title: White matter hyperintensities and cerebral amyloidosis: necessary and sufficient for clinical expression of Alzheimer disease?
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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).
  
  
  METHODS
  The Alzheimer's Disease Neuroimaging Initiative public database.
  
  
  METHODS
  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.
  
  
  METHODS
  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
  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.
authors: Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
authors: Frank A
authors: FA
authors: Provenzano
authors: Jordan
authors: J
authors: Muraskin
authors: Giuseppe
authors: G
authors: Tosto
authors: Atul
authors: A
authors: Narkhede
authors: Ben T
authors: BT
authors: Wasserman
authors: Erica Y
authors: EY
authors: Griffith
authors: Vanessa A
authors: VA
authors: Guzman
authors: Irene B
authors: IB
authors: Meier
authors: Molly E
authors: ME
authors: Zimmerman
authors: Adam M
authors: AM
authors: Brickman
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000150:complications* / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000378:metabolism*; D000686:Amyloidosis / Q000209:etiology*; D000814:Aniline Compounds; D001931:Brain Mapping; D002540:Cerebral Cortex / Q000000981:diagnostic imaging / Q000473:pathology*; D060825:Cognitive Dysfunction / Q000000981:diagnostic imaging / Q000473:pathology; D016208:Databases, Factual / Q000706:statistics & numerical data; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009413:Nerve Fibers, Myelinated / Q000473:pathology*; D049268:Positron-Emission Tomography; D013844:Thiazoles
chemical_list: C475519:2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole; D000814:Aniline Compounds; D013844:Thiazoles