TY - JOUR
T1 - Differential response to donepezil in MRI subtypes of mild cognitive impairment
AU - Diaz-Galvan, Patricia
AU - Lorenzon, Giulia
AU - Mohanty, Rosaleena
AU - Mårtensson, Gustav
AU - Cavedo, Enrica
AU - Lista, Simone
AU - Vergallo, Andrea
AU - Kantarci, Kejal
AU - Hampel, Harald
AU - Dubois, Bruno
AU - Grothe, Michel J.
AU - Ferreira, Daniel
AU - Westman, Eric
N1 - Publisher Copyright:
© 2023, The Author(s).
PY - 2023/12
Y1 - 2023/12
N2 - Background: Donepezil is an approved therapy for the treatment of Alzheimer’s disease (AD). Results across clinical trials have been inconsistent, which may be explained by design-methodological issues, the pathophysiological heterogeneity of AD, and diversity of included study participants. We investigated whether response to donepezil differs in mild cognitive impaired (MCI) individuals demonstrating different magnetic resonance imaging (MRI) subtypes. Methods: From the Hippocampus Study double-blind, randomized clinical trial, we included 173 MCI individuals (donepezil = 83; placebo = 90) with structural MRI data, at baseline and at clinical follow-up assessments (6–12-month). Efficacy outcomes were the annualized percentage change (APC) in hippocampal, ventricular, and total grey matter volumes, as well as in the AD cortical thickness signature. Participants were classified into MRI subtypes as typical AD, limbic-predominant, hippocampal-sparing, or minimal atrophy at baseline. We primarily applied a subtyping approach based on continuous scale of two subtyping dimensions. We also used the conventional categorical subtyping approach for comparison. Results: Donepezil-treated MCI individuals showed slower atrophy rates compared to the placebo group, but only if they belonged to the minimal atrophy or hippocampal-sparing subtypes. Importantly, only the continuous subtyping approach, but not the conventional categorical approach, captured this differential response. Conclusions: Our data suggest that individuals with MCI, with hippocampal-sparing or minimal atrophy subtype, may have improved benefit from donepezil, as compared with MCI individuals with typical or limbic-predominant patterns of atrophy. The newly proposed continuous subtyping approach may have advantages compared to the conventional categorical approach. Future research is warranted to demonstrate the potential of subtype stratification for disease prognosis and response to treatment. Trial registration: ClinicalTrial.gov NCT00403520. Submission Date: November 21, 2006.
AB - Background: Donepezil is an approved therapy for the treatment of Alzheimer’s disease (AD). Results across clinical trials have been inconsistent, which may be explained by design-methodological issues, the pathophysiological heterogeneity of AD, and diversity of included study participants. We investigated whether response to donepezil differs in mild cognitive impaired (MCI) individuals demonstrating different magnetic resonance imaging (MRI) subtypes. Methods: From the Hippocampus Study double-blind, randomized clinical trial, we included 173 MCI individuals (donepezil = 83; placebo = 90) with structural MRI data, at baseline and at clinical follow-up assessments (6–12-month). Efficacy outcomes were the annualized percentage change (APC) in hippocampal, ventricular, and total grey matter volumes, as well as in the AD cortical thickness signature. Participants were classified into MRI subtypes as typical AD, limbic-predominant, hippocampal-sparing, or minimal atrophy at baseline. We primarily applied a subtyping approach based on continuous scale of two subtyping dimensions. We also used the conventional categorical subtyping approach for comparison. Results: Donepezil-treated MCI individuals showed slower atrophy rates compared to the placebo group, but only if they belonged to the minimal atrophy or hippocampal-sparing subtypes. Importantly, only the continuous subtyping approach, but not the conventional categorical approach, captured this differential response. Conclusions: Our data suggest that individuals with MCI, with hippocampal-sparing or minimal atrophy subtype, may have improved benefit from donepezil, as compared with MCI individuals with typical or limbic-predominant patterns of atrophy. The newly proposed continuous subtyping approach may have advantages compared to the conventional categorical approach. Future research is warranted to demonstrate the potential of subtype stratification for disease prognosis and response to treatment. Trial registration: ClinicalTrial.gov NCT00403520. Submission Date: November 21, 2006.
KW - Alzheimer’s disease
KW - Donepezil
KW - Heterogeneity
KW - Mild cognitive impairment
KW - Precision medicine
KW - Randomized controlled trial
KW - Subtypes
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U2 - 10.1186/s13195-023-01253-2
DO - 10.1186/s13195-023-01253-2
M3 - Article
C2 - 37353809
AN - SCOPUS:85162734236
SN - 1758-9193
VL - 15
JO - Alzheimer's Research and Therapy
JF - Alzheimer's Research and Therapy
IS - 1
M1 - 117
ER -