Biomarkers.

Background: Ethnic differences in amyloid-β (Aβ) characteristics and cognitive trajectories should be considered, when designing Aβ-targeted therapies. The clinical effects of co-pathologies of Aβ have not been evaluated extensively across various dementias. We investigated the prevalence of Aβ+ and cognitive trajectories in Koreans and non-Hispanic whites (NHWs) with Alzheimer's clinical syndrome (ACS) and the clinical effects of Aβ+ in other dementias.

Method: We included 5,856 Koreans who underwent Aβ positron emission tomography (PET) in South Korea. The participants were categorized into the following groups: ACS, including cognitively unimpaired (CU), mild cognitive impairment (MCI), and dementia of the Alzheimer type (DAT); subcortical vascular cognitive impairment (SVCI); and frontotemporal dementia (FTD). Data from 929 NHWs were collected from the Alzheimer's Disease Neuroimaging Initiative. Mini-Mental State Examination (MMSE) scores performed at least twice were used to compare cognitive trajectories. We performed multivariable analyses and stabilized inverse probability of treatment weights based on the propensity scores to mitigate imbalances across ethnic groups.

Result: The prevalence of Aβ+ was lower in CU Koreans than in CU NHWs (odds ratio 0·6); however, this pattern was not observed in the MCI and DAT stages. Moreover, Aβ+ Koreans in the CU and MCI stages showed a more rapid decline in MMSE scores than Aβ+ NHWs (CU: B= -0·3136, p=0·004; MCI: B= -0·3847, p<0·001). Compared to CU, SVCI had a higher prevalence of Aβ+ in the 75-90 years age group (p<0·001). Aβ+ was predictive of a more rapid decrease in MMSE scores in SVCI (B= -0·6424, p<0·001) but not in FTD.

Conclusion: Our findings contribute to understanding Aβ biomarker traits in various dementias in Asians and highlight distinct ethnic differences when compared to NHWs.