Amyloid Positivity in the Alzheimer/Subcortical-Vascular Spectrum

Neurology. 2021 Apr 27;96(17):e2201-e2211. doi: 10.1212/WNL.0000000000011833. Epub 2021 Mar 15.


Objective: We investigated the frequency of β-amyloid (Aβ) positivity in 9 groups classified according to a combination of 3 different cognition states and 3 distinct levels of white matter hyperintensities (WMH) (minimal, moderate, and severe) and aimed to determine which factors were associated with Aβ after controlling for WMH and vice versa.

Methods: A total of 1,047 individuals with subjective cognitive decline (SCD, n = 294), mild cognitive impairment (MCI, n = 237), or dementia (n = 516) who underwent Aβ PET scans were recruited from the memory clinic at Samsung Medical Center in Seoul, Korea. We investigated the following: (1) Aβ positivity in the 9 groups, (2) the relationship between Aβ positivity and WMH severity, and (3) clinical and genetic factors independently associated with Aβ or WMH.

Results: Aβ positivity increased as the severity of cognitive impairment increased (SCD [15.7%], MCI [43.5%], and dementia [76.2%]), whereas it decreased as the severity of WMH increased (minimal [54.5%], moderate [53.9%], and severe [41.0%]) or the number of lacunes (0 [59.0%], 1-3 [42.0%], and >3 [23.4%]) increased. Aβ positivity was associated with higher education, absence of diabetes, and presence of APOE ε4 after controlling for cognitive and WMH status.

Conclusion: Our analysis of Aβ positivity involving a large sample classified according to the stratified cognitive states and WMH severity indicates that Alzheimer and cerebral small vessel diseases lie on a continuum. Our results offer clinicians insightful information about the association among Aβ, WMH, and cognition.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / genetics
  • Alzheimer Disease / metabolism*
  • Alzheimer Disease / pathology
  • Amyloid / metabolism*
  • Amyloidogenic Proteins / metabolism*
  • Brain / metabolism*
  • Cerebral Small Vessel Diseases / metabolism
  • Cognition / physiology
  • Cognitive Dysfunction / genetics
  • Cognitive Dysfunction / metabolism*
  • Dementia, Vascular / metabolism
  • Female
  • Humans
  • Magnetic Resonance Imaging / methods
  • Male


  • Amyloid
  • Amyloidogenic Proteins