title: The aging brain and cognition: contribution of vascular injury and aβ to mild cognitive dysfunction.
abstract: OBJECTIVE
  β-Amyloid (Aβ) deposition and vascular brain injury (VBI) frequently co-occur and are both associated with cognitive decline in aging. Determining whether a direct relationship exists between them has been challenging. We sought to understand VBI's influence on cognition and clinical impairment, separate from and in conjunction with pathologic changes associated with Alzheimer disease (AD).
  
  
  OBJECTIVE
  To examine the relationship between neuroimaging measures of VBI and brain Aβ deposition and their associations with cognition.
  
  
  METHODS
  A cross-sectional study in a community- and clinic-based sample recruited for elevated vascular disease risk factors.
  
  
  METHODS
  Clinically normal (mean age, 77.1 years [N = 30]), cognitively impaired (mean age, 78.0 years [N = 24]), and mildly demented (mean age, 79.8 years [N = 7]) participants.
  
  
  METHODS
  Magnetic resonance imaging, Aβ (Pittsburgh Compound B-positron emission tomographic [PiB-PET]) imaging, and cognitive testing.
  
  
  METHODS
  Magnetic resonance images were rated for the presence and location of infarct (34 infarct-positive participants, 27 infarct-negative participants) and were used to quantify white matter lesion volume. The PiB-PET uptake ratios were used to create a PiB index by averaging uptake across regions vulnerable to early Aβ deposition; PiB positivity (29 PiB-positive participants, 32 PiB-negative participants) was determined from a data-derived threshold. Standardized composite cognitive measures included executive function and verbal and nonverbal memory.
  
  
  RESULTS
  Vascular brain injury and Aβ were independent in both cognitively normal and impaired participants. Infarction, particularly in cortical and subcortical gray matter, was associated with lower cognitive performance in all domains (P < .05 for all comparisons). Pittsburgh Compound B positivity was neither a significant predictor of cognition nor interacted with VBI.
  
  
  CONCLUSIONS
  In this elderly sample with normal cognition to mild dementia, enriched for vascular disease, VBI was more influential than Aβ in contemporaneous cognitive function and remained predictive after including the possible influence of Aβ. There was no evidence that VBI increases the likelihood of Aβ deposition. This finding highlights the importance of VBI in mild cognitive impairment and suggests that the impact of cerebrovascular disease should be considered with respect to defining the etiology of mild cognitive impairment.
authors: Helen Wills Neuroscience Institute, University of California, Berkeley, 132 Barker Hall, Mail Code 3190, Berkeley, CA 94720, USA. nlmarchant@gmail.com
authors: Natalie L
authors: NL
authors: Marchant
authors: Bruce R
authors: BR
authors: Reed
authors: Nerses
authors: N
authors: Sanossian
authors: Cindee M
authors: CM
authors: Madison
authors: Stephen
authors: S
authors: Kriger
authors: Roxana
authors: R
authors: Dhada
authors: Wendy J
authors: WJ
authors: Mack
authors: Charles
authors: C
authors: DeCarli
authors: Michael W
authors: MW
authors: Weiner
authors: Dan M
authors: DM
authors: Mungas
authors: Helena C
authors: HC
authors: Chui
authors: William J
authors: WJ
authors: Jagust
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000814:Aniline Compounds; D001057:Apolipoproteins E / Q000235:genetics; D020520:Brain Infarction / Q000209:etiology; D060825:Cognitive Dysfunction / Q000000981:diagnostic imaging / Q000209:etiology* / Q000235:genetics / Q000473:pathology*; D003430:Cross-Sectional Studies; D056344:Executive Function; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008568:Memory; D008609:Mental Status Schedule; D009483:Neuropsychological Tests; D049268:Positron-Emission Tomography; D013844:Thiazoles; D057772:Vascular System Injuries / Q000150:complications*
chemical_list: C475519:2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole; D016229:Amyloid beta-Peptides; D000814:Aniline Compounds; D001057:Apolipoproteins E; D013844:Thiazoles
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