Risk Factors and Prevalence of Alzheimer’s Disease and Related Dementias Among Transgender Adults in South Carolina,2000–2022

South Carolina integrated data system

We utilized the South Carolina Integrated Data System, managed by the South Carolina Revenue and Fiscal Affairs Office (RFAO). ¹⁰ Agencies voluntarily share their data under statute and formal agreements, with explicit project-by-project approval for each use. This system aggregates data from diverse state agencies (see participating entities in Fig. 1), including health care, education, and service delivery, allowing for comprehensive longitudinal analyses. Because inclusion in the integrated data system depends on individuals’ interaction with participating agencies and programs, the dataset primarily captures people who engage with state health and service systems. As a result, individuals who have limited contact with health care or other state-supported services in South Carolina may be underrepresented.

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FIG. 1.

Figure of the available data in the South Carolina Integrated Data System. Used with permission by the South Carolina Revenue and Fiscal Affairs Office. CPS, Child Protective Services; SC, South Carolina; SNAP, Supplemental Nutrition Assistance Program; TNAF, Temporary Assistance for Needy Families.

To access the deidentified data, researchers must apply for each project. Once the application is approved by RFAO, the de-identified data is gathered based on the requesting inclusion and exclusion criteria and sent by RFAO to the requestor via a secured, encrypted file. For this project, our approved data request included only individuals meeting the computable phenotype for transgender status as described below. The study received ethical approval from the University of South Carolina’s Institutional Review Board (Pro00133266) on November 11, 2023. This is an IRB-approved retrospective study; all patient information was deidentified, and patient consent was not required. Patient data will not be shared with third parties.

Transgender data

The RFAO dataset contains encrypted patient identifiers for longitudinal tracking. Transgender adults were identified by RFAO using a computable phenotype based on International Classification of Diseases, Ninth Edition (ICD-9) ¹¹ and Tenth Edition (ICD-10) ¹² diagnosis codes (see Table 1), as described in prior research. ¹³ ADRD was defined using ICD-9 and ICD-10 codes for Alzheimer’s disease, vascular dementia, and other non-Alzheimer’s dementias, as detailed in Supplementary Table S1. We then analyzed this dataset for ADRD and associated risk factors using ICD-9 ¹¹ and ICD-10 ¹² codes (see Supplementary Table S2), as defined by the Chronic Conditions Warehouse. ¹⁴

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Table 1.

Transgender International Classification of Diseases, Ninth Edition and International Classification of Diseases, Tenth Edition Codes

ICD-9	ICD-10
302.50 Transsexualism with unspecified sexual history	F64.0 Transsexualism/ Transgender in adolescence and adulthood
302.51 Transsexualism with asexual history	F64.9 Dysphoria, gender (gender incongruence)
302.52 Transsexualism with homosexual history	F64.2 Gender identity disorder of childhood
302.53 Transsexualism with heterosexual history	Z87.890 Personal history of sex reassignment
302.85 Gender identity disorder in adolescents or adults

Source: ^11,12.

ICD, International Classification of Diseases.

Risk factors of interest

We identified ADRD risk factors from (1) the 2024 Alzheimer’s disease facts and figures special report; ¹ and (2) the 2024 Lancet Commission on dementia prevention, intervention, and care. ⁷ For the 11 risk factors that we could identify in our dataset (i.e., alcohol use disorder, depression, diabetes, hearing impairment, hypercholesterolemia, hypertension, obesity, sleep disorder, smoking, traumatic brain injury, and visual impairment), we compiled ICD-9 ¹¹ and ICD-10 ¹² diagnosis codes using the Chronic Conditions Data Warehouse ¹⁴ criteria. Cases were included in our final dataset if a patient’s record contained at least one ICD-9 ¹¹ or ICD-10 ¹² code for transgender status, ADRD, and any risk factor. Prior to data delivery, we requested that the RFAO categorize patients as metropolitan or rural using 2010 Rural-Urban Commuting Area Codes (RUCA). ¹⁵

Data analysis

We conducted a secondary analysis of deidentified all-payer hospital claims data from 2000 to 2022, including adults aged 18 and older. Consistent with prior claims-based research on ADRD in transgender populations, ³ we included all adults aged 18 years and older to capture early-onset ADRD diagnoses and stratified results by age group (18–49 and ≥50 years) to allow age-specific prevalence estimation. In line with life-course frameworks for modifiable dementia risk, we examined the prevalence of ADRD risk factors among all adults aged ≥18 years and by age group (18–49 and ≥50 years).

Patients were classified as residing in metropolitan or rural areas using 2010 RUCA codes. ¹⁵ The primary outcomes assessed were the prevalence of ADRD and the distribution of the 11 modifiable risk factors identified above. Demographic variables considered included age, race/ethnicity, and urban-rural residence. Prevalence rates for ADRD and each risk factor were calculated as the proportion of the individuals diagnosed with the condition, both overall and stratified by age (18–49 and ≥50 years). Descriptive statistics summarized patient characteristics, ADRD diagnoses, and risk factor prevalence. All statistical analyses were conducted using SAS version 9.4. ¹⁶

South Carolina Alzheimer’s disease registry

To contextualize our findings, we contacted the director of the South Carolina Alzheimer’s Disease Registry, which also leverages the South Carolina Integrated Data System, and requested an estimate of ADRD prevalence among all adults aged 50 years and older in South Carolina. This registry-derived prevalence served as a statewide reference point for comparison.

Comparison to U.S. data

Our findings reveal an overwhelming disparity in ADRD prevalence among transgender adults in South Carolina. The observed 19% prevalence in this cohort is notably higher than the 3.85% and 13% prevalence of ADRD reported among adults aged 50 and older within South Carolina ⁶ and the U.S. population, ¹⁸ respectively. This represents a prevalence rate more than five times greater than that of the general aging population in South Carolina and approximately 46% greater than that of the U.S. population, highlighting a significant and previously unquantified public health crisis for this group in the state.

Although direct U.S. comparisons for diagnosed ADRD in transgender populations are limited, our data are consistent with and extend previous research. Studies have consistently identified high rates of SCD and related functional limitations among transgender adults compared to cisgender adults.^5,8,17 Furthermore, our results build upon findings from Florida, where Guo et al. ³ also identified a significantly higher prevalence of ADRD (1.7% vs. 0.8%) and a greater burden of modifiable risk factors in its transgender population. ³ The magnitude of the disparity observed in South Carolina suggests that regional factors, including limited access to culturally affirming health care and heightened exposure to social stressors, may exacerbate the underlying risks driven by systemic inequities. ¹⁷ These potential mechanisms need to be evaluated further in future research. Although our study population was restricted to transgender adults and did not include a directly comparable cisgender cohort extracted from the same analytic dataset, the comparison to state-level prevalence estimates provides valuable context for interpreting the magnitude of this health disparity.

Because our ADRD prevalence estimates among transgender adults aged 50 years and older aggregate data from 2000 to 2022, they reflect a cohort observed during a period of substantial demographic, clinical, and documentation change. Over this interval, the number of transgender adults surviving into later life and engaging with health systems likely increased, and the age distribution of transgender adults in care may have shifted toward older ages, which would be expected to increase crude ADRD prevalence even if age-specific risks remained stable. Concurrently, evolving dementia awareness, diagnostic practices, and coding conventions, including transition from ICD-9 to ICD-10 and improved ascertainment of transgender status in administrative data, may have increased capture of both transgender identity and ADRD, such that apparent temporal changes in prevalence may partly reflect differences in documentation and health care access rather than underlying disease.

Implications

The results of this study emphasize the importance of addressing the unique challenges encountered by transgender adults in relation to ADRD. Transgender individuals are disproportionately exposed to risk factors such as social isolation, discrimination, and barriers to health care access, ¹⁹ all of which may exacerbate developing ADRD. In addition, chronic diseases such as diabetes, hypertension, and obesity, which are prevalent in transgender populations due to systemic inequities, ¹⁹ further compound their risk. Recent work also demonstrates that these modifiable conditions translate into higher dementia risk scores among transgender and gender-diverse adults. Brady et al. ² found that transgender men, transgender women, and nonbinary adults had higher late-life Alzheimer’s disease risk scores than cisgender adults, driven in part by higher prevalence of depression, hypertension, hypercholesterolemia, and smoking in transgender and gender-diverse groups. The high burden of depression, tobacco use, and hypertension observed in our cohort is therefore likely to contribute meaningfully to ADRD risk across the life course for transgender adults in South Carolina. Our findings indicate the need for targeted interventions and culturally competent care strategies tailored to the needs of transgender adults.

Our findings have important implications for public health and policy. The Alzheimer’s Association has declared ADRD a high-priority disease for transgender individuals, emphasizing the need for inclusive health care practices and research. In South Carolina, where a significant proportion of the population resides in rural areas with limited access to specialized care, ²⁰ it is necessary to develop policies that address these disparities. Public health initiatives should focus on increasing access to early screening and diagnosis for transgender individuals while addressing modifiable risk factors through community-based programs that promote cardiovascular health, mental well-being, and social engagement.

Limitations

A key strength of this study is that the use of a statewide data set with longitudinal tracking capabilities allowed us the opportunity to conduct a comprehensive analysis of ADRD prevalence in transgender adults over time. However, there are limitations. The use of ICD codes to identify transgender individuals may not capture all members of the population due to underreporting and misclassification. In addition, although our inclusion criterion of age 18 and older is consistent with the approach used by Guo et al., ³ the relatively low base rate of ADRD among younger adults means that diagnoses in the 18–49 age group should be interpreted with caution, as they may reflect early-onset dementia or coding variability rather than typical age-related ADRD.

In addition, our reliance on ICD codes to identify both transgender status and ADRD spans a period of substantial change in diagnostic classification and social norms. Over 2000–2022, the transition from ICD-9 to ICD-10, along with the introduction and refinement of codes related to gender identity and dementia, likely altered how clinicians documented transgender identity and ADRD. Increasing awareness and acceptance of transgender populations may have further increased the likelihood that these identities and diagnoses were recorded. Consequently, ascertainment of transgender status and ADRD likely improved over time, so part of the observed burden in our aggregated 2000–2022 estimates may reflect evolving documentation and coding practices rather than solely changes in underlying disease risk.

Although this study describes the prevalence within South Carolina, our approved data extract did not include a cisgender comparison cohort, precluding calculation of internal, age-adjusted prevalence ratios comparing transgender and cisgender adults using the same analytic dataset. This limits our ability to directly quantify the disparity within a single controlled analysis and constrains broader generalizability to other states. Finally, our data arise from an all-payer database based upon hospital and outpatient surgery encounters in South Carolina. This will not include individuals whose care does not utilize these services during the observation period. Hence, it may be that our prevalence estimates are underestimated.

Future directions

The findings from this study have implications that extend across research, clinical practice, and public health policy. The disproportionate burden of ADRD among transgender adults in South Carolina necessitates a multi-pronged response to move from identifying this disparity to actively dismantling the systems that perpetuate it. Future research must first establish a precise baseline of risk by conducting direct comparisons with the cisgender population in South Carolina within the same analytic dataset, using the same stratification or adjustment, to precisely quantify the disparity in ADRD prevalence and associated risk factors. Subsequently, investigators should explore the mediating and moderating factors, such as social determinants of health, chronic stress, and the compounded effects of intersectional identities such as race and rurality, to highlight the mechanisms driving this health inequity. In parallel, these findings call for immediate clinical action through the integration of routine, culturally sensitive cognitive screening into primary care for transgender adults. ²¹ Ultimately, sustainable solutions will depend on developing community-partnered interventions that are co-designed with transgender individuals to promote resilience and address modifiable risks within a culturally relevant and affirming framework.

On a broader scale, public health policy must evolve by mandating the inclusion of sexual orientation and gender identity (SOGI) data ²² in all health surveillance systems to ensure disparities are consistently monitored. ²¹ As the collection of SOGI data becomes an essential component of health equity efforts, prioritizing privacy protections and implementing rigorous data security protocols will be critical to safeguard the well-being of transgender individuals. Some communities may experience heightened concerns regarding disclosure and potential misuse of sensitive personal information; therefore, clinicians, researchers, and policymakers must advocate for and adhere to best practices in confidential and voluntary SOGI data collection to ensure that patient trust is not compromised and that data are used solely to advance health equity and improve clinical outcomes.