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.

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: 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.

Objective: It has been reported that depressive symptoms in older adults are different from those in younger adults, especially when accompanied by cognitive decline. However, few studies have investigated the network structure of depressive symptoms in this population. Methods: The participants consisted of 627 older adults (>60 yr) who were diagnosed with mild cognitive impairment (MCI) or early stage dementia. Among them, 36.7% were male and the mean age was 76.20±7.71 years. The Korean form of Geriatric Depression Scale (KGDS) was used to evaluate their depressive symptoms and network analyses were performed using bootnet R-package to identify the central features among depressive symptoms. Results: Of all the KGDS items, we found that KGDS 2 (often feel helpless) had the highest node strength followed by KGDS 21 (in good spirits), KGDS 14 (not confident at all), and KGDS 15 (cheerful and happy). In terms of node betweenness, KGDS 2 also showed the highest value. The edge weights of edges connected to node KGDS 2 were strongest in KGDS 3 (restless and fidgety) and KGDS 28 (easily get tired). Conclusion In this study, we presented which symptoms are central among the elderly with MCI and early stage dementia. This result not only increases the understanding of depressive symptoms in this group but would also help determine target symptoms in the treatment program.