Abstract
Background
Cognitive decline often follows human immunodeficiency virus (HIV) infection. The objective of this study was to explore the factors present at HIV diagnosis associated with the risk of incident dementia.
Methods
A longitudinal observational study was conducted using a nationwide claim database (2008–2021). A cohort was designed using new diagnosis of HIV infection with antiretroviral therapy. Included in the analysis were individuals aged over 40, with > 3-year follow-up and without a diagnosis of dementia within 2 months post-HIV diagnosis. Dementia was defined as diagnosis and prescription of anti-dementia medication. Cox proportional hazards regression models assessed the association between baseline characteristics and the risk of incident dementia.
Results
Among the 13,289 HIV-infected cohort, 3,929 met the inclusion criteria. The median age was 45 (interquartile range [IQR], 15), and 90.9% were male. During the median follow-up period of 7.6 (IQR, 5.0) years, dementia developed in 114 patients, with cumulative incidence reaching 4% at the 10-year follow-up. The development of dementia was associated with age at diagnosis ≥ 50 (hazard ratio [HR], 2.31; 95% confidence interval [CI], 1.51–3.53), low socioeconomic status (HR, 3.50; 95% CI, 2.22–5.52), and acquired immune deficiency syndrome (AIDS) status at diagnosis (HR, 2.05; 95% CI, 1.38–3.03).
Conclusion
This study underscores the importance of age at HIV diagnosis, socioeconomic status, and AIDS status as determinants of the risk of incident dementia among people living with HIV.
Keywords: Human Immunodeficiency Virus, Acquired Immune Deficiency Syndrome, Dementia, Vascular Dementia
Graphical Abstract
INTRODUCTION
Cognitive impairment is a prevalent comorbidity among individuals living with human immunodeficiency virus (HIV).1 A subset of cognitive impairments, designated as HIV-associated neurocognitive disorders (HAND), encompasses asymptomatic neurocognitive impairment, mild neurocognitive disorder, or HIV-associated dementia (HAD), categorized by the severity of neuropsychological test performance and activities of daily living.2,3 HAD is predominantly observed in advanced HIV infection,4 and its prevalence tends to decrease with the widespread use of combined antiretroviral therapy (ART).5,6
However, compared to individuals without HIV infection, people living with HIV still have a higher risk of developing dementia.7,8 Furthermore, as HIV infection has shifted from a life-limiting disease to a manageable chronic condition,9 and the population of older adults living with HIV is expected to continue rising annually by 2%,10,11 the risk of multiple comorbid conditions, including cognitive decline, is increasing.12,13
Possible links between HIV and dementia have been observed. Autopsy studies showed the prevalence of Alzheimer’s disease (AD) pathology in the brains of patients with HIV infection,14,15 and in-vivo imaging studies showed evidence of β-amyloid (Aβ) deposition in cases of HIV population.16,17,18 Several underlying mechanisms linking AD and HIV have been proposed: increased Aβ oligomers and neuritic plaque formation by HIV,19 and accelerated aging process by HIV infection.20 Vascular dementia (VaD) has also been linked with HIV infection. The increased risk of cardiovascular and cerebrovascular disease associated with HIV can contribute to the development or exacerbation of VaD.21,22,23,24 Furthermore, while ART prolongs patient lifespan and yields positive outcomes, concerns about potential neurotoxicity due to long-term exposure to ART persist.25
Understanding the clinical factors associated with incident dementia among HIV-infected population could help manage and prevent those in high-risk groups. Although risk factor for HAND have been investigated, including uncontrolled HIV infection and aging,10 those associated with incident dementia remained elusive. Previous studies suggested those at risk of developing dementia among HIV populations, such as lower CD4+ T lymphocyte count26 and cerebrospinal fluid or imaging biomarkers suggestive of AD.16,27 However, a longitudinal cohort study needs to be conducted to confirm the risk factors. Furthermore, the challenge lies in distinguishing between HAD and other dementia in this population.27,28
In this study, we used a nationwide longitudinal cohort of people living with HIV based on claim database to elucidate the association between dementia and clinical characteristics, including age, sex, socioeconomic status, and prolonged exposure to HIV infection, by using acquired immune deficiency syndrome (AIDS) status as a surrogate marker. By using both diagnosis and prescription for anti-dementia medication, we focused on the risk of developing dementia that requires symptomatic treatment.
METHODS
Study design and data source
Utilizing nationwide claims data from Korea, we conducted a longitudinal cohort study to assess the risk of dementia in individuals newly diagnosed with HIV infection, identified through diagnosis codes and prescription records.29,30 In Korea, approximately 97% of the population is registered under the obligatory National Health Insurance Service (NHIS), while the remaining 3% is covered by the National Medical Aid (NMA). NMA is divided into Type I and Type II categories based on economic need and ability to work. Type I provides full coverage for those who are socially deprived and unable to work, while Type II offers partial support for financially disadvantaged individuals who are capable of working.31 All medical utilization within NHIS and NMA is closely monitored for reimbursement, and health facilities are responsible for submitting claims for insurance reimbursement. The medical data collected by NHIS and NMA are accessible through the National Health Information Database (NHID).32 As healthcare related to HIV infection is covered by this insurance system, all pertinent healthcare information can be identified through claims data.30
Study population
The study cohort consisted of 13,289 participants enrolled between 2008 and 2021 who met the following conditions30: 1) received HIV-related diagnosis using the Korean Standard Classification of Disease Version 7, a modified version of the International Statistical Classification of Disease and Related Health Problems, 10th Revision, Clinical Modification (ICD-10 CM); 2) underwent essential laboratory tests for HIV infection, such as T cell subset analysis, HIV RNA quantification, and HIV drug resistance mutation testing in accordance with HIV/AIDS guidelines; and 3) were prescribed ART. Participants for this study needed to be 1) aged 40 or older at diagnosis; 2) followed up for over 3 years; and 3) not diagnosed with dementia at the time of HIV diagnosis or within two months following the diagnosis. The primary objective of this study is to investigate dementia epidemiology in the HIV-infected population rather than HAD epidemiology. As HAD is predominantly observed in advanced HIV-infected patients and typically stabilizes upon commencing ART, nearly all HAD cases manifest within a few months of HIV diagnosis. Thus, we excluded individuals whose dementia was confirmed within two months after HIV diagnosis to rule out HAD cases.
Ascertainment of neurodegenerative dementia
Neurodegenerative dementia was defined using the ICD-10 code (Supplementary Table 1). In brief, our scope encompassed AD, VaD, alcohol-related dementia, frontotemporal dementia, Lewy body dementia, and Creutzfeldt-Jakob disease. To validate the diagnosis, we further used prescription claim codes for drugs used for dementia, including anticholinesterase inhibitors (AChEi; donepezil, galantamine, and rivastigmine) and N-methyl-D-aspartate (NMDA) receptor antagonist (memantine). The NHIS mandates cognitive and clinical assessments for the prescription of AChEi and memantine: a Mini-Mental State Examination (MMSE) score ≤ 26 and one of Clinical Dementia Rating (CDR) ≥ 1 or Global Deterioration Scale (GDS) ≥ 3 are required for AChEi prescription, whereas an MMSE score ≤ 20 and one of CDR ≥ 2 or GDS ≥ 4 are necessary for memantine prescription. By requiring both a diagnosis and anti-dementia drugs, we focused on dementia manifesting in symptomatic stages treated with medication. For the diagnosis of VaD, a diagnosis of stroke is further required.
Definition of covariates
Age at diagnosis was categorized into 5-year gaps starting from zero. The baseline status of AIDS was defined as follows: with an AIDS-defining illness (Supplementary Table 1),33 or with a prophylactic dosage of trimethoprim/sulfamethoxazole or dapsone to prevent opportunistic infections such as pneumocystis pneumonia, indicating CD4+ T cell counts < 200/mm3.34 Health insurance type served as a proxy for socioeconomic status, as coverage by the NMA is determined by low income status. Comorbidities such as hypertension, dyslipidemia, diabetes mellitus, myocardial infarction, stroke, and syphilis were identified using ICD-10 codes (Supplementary Table 1).
Statistical analysis
Baseline characteristics were compared using Kruskal-Wallis tests, or chi-square tests as appropriate. Cumulative incidence of dementia was estimated and plotted using Kaplan-Meier method. Univariable and multivariable Cox proportional regression analysis were used to determine hazard ratios (HRs) and 95% confidence intervals (CIs) of age at diagnosis, sex, socioeconomic status, and AIDS at diagnosis on the incident dementia after adjusting for comorbidities including hypertension, diabetes mellitus, dyslipidemia, myocardial infarction, stroke, and syphilis. To evaluate whether the effects of predictors on the risk of dementia differ by the type of dementia, we conducted sensitivity analysis after classifying dementia by VaD or non-VaD. As a significant interaction effect between age and AIDS at diagnosis existed, subgroup analysis stratified by AIDS at baseline was conducted. HRs were calculated by sex, age at diagnosis (< 50 and ≥ 50), and socioeconomic status after adjustment of comorbidities (hypertension, diabetes mellitus, dyslipidemia, myocardial infarction, stroke, and syphilis). The interaction effect between age and AIDS at diagnosis was plotted using a restricted cubic spline curve analysis after adjusting for sex, insurance type, and comorbidities. All analyses were conducted in R version 3.5.1 (R Foundation for Statistical Computing, Vienna, Austria).
Ethics statement
Written informed consent was waived due to the use of an existing secondary database, and the Institutional Review Board (IRB) of the Seoul Metropolitan Government-Seoul National University Boramae Medical Center approved this study (IRB No. 07-2017-8/052).
RESULTS
In total, 3,929 people living with HIV were included in the longitudinal analysis (Fig. 1). The median age (interquartile range, IQR) at diagnosis was 45 (15) years, with 3,573 individuals (90.9%) being male (Table 1). At enrollment, 47.3% of the patients (n = 1,860) were in an AIDS status. Insurance type of NMA, surrogate marker of low socioeconomic status, accounted for 6.6% of the patients (n = 261). During a median follow-up of 7.6 (5.0) years, a total of 114 individuals (2.9%) were diagnosed with dementia and prescribed anti-dementia medication. The cumulative incidence of dementia among people living with HIV showed continuous increase of all-cause dementia, reaching 4% at the 10-year follow-up, and incidence of VaD and non-VaD was similar (Fig. 2).
Fig. 1. Flowchart of the study population selected for analysis.
HIV = human immunodeficiency virus.
Table 1. Baseline characteristics of the study population.
| Characteristics | All participants (N = 3,929) | |
|---|---|---|
| Age at diagnosis, yr | Median (IQR) | 45 (15) |
| Follow-up, yr | Median (IQR) | 7.6 (5.0) |
| Male | No. (%) | 3,573 (90.9) |
| Low socioeconomic statusa | No. (%) | 261 (6.6) |
| AIDS at baseline | No. (%) | 1,860 (47.3) |
| Hypertension | No. (%) | 1,060 (27.0) |
| Diabetes | No. (%) | 1,245 (31.7) |
| Dyslipidemia | No. (%) | 2,167 (55.2) |
| Myocardial infarction | No. (%) | 61 (1.6) |
| Stroke | No. (%) | 224 (5.7) |
| Syphilis | No. (%) | 971 (24.7) |
Results from the Kruskal-Wallis test or chi-square test are presented, as appropriate.
IQR = interquartile range, AIDS = acquired immune deficiency syndrome.
aInsurance type was used for surrogate marker of socioeconomic status.
Fig. 2. Cumulative incidence of dementia among people living with HIV. Cumulative incidence of dementia was estimated using the Kaplan-Meier method. The development of dementia was identified when the diagnosis of dementia occurred more than 2 months after the diagnosis of HIV infection, and anti-dementia medications were prescribed.
HIV = human immunodeficiency virus.
Cox regression analysis with restricted cubic splines showed that age at diagnosis was associated with an increased risk of all-cause dementia after 50 years old (Supplementary Fig. 1). In univariable Cox regression analysis, the risk of all-cause dementia was associated with age ≥ 50 at diagnosis (HR, 2.41; 95% CI, 1.59–3.64), female sex (HR, 1.75; 95% CI, 1.04–2.95), NMA insurance type (HR, 3.53; 95% CI, 2.24–5.55), and AIDS at diagnosis (HR, 2.20; 95% CI, 1.49–3.26) after adjusting for comorbidities (Table 2). In multivariable Cox regression analysis, age ≥ 50 at diagnosis, low socioeconomic status, and AIDS at diagnosis were independently associated with an increased risk of dementia.
Table 2. HRs for dementia by different characteristics.
| Characteristics | Univariable analysis | Multivariable analysis | ||
|---|---|---|---|---|
| HR (95% CI) | P | HR (95% CI) | P | |
| Age at diagnosis ≥ 50 yr | 2.24 (1.48–3.41) | < 0.001 | 2.31 (1.51–3.53) | < 0.001 |
| Female | 1.66 (0.99–2.80) | 0.056 | 1.45 (0.85–2.46) | 0.170 |
| Low socioeconomic statusa | 3.43 (2.18–5.41) | < 0.001 | 3.50 (2.22–5.52) | < 0.001 |
| AIDS at diagnosis | 2.11 (1.43–3.13) | < 0.001 | 2.05 (1.38–3.03) | < 0.001 |
All Cox proportional hazards regression models were adjusted for baseline comorbidities (hypertension, diabetes mellitus, dyslipidemia, myocardial infarction, stroke, and syphilis).
HR = hazard ratio, CI = confidence interval, AIDS = acquired immune deficiency syndrome.
aInsurance type was used for surrogate marker of socioeconomic status.
A significant interaction effect between age ≥ 50 and AIDS at diagnosis on the risk of all-cause dementia was observed after adjusting for comorbidities (Supplementary Table 2). When the participants were subdivided by baseline characteristics, the association between AIDS at diagnosis and dementia was considerably stronger among individuals with age < 50 at diagnosis compared to those with age ≥ 50 (< 50 years: HR, 5.33; 95% CI, 2.21–12.88 vs. ≥ 50 years: HR, 1.60; 95% CI, 1.02–2.51; P for interaction = 0.02) (Table 3). The association was not modified by sex (P for interaction = 0.38) and insurance type (P for interaction = 0.30). Similar relationships were observed when restricted cubic splines were used to treat age as continuous variables for those with and without AIDS (Fig. 3). When the participants were further divided by AIDS status at diagnosis, increasing age was associated with the risk of dementia after age greater than approximately 50 and 60 years old in those with AIDS and without AIDS, respectively (Supplementary Fig. 1).
Table 3. Adjusted HRs for dementia stratified by baseline status of AIDS.
| Characteristics | No. of dementia/Total | HR (95% CI) | P for interaction | ||
|---|---|---|---|---|---|
| AIDS (−) | AIDS (+) | ||||
| Sex | 0.37 | ||||
| Male | 33/1,867 | 64/1,706 | 1.94 (1.27–2.97) | ||
| Female | 5/202 | 12/154 | 3.95 (1.37–11.44) | ||
| Age at diagnosis, yr | 0.01 | ||||
| < 50 | 6/1,098 | 29/970 | 5.03 (2.08–12.19) | ||
| ≥ 50 | 32/971 | 47/890 | 1.51 (0.96–2.39) | ||
| Socioeconomic statusa | 0.26 | ||||
| High | 28/1,936 | 62/1,732 | 2.37 (1.51–3.72) | ||
| Low | 10/133 | 14/128 | 1.46 (0.64–3.34) | ||
Cox proportional hazards regression models were stratified by sex, age at diagnosis, and socioeconomic status and adjusted for baseline comorbidities (hypertension, diabetes mellitus, dyslipidemia, myocardial infarction, stroke, and syphilis).
HR = hazard ratio, AIDS = acquired immune deficiency syndrome, CI = confidence interval.
aInsurance type was used for surrogate marker of socioeconomic status.
Fig. 3. Spline curve analysis for the effect of age on the development of dementia. The solid line depicts the hazard function, while the dashed line represents the 95% CI. We employed a restricted cubic spline model for dementia, incorporating age at diagnosis as predictors. The model is adjusted for sex, insurance type, and comorbidities (hypertension, diabetes mellitus, dyslipidemia, myocardial infarction, stroke, and syphilis). The development of dementia was identified when the diagnosis of dementia occurred more than 2 months after the diagnosis of HIV infection, and anti-dementia medications were prescribed.
CI = confidence interval, HIV = human immunodeficiency virus, HR = hazard ratio.
In sensitivity analysis conducted after classifying all-cause dementia by VaD and non-VaD (Table 4), female sex was associated with an increased risk of non-VaD (HR, 2.15; 95% CI, 1.02–4.52), while age ≥ 50 at diagnosis increased the risk of VaD (HR, 4.60; 95% CI, 2.33–9.11). Insurance type of NMA and AIDS at diagnosis still showed an increased HR in both non-VaD and VaD. In Kaplan-Meier curve analysis (Fig. 4), female sex was associated with an increased risk of non-VaD compared to male sex (P = 0.039), while age ≥ 50 at diagnosis was associated with an increased risk of VaD compared to those < 50 at diagnosis (P < 0.001).
Table 4. Adjusted HRs for non-VaD and VaD.
| Characteristics | HR (95% CI) | |
|---|---|---|
| Non-VaD | VaD | |
| Age at diagnosis ≥ 50 yr | 1.46 (0.82–2.58) | 4.57 (2.31–9.05) |
| Female | 2.15 (1.02–4.51) | 1.11 (0.52–2.37) |
| Low socioeconomic statusa | 3.63 (1.86–7.10) | 3.71 (1.99–6.93) |
| AIDS at diagnosis | 2.31 (1.30–4.09) | 2.20 (1.29–3.77) |
All Cox proportional hazards regression models were adjusted for baseline comorbidities (hypertension, diabetes mellitus, dyslipidemia, myocardial infarction, and syphilis).
HR = hazard ratio, VaD = vascular dementia, CI = confidence interval, AIDS = acquired immune deficiency syndrome.
aInsurance type was used for surrogate marker of socioeconomic status.
Fig. 4. Cumulative incidence of non-VaD and VaD by sex and age at diagnosis. Cumulative incidence of non-VaD and VaD was estimated using the Kaplan-Meier method. The cohort was stratified by sex and age at diagnosis. The development of dementia was identified when the diagnosis of dementia occurred more than 2 months after the diagnosis of HIV infection, and anti-dementia medications were prescribed.
VaD = vascular dementia, HIV = human immunodeficiency virus.
DISCUSSION
In this study, we evaluated the factors associated with the increased risk of developing dementia among people living with HIV. This nationwide claim-based longitudinal cohort study identified age ≥ 50 at diagnosis, low socioeconomic status, and AIDS at baseline as independently associated with developing dementia. In addition, age and AIDS at baseline showed a significant interaction effect on the risk of dementia, with the risk of AIDS at baseline being more pronounced in individuals under 50 years of age at diagnosis. Furthermore, when the dementia was divided into VaD and non-VaD, we found that age and gender had different effects on the risk of dementia subtypes.
In the pre-ART era, the incidence of dementia was prominent at an annual rate of 7% during the first 2 years post-diagnosis.35 In the era of ART, while HAD became a rare complication, the incidence of HAND continued to increase as people living with HIV aged.36 A recent study involving patient from 2000 to 2016 showed a decreased incidence of dementia among people living with HIV, but a higher risk compared to those living without HIV.7 Our study identified that the cumulative incidence of dementia reached 4% at 10 years after the diagnosis of HIV among those diagnosed after 40 years old.
We further identified factors associated with the increased risk of dementia. First, age ≥ 50 at diagnosis of HIV infection was associated with an increased risk of developing dementia. Cox regression analysis using age at diagnosis as a continuous variable showed that the increased risk of dementia among people living with HIV started to rise at the age of 50 and continued to increase with age at diagnosis. Given that aging is a risk factor for dementia in those without HIV, it is anticipated that dementia prevalence will rise as the HIV-infected population ages. Considering that the prevalence of age-related comorbidities is higher in people living with HIV, there is a hypothesis that aging due to HIV progresses at a rapid rate.13,37 In a previous study based on DNA methylation, the biological age of those living with HIV infection was found to be accelerated after 3 years of follow-up.20 According to epidemiological studies, diseases related to aging are estimated to occur 10 years earlier,38 and those who started ART at high CD4 cell counts live approximately 10 fewer healthy years without comorbidities compared to uninfected individuals.39 Our result also supported the hypothesis of accelerated aging in those living with HIV, as the risk of dementia starting at an earlier age of 50. The increase in risk due to aging has significant implications at a time when many people infected with HIV are over the age of 50 and the number of newly infected elderly HIV patients is increasing.
Initial AIDS status at baseline is associated with an elevated risk of dementia. This suggests that baseline immunosuppression or extended exposure to HIV may play pivotal roles in the prognostic trajectory of dementia. This finding is consistent with a previous longitudinal cohort study, showing that AIDS status is the most important predictor for cognitive impairment.40 Several hypotheses link prolonged exposure to HIV with an increased risk of dementia. First, HIV causes changes in brain volume in the hippocampus. According to previous studies, brain HIV load was higher in the hippocampus,41 and hippocampus damage was known to be more common in the HIV-infected population.42 Additionally, imaging studies have shown changes in the hippocampus and entorhinal structure in association with HIV.26 Second, Aβ processing is affected by HIV through HIV-associated proteins, such as gp120 and Tat, inducing the increased production of Aβ.28,43 Third, sustained inflammatory responses could lead to chronic subcortical degeneration.44 In summary, our study underscores the potential heightened risk of dementia among individuals diagnosed with AIDS at their initial HIV diagnosis.
Low socioeconomic status was also associated with an increased risk of dementia in those living with HIV. Low socioeconomic status, including low income and education level, is a well-known risk factor for developing dementia in general population.45 Furthermore, in those living with HIV, lower socioeconomic status was also related to lower adherence with ART, which could lead to failure in suppressing systemic HIV load.30
Notably, age and AIDS at baseline showed a significant interaction effect, indicating that the effect of AIDS on the risk of developing dementia was more pronounced in those < 50 at diagnosis, raising the risk of dementia by over 5 times in this age group (Table 3). Furthermore, the onset of dementia appeared to be accelerated by approximately a decade in individuals with AIDS (Supplementary Fig. 1). This result support the notion that HIV duration measured by AIDS status and age at HIV diagnosis are important factors when assessing the risk of cognitive decline in people living with HIV.46 Given that baseline AIDS status reflects prolonged exposure to HIV and immunosuppressive status, these findings reinforce the significance of early diagnosis, prompt initiation of treatment, and the need for increased attention to dementia in newly diagnosed HIV infection, particularly among patients diagnosed with AIDS.
The effects of sex and age on dementia were distinct by subtype of dementia. The increased risk of non-VaD was associated female sex. This might reflect the fact that female sex is a risk factor of AD, which is the most common cause of neurodegenerative dementia. On the other hand, older age at diagnosis was associated with the risk of VaD. The association between older age at diagnosis and vascular cognitive impairment can reflect the higher incidence of cardiovascular and cerebrovascular comorbidities in those with older ages.47 There is also several evidence supporting the association between vascular cognitive impairment and HIV infection. First, chronic infection to HIV itself and HIV-specific immune activation may dysregulate neurovascular unit, which may cause dysfunction in microvascular structure and brain perfusion.48 Second, chronic inflammation due to non-specific immune activation is associated with viral reservoir activity and may result in a hypercoagulable state and systemic vascular endothelial cell dysfunction.49 These factors can increase the risk of VaD by increasing stroke and cardiovascular comorbidity.21,22,23,50 Furthermore, a previous imaging study revealed white matter hyperintensities, a marker for cerebral small vessel disease, are associated with HIV infection.51 Our data suggest that the risk of vascular cognitive impairment in older people living with HIV could be higher.
There are some limitations in this study. Frist, the challenge of distinguishing between incident dementia and HAND remains significant. We used the administration of AChEi and memantine as criteria for defining dementia to delineate between HAND and incident dementia. Moreover, instances where dementia diagnoses preceded or were concurrent (within 2 months) with HIV infection were excluded. Yet, even with these measures, distinguishing incident dementia from HAND using clinical data alone proves challenging. There is an imperative need to develop more refined diagnostic methodologies for differentiation.27 Second, our study lacks direct patient data, including RNA level or CD4 count, and demographic information, including education years, obesity, smoking, or alcohol consumption, which are unnecessary for the claims process. Nonetheless, the description of HIV clinics in Korea highlights several advantages aligned with the strengths of claims database research. Since these clinics are primarily staffed by specialized infectious disease doctors who adhere to internationally recognized treatment guidelines, the clinical data captured in claims databases reflect standardized, high-quality care practices. Furthermore, the doctor’s evaluation of the patient’s condition is clearly reflected in the data of the treatment pattern, encompassing diagnosis and prescription.
In conclusion, age over 50, low socioeconomic status, and AIDS status at diagnosis of HIV infection raises the likelihood of developing incident dementia, in the era of ART. These findings suggest that cognitive impairment in people living with HIV should be considered in those with higher risk.
Footnotes
Funding: This research received partial support from Boramae Medical Center under grant number 07-2021-43, and was supported by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HI22C0977).
Disclosure: The authors have no potential conflicts of interest to disclose.
Data Availability Statement: The data of this study can be made available from the National Health Insurance Service of Korea upon reasonable request. Restrictions may be imposed on the availability of these data due to privacy or ethical concerns.
- Conceptualization: Lee E, Lee YG, Bang J.
- Data curation: Lee E, Lee YG, Bang J.
- Formal analysis: Lee E, Lee YG, Bang J.
- Methodology: Lee E, Lee YG, Bang J.
- Writing - original draft: Lee E, Lee YG, Bang J.
- Writing - review & editing: Lee E, Lee YG, Bang J.
SUPPLEMENTARY MATERIALS
ICD-10 codes used for diagnosis
Interaction effect of age at diagnosis and AIDS at baseline on the risk of dementia
Spline curve analysis for the effect of age on the development of dementia, stratified by AIDS. The solid line depicts the hazard function, while the shaded area represents the 95% CI. We employed a restricted cubic spline model for dementia, incorporating age, baseline AIDS status, and an interaction term between age and baseline AIDS status as predictors. The model is adjusted for sex, insurance type, and comorbidities (hypertension, diabetes, dyslipidemia, myocardial infarction, stroke, and syphilis). The development of dementia was identified when the diagnosis of dementia occurred more than 2 months after the diagnosis of HIV infection, and anti-dementia medications were prescribed.
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Associated Data
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Supplementary Materials
ICD-10 codes used for diagnosis
Interaction effect of age at diagnosis and AIDS at baseline on the risk of dementia
Spline curve analysis for the effect of age on the development of dementia, stratified by AIDS. The solid line depicts the hazard function, while the shaded area represents the 95% CI. We employed a restricted cubic spline model for dementia, incorporating age, baseline AIDS status, and an interaction term between age and baseline AIDS status as predictors. The model is adjusted for sex, insurance type, and comorbidities (hypertension, diabetes, dyslipidemia, myocardial infarction, stroke, and syphilis). The development of dementia was identified when the diagnosis of dementia occurred more than 2 months after the diagnosis of HIV infection, and anti-dementia medications were prescribed.