Prevalence of Alzheimer’s and Related Dementia Diseases and Risk Factors Among Transgender Adults, Florida, 2012‒2020

Abstract

Objectives. To estimate the prevalence rates of Alzheimer’s disease and related dementias (ADRD) and their risk factors in the transgender population and compare the rates to those in cisgender adults.

Methods. We identified 1784 transgender adults in the linked electronic health records and claims data between 2012 and 2020 from the OneFlorida Clinical Research Consortium. We calculated the prevalence of ADRD and ADRD risk factors for the transgender and matched cisgender control adults.

Results. The prevalence of ADRD was higher in the transgender adults compared with the cisgender control adults. Overall, the prevalence of ADRD risk factors was significantly higher in the transgender adults than the cisgender controls for 11 out of the 13 risk factors, with the only exceptions being traumatic brain injury and visual impairment.

Conclusions. Transgender adults are at significantly higher risk for ADRD than cisgender adults. Our study highlights the urgent need for more research on the unique ADRD risks among the aging transgender and larger sexual- and gender-minority populations. (Am J Public Health. 2022;112(5):754–757. https://doi.org/10.2105/AJPH.2022.306720)

Alzheimer’s disease (AD) is the sixth leading cause of death in the United States.¹ More than 6 million Americans live with AD and related dementias (ADRD),¹ yet there exists no effective treatment of AD because of its complex pathogenesis mechanisms. Targeting relevant risk factors for early AD prevention is therefore crucial for alleviating population-level AD burden. It is suggested that addressing modifiable ADRD risk factors could prevent or delay up to 40% of all dementia cases.²

Transgender people, a subgroup of sexual and gender minorities (SGMs), are individuals who have a gender identity that differs from their sex assigned at birth. The transgender population is disproportionately exposed to health risks, many of which are related to ADRD.³ As the older transgender and SGM population is rapidly growing in the United States,⁴ the Alzheimer’s Association has declared that ADRD is a disease of high priority in SGM, including transgender, individuals.⁵

In this study, using real-world data in a large clinical research network, we estimated the prevalence rates of ADRD and their risk factors in transgender adults and compared the rates with those in cisgender adults.

METHODS

We obtained linked electronic health records and claims data between January 1, 2012, and July 31, 2020, from the OneFlorida clinical research network, 1 of 9 clinical research networks in the National PCORnet.⁶ OneFlorida contains patient data for more than 1.5 million (> 60%) Floridians. These data follow the PCORnet common data model, which includes detailed demographics and clinical variables.

In OneFlorida, we identified transgender adults using a computable phenotyping algorithm previously developed and validated by our group.⁷ The algorithm determines whether an individual is transgender or not based on (1) the gender identity field in the PCORnet common data model and (2) International Classification of Diseases (ICD), Ninth Revision, Clinical Modification (ICD-9-CM; https://www.cdc.gov/nchs/icd/icd9cm.htm); ICD, Tenth Revision, Clinical Modification (ICD-10-CM; https://www.cdc.gov/nchs/icd/icd10cm.htm); and Current Procedural Terminology codes (https://www.ama-assn.org/amaone/cpt-current-procedural-terminology) related to transgender status (e.g., ICD-10-CM code F64 for gender-identity disorders). To avoid bias in prevalence estimation because of insufficient encounter, we included only transgender adults who had at least 1 outpatient encounter every 2 years. We used the exact matching methods to match each transgender adult with 10 men and 10 women based on age (within 1 year) and race (non-Hispanic White, non-Hispanic Black, non-Hispanic other, Hispanic, and unknown). The cisgender control adults were randomly selected in OneFlorida who were not transgender as determined by the phenotyping algorithm and had at least 1 outpatient encounter every 2 years.

Risk Factors of Interest

We defined ADRD using ICD codes provided by the Centers for Medicare and Medicaid Services’ (CMS’s) Chronic Conditions Data Warehouse.⁸ We summarized the ADRD risk factors from 3 creditable sources: (1) the 2021 Alzheimer’s disease facts and figures published by the Alzheimer’s Association¹; (2) the 2020 Lancet Commission report on dementia prevention, intervention, and care²; and (3) 2 systematic reviews identified in PubMed.^9,10 For the 13 risk factors that could be identified in OneFlorida data (Table 1), we compiled diagnosis or drug (Tables A and B, available as supplements to the online version of this article at http://www.ajph.org) codes and extracted information on these factors. Consistent with Chronic Conditions Data Warehouse criteria, diagnosis of ADRD and the risk factors related to diseases was confirmed with the presence of 1 inpatient or 2 outpatient ICD codes within 1 year.⁸ ADRD risk factors related to medication use were identified from both prescriptions and dispensing records using the RxNorm or National Drug Code.

TABLE 1—

Prevalence of Alzheimer’s Disease and Related Dementias (ADRD) and Its Modifiable Risk Factors in the Study Population in OneFlorida: 2012‒2020

	Overall			18–49 y			≥ 50 y
	Cisgender (n = 35 285), Mean (SD) or %	Transgender (n = 1784), Mean (SD) or %	P	Cisgender (n = 26 272), Mean (SD) or %	Transgender (n = 1332), Mean (SD) or %	P	Cisgender (n = 9013), Mean (SD) or %	Transgender (n = 452), Mean (SD) or %	P
Matching variables
Age, y	39.3 (15.2)	39.2 (15.3)	.74	31.7 (8.0)	31.6 (8.0)	.72	61.5 (7.7)	61.5 (7.7)	> .99
Race/ethnicity
Non-Hispanic White	50.6	50.6	> .99	48.2	48.3	> .99	57.4	57.3	> .99
Non-Hispanic Black	14.8	14.7		15.6	15.5		12.2	12.2
Non-Hispanic other	2.9	2.9		3.1	3.2		2.0	2.0
Hispanic	16.7	16.6		16.5	16.4		17.4	17.3
Unknown	15.1	15.2		16.5	16.5		11.1	11.3
Outcome of interest
ADRD	0.8	1.7	< .001*	0.3	1.1	< .001*	2.2	3.5	.07
ADRD risk factors
Ever smoking	17.9	26.6	< .001*	15.4	24.4	< .001*	25.4	33.2	< .001*
Alcohol use disorder	3.4	6.8	< .001*	2.6	6.3	< .001*	6.0	8.2	.06
Depression	6.4	17.9	< .001*	5.2	15.0	< .001*	9.8	26.5	< .001*
Diabetes	6.0	8.5	< .001*	3.6	5.3	.001	13.0	18.1	.002*
On antidiabetic drug	7.1	10.8	< .001*	4.2	6.6	< .001*	15.8	23.0	< .001*
Hearing loss	0.3	0.8	<.001*	0.3	0.8	<.001*	0.6	1.1	.16
High cholesterol	3.4	6.8	< .001*	2.4	6.8	< .001*	6.2	6.9	.66
Hypertension	12.7	18.3	< .001*	7.6	11.4	< .001*	27.7	38.7	< .001*
On antihypertensives	9.8	15.5	< .001*	6.4	12.3	< .001*	19.5	25.0	< .001*
Obesity	6.8	9.5	< .001*	5.4	8.0	< .001*	10.9	14.2	.03
Sleep disorders	3.1	6.8	< .001*	1.9	5.0	< .001*	6.5	12.4	< .001*
Traumatic brain injury	2.0	3.1	.002	1.9	2.7	.054	2.3	4.2	.008
Visual impairment	0.3	0.3	.94	0.2	0.2	.72	0.5	0.4	.81

^*Significant at the 0.05 ÷ 14 = 0.0036 level.

Statistical Analysis

For the transgender and cisgender control adults, we calculated the prevalence rate of ADRD and each risk factor as the fraction of the population who had the risk factor, both overall and stratified by age (18–49 or ≥ 50 years). We used the χ² or Fisher exact test to test differences in rates. Using the Bonferroni correction, we controlled for multiple testing by considering a significance level of 0.05 ÷ 14 (ADRD and 13 ADRD risk factors) = 0.0036. We performed all statistical analysis in SAS version 9.4 (SAS Institute, Cary, NC).

RESULTS

We identified 1784 transgender adults in OneFlorida, among whom 452 (25.3%) were aged 50 years or older (Table 1). The average age of the transgender adults was 39.2 years. As seen in Table 1, the transgender and matched cisgender adults had comparable age and race distribution.

The prevalence of ADRD was significantly higher in the transgender adults than the cisgender controls both overall (1.7% vs 0.8%; P < .001) and in adults aged 18 to 49 years (1.1% vs 0.3%; P < .001). Among adults aged 50 years or older, the prevalence of ADRD was higher in the transgender adults (3.5%) than the cisgender controls (2.2%), although the difference was statistically nonsignificant because of insufficient statistical power (P = .067).

Overall, the prevalence of ADRD risk factors was significantly higher in the transgender adults than the cisgender controls for 11 out of the 13 risk factors, with the only exceptions being traumatic brain injury and visual impairment, for which the prevalence was statistically the same in the 2 groups. When we restricted age to 18 to 49 years, the transgender adults had significantly higher rates of ADRD risk factors than did the cisgender controls for 10 out of the 13 risk factors, with the only exceptions being diabetes, traumatic brain injury, and visual impairment. When we restricted age to 50 years or older, the transgender adults had significantly higher rates of ADRD risk factors than the cisgender controls for 7 out of the 13 risk factors, with the exceptions being alcohol use disorders, hearing loss, high cholesterol, obesity, traumatic brain injury, and visual impairment. For the nonsignificant risk factors, the statistical tests were likely underpowered because of small disease counts in transgender adults when we restricted age to 50 years or older.

DISCUSSION

Using OneFlorida electronic health record data, we found that the prevalence of ADRD and most of the ADRD risk factors was significantly elevated in transgender adults compared with cisgender controls. To our knowledge, no previous studies have examined the prevalence of ADRD risk factors in the older transgender population using clinical data as most previous research on transgender individuals was survey-based. Results from our study support that ADRD is a disease of high priority in the growing population of older transgender adults.⁵

The observed higher ADRD risk in the transgender population was largely expected as previous studies have documented a high prevalence of adverse health outcomes in this population.¹¹ However, we found that prevalence of ADRD and more than half of the risk factors was more than twice or even 3 times higher in the transgender adults, suggesting that ADRD could be a much more serious problem in this population and deserves more attention as the transgender population continues to grow and age.

In general, the transgender and the larger SGM populations are understudied, largely because of the scarcity of relevant data. There exists few population-based representative samples or routine surveillance efforts for SGM population health studies. Our study shows that decent-sized cohorts of transgender individuals can be identified in real-world data from large clinical research networks for ADRD research. These data contain important demographic and clinical variables that are critical for studying the complex ADRD risks and outcomes in the transgender and the larger SGM populations.

PUBLIC HEALTH IMPLICATIONS

Transgender adults are at significantly higher risk for ADRD than are cisgender adults. Our study highlights the urgent need for more research on the unique ADRD risks among the aging transgender and larger SGM populations.