Amyloid Positivity in the Alzheimer/Subcortical-Vascular Spectrum

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.

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.

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.

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.