) and 283 control subjects free of neurologic disease nested in the Harvard Biomarker Study. Results: Plasma levels of 25-hydroxy-vitamin D3 were associated with PD in both univariate and multivariate analyses with p values = 0.0034 and 0.047, respectively. Total 25-hydroxy-vitamin D levels, the traditional composite measure of endogenous and exogenous vitamin D, were deficient in 17.6% of patients with PD compared with 9.3% of controls. Low 25-hydroxy-vitamin D3 as well as total 25-hydroxy-vitamin D levels were correlated with higher total Unified Parkinson's Disease Rating Scale scores at baseline and during follow-up. Conclusions: Our study reveals an association between 25-hydroxy-vitamin D3 and PD and suggests that thousands of patients with PD in North America alone may be vitamin D-deficient. This finding has immediate relevance for individual patients at risk of falls as well as public health, and warrants further investigation into the mechanism underlying this association.
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| NO : | PASCAL 13-0345091 INIST |
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| ET : | Unrecognized vitamin D3 deficiency is common in Parkinson disease: Harvard Biomarker Study |
| AU : | HONGLIU DING; DHIMA (Kaltra); LOCKHART (Kaitlin C.); LOCASCIO (Joseph J.); HOESING (Ashley N.); DUONG (Karen); TRISINI-LIPSANOPOULOS (Ana); HAYES (Michael T.); SHIVRAJ SOHUR (U.); WILLS (Anne-Marie); MOLLENHAUER (Brit); FLAHERTY (Alice W.); HUNG (Albert Y.); MEJIA (Nicte); KHURANA (Vikram); GOMPERTS (Stephen N.); SELKOE (Dennis J.); SCHWARZSCHILD (Michael A.); SCHLOSSMACHER (Michael G.); HYMAN (Bradley T.); SUDARSKY (Lewis R.); GROWDON (John H.); SCHERZER (Clemens R.) |
| AF : | Neurogenomics Laboratory, Harvard Medical School and Brigham & Women's Hospital/Cambridge/Royaume-Uni (1 aut., 2 aut., 3 aut., 5 aut., 6 aut., 7 aut., 23 aut.); Biomarkers Program, Harvard NeuroDiscovery Center/Boston/Etats-Unis (2 aut., 3 aut., 5 aut., 6 aut., 7 aut., 8 aut., 9 aut., 11 aut., 14 aut., 15 aut., 16 aut., 17 aut., 18 aut., 19 aut., 20 aut., 22 aut., 23 aut.); Department of Neurology, Massachusetts General Hospital/Boston/Etats-Unis (4 aut., 9 aut., 10 aut., 12 aut., 13 aut., 14 aut., 15 aut., 16 aut., 18 aut., 20 aut., 22 aut., 23 aut.); Department of Neurology, Brigham and Women's Hospital/Boston, MA/Etats-Unis (8 aut., 13 aut., 17 aut., 21 aut., 23 aut.); Paracelsus-Elena-Klinik/Kassel/Allemagne (11 aut.); Division of Neurology, the Ottawa Hospital, University of Ottawa/Canada (19 aut.) |
| DT : | Publication en série; Niveau analytique |
| SO : | Neurology; ISSN 0028-3878; Coden NEURAI; Etats-Unis; Da. 2013; Vol. 81; No. 17; Pp. 1531-1537; Bibl. 20 ref. |
| LA : | Anglais |
| EA : | Objective: To conclusively test for a specific association between the biological marker 25-hydroxy-vitamin D3, a transcriptionally active hormone produced in human skin and liver, and the prevalence and severity of Parkinson disease (PD). Methods: We used liquid chromatography/tandem mass spectrometry to establish an association specifically between deficiency of 25-hydroxy-vitamin D3 and PD in a cross-sectional and longitudinal case-control study of 388 patients (mean Hoehn and Yahr stage of 2.1 ± 0.6) and 283 control subjects free of neurologic disease nested in the Harvard Biomarker Study. Results: Plasma levels of 25-hydroxy-vitamin D3 were associated with PD in both univariate and multivariate analyses with p values = 0.0034 and 0.047, respectively. Total 25-hydroxy-vitamin D levels, the traditional composite measure of endogenous and exogenous vitamin D, were deficient in 17.6% of patients with PD compared with 9.3% of controls. Low 25-hydroxy-vitamin D3 as well as total 25-hydroxy-vitamin D levels were correlated with higher total Unified Parkinson's Disease Rating Scale scores at baseline and during follow-up. Conclusions: Our study reveals an association between 25-hydroxy-vitamin D3 and PD and suggests that thousands of patients with PD in North America alone may be vitamin D-deficient. This finding has immediate relevance for individual patients at risk of falls as well as public health, and warrants further investigation into the mechanism underlying this association. |
| CC : | 002B17G; 002B22C; 002B17A01; 002B17A03 |
| FD : | Carence vitaminique; Maladie de Parkinson; Pathologie du système nerveux; Colécalciférol |
| FG : | Etat nutritionnel; Malnutrition; Trouble métabolique; Trouble de la nutrition; Pathologie de l'encéphale; Syndrome extrapyramidal; Maladie dégénérative; Pathologie du système nerveux central |
| ED : | Vitamin deficiency; Parkinson disease; Nervous system diseases; Colecalciferol |
| EG : | Nutritional status; Malnutrition; Metabolic disorder; Nutrition disorder; Cerebral disorder; Extrapyramidal syndrome; Degenerative disease; Central nervous system disease |
| SD : | Carencia vitamínica; Parkinson enfermedad; Sistema nervioso patología; Colecalciferol |
| LO : | INIST-6345.354000504235330090 |
| ID : | 13-0345091 |
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Hung</name><affiliation><inist:fA14 i1="03"><s1>Department of Neurology, Massachusetts General Hospital</s1><s2>Boston</s2><s3>USA</s3><sZ>4 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>12 aut.</sZ><sZ>13 aut.</sZ><sZ>14 aut.</sZ><sZ>15 aut.</sZ><sZ>16 aut.</sZ><sZ>18 aut.</sZ><sZ>20 aut.</sZ><sZ>22 aut.</sZ><sZ>23 aut.</sZ></inist:fA14></affiliation><affiliation><inist:fA14 i1="04"><s1>Department of Neurology, Brigham and Women's Hospital</s1><s2>Boston, MA</s2><s3>USA</s3><sZ>8 aut.</sZ><sZ>13 aut.</sZ><sZ>17 aut.</sZ><sZ>21 aut.</sZ><sZ>23 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Mejia, Nicte" sort="Mejia, Nicte" uniqKey="Mejia N" first="Nicte" last="Mejia">Nicte Mejia</name><affiliation><inist:fA14 i1="02"><s1>Biomarkers Program, Harvard NeuroDiscovery Center</s1><s2>Boston</s2><s3>USA</s3><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>11 aut.</sZ><sZ>14 aut.</sZ><sZ>15 aut.</sZ><sZ>16 aut.</sZ><sZ>17 aut.</sZ><sZ>18 aut.</sZ><sZ>19 aut.</sZ><sZ>20 aut.</sZ><sZ>22 aut.</sZ><sZ>23 aut.</sZ></inist:fA14></affiliation><affiliation><inist:fA14 i1="03"><s1>Department of Neurology, Massachusetts General Hospital</s1><s2>Boston</s2><s3>USA</s3><sZ>4 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>12 aut.</sZ><sZ>13 aut.</sZ><sZ>14 aut.</sZ><sZ>15 aut.</sZ><sZ>16 aut.</sZ><sZ>18 aut.</sZ><sZ>20 aut.</sZ><sZ>22 aut.</sZ><sZ>23 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Khurana, Vikram" sort="Khurana, Vikram" uniqKey="Khurana V" first="Vikram" last="Khurana">Vikram Khurana</name><affiliation><inist:fA14 i1="02"><s1>Biomarkers Program, Harvard NeuroDiscovery Center</s1><s2>Boston</s2><s3>USA</s3><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>11 aut.</sZ><sZ>14 aut.</sZ><sZ>15 aut.</sZ><sZ>16 aut.</sZ><sZ>17 aut.</sZ><sZ>18 aut.</sZ><sZ>19 aut.</sZ><sZ>20 aut.</sZ><sZ>22 aut.</sZ><sZ>23 aut.</sZ></inist:fA14></affiliation><affiliation><inist:fA14 i1="03"><s1>Department of Neurology, Massachusetts General Hospital</s1><s2>Boston</s2><s3>USA</s3><sZ>4 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>12 aut.</sZ><sZ>13 aut.</sZ><sZ>14 aut.</sZ><sZ>15 aut.</sZ><sZ>16 aut.</sZ><sZ>18 aut.</sZ><sZ>20 aut.</sZ><sZ>22 aut.</sZ><sZ>23 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Gomperts, Stephen N" sort="Gomperts, Stephen N" uniqKey="Gomperts S" first="Stephen N." last="Gomperts">Stephen N. Gomperts</name><affiliation><inist:fA14 i1="02"><s1>Biomarkers Program, Harvard NeuroDiscovery Center</s1><s2>Boston</s2><s3>USA</s3><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>11 aut.</sZ><sZ>14 aut.</sZ><sZ>15 aut.</sZ><sZ>16 aut.</sZ><sZ>17 aut.</sZ><sZ>18 aut.</sZ><sZ>19 aut.</sZ><sZ>20 aut.</sZ><sZ>22 aut.</sZ><sZ>23 aut.</sZ></inist:fA14></affiliation><affiliation><inist:fA14 i1="03"><s1>Department of Neurology, Massachusetts General Hospital</s1><s2>Boston</s2><s3>USA</s3><sZ>4 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>12 aut.</sZ><sZ>13 aut.</sZ><sZ>14 aut.</sZ><sZ>15 aut.</sZ><sZ>16 aut.</sZ><sZ>18 aut.</sZ><sZ>20 aut.</sZ><sZ>22 aut.</sZ><sZ>23 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Selkoe, Dennis J" sort="Selkoe, Dennis J" uniqKey="Selkoe D" first="Dennis J." last="Selkoe">Dennis J. Selkoe</name><affiliation><inist:fA14 i1="02"><s1>Biomarkers Program, Harvard NeuroDiscovery Center</s1><s2>Boston</s2><s3>USA</s3><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>11 aut.</sZ><sZ>14 aut.</sZ><sZ>15 aut.</sZ><sZ>16 aut.</sZ><sZ>17 aut.</sZ><sZ>18 aut.</sZ><sZ>19 aut.</sZ><sZ>20 aut.</sZ><sZ>22 aut.</sZ><sZ>23 aut.</sZ></inist:fA14></affiliation><affiliation><inist:fA14 i1="04"><s1>Department of Neurology, Brigham and Women's Hospital</s1><s2>Boston, MA</s2><s3>USA</s3><sZ>8 aut.</sZ><sZ>13 aut.</sZ><sZ>17 aut.</sZ><sZ>21 aut.</sZ><sZ>23 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Schwarzschild, Michael A" sort="Schwarzschild, Michael A" uniqKey="Schwarzschild M" first="Michael A." last="Schwarzschild">Michael A. 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Schlossmacher</name><affiliation><inist:fA14 i1="02"><s1>Biomarkers Program, Harvard NeuroDiscovery Center</s1><s2>Boston</s2><s3>USA</s3><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>11 aut.</sZ><sZ>14 aut.</sZ><sZ>15 aut.</sZ><sZ>16 aut.</sZ><sZ>17 aut.</sZ><sZ>18 aut.</sZ><sZ>19 aut.</sZ><sZ>20 aut.</sZ><sZ>22 aut.</sZ><sZ>23 aut.</sZ></inist:fA14></affiliation><affiliation><inist:fA14 i1="06"><s1>Division of Neurology, the Ottawa Hospital, University of Ottawa</s1><s3>CAN</s3><sZ>19 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Hyman, Bradley T" sort="Hyman, Bradley T" uniqKey="Hyman B" first="Bradley T." last="Hyman">Bradley T. Hyman</name><affiliation><inist:fA14 i1="02"><s1>Biomarkers Program, Harvard NeuroDiscovery Center</s1><s2>Boston</s2><s3>USA</s3><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>11 aut.</sZ><sZ>14 aut.</sZ><sZ>15 aut.</sZ><sZ>16 aut.</sZ><sZ>17 aut.</sZ><sZ>18 aut.</sZ><sZ>19 aut.</sZ><sZ>20 aut.</sZ><sZ>22 aut.</sZ><sZ>23 aut.</sZ></inist:fA14></affiliation><affiliation><inist:fA14 i1="03"><s1>Department of Neurology, Massachusetts General Hospital</s1><s2>Boston</s2><s3>USA</s3><sZ>4 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>12 aut.</sZ><sZ>13 aut.</sZ><sZ>14 aut.</sZ><sZ>15 aut.</sZ><sZ>16 aut.</sZ><sZ>18 aut.</sZ><sZ>20 aut.</sZ><sZ>22 aut.</sZ><sZ>23 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Sudarsky, Lewis R" sort="Sudarsky, Lewis R" uniqKey="Sudarsky L" first="Lewis R." last="Sudarsky">Lewis R. Sudarsky</name><affiliation><inist:fA14 i1="04"><s1>Department of Neurology, Brigham and Women's Hospital</s1><s2>Boston, MA</s2><s3>USA</s3><sZ>8 aut.</sZ><sZ>13 aut.</sZ><sZ>17 aut.</sZ><sZ>21 aut.</sZ><sZ>23 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Growdon, John H" sort="Growdon, John H" uniqKey="Growdon J" first="John H." last="Growdon">John H. Growdon</name><affiliation><inist:fA14 i1="02"><s1>Biomarkers Program, Harvard NeuroDiscovery Center</s1><s2>Boston</s2><s3>USA</s3><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>11 aut.</sZ><sZ>14 aut.</sZ><sZ>15 aut.</sZ><sZ>16 aut.</sZ><sZ>17 aut.</sZ><sZ>18 aut.</sZ><sZ>19 aut.</sZ><sZ>20 aut.</sZ><sZ>22 aut.</sZ><sZ>23 aut.</sZ></inist:fA14></affiliation><affiliation><inist:fA14 i1="03"><s1>Department of Neurology, Massachusetts General Hospital</s1><s2>Boston</s2><s3>USA</s3><sZ>4 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>12 aut.</sZ><sZ>13 aut.</sZ><sZ>14 aut.</sZ><sZ>15 aut.</sZ><sZ>16 aut.</sZ><sZ>18 aut.</sZ><sZ>20 aut.</sZ><sZ>22 aut.</sZ><sZ>23 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Scherzer, Clemens R" sort="Scherzer, Clemens R" uniqKey="Scherzer C" first="Clemens R." last="Scherzer">Clemens R. Scherzer</name><affiliation><inist:fA14 i1="01"><s1>Neurogenomics Laboratory, Harvard Medical School and Brigham & Women's Hospital</s1><s2>Cambridge</s2><s3>GBR</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>23 aut.</sZ></inist:fA14></affiliation><affiliation><inist:fA14 i1="02"><s1>Biomarkers Program, Harvard NeuroDiscovery Center</s1><s2>Boston</s2><s3>USA</s3><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>11 aut.</sZ><sZ>14 aut.</sZ><sZ>15 aut.</sZ><sZ>16 aut.</sZ><sZ>17 aut.</sZ><sZ>18 aut.</sZ><sZ>19 aut.</sZ><sZ>20 aut.</sZ><sZ>22 aut.</sZ><sZ>23 aut.</sZ></inist:fA14></affiliation><affiliation><inist:fA14 i1="03"><s1>Department of Neurology, Massachusetts General Hospital</s1><s2>Boston</s2><s3>USA</s3><sZ>4 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>12 aut.</sZ><sZ>13 aut.</sZ><sZ>14 aut.</sZ><sZ>15 aut.</sZ><sZ>16 aut.</sZ><sZ>18 aut.</sZ><sZ>20 aut.</sZ><sZ>22 aut.</sZ><sZ>23 aut.</sZ></inist:fA14></affiliation><affiliation><inist:fA14 i1="04"><s1>Department of Neurology, Brigham and Women's Hospital</s1><s2>Boston, MA</s2><s3>USA</s3><sZ>8 aut.</sZ><sZ>13 aut.</sZ><sZ>17 aut.</sZ><sZ>21 aut.</sZ><sZ>23 aut.</sZ></inist:fA14></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">INIST</idno><idno type="inist">13-0345091</idno><date when="2013">2013</date><idno type="stanalyst">PASCAL 13-0345091 INIST</idno><idno type="RBID">Pascal:13-0345091</idno><idno type="wicri:Area/PascalFrancis/Corpus">000064</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">Unrecognized vitamin D<sub>3</sub> deficiency is common in Parkinson disease: Harvard Biomarker Study</title><author><name sortKey="Hongliu Ding" sort="Hongliu Ding" uniqKey="Hongliu Ding" last="Hongliu Ding">HONGLIU DING</name><affiliation><inist:fA14 i1="01"><s1>Neurogenomics Laboratory, Harvard Medical School and Brigham & Women's Hospital</s1><s2>Cambridge</s2><s3>GBR</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>23 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Dhima, Kaltra" sort="Dhima, Kaltra" uniqKey="Dhima K" first="Kaltra" last="Dhima">Kaltra Dhima</name><affiliation><inist:fA14 i1="01"><s1>Neurogenomics Laboratory, Harvard Medical School and Brigham & Women's Hospital</s1><s2>Cambridge</s2><s3>GBR</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>23 aut.</sZ></inist:fA14></affiliation><affiliation><inist:fA14 i1="02"><s1>Biomarkers Program, Harvard NeuroDiscovery Center</s1><s2>Boston</s2><s3>USA</s3><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>11 aut.</sZ><sZ>14 aut.</sZ><sZ>15 aut.</sZ><sZ>16 aut.</sZ><sZ>17 aut.</sZ><sZ>18 aut.</sZ><sZ>19 aut.</sZ><sZ>20 aut.</sZ><sZ>22 aut.</sZ><sZ>23 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Lockhart, Kaitlin C" sort="Lockhart, Kaitlin C" uniqKey="Lockhart K" first="Kaitlin C." last="Lockhart">Kaitlin C. Lockhart</name><affiliation><inist:fA14 i1="01"><s1>Neurogenomics Laboratory, Harvard Medical School and Brigham & Women's Hospital</s1><s2>Cambridge</s2><s3>GBR</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>23 aut.</sZ></inist:fA14></affiliation><affiliation><inist:fA14 i1="02"><s1>Biomarkers Program, Harvard NeuroDiscovery Center</s1><s2>Boston</s2><s3>USA</s3><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>11 aut.</sZ><sZ>14 aut.</sZ><sZ>15 aut.</sZ><sZ>16 aut.</sZ><sZ>17 aut.</sZ><sZ>18 aut.</sZ><sZ>19 aut.</sZ><sZ>20 aut.</sZ><sZ>22 aut.</sZ><sZ>23 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Locascio, Joseph J" sort="Locascio, Joseph J" uniqKey="Locascio J" first="Joseph J." last="Locascio">Joseph J. Locascio</name><affiliation><inist:fA14 i1="03"><s1>Department of Neurology, Massachusetts General Hospital</s1><s2>Boston</s2><s3>USA</s3><sZ>4 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>12 aut.</sZ><sZ>13 aut.</sZ><sZ>14 aut.</sZ><sZ>15 aut.</sZ><sZ>16 aut.</sZ><sZ>18 aut.</sZ><sZ>20 aut.</sZ><sZ>22 aut.</sZ><sZ>23 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Hoesing, Ashley N" sort="Hoesing, Ashley N" uniqKey="Hoesing A" first="Ashley N." last="Hoesing">Ashley N. Hoesing</name><affiliation><inist:fA14 i1="01"><s1>Neurogenomics Laboratory, Harvard Medical School and Brigham & Women's Hospital</s1><s2>Cambridge</s2><s3>GBR</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>23 aut.</sZ></inist:fA14></affiliation><affiliation><inist:fA14 i1="02"><s1>Biomarkers Program, Harvard NeuroDiscovery Center</s1><s2>Boston</s2><s3>USA</s3><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>11 aut.</sZ><sZ>14 aut.</sZ><sZ>15 aut.</sZ><sZ>16 aut.</sZ><sZ>17 aut.</sZ><sZ>18 aut.</sZ><sZ>19 aut.</sZ><sZ>20 aut.</sZ><sZ>22 aut.</sZ><sZ>23 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Duong, Karen" sort="Duong, Karen" uniqKey="Duong K" first="Karen" last="Duong">Karen Duong</name><affiliation><inist:fA14 i1="01"><s1>Neurogenomics Laboratory, Harvard Medical School and Brigham & Women's Hospital</s1><s2>Cambridge</s2><s3>GBR</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>23 aut.</sZ></inist:fA14></affiliation><affiliation><inist:fA14 i1="02"><s1>Biomarkers Program, Harvard NeuroDiscovery Center</s1><s2>Boston</s2><s3>USA</s3><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>11 aut.</sZ><sZ>14 aut.</sZ><sZ>15 aut.</sZ><sZ>16 aut.</sZ><sZ>17 aut.</sZ><sZ>18 aut.</sZ><sZ>19 aut.</sZ><sZ>20 aut.</sZ><sZ>22 aut.</sZ><sZ>23 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Trisini Lipsanopoulos, Ana" sort="Trisini Lipsanopoulos, Ana" uniqKey="Trisini Lipsanopoulos A" first="Ana" last="Trisini-Lipsanopoulos">Ana Trisini-Lipsanopoulos</name><affiliation><inist:fA14 i1="01"><s1>Neurogenomics Laboratory, Harvard Medical School and Brigham & Women's Hospital</s1><s2>Cambridge</s2><s3>GBR</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>23 aut.</sZ></inist:fA14></affiliation><affiliation><inist:fA14 i1="02"><s1>Biomarkers Program, Harvard NeuroDiscovery Center</s1><s2>Boston</s2><s3>USA</s3><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>11 aut.</sZ><sZ>14 aut.</sZ><sZ>15 aut.</sZ><sZ>16 aut.</sZ><sZ>17 aut.</sZ><sZ>18 aut.</sZ><sZ>19 aut.</sZ><sZ>20 aut.</sZ><sZ>22 aut.</sZ><sZ>23 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Hayes, Michael T" sort="Hayes, Michael T" uniqKey="Hayes M" first="Michael T." last="Hayes">Michael T. Hayes</name><affiliation><inist:fA14 i1="02"><s1>Biomarkers Program, Harvard NeuroDiscovery Center</s1><s2>Boston</s2><s3>USA</s3><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>11 aut.</sZ><sZ>14 aut.</sZ><sZ>15 aut.</sZ><sZ>16 aut.</sZ><sZ>17 aut.</sZ><sZ>18 aut.</sZ><sZ>19 aut.</sZ><sZ>20 aut.</sZ><sZ>22 aut.</sZ><sZ>23 aut.</sZ></inist:fA14></affiliation><affiliation><inist:fA14 i1="04"><s1>Department of Neurology, Brigham and Women's Hospital</s1><s2>Boston, MA</s2><s3>USA</s3><sZ>8 aut.</sZ><sZ>13 aut.</sZ><sZ>17 aut.</sZ><sZ>21 aut.</sZ><sZ>23 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Shivraj Sohur, U" sort="Shivraj Sohur, U" uniqKey="Shivraj Sohur U" first="U." last="Shivraj Sohur">U. Shivraj Sohur</name><affiliation><inist:fA14 i1="02"><s1>Biomarkers Program, Harvard NeuroDiscovery Center</s1><s2>Boston</s2><s3>USA</s3><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>11 aut.</sZ><sZ>14 aut.</sZ><sZ>15 aut.</sZ><sZ>16 aut.</sZ><sZ>17 aut.</sZ><sZ>18 aut.</sZ><sZ>19 aut.</sZ><sZ>20 aut.</sZ><sZ>22 aut.</sZ><sZ>23 aut.</sZ></inist:fA14></affiliation><affiliation><inist:fA14 i1="03"><s1>Department of Neurology, Massachusetts General Hospital</s1><s2>Boston</s2><s3>USA</s3><sZ>4 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>12 aut.</sZ><sZ>13 aut.</sZ><sZ>14 aut.</sZ><sZ>15 aut.</sZ><sZ>16 aut.</sZ><sZ>18 aut.</sZ><sZ>20 aut.</sZ><sZ>22 aut.</sZ><sZ>23 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Wills, Anne Marie" sort="Wills, Anne Marie" uniqKey="Wills A" first="Anne-Marie" last="Wills">Anne-Marie Wills</name><affiliation><inist:fA14 i1="03"><s1>Department of Neurology, Massachusetts General Hospital</s1><s2>Boston</s2><s3>USA</s3><sZ>4 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>12 aut.</sZ><sZ>13 aut.</sZ><sZ>14 aut.</sZ><sZ>15 aut.</sZ><sZ>16 aut.</sZ><sZ>18 aut.</sZ><sZ>20 aut.</sZ><sZ>22 aut.</sZ><sZ>23 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Mollenhauer, Brit" sort="Mollenhauer, Brit" uniqKey="Mollenhauer B" first="Brit" last="Mollenhauer">Brit Mollenhauer</name><affiliation><inist:fA14 i1="02"><s1>Biomarkers Program, Harvard NeuroDiscovery Center</s1><s2>Boston</s2><s3>USA</s3><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>11 aut.</sZ><sZ>14 aut.</sZ><sZ>15 aut.</sZ><sZ>16 aut.</sZ><sZ>17 aut.</sZ><sZ>18 aut.</sZ><sZ>19 aut.</sZ><sZ>20 aut.</sZ><sZ>22 aut.</sZ><sZ>23 aut.</sZ></inist:fA14></affiliation><affiliation><inist:fA14 i1="05"><s1>Paracelsus-Elena-Klinik</s1><s2>Kassel</s2><s3>DEU</s3><sZ>11 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Flaherty, Alice W" sort="Flaherty, Alice W" uniqKey="Flaherty A" first="Alice W." last="Flaherty">Alice W. Flaherty</name><affiliation><inist:fA14 i1="03"><s1>Department of Neurology, Massachusetts General Hospital</s1><s2>Boston</s2><s3>USA</s3><sZ>4 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>12 aut.</sZ><sZ>13 aut.</sZ><sZ>14 aut.</sZ><sZ>15 aut.</sZ><sZ>16 aut.</sZ><sZ>18 aut.</sZ><sZ>20 aut.</sZ><sZ>22 aut.</sZ><sZ>23 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Hung, Albert Y" sort="Hung, Albert Y" uniqKey="Hung A" first="Albert Y." last="Hung">Albert Y. Hung</name><affiliation><inist:fA14 i1="03"><s1>Department of Neurology, Massachusetts General Hospital</s1><s2>Boston</s2><s3>USA</s3><sZ>4 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>12 aut.</sZ><sZ>13 aut.</sZ><sZ>14 aut.</sZ><sZ>15 aut.</sZ><sZ>16 aut.</sZ><sZ>18 aut.</sZ><sZ>20 aut.</sZ><sZ>22 aut.</sZ><sZ>23 aut.</sZ></inist:fA14></affiliation><affiliation><inist:fA14 i1="04"><s1>Department of Neurology, Brigham and Women's Hospital</s1><s2>Boston, MA</s2><s3>USA</s3><sZ>8 aut.</sZ><sZ>13 aut.</sZ><sZ>17 aut.</sZ><sZ>21 aut.</sZ><sZ>23 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Mejia, Nicte" sort="Mejia, Nicte" uniqKey="Mejia N" first="Nicte" last="Mejia">Nicte Mejia</name><affiliation><inist:fA14 i1="02"><s1>Biomarkers Program, Harvard NeuroDiscovery Center</s1><s2>Boston</s2><s3>USA</s3><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>11 aut.</sZ><sZ>14 aut.</sZ><sZ>15 aut.</sZ><sZ>16 aut.</sZ><sZ>17 aut.</sZ><sZ>18 aut.</sZ><sZ>19 aut.</sZ><sZ>20 aut.</sZ><sZ>22 aut.</sZ><sZ>23 aut.</sZ></inist:fA14></affiliation><affiliation><inist:fA14 i1="03"><s1>Department of Neurology, Massachusetts General Hospital</s1><s2>Boston</s2><s3>USA</s3><sZ>4 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>12 aut.</sZ><sZ>13 aut.</sZ><sZ>14 aut.</sZ><sZ>15 aut.</sZ><sZ>16 aut.</sZ><sZ>18 aut.</sZ><sZ>20 aut.</sZ><sZ>22 aut.</sZ><sZ>23 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Khurana, Vikram" sort="Khurana, Vikram" uniqKey="Khurana V" first="Vikram" last="Khurana">Vikram Khurana</name><affiliation><inist:fA14 i1="02"><s1>Biomarkers Program, Harvard NeuroDiscovery Center</s1><s2>Boston</s2><s3>USA</s3><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>11 aut.</sZ><sZ>14 aut.</sZ><sZ>15 aut.</sZ><sZ>16 aut.</sZ><sZ>17 aut.</sZ><sZ>18 aut.</sZ><sZ>19 aut.</sZ><sZ>20 aut.</sZ><sZ>22 aut.</sZ><sZ>23 aut.</sZ></inist:fA14></affiliation><affiliation><inist:fA14 i1="03"><s1>Department of Neurology, Massachusetts General Hospital</s1><s2>Boston</s2><s3>USA</s3><sZ>4 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>12 aut.</sZ><sZ>13 aut.</sZ><sZ>14 aut.</sZ><sZ>15 aut.</sZ><sZ>16 aut.</sZ><sZ>18 aut.</sZ><sZ>20 aut.</sZ><sZ>22 aut.</sZ><sZ>23 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Gomperts, Stephen N" sort="Gomperts, Stephen N" uniqKey="Gomperts S" first="Stephen N." last="Gomperts">Stephen N. Gomperts</name><affiliation><inist:fA14 i1="02"><s1>Biomarkers Program, Harvard NeuroDiscovery Center</s1><s2>Boston</s2><s3>USA</s3><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>11 aut.</sZ><sZ>14 aut.</sZ><sZ>15 aut.</sZ><sZ>16 aut.</sZ><sZ>17 aut.</sZ><sZ>18 aut.</sZ><sZ>19 aut.</sZ><sZ>20 aut.</sZ><sZ>22 aut.</sZ><sZ>23 aut.</sZ></inist:fA14></affiliation><affiliation><inist:fA14 i1="03"><s1>Department of Neurology, Massachusetts General Hospital</s1><s2>Boston</s2><s3>USA</s3><sZ>4 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>12 aut.</sZ><sZ>13 aut.</sZ><sZ>14 aut.</sZ><sZ>15 aut.</sZ><sZ>16 aut.</sZ><sZ>18 aut.</sZ><sZ>20 aut.</sZ><sZ>22 aut.</sZ><sZ>23 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Selkoe, Dennis J" sort="Selkoe, Dennis J" uniqKey="Selkoe D" first="Dennis J." last="Selkoe">Dennis J. Selkoe</name><affiliation><inist:fA14 i1="02"><s1>Biomarkers Program, Harvard NeuroDiscovery Center</s1><s2>Boston</s2><s3>USA</s3><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>11 aut.</sZ><sZ>14 aut.</sZ><sZ>15 aut.</sZ><sZ>16 aut.</sZ><sZ>17 aut.</sZ><sZ>18 aut.</sZ><sZ>19 aut.</sZ><sZ>20 aut.</sZ><sZ>22 aut.</sZ><sZ>23 aut.</sZ></inist:fA14></affiliation><affiliation><inist:fA14 i1="04"><s1>Department of Neurology, Brigham and Women's Hospital</s1><s2>Boston, MA</s2><s3>USA</s3><sZ>8 aut.</sZ><sZ>13 aut.</sZ><sZ>17 aut.</sZ><sZ>21 aut.</sZ><sZ>23 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Schwarzschild, Michael A" sort="Schwarzschild, Michael A" uniqKey="Schwarzschild M" first="Michael A." last="Schwarzschild">Michael A. Schwarzschild</name><affiliation><inist:fA14 i1="02"><s1>Biomarkers Program, Harvard NeuroDiscovery Center</s1><s2>Boston</s2><s3>USA</s3><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>11 aut.</sZ><sZ>14 aut.</sZ><sZ>15 aut.</sZ><sZ>16 aut.</sZ><sZ>17 aut.</sZ><sZ>18 aut.</sZ><sZ>19 aut.</sZ><sZ>20 aut.</sZ><sZ>22 aut.</sZ><sZ>23 aut.</sZ></inist:fA14></affiliation><affiliation><inist:fA14 i1="03"><s1>Department of Neurology, Massachusetts General Hospital</s1><s2>Boston</s2><s3>USA</s3><sZ>4 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>12 aut.</sZ><sZ>13 aut.</sZ><sZ>14 aut.</sZ><sZ>15 aut.</sZ><sZ>16 aut.</sZ><sZ>18 aut.</sZ><sZ>20 aut.</sZ><sZ>22 aut.</sZ><sZ>23 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Schlossmacher, Michael G" sort="Schlossmacher, Michael G" uniqKey="Schlossmacher M" first="Michael G." last="Schlossmacher">Michael G. Schlossmacher</name><affiliation><inist:fA14 i1="02"><s1>Biomarkers Program, Harvard NeuroDiscovery Center</s1><s2>Boston</s2><s3>USA</s3><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>11 aut.</sZ><sZ>14 aut.</sZ><sZ>15 aut.</sZ><sZ>16 aut.</sZ><sZ>17 aut.</sZ><sZ>18 aut.</sZ><sZ>19 aut.</sZ><sZ>20 aut.</sZ><sZ>22 aut.</sZ><sZ>23 aut.</sZ></inist:fA14></affiliation><affiliation><inist:fA14 i1="06"><s1>Division of Neurology, the Ottawa Hospital, University of Ottawa</s1><s3>CAN</s3><sZ>19 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Hyman, Bradley T" sort="Hyman, Bradley T" uniqKey="Hyman B" first="Bradley T." last="Hyman">Bradley T. Hyman</name><affiliation><inist:fA14 i1="02"><s1>Biomarkers Program, Harvard NeuroDiscovery Center</s1><s2>Boston</s2><s3>USA</s3><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>11 aut.</sZ><sZ>14 aut.</sZ><sZ>15 aut.</sZ><sZ>16 aut.</sZ><sZ>17 aut.</sZ><sZ>18 aut.</sZ><sZ>19 aut.</sZ><sZ>20 aut.</sZ><sZ>22 aut.</sZ><sZ>23 aut.</sZ></inist:fA14></affiliation><affiliation><inist:fA14 i1="03"><s1>Department of Neurology, Massachusetts General Hospital</s1><s2>Boston</s2><s3>USA</s3><sZ>4 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>12 aut.</sZ><sZ>13 aut.</sZ><sZ>14 aut.</sZ><sZ>15 aut.</sZ><sZ>16 aut.</sZ><sZ>18 aut.</sZ><sZ>20 aut.</sZ><sZ>22 aut.</sZ><sZ>23 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Sudarsky, Lewis R" sort="Sudarsky, Lewis R" uniqKey="Sudarsky L" first="Lewis R." last="Sudarsky">Lewis R. Sudarsky</name><affiliation><inist:fA14 i1="04"><s1>Department of Neurology, Brigham and Women's Hospital</s1><s2>Boston, MA</s2><s3>USA</s3><sZ>8 aut.</sZ><sZ>13 aut.</sZ><sZ>17 aut.</sZ><sZ>21 aut.</sZ><sZ>23 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Growdon, John H" sort="Growdon, John H" uniqKey="Growdon J" first="John H." last="Growdon">John H. Growdon</name><affiliation><inist:fA14 i1="02"><s1>Biomarkers Program, Harvard NeuroDiscovery Center</s1><s2>Boston</s2><s3>USA</s3><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>11 aut.</sZ><sZ>14 aut.</sZ><sZ>15 aut.</sZ><sZ>16 aut.</sZ><sZ>17 aut.</sZ><sZ>18 aut.</sZ><sZ>19 aut.</sZ><sZ>20 aut.</sZ><sZ>22 aut.</sZ><sZ>23 aut.</sZ></inist:fA14></affiliation><affiliation><inist:fA14 i1="03"><s1>Department of Neurology, Massachusetts General Hospital</s1><s2>Boston</s2><s3>USA</s3><sZ>4 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>12 aut.</sZ><sZ>13 aut.</sZ><sZ>14 aut.</sZ><sZ>15 aut.</sZ><sZ>16 aut.</sZ><sZ>18 aut.</sZ><sZ>20 aut.</sZ><sZ>22 aut.</sZ><sZ>23 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Scherzer, Clemens R" sort="Scherzer, Clemens R" uniqKey="Scherzer C" first="Clemens R." last="Scherzer">Clemens R. Scherzer</name><affiliation><inist:fA14 i1="01"><s1>Neurogenomics Laboratory, Harvard Medical School and Brigham & Women's Hospital</s1><s2>Cambridge</s2><s3>GBR</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>23 aut.</sZ></inist:fA14></affiliation><affiliation><inist:fA14 i1="02"><s1>Biomarkers Program, Harvard NeuroDiscovery Center</s1><s2>Boston</s2><s3>USA</s3><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>11 aut.</sZ><sZ>14 aut.</sZ><sZ>15 aut.</sZ><sZ>16 aut.</sZ><sZ>17 aut.</sZ><sZ>18 aut.</sZ><sZ>19 aut.</sZ><sZ>20 aut.</sZ><sZ>22 aut.</sZ><sZ>23 aut.</sZ></inist:fA14></affiliation><affiliation><inist:fA14 i1="03"><s1>Department of Neurology, Massachusetts General Hospital</s1><s2>Boston</s2><s3>USA</s3><sZ>4 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>12 aut.</sZ><sZ>13 aut.</sZ><sZ>14 aut.</sZ><sZ>15 aut.</sZ><sZ>16 aut.</sZ><sZ>18 aut.</sZ><sZ>20 aut.</sZ><sZ>22 aut.</sZ><sZ>23 aut.</sZ></inist:fA14></affiliation><affiliation><inist:fA14 i1="04"><s1>Department of Neurology, Brigham and Women's Hospital</s1><s2>Boston, MA</s2><s3>USA</s3><sZ>8 aut.</sZ><sZ>13 aut.</sZ><sZ>17 aut.</sZ><sZ>21 aut.</sZ><sZ>23 aut.</sZ></inist:fA14></affiliation></author></analytic><series><title level="j" type="main">Neurology</title><title level="j" type="abbreviated">Neurology</title><idno type="ISSN">0028-3878</idno><imprint><date when="2013">2013</date></imprint></series></biblStruct></sourceDesc><seriesStmt><title level="j" type="main">Neurology</title><title level="j" type="abbreviated">Neurology</title><idno type="ISSN">0028-3878</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Colecalciferol</term><term>Nervous system diseases</term><term>Parkinson disease</term><term>Vitamin deficiency</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Carence vitaminique</term><term>Maladie de Parkinson</term><term>Pathologie du système nerveux</term><term>Colécalciférol</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Objective: To conclusively test for a specific association between the biological marker 25-hydroxy-vitamin D<sub>3</sub>, a transcriptionally active hormone produced in human skin and liver, and the prevalence and severity of Parkinson disease (PD). Methods: We used liquid chromatography/tandem mass spectrometry to establish an association specifically between deficiency of 25-hydroxy-vitamin D<sub>3</sub> and PD in a cross-sectional and longitudinal case-control study of 388 patients (mean Hoehn and Yahr stage of 2.1 ± 0.6) and 283 control subjects free of neurologic disease nested in the Harvard Biomarker Study. Results: Plasma levels of 25-hydroxy-vitamin D<sub>3</sub> were associated with PD in both univariate and multivariate analyses with p values = 0.0034 and 0.047, respectively. Total 25-hydroxy-vitamin D levels, the traditional composite measure of endogenous and exogenous vitamin D, were deficient in 17.6% of patients with PD compared with 9.3% of controls. Low 25-hydroxy-vitamin D<sub>3</sub> as well as total 25-hydroxy-vitamin D levels were correlated with higher total Unified Parkinson's Disease Rating Scale scores at baseline and during follow-up. Conclusions: Our study reveals an association between 25-hydroxy-vitamin D<sub>3</sub> and PD and suggests that thousands of patients with PD in North America alone may be vitamin D-deficient. This finding has immediate relevance for individual patients at risk of falls as well as public health, and warrants further investigation into the mechanism underlying this association.</div></front></TEI><inist><standard h6="B"><pA><fA01 i1="01" i2="1"><s0>0028-3878</s0></fA01><fA02 i1="01"><s0>NEURAI</s0></fA02><fA03 i2="1"><s0>Neurology</s0></fA03><fA05><s2>81</s2></fA05><fA06><s2>17</s2></fA06><fA08 i1="01" i2="1" l="ENG"><s1>Unrecognized vitamin D<sub>3</sub> deficiency is common in Parkinson disease: Harvard Biomarker Study</s1></fA08><fA11 i1="01" i2="1"><s1>HONGLIU DING</s1></fA11><fA11 i1="02" i2="1"><s1>DHIMA (Kaltra)</s1></fA11><fA11 i1="03" i2="1"><s1>LOCKHART (Kaitlin C.)</s1></fA11><fA11 i1="04" i2="1"><s1>LOCASCIO (Joseph J.)</s1></fA11><fA11 i1="05" i2="1"><s1>HOESING (Ashley N.)</s1></fA11><fA11 i1="06" i2="1"><s1>DUONG (Karen)</s1></fA11><fA11 i1="07" i2="1"><s1>TRISINI-LIPSANOPOULOS (Ana)</s1></fA11><fA11 i1="08" i2="1"><s1>HAYES (Michael T.)</s1></fA11><fA11 i1="09" i2="1"><s1>SHIVRAJ SOHUR (U.)</s1></fA11><fA11 i1="10" i2="1"><s1>WILLS (Anne-Marie)</s1></fA11><fA11 i1="11" i2="1"><s1>MOLLENHAUER (Brit)</s1></fA11><fA11 i1="12" i2="1"><s1>FLAHERTY (Alice W.)</s1></fA11><fA11 i1="13" i2="1"><s1>HUNG (Albert Y.)</s1></fA11><fA11 i1="14" i2="1"><s1>MEJIA (Nicte)</s1></fA11><fA11 i1="15" i2="1"><s1>KHURANA (Vikram)</s1></fA11><fA11 i1="16" i2="1"><s1>GOMPERTS (Stephen N.)</s1></fA11><fA11 i1="17" i2="1"><s1>SELKOE (Dennis J.)</s1></fA11><fA11 i1="18" i2="1"><s1>SCHWARZSCHILD (Michael A.)</s1></fA11><fA11 i1="19" i2="1"><s1>SCHLOSSMACHER (Michael G.)</s1></fA11><fA11 i1="20" i2="1"><s1>HYMAN (Bradley T.)</s1></fA11><fA11 i1="21" i2="1"><s1>SUDARSKY (Lewis R.)</s1></fA11><fA11 i1="22" i2="1"><s1>GROWDON (John H.)</s1></fA11><fA11 i1="23" i2="1"><s1>SCHERZER (Clemens R.)</s1></fA11><fA14 i1="01"><s1>Neurogenomics Laboratory, Harvard Medical School and Brigham & Women's Hospital</s1><s2>Cambridge</s2><s3>GBR</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>23 aut.</sZ></fA14><fA14 i1="02"><s1>Biomarkers Program, Harvard NeuroDiscovery Center</s1><s2>Boston</s2><s3>USA</s3><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>11 aut.</sZ><sZ>14 aut.</sZ><sZ>15 aut.</sZ><sZ>16 aut.</sZ><sZ>17 aut.</sZ><sZ>18 aut.</sZ><sZ>19 aut.</sZ><sZ>20 aut.</sZ><sZ>22 aut.</sZ><sZ>23 aut.</sZ></fA14><fA14 i1="03"><s1>Department of Neurology, Massachusetts General Hospital</s1><s2>Boston</s2><s3>USA</s3><sZ>4 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>12 aut.</sZ><sZ>13 aut.</sZ><sZ>14 aut.</sZ><sZ>15 aut.</sZ><sZ>16 aut.</sZ><sZ>18 aut.</sZ><sZ>20 aut.</sZ><sZ>22 aut.</sZ><sZ>23 aut.</sZ></fA14><fA14 i1="04"><s1>Department of Neurology, Brigham and Women's Hospital</s1><s2>Boston, MA</s2><s3>USA</s3><sZ>8 aut.</sZ><sZ>13 aut.</sZ><sZ>17 aut.</sZ><sZ>21 aut.</sZ><sZ>23 aut.</sZ></fA14><fA14 i1="05"><s1>Paracelsus-Elena-Klinik</s1><s2>Kassel</s2><s3>DEU</s3><sZ>11 aut.</sZ></fA14><fA14 i1="06"><s1>Division of Neurology, the Ottawa Hospital, University of Ottawa</s1><s3>CAN</s3><sZ>19 aut.</sZ></fA14><fA20><s1>1531-1537</s1></fA20><fA21><s1>2013</s1></fA21><fA23 i1="01"><s0>ENG</s0></fA23><fA43 i1="01"><s1>INIST</s1><s2>6345</s2><s5>354000504235330090</s5></fA43><fA44><s0>0000</s0><s1>© 2013 INIST-CNRS. All rights reserved.</s1></fA44><fA45><s0>20 ref.</s0></fA45><fA47 i1="01" i2="1"><s0>13-0345091</s0></fA47><fA60><s1>P</s1></fA60><fA61><s0>A</s0></fA61><fA64 i1="01" i2="1"><s0>Neurology</s0></fA64><fA66 i1="01"><s0>USA</s0></fA66><fC01 i1="01" l="ENG"><s0>Objective: To conclusively test for a specific association between the biological marker 25-hydroxy-vitamin D<sub>3</sub>, a transcriptionally active hormone produced in human skin and liver, and the prevalence and severity of Parkinson disease (PD). Methods: We used liquid chromatography/tandem mass spectrometry to establish an association specifically between deficiency of 25-hydroxy-vitamin D<sub>3</sub> and PD in a cross-sectional and longitudinal case-control study of 388 patients (mean Hoehn and Yahr stage of 2.1 ± 0.6) and 283 control subjects free of neurologic disease nested in the Harvard Biomarker Study. Results: Plasma levels of 25-hydroxy-vitamin D<sub>3</sub> were associated with PD in both univariate and multivariate analyses with p values = 0.0034 and 0.047, respectively. Total 25-hydroxy-vitamin D levels, the traditional composite measure of endogenous and exogenous vitamin D, were deficient in 17.6% of patients with PD compared with 9.3% of controls. Low 25-hydroxy-vitamin D<sub>3</sub> as well as total 25-hydroxy-vitamin D levels were correlated with higher total Unified Parkinson's Disease Rating Scale scores at baseline and during follow-up. Conclusions: Our study reveals an association between 25-hydroxy-vitamin D<sub>3</sub> and PD and suggests that thousands of patients with PD in North America alone may be vitamin D-deficient. This finding has immediate relevance for individual patients at risk of falls as well as public health, and warrants further investigation into the mechanism underlying this association.</s0></fC01><fC02 i1="01" i2="X"><s0>002B17G</s0></fC02><fC02 i1="02" i2="X"><s0>002B22C</s0></fC02><fC02 i1="03" i2="X"><s0>002B17A01</s0></fC02><fC02 i1="04" i2="X"><s0>002B17A03</s0></fC02><fC03 i1="01" i2="X" l="FRE"><s0>Carence vitaminique</s0><s5>01</s5></fC03><fC03 i1="01" i2="X" l="ENG"><s0>Vitamin deficiency</s0><s5>01</s5></fC03><fC03 i1="01" i2="X" l="SPA"><s0>Carencia vitamínica</s0><s5>01</s5></fC03><fC03 i1="02" i2="X" l="FRE"><s0>Maladie de Parkinson</s0><s2>NM</s2><s5>02</s5></fC03><fC03 i1="02" i2="X" l="ENG"><s0>Parkinson disease</s0><s2>NM</s2><s5>02</s5></fC03><fC03 i1="02" i2="X" l="SPA"><s0>Parkinson enfermedad</s0><s2>NM</s2><s5>02</s5></fC03><fC03 i1="03" i2="X" l="FRE"><s0>Pathologie du système nerveux</s0><s5>03</s5></fC03><fC03 i1="03" i2="X" l="ENG"><s0>Nervous system diseases</s0><s5>03</s5></fC03><fC03 i1="03" i2="X" l="SPA"><s0>Sistema nervioso patología</s0><s5>03</s5></fC03><fC03 i1="04" i2="X" l="FRE"><s0>Colécalciférol</s0><s2>NK</s2><s2>FR</s2><s5>09</s5></fC03><fC03 i1="04" i2="X" l="ENG"><s0>Colecalciferol</s0><s2>NK</s2><s2>FR</s2><s5>09</s5></fC03><fC03 i1="04" i2="X" l="SPA"><s0>Colecalciferol</s0><s2>NK</s2><s2>FR</s2><s5>09</s5></fC03><fC07 i1="01" i2="X" l="FRE"><s0>Etat nutritionnel</s0><s5>37</s5></fC07><fC07 i1="01" i2="X" l="ENG"><s0>Nutritional status</s0><s5>37</s5></fC07><fC07 i1="01" i2="X" l="SPA"><s0>Estado nutricional</s0><s5>37</s5></fC07><fC07 i1="02" i2="X" l="FRE"><s0>Malnutrition</s0><s5>38</s5></fC07><fC07 i1="02" i2="X" l="ENG"><s0>Malnutrition</s0><s5>38</s5></fC07><fC07 i1="02" i2="X" l="SPA"><s0>Malnutrición</s0><s5>38</s5></fC07><fC07 i1="03" i2="X" l="FRE"><s0>Trouble métabolique</s0><s5>39</s5></fC07><fC07 i1="03" i2="X" l="ENG"><s0>Metabolic disorder</s0><s5>39</s5></fC07><fC07 i1="03" i2="X" l="SPA"><s0>Trastorno metabolismo</s0><s5>39</s5></fC07><fC07 i1="04" i2="X" l="FRE"><s0>Trouble de la nutrition</s0><s5>40</s5></fC07><fC07 i1="04" i2="X" l="ENG"><s0>Nutrition disorder</s0><s5>40</s5></fC07><fC07 i1="04" i2="X" l="SPA"><s0>Trastorno nutricíon</s0><s5>40</s5></fC07><fC07 i1="05" i2="X" l="FRE"><s0>Pathologie de l'encéphale</s0><s5>41</s5></fC07><fC07 i1="05" i2="X" l="ENG"><s0>Cerebral disorder</s0><s5>41</s5></fC07><fC07 i1="05" i2="X" l="SPA"><s0>Encéfalo patología</s0><s5>41</s5></fC07><fC07 i1="06" i2="X" l="FRE"><s0>Syndrome extrapyramidal</s0><s5>42</s5></fC07><fC07 i1="06" i2="X" l="ENG"><s0>Extrapyramidal syndrome</s0><s5>42</s5></fC07><fC07 i1="06" i2="X" l="SPA"><s0>Extrapiramidal síndrome</s0><s5>42</s5></fC07><fC07 i1="07" i2="X" l="FRE"><s0>Maladie dégénérative</s0><s5>43</s5></fC07><fC07 i1="07" i2="X" l="ENG"><s0>Degenerative disease</s0><s5>43</s5></fC07><fC07 i1="07" i2="X" l="SPA"><s0>Enfermedad degenerativa</s0><s5>43</s5></fC07><fC07 i1="08" i2="X" l="FRE"><s0>Pathologie du système nerveux central</s0><s5>44</s5></fC07><fC07 i1="08" i2="X" l="ENG"><s0>Central nervous system disease</s0><s5>44</s5></fC07><fC07 i1="08" i2="X" l="SPA"><s0>Sistema nervosio central patología</s0><s5>44</s5></fC07><fN21><s1>329</s1></fN21><fN44 i1="01"><s1>OTO</s1></fN44><fN82><s1>OTO</s1></fN82></pA></standard><server><NO>PASCAL 13-0345091 INIST</NO><ET>Unrecognized vitamin D<sub>3</sub> deficiency is common in Parkinson disease: Harvard Biomarker Study</ET><AU>HONGLIU DING; DHIMA (Kaltra); LOCKHART (Kaitlin C.); LOCASCIO (Joseph J.); HOESING (Ashley N.); DUONG (Karen); TRISINI-LIPSANOPOULOS (Ana); HAYES (Michael T.); SHIVRAJ SOHUR (U.); WILLS (Anne-Marie); MOLLENHAUER (Brit); FLAHERTY (Alice W.); HUNG (Albert Y.); MEJIA (Nicte); KHURANA (Vikram); GOMPERTS (Stephen N.); SELKOE (Dennis J.); SCHWARZSCHILD (Michael A.); SCHLOSSMACHER (Michael G.); HYMAN (Bradley T.); SUDARSKY (Lewis R.); GROWDON (John H.); SCHERZER (Clemens R.)</AU><AF>Neurogenomics Laboratory, Harvard Medical School and Brigham & Women's Hospital/Cambridge/Royaume-Uni (1 aut., 2 aut., 3 aut., 5 aut., 6 aut., 7 aut., 23 aut.); Biomarkers Program, Harvard NeuroDiscovery Center/Boston/Etats-Unis (2 aut., 3 aut., 5 aut., 6 aut., 7 aut., 8 aut., 9 aut., 11 aut., 14 aut., 15 aut., 16 aut., 17 aut., 18 aut., 19 aut., 20 aut., 22 aut., 23 aut.); Department of Neurology, Massachusetts General Hospital/Boston/Etats-Unis (4 aut., 9 aut., 10 aut., 12 aut., 13 aut., 14 aut., 15 aut., 16 aut., 18 aut., 20 aut., 22 aut., 23 aut.); Department of Neurology, Brigham and Women's Hospital/Boston, MA/Etats-Unis (8 aut., 13 aut., 17 aut., 21 aut., 23 aut.); Paracelsus-Elena-Klinik/Kassel/Allemagne (11 aut.); Division of Neurology, the Ottawa Hospital, University of Ottawa/Canada (19 aut.)</AF><DT>Publication en série; Niveau analytique</DT><SO>Neurology; ISSN 0028-3878; Coden NEURAI; Etats-Unis; Da. 2013; Vol. 81; No. 17; Pp. 1531-1537; Bibl. 20 ref.</SO><LA>Anglais</LA><EA>Objective: To conclusively test for a specific association between the biological marker 25-hydroxy-vitamin D<sub>3</sub>, a transcriptionally active hormone produced in human skin and liver, and the prevalence and severity of Parkinson disease (PD). Methods: We used liquid chromatography/tandem mass spectrometry to establish an association specifically between deficiency of 25-hydroxy-vitamin D<sub>3</sub> and PD in a cross-sectional and longitudinal case-control study of 388 patients (mean Hoehn and Yahr stage of 2.1 ± 0.6) and 283 control subjects free of neurologic disease nested in the Harvard Biomarker Study. Results: Plasma levels of 25-hydroxy-vitamin D<sub>3</sub> were associated with PD in both univariate and multivariate analyses with p values = 0.0034 and 0.047, respectively. Total 25-hydroxy-vitamin D levels, the traditional composite measure of endogenous and exogenous vitamin D, were deficient in 17.6% of patients with PD compared with 9.3% of controls. Low 25-hydroxy-vitamin D<sub>3</sub> as well as total 25-hydroxy-vitamin D levels were correlated with higher total Unified Parkinson's Disease Rating Scale scores at baseline and during follow-up. Conclusions: Our study reveals an association between 25-hydroxy-vitamin D<sub>3</sub> and PD and suggests that thousands of patients with PD in North America alone may be vitamin D-deficient. This finding has immediate relevance for individual patients at risk of falls as well as public health, and warrants further investigation into the mechanism underlying this association.</EA><CC>002B17G; 002B22C; 002B17A01; 002B17A03</CC><FD>Carence vitaminique; Maladie de Parkinson; Pathologie du système nerveux; Colécalciférol</FD><FG>Etat nutritionnel; Malnutrition; Trouble métabolique; Trouble de la nutrition; Pathologie de l'encéphale; Syndrome extrapyramidal; Maladie dégénérative; Pathologie du système nerveux central</FG><ED>Vitamin deficiency; Parkinson disease; Nervous system diseases; Colecalciferol</ED><EG>Nutritional status; Malnutrition; Metabolic disorder; Nutrition disorder; Cerebral disorder; Extrapyramidal syndrome; Degenerative disease; Central nervous system disease</EG><SD>Carencia vitamínica; Parkinson enfermedad; Sistema nervioso patología; Colecalciferol</SD><LO>INIST-6345.354000504235330090</LO><ID>13-0345091</ID></server></inist></record>Pour manipuler ce document sous Unix (Dilib)
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