title: Exploring the effects of coexisting amyloid in subcortical vascular cognitive impairment.
abstract: BACKGROUND
  Mixed pathology, particularly Alzheimer's disease with cerebrovascular lesions, is reported as the second most common cause of dementia. Research on mixed dementia typically includes people with a primary AD diagnosis and hence, little is known about the effects of co-existing amyloid pathology in people with vascular cognitive impairment (VCI). The purpose of this study was to understand whether individual differences in amyloid pathology might explain variations in cognitive impairment among individuals with clinical subcortical VCI (SVCI).
  
  
  METHODS
  Twenty-two participants with SVCI completed an (11)C Pittsburgh compound B (PIB) position emission tomography (PET) scan to quantify global amyloid deposition. Cognitive function was measured using: 1) MOCA; 2) ADAS-Cog; 3) EXIT-25; and 4) specific executive processes including a) Digits Forward and Backwards Test, b) Stroop-Colour Word Test, and c) Trail Making Test. To assess the effect of amyloid deposition on cognitive function we conducted Pearson bivariate correlations to determine which cognitive measures to include in our regression models. Cognitive variables that were significantly correlated with PIB retention values were entered in a hierarchical multiple linear regression analysis to determine the unique effect of amyloid on cognitive function. We controlled for age, education, and ApoE ε4 status.
  
  
  RESULTS
  Bivariate correlation results showed that PIB binding was significantly correlated with ADAS-Cog (p < 0.01) and MOCA (p < 0.01); increased PIB binding was associated with worse cognitive function on both cognitive measures. PIB binding was not significantly correlated with the EXIT-25 or with specific executive processes (p > 0.05). Regression analyses controlling for age, education, and ApoE ε4 status indicated an independent association between PIB retention and the ADAS-Cog (adjusted R-square change of 15.0%, Sig F Change = 0.03). PIB retention was also independently associated with MOCA scores (adjusted R-Square Change of 27.0%, Sig F Change = 0.02).
  
  
  CONCLUSIONS
  We found that increased global amyloid deposition was significantly associated with greater memory and executive dysfunctions as measured by the ADAS-Cog and MOCA. Our findings point to the important role of co-existing amyloid deposition for cognitive function in those with a primary SVCI diagnosis. As such, therapeutic approaches targeting SVCI must consider the potential role of amyloid for the optimal care of those with mixed dementia.
  
  
  BACKGROUND
  NCT01027858.
authors.affiliation: Djavad Mowafaghian Centre for Brain Health, University of British Columbia, 2215 Wesbrook Mall, Vancouver, BC, V6S 0A9, Canada. lizdao@mail.ubc.ca.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Dao
authors.affiliation: Department of Medicine, University of British Columbia, 2211 Wesbrook Mall, Vancouver, BC, V6T 2B5, Canada. hsiung@mail.ubc.ca.
authors.forename: Ging-Yuek Robin
authors.initials: GY
authors.lastname: Hsiung
authors.affiliation: Department of Physics and Astronomy, University of British Columbia, 6224 Agricultural Road, Vancouver, BC, V6T 1Z1, Canada. vesna@physics.ubc.ca.|UBC PET, Brain Research Centre, 2211 Westboork Mall, Vancouver, BC, V6T 2B5, Canada. vesna@physics.ubc.ca.
authors.forename: Vesna
authors.initials: V
authors.lastname: Sossi
authors.affiliation: School of Professional Psychology, Pacific University, 190 SE 8th Avenue, Hillsboro, OR, 97123, USA. cjacova@pacific.edu.
authors.forename: Claudia
authors.initials: C
authors.lastname: Jacova
authors.affiliation: Department of Radiology, University of British Columbia, 3350-950 W 10th Avenue, Vancouver, BC, V5Z 1 M9, Canada. roger.tam@ubc.ca.|MS/MRI Research Group, University of British Columbia, 2215 Wesbrook Mall, Vancouver, BC, V6S 0A9, Canada. roger.tam@ubc.ca.
authors.forename: Roger
authors.initials: R
authors.lastname: Tam
authors.affiliation: UBC PET, Brain Research Centre, 2211 Westboork Mall, Vancouver, BC, V6T 2B5, Canada. kdinelle@phas.ubc.ca.
authors.forename: Katie
authors.initials: K
authors.lastname: Dinelle
authors.affiliation: Djavad Mowafaghian Centre for Brain Health, University of British Columbia, 2215 Wesbrook Mall, Vancouver, BC, V6S 0A9, Canada. john.best@ubc.ca.|Department of Physical Therapy, University of British Columbia, 212-2177 Wesbrook Mall, Vancouver, BC, V6T 1Z3, Canada. john.best@ubc.ca.
authors.forename: John R
authors.initials: JR
authors.lastname: Best
authors.affiliation: Djavad Mowafaghian Centre for Brain Health, University of British Columbia, 2215 Wesbrook Mall, Vancouver, BC, V6S 0A9, Canada. teresa.ambrose@ubc.ca.|Department of Physical Therapy, University of British Columbia, 212-2177 Wesbrook Mall, Vancouver, BC, V6T 1Z3, Canada. teresa.ambrose@ubc.ca.
authors.forename: Teresa
authors.initials: T
authors.lastname: Liu-Ambrose
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D003072:Cognition Disorders / Q000378:metabolism / Q000503:physiopathology; D015140:Dementia, Vascular / Q000378:metabolism / Q000503:physiopathology; D005260:Female; D006801:Humans; D008297:Male; D049268:Positron-Emission Tomography; D016032:Randomized Controlled Trials as Topic
chemical_list: D016229:Amyloid beta-Peptides