Donepezil, an acetylcholinesterase inhibitor, is widely used for managing the symptoms of Alzheimer’s disease (AD), yet its clinical response varies widely among individuals. This study aims to investigate the influence of CYP2D6 genetic variants on donepezil concentration, treatment response, and adverse effects in Korean patients with AD dementia. We conducted a longitudinal study involving 76 patients receiving either 5 mg or 10 mg of donepezil. Genetic testing identified 9 CYP2D6 alleles, categorizing patients by metabolizing abilities. Blood sampling for plasma concentrations of donepezil were performed at steady-state. Mini-Mental State Examination (MMSE) were conducted at 12, 24 and 36 months after the initiation of treatment. Adverse events were collected throughout the study period.Donepezil plasma concentrations differed significantly among metabolizer statuses (mean 56.8 ± 27.1 ng/ml in normal metabolizers vs. 69.6 ± 30.1 ng/ml in intermediate metabolizers, p = 0.042), but these differences did not affect cognitive function over three years as assessed by MMSE. Additionally, there was no significant correlation between donepezil plasma concentration and adverse events. Our study is the first to elucidate the associations between CYP2D6 genotype and the concentration, clinical response or adverse events of donepezil in Korean patients with AD dementia. Larger studies are necessary to fully understand the impact of CYP2D6 genetic variants on therapeutic outcomes with donepezil.

Background: and Purpose: Recognizing cognitive decline patterns in mild cognitive impairment (MCI) is crucial for early screening and preventive interventions. However, studies on the trajectory of individual cognitive functions in MCI are limited. Thus, the purpose of this study was to identify subtypes and stages of cognitive decline in MCI using a machine learning method. Methods: A total of 944 subjects consisting of those who were cognitively normal and those with MCI were enrolled. Fifteen neuropsychological tasks were used in the analysis.The optimal number of subtypes was determined based on the cross-validation information criterion. Fifteen stages of cognitive trajectory were estimated for each subtype. Results: The following three subtypes were identified: amnestic-verbal subtype, dysexecutive subtype, and amnestic-visual subtype. Of 723 (76.6%) subjects who had reached stage 1 at least, amnestic-verbal subtype accounted for the most (n=340, 47.0%), followed by dysexecutive subtype (n=253, 35.0%) and amnestic-visual subtype (n=130, 18%). The amnestic-verbal subtype had significantly more males (amnestic-verbal: 41.8%, dysexecutive: 31.2%, and amnestic-visual: 28.5%), younger subjects (amnestic-verbal: 72.01 years, dysexecutive: 74.43 years, and amnestic-visual: 75.06 years), higher educational years (amnestic-verbal: 11.06 years, dysexecutive: 9.53 years, and amnestic-visual: 9.79 years), lower Clinical Dementia Rating sum of boxes (amnestic-verbal: 1.40, dysexecutive: 1.61, and amnestic-visual: 1.71), and lower Korean-Instrumental Activities of Daily Living score (amnestic-verbal: 0.20, dysexecutive: 0.27, and amnestic-visual: 0.26). Conclusions Three types of MCIs were extracted using SuStaIn. Pathways of MCI deterioration could be different. The amnestic type could be bisected based on whether episodic verbal or visual memory is degraded first.

Donepezil, an acetylcholinesterase inhibitor, is widely used for managing the symptoms of Alzheimer’s disease (AD), yet its clinical response varies widely among individuals. This study aims to investigate the influence of CYP2D6 genetic variants on donepezil concentration, treatment response, and adverse effects in Korean patients with AD dementia. We conducted a longitudinal study involving 76 patients receiving either 5 mg or 10 mg of donepezil. Genetic testing identified 9 CYP2D6 alleles, categorizing patients by metabolizing abilities. Blood sampling for plasma concentrations of donepezil were performed at steady-state. Mini-Mental State Examination (MMSE) were conducted at 12, 24 and 36 months after the initiation of treatment. Adverse events were collected throughout the study period.Donepezil plasma concentrations differed significantly among metabolizer statuses (mean 56.8 ± 27.1 ng/ml in normal metabolizers vs. 69.6 ± 30.1 ng/ml in intermediate metabolizers, p = 0.042), but these differences did not affect cognitive function over three years as assessed by MMSE. Additionally, there was no significant correlation between donepezil plasma concentration and adverse events. Our study is the first to elucidate the associations between CYP2D6 genotype and the concentration, clinical response or adverse events of donepezil in Korean patients with AD dementia. Larger studies are necessary to fully understand the impact of CYP2D6 genetic variants on therapeutic outcomes with donepezil.

Donepezil, an acetylcholinesterase inhibitor, is widely used for managing the symptoms of Alzheimer’s disease (AD), yet its clinical response varies widely among individuals. This study aims to investigate the influence of CYP2D6 genetic variants on donepezil concentration, treatment response, and adverse effects in Korean patients with AD dementia. We conducted a longitudinal study involving 76 patients receiving either 5 mg or 10 mg of donepezil. Genetic testing identified 9 CYP2D6 alleles, categorizing patients by metabolizing abilities. Blood sampling for plasma concentrations of donepezil were performed at steady-state. Mini-Mental State Examination (MMSE) were conducted at 12, 24 and 36 months after the initiation of treatment. Adverse events were collected throughout the study period.Donepezil plasma concentrations differed significantly among metabolizer statuses (mean 56.8 ± 27.1 ng/ml in normal metabolizers vs. 69.6 ± 30.1 ng/ml in intermediate metabolizers, p = 0.042), but these differences did not affect cognitive function over three years as assessed by MMSE. Additionally, there was no significant correlation between donepezil plasma concentration and adverse events. Our study is the first to elucidate the associations between CYP2D6 genotype and the concentration, clinical response or adverse events of donepezil in Korean patients with AD dementia. Larger studies are necessary to fully understand the impact of CYP2D6 genetic variants on therapeutic outcomes with donepezil.

Background: and Purpose: Recognizing cognitive decline patterns in mild cognitive impairment (MCI) is crucial for early screening and preventive interventions. However, studies on the trajectory of individual cognitive functions in MCI are limited. Thus, the purpose of this study was to identify subtypes and stages of cognitive decline in MCI using a machine learning method. Methods: A total of 944 subjects consisting of those who were cognitively normal and those with MCI were enrolled. Fifteen neuropsychological tasks were used in the analysis.The optimal number of subtypes was determined based on the cross-validation information criterion. Fifteen stages of cognitive trajectory were estimated for each subtype. Results: The following three subtypes were identified: amnestic-verbal subtype, dysexecutive subtype, and amnestic-visual subtype. Of 723 (76.6%) subjects who had reached stage 1 at least, amnestic-verbal subtype accounted for the most (n=340, 47.0%), followed by dysexecutive subtype (n=253, 35.0%) and amnestic-visual subtype (n=130, 18%). The amnestic-verbal subtype had significantly more males (amnestic-verbal: 41.8%, dysexecutive: 31.2%, and amnestic-visual: 28.5%), younger subjects (amnestic-verbal: 72.01 years, dysexecutive: 74.43 years, and amnestic-visual: 75.06 years), higher educational years (amnestic-verbal: 11.06 years, dysexecutive: 9.53 years, and amnestic-visual: 9.79 years), lower Clinical Dementia Rating sum of boxes (amnestic-verbal: 1.40, dysexecutive: 1.61, and amnestic-visual: 1.71), and lower Korean-Instrumental Activities of Daily Living score (amnestic-verbal: 0.20, dysexecutive: 0.27, and amnestic-visual: 0.26). Conclusions Three types of MCIs were extracted using SuStaIn. Pathways of MCI deterioration could be different. The amnestic type could be bisected based on whether episodic verbal or visual memory is degraded first.

Background: and Purpose: Recognizing cognitive decline patterns in mild cognitive impairment (MCI) is crucial for early screening and preventive interventions. However, studies on the trajectory of individual cognitive functions in MCI are limited. Thus, the purpose of this study was to identify subtypes and stages of cognitive decline in MCI using a machine learning method. Methods: A total of 944 subjects consisting of those who were cognitively normal and those with MCI were enrolled. Fifteen neuropsychological tasks were used in the analysis.The optimal number of subtypes was determined based on the cross-validation information criterion. Fifteen stages of cognitive trajectory were estimated for each subtype. Results: The following three subtypes were identified: amnestic-verbal subtype, dysexecutive subtype, and amnestic-visual subtype. Of 723 (76.6%) subjects who had reached stage 1 at least, amnestic-verbal subtype accounted for the most (n=340, 47.0%), followed by dysexecutive subtype (n=253, 35.0%) and amnestic-visual subtype (n=130, 18%). The amnestic-verbal subtype had significantly more males (amnestic-verbal: 41.8%, dysexecutive: 31.2%, and amnestic-visual: 28.5%), younger subjects (amnestic-verbal: 72.01 years, dysexecutive: 74.43 years, and amnestic-visual: 75.06 years), higher educational years (amnestic-verbal: 11.06 years, dysexecutive: 9.53 years, and amnestic-visual: 9.79 years), lower Clinical Dementia Rating sum of boxes (amnestic-verbal: 1.40, dysexecutive: 1.61, and amnestic-visual: 1.71), and lower Korean-Instrumental Activities of Daily Living score (amnestic-verbal: 0.20, dysexecutive: 0.27, and amnestic-visual: 0.26). Conclusions Three types of MCIs were extracted using SuStaIn. Pathways of MCI deterioration could be different. The amnestic type could be bisected based on whether episodic verbal or visual memory is degraded first.

Donepezil, an acetylcholinesterase inhibitor, is widely used for managing the symptoms of Alzheimer’s disease (AD), yet its clinical response varies widely among individuals. This study aims to investigate the influence of CYP2D6 genetic variants on donepezil concentration, treatment response, and adverse effects in Korean patients with AD dementia. We conducted a longitudinal study involving 76 patients receiving either 5 mg or 10 mg of donepezil. Genetic testing identified 9 CYP2D6 alleles, categorizing patients by metabolizing abilities. Blood sampling for plasma concentrations of donepezil were performed at steady-state. Mini-Mental State Examination (MMSE) were conducted at 12, 24 and 36 months after the initiation of treatment. Adverse events were collected throughout the study period.Donepezil plasma concentrations differed significantly among metabolizer statuses (mean 56.8 ± 27.1 ng/ml in normal metabolizers vs. 69.6 ± 30.1 ng/ml in intermediate metabolizers, p = 0.042), but these differences did not affect cognitive function over three years as assessed by MMSE. Additionally, there was no significant correlation between donepezil plasma concentration and adverse events. Our study is the first to elucidate the associations between CYP2D6 genotype and the concentration, clinical response or adverse events of donepezil in Korean patients with AD dementia. Larger studies are necessary to fully understand the impact of CYP2D6 genetic variants on therapeutic outcomes with donepezil.

Background: and Purpose: Recognizing cognitive decline patterns in mild cognitive impairment (MCI) is crucial for early screening and preventive interventions. However, studies on the trajectory of individual cognitive functions in MCI are limited. Thus, the purpose of this study was to identify subtypes and stages of cognitive decline in MCI using a machine learning method. Methods: A total of 944 subjects consisting of those who were cognitively normal and those with MCI were enrolled. Fifteen neuropsychological tasks were used in the analysis.The optimal number of subtypes was determined based on the cross-validation information criterion. Fifteen stages of cognitive trajectory were estimated for each subtype. Results: The following three subtypes were identified: amnestic-verbal subtype, dysexecutive subtype, and amnestic-visual subtype. Of 723 (76.6%) subjects who had reached stage 1 at least, amnestic-verbal subtype accounted for the most (n=340, 47.0%), followed by dysexecutive subtype (n=253, 35.0%) and amnestic-visual subtype (n=130, 18%). The amnestic-verbal subtype had significantly more males (amnestic-verbal: 41.8%, dysexecutive: 31.2%, and amnestic-visual: 28.5%), younger subjects (amnestic-verbal: 72.01 years, dysexecutive: 74.43 years, and amnestic-visual: 75.06 years), higher educational years (amnestic-verbal: 11.06 years, dysexecutive: 9.53 years, and amnestic-visual: 9.79 years), lower Clinical Dementia Rating sum of boxes (amnestic-verbal: 1.40, dysexecutive: 1.61, and amnestic-visual: 1.71), and lower Korean-Instrumental Activities of Daily Living score (amnestic-verbal: 0.20, dysexecutive: 0.27, and amnestic-visual: 0.26). Conclusions Three types of MCIs were extracted using SuStaIn. Pathways of MCI deterioration could be different. The amnestic type could be bisected based on whether episodic verbal or visual memory is degraded first.

Donepezil, an acetylcholinesterase inhibitor, is widely used for managing the symptoms of Alzheimer’s disease (AD), yet its clinical response varies widely among individuals. This study aims to investigate the influence of CYP2D6 genetic variants on donepezil concentration, treatment response, and adverse effects in Korean patients with AD dementia. We conducted a longitudinal study involving 76 patients receiving either 5 mg or 10 mg of donepezil. Genetic testing identified 9 CYP2D6 alleles, categorizing patients by metabolizing abilities. Blood sampling for plasma concentrations of donepezil were performed at steady-state. Mini-Mental State Examination (MMSE) were conducted at 12, 24 and 36 months after the initiation of treatment. Adverse events were collected throughout the study period.Donepezil plasma concentrations differed significantly among metabolizer statuses (mean 56.8 ± 27.1 ng/ml in normal metabolizers vs. 69.6 ± 30.1 ng/ml in intermediate metabolizers, p = 0.042), but these differences did not affect cognitive function over three years as assessed by MMSE. Additionally, there was no significant correlation between donepezil plasma concentration and adverse events. Our study is the first to elucidate the associations between CYP2D6 genotype and the concentration, clinical response or adverse events of donepezil in Korean patients with AD dementia. Larger studies are necessary to fully understand the impact of CYP2D6 genetic variants on therapeutic outcomes with donepezil.

Background: and Purpose: Each item in the instrumental activities of daily living (IADL) questionnaire has differential importance to an individual’s life functioning based on gender.However, IADL has mostly been utilized for its total score alone, without gender specificity.We identify the impact of each item on the transition from amnestic mild cognitive impairment (aMCI) to Alzheimer’s disease dementia (ADD), and determine if the impact of each item differs by gender. Methods: Subjects were aMCI or ADD with a global clinical dementia rating of 0.5 or 1. The sample size was 146 men and 154 women. We used logistic regression analysis to determine the effect of each item of IADL on the transition from aMCI to ADD. Results: The odds ratio (OR) for “remembering recent events” had similar values: 27.2 for men, and 27.7 for women. Gender difference was identified in the item with the highest OR value. For women, the “using transportation” item was 63.3, and for men, “conducting financial affairs” was overwhelmingly high at 89.1. Conclusions Functional decline on items with relatively higher ORs may indicate higher probability of a transition from aMCI to ADD. The OR of “conducting financial affairs” was relatively higher for both genders. In terms of gender differences, “conducting home repair” for men, and “using transportation” for women, have relatively higher impact. This study demonstrates that during the transition from aMCI to ADD, each item of IADL shows a staggered decline in functioning, and that this decline is gender-specific.