Document Detail

White matter hyperintensities and cerebral amyloidosis: necessary and sufficient for clinical expression of Alzheimer disease?
MedLine Citation:
PMID:  23420027     Owner:  NLM     Status:  MEDLINE    
IMPORTANCE: Current hypothetical models emphasize the importance of β-amyloid in Alzheimer disease (AD) pathogenesis, although amyloid alone is not sufficient to account for the dementia syndrome. The impact of small-vessel cerebrovascular disease, visualized as white matter hyperintensities (WMHs) on magnetic resonance imaging scans, may be a key factor that contributes independently to AD presentation.
OBJECTIVE: To determine the impact of WMHs and Pittsburgh Compound B (PIB) positron-emission tomography-derived amyloid positivity on the clinical expression of AD.
DESIGN: Baseline PIB-positron-emission tomography values were downloaded from the Alzheimer's Disease Neuroimaging Initiative database. Total WMH volume was derived on accompanying structural magnetic resonance imaging data. We examined whether PIB positivity and total WMHs predicted diagnostic classification of patients with AD (n = 20) and control subjects (n = 21). A second analysis determined whether WMHs discriminated between those with and without the clinical diagnosis of AD among those who were classified as PIB positive (n = 28). A third analysis examined whether WMHs, in addition to PIB status, could be used to predict future risk for AD among subjects with mild cognitive impairment (n = 59).
SETTING: The Alzheimer's Disease Neuroimaging Initiative public database.
PARTICIPANTS: The study involved data from 21 normal control subjects, 59 subjects with mild cognitive impairment, and 20 participants with clinically defined AD from the Alzheimer Disease's Neuroimaging Initiative database.
MAIN OUTCOME MEASURES: Clinical AD diagnosis and WMH volume.
RESULTS: Pittsburgh Compound B positivity and increased total WMH volume independently predicted AD diagnosis. Among PIB-positive subjects, those diagnosed as having AD had greater WMH volume than normal control subjects. Among subjects with mild cognitive impairment, both WMH and PIB status at baseline conferred risk for future diagnosis of AD.
CONCLUSIONS AND RELEVANCE: White matter hyperintensities contribute to the presentation of AD and, in the context of significant amyloid deposition, may provide a second hit necessary for the clinical manifestation of the disease. As risk factors for the development of WMHs are modifiable, these findings suggest intervention and prevention strategies for the clinical syndrome of AD.
Frank A Provenzano; Jordan Muraskin; Giuseppe Tosto; Atul Narkhede; Ben T Wasserman; Erica Y Griffith; Vanessa A Guzman; Irene B Meier; Molly E Zimmerman; Adam M Brickman;
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  JAMA neurology     Volume:  70     ISSN:  2168-6157     ISO Abbreviation:  JAMA Neurol     Publication Date:  2013 Apr 
Date Detail:
Created Date:  2013-04-09     Completed Date:  2013-05-31     Revised Date:  2014-08-10    
Medline Journal Info:
Nlm Unique ID:  101589536     Medline TA:  JAMA Neurol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  455-61     Citation Subset:  AIM; IM    
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MeSH Terms
Aged, 80 and over
Alzheimer Disease / complications*,  diagnosis*,  metabolism*,  radionuclide imaging
Amyloidosis / etiology*
Aniline Compounds / diagnostic use
Brain Mapping
Cerebral Cortex / pathology*,  radionuclide imaging
Databases, Factual / statistics & numerical data
Longitudinal Studies
Magnetic Resonance Imaging
Middle Aged
Mild Cognitive Impairment / pathology,  radionuclide imaging
Nerve Fibers, Myelinated / pathology*
Positron-Emission Tomography
Thiazoles / diagnostic use
Grant Support
AG029949/AG/NIA NIH HHS; AG034189/AG/NIA NIH HHS; K01 AG030514/AG/NIA NIH HHS; P30 AG010129/AG/NIA NIH HHS; P30 AG010129/AG/NIA NIH HHS; R01 AG034189/AG/NIA NIH HHS; U01 AG024904/AG/NIA NIH HHS; //Canadian Institutes of Health Research
Reg. No./Substance:
0/2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole; 0/Aniline Compounds; 0/Thiazoles
Comment In:
JAMA Neurol. 2013 Apr;70(4):438-9   [PMID:  23420043 ]

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