title: Synergistic effects of ischemia and β-amyloid burden on cognitive decline in patients with subcortical vascular mild cognitive impairment.
abstract: OBJECTIVE
  Cerebrovascular disease (CVD) and Alzheimer disease are significant causes of cognitive impairment in the elderly. However, few studies have evaluated the relationship between CVD and β-amyloid burden in living humans or their synergistic effects on cognition. Thus, there is a need for better understanding of mild cognitive impairment (MCI) before clinical deterioration begins.
  
  
  OBJECTIVE
  To determine the synergistic effects of β-amyloid burden and CVD on cognition in patients with subcortical vascular MCI (svMCI).
  
  
  METHODS
  A cross-sectional study was conducted using a hospital-based sample at a tertiary referral center. We prospectively recruited 95 patients with svMCI; 67 of these individuals participated in the study. Forty-five patients with amnestic MCI (aMCI) were group matched with those with svMCI by the Clinical Dementia Rating Scale Sum of Boxes.
  
  
  METHODS
  We measured β-amyloid burden using positron emission tomography with carbon 11-labeled Pittsburgh Compound B (PiB). Cerebrovascular disease was quantified as white matter hyperintensity volume detected by magnetic resonance imaging fluid-attenuated inversion recovery. Detailed neuropsychological tests were performed to determine the level of patients' cognitive impairment.
  
  
  RESULTS
  On evaluation, 22 of the svMCI group (33%) and 28 of the aMCI group (62%) were found to be PiB positive. The mean PiB retention ratio was lower in patients with svMCI than in those with aMCI. In svMCI, the PiB retention ratio was associated with cognitive impairments in multiple domains, including language, visuospatial, memory, and frontal executive functions, but was associated only with memory dysfunction in aMCI. A significant interaction between PiB retention ratio and white matter hyperintensity volume was found to affect visuospatial function in patients with svMCI.
  
  
  CONCLUSIONS
  Most patients with svMCI do not exhibit substantial amyloid burden, and CVD does not increase β-amyloid burden as measured by amyloid imaging. However, in patients with svMCI, amyloid burden and white matter hyperintensity act synergistically to impair visuospatial function. Therefore, our findings highlight the need for accurate biomarkers, including neuroimaging tools, for early diagnosis and the need to relate these biomarkers to cognitive measurements for effective use in the clinical setting.
authors.affiliation: Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Mi Ji
authors.initials: MJ
authors.lastname: Lee
authors.affiliation: Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Sang Won
authors.initials: SW
authors.lastname: Seo
authors.affiliation: Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Duk L
authors.initials: DL
authors.lastname: Na
authors.affiliation: Department of Preventive Medicine, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Changsoo
authors.initials: C
authors.lastname: Kim
authors.affiliation: Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Jae Hyun
authors.initials: JH
authors.lastname: Park
authors.affiliation: Department of Neurology, Ewha Womans University Mokdong Hospital, Ewha Womans University School of Medicine, Seoul, Korea.
authors.forename: Geon Ha
authors.initials: GH
authors.lastname: Kim
authors.affiliation: Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Chi Hun
authors.initials: CH
authors.lastname: Kim
authors.affiliation: Department of Neurology, Gachon University Gil Medical Center, Incheon, Korea.
authors.forename: Young
authors.initials: Y
authors.lastname: Noh
authors.affiliation: Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea5Department of Neurology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Hanna
authors.initials: H
authors.lastname: Cho
authors.affiliation: Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Hee Jin
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Department of Neurology, Inha University School of Medicine, Incheon, Korea.
authors.forename: Cindy W
authors.initials: CW
authors.lastname: Yoon
authors.affiliation: Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Byoung Seok
authors.initials: BS
authors.lastname: Ye
authors.affiliation: Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Juhee
authors.initials: J
authors.lastname: Chin
authors.affiliation: Department of Biomedical Engineering, Hanyang University, Seoul, Korea.
authors.forename: Seun
authors.initials: S
authors.lastname: Jeon
authors.affiliation: Department of Biomedical Engineering, Hanyang University, Seoul, Korea.
authors.forename: Jong-Min
authors.initials: JM
authors.lastname: Lee
authors.affiliation: Department of Nuclear Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Yearn Seong
authors.initials: YS
authors.lastname: Choe
authors.affiliation: Department of Nuclear Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Kyung-Han
authors.initials: KH
authors.lastname: Lee
authors.affiliation: Department of Nuclear Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Jae Seung
authors.initials: JS
authors.lastname: Kim
authors.affiliation: Department of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Sung Tae
authors.initials: ST
authors.lastname: Kim
authors.affiliation: Department of Neurology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Jae-Hong
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Institute for Stroke and Dementia Research, Ludwig-Maximilians University, Munich, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Ewers
authors.affiliation: Department of Brain Repair and Rehabilitation, University College London Institute of Neurology, Queen Square, London, England.
authors.forename: David J
authors.initials: DJ
authors.lastname: Werring
authors.affiliation: Department of Radiology, University of California, San Francisco15Center for Imaging of Neurodegenerative Diseases, Department of Veterans Affairs Medical Center, San Francisco, California.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Weiner
mesh_terms: D000368:Aged; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D001921:Brain / Q000473:pathology; D002545:Brain Ischemia / Q000175:diagnosis* / Q000523:psychology; D016657:Cerebral Amyloid Angiopathy / Q000175:diagnosis* / Q000523:psychology; D060825:Cognitive Dysfunction / Q000175:diagnosis* / Q000523:psychology; D015897:Comorbidity; D003430:Cross-Sectional Studies; D015140:Dementia, Vascular / Q000175:diagnosis* / Q000523:psychology; D018450:Disease Progression; D005260:Female; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D021621:Imaging, Three-Dimensional; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D049268:Positron-Emission Tomography; D011446:Prospective Studies; D013223:Statistics as Topic
chemical_list: D016229:Amyloid beta-Peptides