TY - JOUR
T1 - White matter hyperintensities in cholinergic pathways are associated with dementia severity in e4 carriers but not in non-carriers
AU - Yu, Ming Chun
AU - Chuang, Yi Fang
AU - Wu, Shu Ching
AU - Ho, Cheng Feng
AU - Liu, Yi Chien
AU - Chou, Chia Ju
N1 - Publisher Copyright:
Copyright © 2023 Yu, Chuang, Wu, Ho, Liu and Chou.
PY - 2023
Y1 - 2023
N2 - Background and objectives: Among individuals with Alzheimer's disease (AD), APOE e4 carriers with increased white matter hyperintensities (WMHs) may selectively be at increased risk of cognitive impairment. Given that the cholinergic system plays a crucial role in cognitive impairment, this study aimed to identify how APOE status modulates the associations between dementia severity and white matter hyperintensities in cholinergic pathways. Methods: From 2018 to 2022, we recruited participants (APOE e4 carriers, n = 49; non-carriers, n = 117) from the memory clinic of Cardinal Tien Hospital, Taipei, Taiwan. Participants underwent brain MRI, neuropsychological testing, and APOE genotyping. In this study, we applied the visual rating scale of the Cholinergic Pathways Hyperintensities Scale (CHIPS) to evaluate WMHs in cholinergic pathways compared with the Fazekas scale. Multiple regression was used to assess the influence of CHIPS score and APOE carrier status on dementia severity based on Clinical Dementia Rating—Sum of Boxes (CDR-SB). Results: After adjusting for age, education and sex, higher CHIPS scores tended to be associated with higher CDR-SB in APOE e4 carriers but not in the non-carrier group. Conclusions: Carriers and non-carriers present distinct associations between dementia severity and WMHs in cholinergic pathways. In APOE e4 carriers, increased white matter in cholinergic pathways are associated with greater dementia severity. In non-carriers, WMHs exhibit less predictive roles for clinical dementia severity. WMHs on the cholinergic pathway may have a different impact on APOE e4 carriers vs. non-carriers.
AB - Background and objectives: Among individuals with Alzheimer's disease (AD), APOE e4 carriers with increased white matter hyperintensities (WMHs) may selectively be at increased risk of cognitive impairment. Given that the cholinergic system plays a crucial role in cognitive impairment, this study aimed to identify how APOE status modulates the associations between dementia severity and white matter hyperintensities in cholinergic pathways. Methods: From 2018 to 2022, we recruited participants (APOE e4 carriers, n = 49; non-carriers, n = 117) from the memory clinic of Cardinal Tien Hospital, Taipei, Taiwan. Participants underwent brain MRI, neuropsychological testing, and APOE genotyping. In this study, we applied the visual rating scale of the Cholinergic Pathways Hyperintensities Scale (CHIPS) to evaluate WMHs in cholinergic pathways compared with the Fazekas scale. Multiple regression was used to assess the influence of CHIPS score and APOE carrier status on dementia severity based on Clinical Dementia Rating—Sum of Boxes (CDR-SB). Results: After adjusting for age, education and sex, higher CHIPS scores tended to be associated with higher CDR-SB in APOE e4 carriers but not in the non-carrier group. Conclusions: Carriers and non-carriers present distinct associations between dementia severity and WMHs in cholinergic pathways. In APOE e4 carriers, increased white matter in cholinergic pathways are associated with greater dementia severity. In non-carriers, WMHs exhibit less predictive roles for clinical dementia severity. WMHs on the cholinergic pathway may have a different impact on APOE e4 carriers vs. non-carriers.
KW - Alzheimer's disease
KW - Cholinergic Pathways Hyperintensities Scale (CHIPS)
KW - apolipoprotein E (APOE)
KW - mild cognitive impairment
KW - white matter hyperintensities (WMHs)
UR - http://www.scopus.com/inward/record.url?scp=85149505020&partnerID=8YFLogxK
U2 - 10.3389/fneur.2023.1100322
DO - 10.3389/fneur.2023.1100322
M3 - Article
AN - SCOPUS:85149505020
SN - 1664-2295
VL - 14
JO - Frontiers in Neurology
JF - Frontiers in Neurology
M1 - 1100322
ER -