Use of choline alfoscerate for newly diagnosed patients with Alzheimer’s disease in Korea

doi:10.21203/rs.3.rs-3321042/v1

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Research Article

Use of choline alfoscerate for newly diagnosed patients with Alzheimer’s disease in Korea

https://doi.org/10.21203/rs.3.rs-3321042/v1

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Purpose:

Choline alfoscerate, a cholinergic precursor in the brain, improves dementia-related symptoms. Although it is widely available as a dietary supplement in several countries, including the U.S., the Korean healthcare system has incorporated it into its insurance coverage. Therefore, in this study, we aimed to investigate the utilization status of choline alfoscerate and factors influencing it in patients newly diagnosed with Alzheimer’s disease (AD) using real-world data.

Methods:

We analyzed the Health Insurance Review and Assessment Service research dataset to identify patients ≥ 60 years old who were newly diagnosed with AD. We determined whether the study population was prescribed choline alfoscerate in addition to AD medications (donepezil, rivastigmine, galantamine, and memantine) within 60 d of the initial diagnosis. Moreover, the Cochran–Armitage test was used to confirm the statistical differences in the annual drug utilization trends.

Results:

Among the 330,326 study participants, 99,845 (33.08%) were consuming choline alfoscerate. Its use increased from 15.96% in 2012 to 47.65% in 2019. Factors that positively influenced the use of choline alfoscerate included male sex, MedAid insurance, and osteoarthritis. However, its use tended to decrease in the presence of certain comorbidities (hypertension, congestive heart failure, stroke/transient ischemic attack, chronic kidney disease, and depression).

Conclusion:

Utilization of choline alfoscerate has gradually increased in Korea, in part due to the absence of a disease-modifying therapy for AD and its inclusion in the country’s insurance coverage system. However, its use should be monitored due to the unclear efficacy and risk profile of this drug.

Alzheimer’s disease

Choline alfoscerate

Acetylcholinesterase inhibitors

Memantine

Alzheimer's disease (AD), the most common type of dementia, mainly affects individuals aged ≥ 65 years [1]. According to the World Health Organization Global Health Estimates, AD was the 20th leading cause of death in 2000 but rose to the 7th position in 2019 [2]. This increase highlights the escalating social and economic burden of AD worldwide [3].

Acetylcholinesterase inhibitors (AChEIs) and N-methyl-D-aspartate (NMDA) receptor antagonists are the main pharmacotherapeutic agents for AD. AChEIs enhance the cortical cholinergic function by reversibly inhibiting cholinesterase activity. Currently, three drugs (donepezil, galantamine, and rivastigmine) with similar efficacies are used to treat mild-to-moderate AD [4]. Glutamate overactivation of NMDA in the brain is associated with memory and learning impairments. This process can be reversed by NMDA receptor antagonists [5]. In 2003, the U.S. Food and Drug Administration approved memantine for the treatment of moderate-to-severe AD [6].

However, these AChEIs and memantine are only useful for symptomatic treatment, providing temporary relief from memory and cognitive impairments. They do not target the underlying cause or stop the progression of AD. Therefore, these drugs are not used for disease-modifying therapy (DMT) [7].

Choline alfoscerate (L-alpha-glycerylphosphorylcholine) is a supplemental therapeutic agent for AD, functioning as a common choline compound and acetylcholine precursor in the brain [8]. This drug restores the damaged neurons and increases the release of acetylcholine between synapses, thereby improving memory and cognition [8, 9].

Although the cognitive benefits of choline alfoscerate are widely acknowledged, the lack of robust clinical trials and definitive evidence of its efficacy has limited its use. Interestingly, it is commonly used as a dietary supplement in many countries, including the US, but the Korean healthcare system has taken a distinct approach by including it in its insurance coverage system [10].

Notably, choline alfoscerate ranks first in prescription expenditures in Korea, reaching 152.8 billion Korean won (KRW, approximately 114 million US Dollars) in the first quarter (Q1) of 2023, surpassing that of atorvastatin [11]. This figure represents an 18.4% increase in its expenditure compared with that in the Q1 report of 2022. However, the prescription trends of choline alfoscerate and its influencing factors remain largely unknown. Therefore, in this study, we conducted an in-depth investigation of the utilization trends of choline alfoscerate in Korea using real-world data. Furthermore, we comprehensively analyzed the factors influencing its usage and assessed the consequences of its inclusion in the insurance coverage system.

Data source

Data for this study were obtained from the Korean Health Insurance Review and Assessment Service (HIRA) database (https://opendata.hira.or.kr/home.do). Most Koreans are covered by the National Health Insurance (NHI), which provides comprehensive healthcare services. Under this system, all healthcare institutions submit insurance claims to HIRA for review and approval. Therefore, HIRA has several datasets consisting of de-identified claims information, including patient characteristics, medical treatments, diseases, drug prescriptions, and healthcare facility details [12]. These data are available to researchers for study purposes.

The diagnostic codes used in the dataset were obtained from the Korean Classification of Diseases 6th and 7th revisions (KCD-6 and 7), which are modified version of the International Statistical Classification of Diseases and Related Health Problems 10th Edition (ICD-10) [13]. For drug coding, HIRA Health Insurance Medical Care Expenses and HIRA Drug Ingredient codes, specifically the 2011–2020 versions, were used (Appendix 1) [14].

Study population

Study population consisted of individuals aged ≥ 60 years who were newly diagnosed with AD between 2012 and 2019 based on KCD codes (F00 and G30). Patients were included if they had a prescription record for any AChEI (donepezil, galantamine, or rivastigmine) or memantine within 60 d of the first date of AD diagnosis (index date). Patients with a history of AD diagnosis or recent use of AChEIs, memantine, or choline alfoscerate within the one-year period preceding the date of the first diagnosis were excluded from the study.

Data on the age, sex, insurance types (NHI and Medical Aid [MedAid]), and comorbidities of patients as well as characteristics of healthcare institutions were assessed to define the covariates. All patients were categorized into five age groups: 60–64, 65–69, 70–74, 75–79 and ≥ 80 years old. Healthcare institutions were grouped according to their geographical regions: metropolitan, urban, and rural. Furthermore, hospitals were classified based on their type: tertiary hospitals, general hospitals, and clinics. Physicians were also classified based on their specialties: general physicians, internal medicine (IM), family medicine (FM), rehabilitation medicine (RM), neurology, and psychiatry. To simplify the analysis, we combined IM, FM, and RM and analyzed them as a single group. Patient comorbidities were investigated by referencing the major chronic diseases of the elderly in Korea based on the 2020 National Survey of Living Conditions and Welfare Needs of Older Koreans by the Ministry of Health and Welfare (Appendix 1) [15].

Choline alfoscerate utilization

We identified patients who were prescribed choline alfoscerate within 60 d of the index date. The utilization of choline alfoscerate was defined as the outcome variable, and patients were categorized into two groups: patients taking choline alfoscerate and those not taking choline alfoscerate.

Statistical analyses

Categorical variables, including the underlying characteristics of the patients, such as sex, age group, insurance type, comorbidities, AD drug type, region, location, and type of medical institution, and annual choline alfoscerate usage, were expressed as absolute values and percentages. These variables were compared using a chi-square test.

Multiple logistic regression analyses were performed to identify the factors affecting the use of choline alfoscerate. To evaluate the goodness of fit of the logistic model, C-statistics and the Hosmer–Lemeshow test were performed. In addition, the trends of choline alfoscerate use across the years were determined using the Cochran–Armitage Trend test.

Data and statistical analyses were performed using the R software (version 3.5.1; R Foundation for Statistical Computing, Vienna, Austria). Statistical significance was set at p < 0.05.

Characteristics of the study population

HIRA database includes the data of 1,155,699 patients diagnosed with AD between 2012 and 2019. Among them, 1,131,046 patients were aged ≥ 60 years and 548,896 had no prior AD diagnosis or drug use in the previous year. After further exclusion, a final cohort of 324,277 patients administered AD drugs within 60 d of the index date was included in the analysis.

More than half of the study population consisted of individuals aged ≥ 80 years (51.22%), followed by those aged 75–79 years (24.88%) and 70–74 years (14.49%). Female patients accounted for more than twice the number of male patients. Most patients were covered by NHI (89.44%). The most prevalent comorbidity was hypertension (64.01%), followed by osteoarthritis (45.18%), hyperlipidemia (42.56%), and diabetes mellitus (34.71%).

Most patients (94.33%) received AChEIs as monotherapy, which is commonly recommended for mild-to-moderate AD. The prescription rates for memantine/AChEI combination therapy and memantine monotherapy were low (3.38 and 2.29%, respectively).

General hospitals were the most common treatment facilities (41.43%), followed by clinics (24.38%), and hospitals (20.70%). In terms of physician specialties, most were in neurology (56.79%), followed by psychiatry (26.29%) and the combined IM/FM/RM group (8.50%; Table 1).

Table 1

Demographic characteristics of the study population.
	Study Population		Choline Alfoscerate Users
	N	(%)	N	(%)	P-value
Overall	324,277	100	99,845	30.79
Age (years)					< 0.001
60–64	9,282	2.86	2,953	31.81
65–69	21,240	6.55	6,583	30.99
70–74	46,980	14.49	13,921	29.63
75–79	80,683	24.88	24,961	30.94
≥ 80	166,092	51.22	51,427	30.96
Sex					< 0.001
Male	98,358	30.33	31,681	32.21
Female	225,919	69.67	68,164	30.17
Insurance					< 0.001
NHI	290,040	89.44	88,719	30.59
MedAid	34,237	10.56	11,126	32.50
Coexisting Disease
Hypertension					< 0.001
No	116,693	35.99	36,920	31.64
Yes	207,584	64.01	62,925	30.31
Diabetes mellitus					0.580
No	211,706	65.29	65,254	30.82
Yes	112,571	34.71	34,591	30.73
Hyperlipidemia					< 0.001
No	186,271	57.44	56,319	30.24
Yes	138,006	42.56	43,526	31.54
Coronary artery disease					< 0.001
No	258,767	79.80	80,250	31.01
Yes	65,510	20.20	19,595	29.91
Congestive heart failure					0.153
No	285,807	88.14	88,122	30.83
Yes	38,470	11.86	11,723	30.47
Stroke/TIA					< 0.001
No	276,313	85.21	87,379	31.62
Yes	47,964	14.79	12,466	25.99
Osteoarthritis					< 0.001
No	177,757	54.82	53,665	30.19
Yes	146,520	45.18	46,180	31.52
Rheumatoid arthritis					0.254
No	308,679	95.19	95,107	30.81
Yes	15,598	4.81	4,738	30.38
Chronic kidney disease					< 0.001
No	314,814	97.08	97,212	30.88
Yes	9,463	2.92	2,633	27.82
COPD					0.168
No	263,166	81.16	81,171	30.84
Yes	61,111	18.84	18,674	30.56
Depression					< 0.001
No	270,272	83.35	84,209	31.16
Yes	54,005	16.65	15,636	28.95
Insomnia					< 0.001
No	280,465	86.49	87,046	31.04
Yes	43,812	13.51	12,799	29.21
Prescription type					< 0.001
AChEI	305,873	94.33	93,346	30.52
Memantine	7,454	2.29	1,935	25.96
COMBI*	10,950	3.38	4,564	41.68
Region					< 0.001
Metropolitan	119,248	36.77	33,888	28.42
Urban area	67,631	20.86	19.690	29.11
Rural area	137,398	42.37	46,267	33.67
Level of healthcare facility					< 0.001
Tertiary hospitals	22,318	6.88	4,237	18.99
General hospitals	134,359	41.43	47,283	35.19
Hospitals	67,116	20.70	24,324	36.24
Clinics	79,055	24.38	20,670	26.15
Others	21,429	6.61	3,331	15.54
Medical department					< 0.001
General physician	1,355	0.42	282	20.81
IM/FM/RM*	27,573	8.50	6,810	24.70
Neurology	184,165	56.79	64,639	35.10
Psychiatry	85,267	26.29	18,122	21.25
Others	25,917	7.99	9,992	38.55
Year					< 0.001
2012	34,442	10.62	5,496	15.96
2013	38,228	11.79	6,843	17.90
2014	37,930	11.70	8,382	22.10
2015	39,046	12.04	9,643	24.70
2016	40,260	12.42	12,491	31.03
2017	40,697	12.55	15,323	37.65
2018	45,837	14.14	18,874	41.18
2019	47,837	14.75	22,793	47.65
NHI, National Health Insurance; AChEI, acetylcholinesterase inhibitor; TIA, transient ischemic attack; COPD, chronic obstructive pulmonary disease; COMBI, acetylcholinesterase inhibitor; MEM, concomitant memantine use; IM, internal medicine; FM, family medicine; RM; rehabilitation medicine

Choline alfoscerate utilization

Among the 330,326 patients prescribed AD medication within 60 d of the index date, 99,845 (33.08%) were taking choline alfoscerate as an additional medication (Fig. 1).

Choline alfoscerate utilization was higher in males than in females (32.21 vs. 30.17%; p < 0.001), and compared to the 60–64 year old age group, the use of choline alfoscerate was slightly lower in the other age groups. Patients covered by the NHI were prescribed choline alfoscerate at a lower frequency than those covered by MedAid (30.59 vs. 32.50%; p < 0.001).

Choline alfoscerate use was higher in patients with hyperlipidemia and osteoarthritis and lower in those with hypertension, coronary artery disease, stroke/TIA, chronic kidney disease, depression, and insomnia. Choline alfoscerate use was the highest in the memantine/AChEI combination therapy group (41.68%), followed by the AChEI monotherapy (30.52%) and memantine monotherapy (25.96%) groups.

Choline alfoscerate utilization was higher use in rural areas (33.67%) than in the metropolitan areas (28.42%). Moreover, highest utilization of choline alfoscerate was observed in hospitals (36.24%) and the lowest in other facilities, such as nursing hospitals or health centers (15.54%). Choline alfoscerate was most commonly prescribed by specialists categorized as “others” (38.55%), followed by those in neurology (35.09%), IM/FM/RM (24.70%), and psychiatry (21.25%; Table 1).

Factors affecting the use of choline alfoscerate

The results of the multiple logistic regression analyses are presented in Table 2. Patients aged ≥ 80 years had lower odds of using choline alfoscerate compared to the reference age group of 60–64 years (odds ratio [OR] = 0.910; 95% confidence interval [CI] = 0.868–0.954). Women were less likely to use choline alfoscerate than men (OR = 0.949; 95% CI = 0.933–0.966), and those covered under MedAid exhibited higher odds of using choline alfoscerate than those covered under NHI (OR = 1.069; 95% CI = 1.042–1.097).

Table 2

Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) from multiple logistic regression analyses of choline alfoscerate prescription.
	Choline alfoscerate utilization
	OR	95%CI	p-value
Age (years)
60–64(R)
65–69	0.998	0.945–1.055	0.954
70–74	0.989	0.941–1.041	0.679
75–79	0.971	0.925–1.020	0.239
≥80	0.910	0.868–0.955	<0.001
Sex
Male(R)
Female	0.949	0.933–0.966	< 0.001
Insurance
NHI(R)
MedAid	1.069	1.042–1.097	< 0.001
Coexisting Disease
Hypertension
No(R)
Yes	0.957	0.940–0.975	< 0.001
Diabetes mellitus
No(R)
Yes	0.999	0.981–1.017	0.885
Hyperlipidemia
No(R)
Yes	0.993	0.974–1.011	0.426
Coronary artery disease
No(R)
Yes	0.986	0.965–1.008	0.204
Congestive heart failure
No(R)
Yes	0.957	0.932–0.982	< 0.001
Stroke/TIA*
No(R)
Yes	0.795	0.777–0.814	< 0.001
Osteoarthritis
No(R)
Yes	1.051	1.034–1.069	< 0.001
Reumatoid Arthritis
No(R)
Yes	1.018	0.980–1.056	0.354
Chronic kidney disease
No(R)
Yes	0.797	0.759–0.836	< 0.001
COPD*
No(R)
Yes	1.005	0.985–1.026	0.624
Depression
No(R)
Yes	0.932	0.911–0.953	< 0.001
Insomnia
No(R)
Yes	0.983	0.960–1.007	0.159
Prescription type
AChEI(R)
Memantine	0.907	0.858–0.958	< 0.001
COMBI*	1.298	1.246–1.352	< 0.001
Region
Metropolitan(R)
City	1.024	1.002–1.047	0.035
Rural	1.283	1.260–1.306	< 0.001
Level of healthcare facility
Tertiary hospitals(R)
General hospitals	1.833	1.767–1.902	< 0.001
Hospitals	1.996	1.920–2.076	< 0.001
Clinics	1.793	1.722–1.867	< 0.001
Others	0.736	0.698–0.775	< 0.001
Medical department*
General physician(R)
IM/FM/RM*	0.771	0.672–0.888	< 0.001
Neurology	1.253	1.093–1.439	0.001
Psychiatry	0.568	0.495–0.653	< 0.001
Others	1.382	1.205–1.591	< 0.001
Year
2012(R)
2013	1.163	1.118–1.209	< 0.001
2014	1.515	1.458–1.574	< 0.001
2015	1.736	1.672–1.802	< 0.001
2016	2.393	2.307–2.482	< 0.001
2017	3.244	3.130–3.363	< 0.001
2018	3.713	3.585–3.847	< 0.001
2019	4.804	4.639–4.975	< 0.001
c statistic	0.697
p-value of Hosmer-Lemeshow test	< 0.001
NHI, National Health Insurance; AChEI, acetylcholinesterase inhibitor; TIA, transient ischemic attack; COPD, chronic obstructive pulmonary disease; COMBI, acetylcholinesterase inhibitor; MEM, concomitant memantine use; IM, internal medicine; FM, family medicine; RM; rehabilitation medicine

Osteoarthritis was associated with a higher likelihood of choline alfoscerate use (OR = 1.051; 95% CI = 1.034–1.069) compared to other comorbidities. Conversely, stroke/TIA was the main negative influencing factor (OR = 0.795; 95% CI = 0.777–0.814), followed by chronic kidney disease (OR = 0.797; 95% CI = 0.759–0.836), depression (OR = 0.932; 95% CI = 0.911–0.952), hypertension (OR = 0.957; 95% CI = 0.940–0.975), and congestive heart failure (OR = 0.957; 95% CI = 0.932–0.982) for choline alfoscerate use.

Patients receiving AChEI/memantine combination therapy were more likely to use choline alfoscerate (OR = 1.298; 95% CI = 1.248–1.3529) than those receiving memantine monotherapy (OR = 0.907; 95% CI = 0.858–0.958).

Patients in rural areas had a higher OR for being prescribed choline alfoscerate (OR = 1.283; 95% CI = 1.259–1.306) than those in metropolitan areas. Patients in urban areas also had a slightly higher OR (OR = 1.024; 95% CI = 1.002–1.047) of utilizing choline alfoscerate compared to their metropolitan counterparts.

Regarding healthcare facilities, the odds of being prescribed choline alfoscerate were higher in hospitals (OR = 1.996; 95% CI = 1.920–2.076) and general hospitals (OR = 1.833; 95% CI = 1.767–1.902) than in tertiary hospitals.

Physician specialties played a role in prescription patterns, with neurology having significantly higher odds of prescribing choline alfoscerate (OR = 1.253; 95% CI = 1.093–1.439) than psychiatry (OR = 0.568; 95% CI = 0.495–0.653) and IM/FM/RM group (OR = 0.771; 95% CI = 0.672–0.888).

Notably, the odds of receiving a prescription for choline alfoscerate increased steadily throughout the study period. In 2019, patients with AD exhibited four-fold greater odds of utilizing choline alfoscerate (OR = 4.828; 95% CI = 4.662–5.000) than those in 2012 (Table 2).

Initial prescription trends of choline alfoscerate by year

The number of individuals who started choline treatment within 60 d of their first AD diagnosis showed a remarkable upward trajectory. In 2012, the proportion of patients starting choline alfoscerate therapy was 15.96%, which increased to 47.65% in 2019. To determine the significance of this trend, we performed the Cochran–Armitage test and observed a statistically significant difference in choline alfoscerate utilization across the years (p < 0.001; Fig. 2).

This study used nationally representative real-world data to investigate the use of choline alfoscerate in patients newly diagnosed with AD. We observed a significant increase in the number of choline alfoscerate users over the duration of the study. Choline alfoscerate utilization was observed in 33.08% of the total study population, and this percentage consistently increased from 15.96% in 2012 to 47.65% in 2019.

In a previous study that examined the prescription patterns of choline alfoscerate in patients with AD using one year claim data from 2016 (HIRA-NPS data), 30.9% of patients were prescribed choline alfoscerate at least once in 2016 [16]. Remarkably, this figure closely aligns with the results of our study (31.03%), even though our study specifically focused on patients newly diagnosed with AD.

Increased utilization of choline alfoscerate can be attributed to the insufficient therapeutic options available for treating AD. Researchers worldwide have made numerous attempts to develop DMT targeting various AD pathophysiological mechanisms, including intracellular neurofibrillary tangles, extracellular amyloid β plaques, and approaches involving neuroprotection, anti-inflammation, and metabolic efficacy [17]. However, various AD drug candidates do not reach the clinical treatment stage and struggle to overcome their limitations [17].

Two monoclonal antibodies, aducanumab and lecanemab, both targeting amyloid beta, have been approved for the treatment of patients with early AD with confirmed brain amyloid pathology [18]. However, despite their rapid approval, their utilization has been limited by narrow therapeutic indications, cost concerns, and uncertainty about their efficacy and safety [19]. These accelerated conditional approvals reflect the urgent need for new treatment methods for AD [20].

Increasing utilization and lack of proven effectiveness of choline alfoscerate are serious concerns that warrant a reevaluation of its efficacy in Korea [21–23]. The Korean Ministry of Health and Welfare has requested that choline alfoscerate manufacturing companies conduct a phase IV clinical trial to evaluate its efficacy and safety in patients with mild-to-moderate AD, with data submission expected by 2025 [23]. Therefore, a cautious prescription of choline alfoscerate is warranted until more convincing evidence emerges.

This study identified the factors affecting the utilization of choline alfoscerate. Age group analysis revealed that as age increased, the odds of choline alfoscerate use decreased, especially in patients aged > 80 years. The active use of choline alfoscerate from an early stage of the disease can be attributed to studies showing its effectiveness in improving cognitive function in mild-to-moderate AD [9, 24, 25].

We found that female patients were less likely to be prescribed choline alfoscerate compared than male patients, consistent with a previous report [16]. AD-related cognitive decline is faster and more severe in women than in men at the time of initial diagnosis, which may contribute to lower utilization of choline alfoscerate in women [26].

Patients covered under MedAid exhibited higher utilization of choline alfoscerate than those covered under the NHI. This can be attributed to increased medical service utilization due to low co-payments [27].

Variations in choline alfoscerate utilization were observed among different comorbidities. Osteoarthritis was associated with a higher likelihood of choline alfoscerate utilization, possibly because of its involvement in neuroinflammation and its role as a risk factor for accelerating AD [28]. Conversely, hypertension, congestive heart failure, stroke/TIA, chronic kidney disease, and depression were identified as negative influencing factors. These conditions are known risk factors for AD [29]. The low preference for and utilization of choline alfoscerate among four patients with multiple chronic diseases already taking multiple medications (polypharmacy) [30] can explain these findings.

Lower odds ratio of congestive heart failure in choline alfoscerate use can be attributed to the potential risks associated with increased acetylcholine accumulation and parasympathetic nerve-mediated heart rate reduction, which may be of concern in patients with heart failure [31–33]. Trimethylamine N-oxide, a phosphatidylcholine metabolite, is associated with increased atherosclerotic plaque formation and cardiovascular disease risk [34].

This study has several limitations. First, we used ICD or KCD codes to identify patients with AD, but some diagnosis codes may have been incorrect or missed within the claims data. Second, information regarding physical characteristics (e.g., age, height, weight, and blood pressure), socioeconomic status (e.g., income and education), and health behaviors (e.g., drinking, smoking, and exercise) was not included in this study. This may have affected our analysis of the influence of various risk factors. Finally, prescription data may not accurately reflect medication adherence, which may have affected the actual utilization of drugs by patients.

Despite these limitations, this study has a significant advantage. As choline alfoscerate is used as a non-prescription drug or nutritional supplement in most countries, this study outlines a method to examine the utilization of choline alfoscerate in the absence of a fundamental treatment strategy for AD using nationally representative claims data.

In conclusion, use of choline alfoscerate in Korea has consistently increased over the years due to the absence of DMT for AD and its inclusion in the country’s insurance coverage system. However, its use is limited by the unclear efficacy and risk profile of this drug. Positive factors influencing the utilization of choline alfoscerate included MedAid insurance coverage, osteoarthritis, area and level of institutions, use of combination therapy with AChEIs and memantine, and prescription by neurology specialists. Negative factors affecting its utilization included advanced age, female sex, hypertension, congestive heart failure, stroke/TIA, chronic kidney disease, depression, use of memantine, and prescription by psychiatry specialists.

Acknowledgments

The Health Insurance Review and Assessment Service research data (M20220517996) was used in this study. However, the results are not influenced by the Ministry of Health and Welfare or HIRA.

Competing Interests

The authors declare no potential conflicts of interest related to the research, authorship, and/or publication of this article.

Funding

This study was supported by the National Research Foundation of Korea (NRF) grant funded by the Korean Government (MSIT; grant no. 2021R1G1A10938361262182065300102).

Financial interests

Non-financial interests

Ethics approval

This study was performed using a HIRA dataset that did not contain any personal patient information and was exempt from review by the Institutional Review Board of Pusan National University College in Korea (PNU IRB/2022_46_HR).

Consent to participate

Not applicable

Consent to publish

Not applicable

Data availability

The dataset used in this study can be accessed using the Health Insurance Review and Assessment website (https://opendata.hira.or.kr).

Contributions of Authors

YHK and NKJ conceived and designed the study; YHK and NKJ performed the analysis; YHK drafted the manuscript; all authors participated in writing the manuscript and approved the final version to be submitted for publication.

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Use of choline alfoscerate for newly diagnosed patients with Alzheimer’s disease in Korea

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Abstract

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Introduction

Materials and Methods

Data source

Study population

Choline alfoscerate utilization

Statistical analyses

Results

Characteristics of the study population

Choline alfoscerate utilization

Factors affecting the use of choline alfoscerate

Initial prescription trends of choline alfoscerate by year

Discussion

Conclusion

Declarations

References

Additional Declarations

Supplementary Files

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