Abstract
Although type 2 diabetes mellitus (T2DM) frequently co-occurs with Parkinson’s disease (PD) and Alzheimer’s disease (AD), a systematic comparison of their combined mortality burdens remains lacking. This study aimed to compare long-term mortality trends and project future burdens among older US adults with T2DM comorbid with either PD or AD. A retrospective cohort study was conducted using national mortality data (1999–2023) from the CDC WONDER database. Decedents were identified using ICD-10 codes for T2DM with PD (E11 + G20) or AD (E11 + G30). Temporal trends were analyzed to estimate annual percentage change (APC) and average annual percentage change (AAPC), and future age-adjusted mortality rates were projected through 2030. Both conditions exhibited sustained upward mortality trends from 1999 to 2023, with T2DM with PD showing higher relative growth (AAPCs) but lower absolute burden than T2DM with AD. The steepest increases in death counts occurred among Hispanic/Latino individuals and in the Western United States, while the highest AAPCs in age-adjusted mortality were seen among Hispanic/Latino adults with T2DM and AD and in the Western United States for both conditions. Males had higher age-adjusted mortality for T2DM with PD, whereas females had higher absolute death counts for T2DM with AD. Mortality for T2DM with PD peaked at ages 75 to 84, while for T2DM with AD it rose continuously with age. A marked shift from institutional to home-based deaths was observed. Projections indicate age-adjusted mortality will exceed 2023 levels by over 20% by 2030, reaching 6.66 (T2DM with PD) and 15.99 (T2DM with AD) per 1,00,000. Mortality associated with T2DM comorbid with PD or AD is escalating, characterized by distinct demographic and geographic disparities. These findings underscore the urgent need for integrated clinical screening, stratified prevention strategies, and strengthened community-based care to mitigate the growing burden of these complex multimorbidities.
Keywords: Alzheimer’s disease, mortality trends, Parkinson’s disease, type 2 diabetes, United States
1. Introduction
Diabetes mellitus is a chronic metabolic disorder characterized by persistent hyperglycemia stemming from impaired insulin secretion, action, or both.[1] Chronic poor glycemic control precipitates widespread microvascular and macrovascular complications, substantially elevating the risk of cardiovascular, cerebrovascular, and renal diseases, thereby imposing a profound global disease burden.[2-4] In recent years, the convergence of global population aging and shifting lifestyle patterns has driven a marked rise in comorbidities involving type 2 diabetes mellitus (T2DM) and major neurodegenerative disorders. In particular, the co-occurrence of T2DM with Parkinson’s disease (PD) and Alzheimer’s disease (AD) has garnered significant clinical and public health attention due to high disability rates, excess mortality, and intricate pathophysiological interactions.[5-8]
Although substantial evidence supports a bidirectional relationship between T2DM and both PD and AD, mediated through shared mechanisms such as insulin resistance, chronic inflammation, and abnormal protein aggregation,[5-8] the comparative mortality burden of these comorbidities remains insufficiently characterized. Previous research has largely examined T2DM with PD or AD in isolation; consequently, a systematic comparison of mortality trends, demographic and geographic disparities, and end-of-life care settings between these 2 distinct comorbidity profiles remains absent. The lack of direct comparative data impedes the development of targeted prevention and management strategies for these high-risk populations.
To bridge this knowledge gap, this study systematically compares mortality rates, temporal trends, and demographic and geographic disparities between T2DM with PD and T2DM with AD in the United States, alongside an examination of shifts in the place of death. By delineating these distinct epidemiological patterns, this research aims to provide the evidence base necessary to inform precise public health interventions and optimize clinical management pathways for patients navigating T2DM comorbid with neurodegenerative diseases.
2. Materials and methods
2.1. Data sources and study design
We conducted a retrospective cohort study utilizing mortality data from the Centers for Disease Control and Prevention’s (CDC) Wide-ranging Online Data for Epidemiologic Research (WONDER) database.[9,10] This national surveillance system aggregates death certificate records from all 50 US states and the District of Columbia. The study population included decedents aged≥65 years who died between 1999 and 2023. Cases were identified using International Classification of Diseases, 10th Revision (ICD-10) codes for “Type 2 diabetes mellitus with Parkinson’s disease” (T2DM with PD; codes E11 + G20) or “Type 2 diabetes mellitus with Alzheimer’s disease” (T2DM with AD; codes E11 + G30) listed as an underlying or contributing cause-of-death. To ensure diagnostic specificity, records with ambiguous or unspecified diabetes codes (e.g., E13, E14) were excluded, as were instances where the neurodegenerative comorbidity (PD or AD) was not explicitly linked to T2DM in the cause-of-death coding.
2.2. Variables and definitions
Demographic and geographic variables were extracted in accordance with standard CDC WONDER classifications. Race and ethnicity were categorized as Hispanic/Latino, non-Hispanic Black or African American, non-Hispanic White, and non-Hispanic Other (comprising American Indian/Alaska Native, Asian, Native Hawaiian/Pacific Islander, and multiracial individuals). In compliance with CDC suppression rules, data cells containing fewer than 10 deaths or counts deemed unreliable were suppressed (indicated as “NA”); these were treated as missing values and excluded from subsequent trend analyses.[9,11] Age was stratified into 3 clinically relevant categories (65–74, 75–84, and ≥85 years) to capture distinct stages of older adulthood and align with neurodegenerative disease progression.[12] Census regions (Northeast, Midwest, South, West) and place of death (inpatient facility, outpatient/emergency room, decedent’s home, hospice facility, and nursing home/long-term care) were defined per CDC documentation. Age-adjusted mortality rates (AAMRs) were standardized to the 2000 US standard population.[9] Ethical review was waived as the study utilized fully de-identified, aggregate public data.
2.3. Statistical analysis
Temporal trends in AAMRs (1999–2023) were analyzed using the Joinpoint Regression Program (version 5.0; National Cancer Institute) to identify significant inflection points and estimate the annual percentage change (APC) and average annual percentage change (AAPC) with 95% confidence intervals. This regression method facilitates the detection of period-specific shifts in mortality trends, which may reflect changes in diagnostic practices or risk factors. Segments with insufficient data points due to suppression were not fitted.[13]
To forecast future mortality burdens, we employed the Autoregressive Integrated Moving Average (ARIMA) model, a robust method for epidemiological time-series forecasting.[14,15] The ARIMA model was selected for its capacity to account for autocorrelation and seasonality in mortality data. Model parameters were optimized based on the Akaike Information Criterion, and projections were extended to 2030. For both Joinpoint and ARIMA analyses, suppressed or unstable counts were excluded to ensure analytical reliability. Sensitivity analyses regarding ICD-10 coding changes were not performed, as the coding framework for the specific conditions under study remained consistent throughout the observation period.[9]
Data management and statistical processing were performed using Excel 2016 (Microsoft Corporation) and SPSS 23.0 (IBM Corporation), Armonk, NY, USA), with visualizations generated in Python 3.8.0. (Python Software Foundation), Wilmington, DE, USA) Statistical significance was defined as P < .05.
3. Results
3.1. Overall mortality trends
Between 1999 and 2023, the United States recorded increases in the number of deaths, crude mortality rates, and AAMRs for both T2DM with PD and T2DM with AD (all P < .05). Throughout the study period, the number of deaths, crude mortality rates, and AAMRs for T2DM with AD were higher than those for T2DM with PD. However, the AAPCs for the number of deaths, crude mortality rates, and AAMRs were higher for T2DM with PD than for T2DM with AD. The number of deaths rose by 425.35% for T2DM with PD and by 391.62% for T2DM with AD (Table 1).
Table 1.
National mortality trends for T2DM with PD and T2DM with AD among adults aged ≥65 years in the United States, 1999–2023.
| T2DM with PD | T2DM with AD | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| 1999 | 2023 | Rate of change (%) | AAPC (%, 95% CI) | 1999 | 2023 | Rate of change (%) | AAPC (%, 95%CI) | |||
| Number of deaths | Total | 564 | 2963 | 425.35 | 6.97* (5.78–8.16) | 1408 | 6922 | 391.62 | 6.63* (5.30–7.98) | |
| Census region | Northeast | 95 | 323 | 240.00 | 4.86* (3.14–6.60) | 233 | 607 | 160.52 | 3.66* (2.12–5.23) | |
| Midwest | 185 | 692 | 274.05 | 5.44* (3.05–7.90) | 420 | 1609 | 283.10 | 5.44* (3.75–7.16) | ||
| South | 186 | 1088 | 484.95 | 7.41* (5.89–8.96) | 539 | 2335 | 333.21 | 6.08* (4.48–7.71) | ||
| West | 98 | 860 | 777.55 | 9.73* (7.85–11.64) | 216 | 2371 | 997.69 | 10.39* (8.09–12.74) | ||
| Race | Hispanic or Latino | 19 | 331 | 1642.11 | 11.96* (11.12–12.81) | 38 | 883 | 2223.68 | 13.80* (10.44–17.27) | |
| Black or African American | 31 | 165 | 432.26 | 8.27* (6.39–10.19) | 129 | 623 | 382.95 | 7.09* (5.42–8.79) | ||
| White | 505 | 2288 | 353.07 | 6.24* (4.81–7.69) | 1224 | 4952 | 304.58 | 5.69* (4.22–7.19) | ||
| Other | NA | 163 | NA | 16 | 425 | 2556.25 | 15.68* (13.51–17.90) | |||
| Crude mortality rates (/1,00,000) | Total | 1.62 | 5.00 | 208.64 | 4.67* (3.62–5.73) | 4.05 | 11.68 | 188.40 | 4.33* (2.92–5.76) | |
| Census Region | Northeast | 1.29 | 2.98 | 131.01 | 2.87* (0.11–5.70) | 3.17 | 5.61 | 76.97 | 2.04* (0.49–3.61) | |
| Midwest | 2.24 | 5.51 | 145.98 | 3.66* (1.39–5.98) | 5.09 | 12.81 | 151.67 | 3.68* (1.29–6.13) | ||
| South | 1.51 | 4.83 | 219.87 | 4.57* (3.10–6.06) | 4.36 | 10.37 | 137.84 | 3.56* (1.74–5.41) | ||
| West | 1.43 | 6.45 | 351.05 | 6.74* (4.95–8.56) | 3.15 | 17.77 | 464.13 | 7.38* (4.99–9.83) | ||
| Race | Hispanic or Latino | NA | 5.93 | NA | 2.29 | 15.82 | 590.83 | 9.21* (6.54–11.95) | ||
| Black or African American | 1.10 | 2.91 | 164.55 | 4.48* (3.49–5.47) | 4.59 | 10.97 | 139.00 | 3.94* (2.24–5.66) | ||
| White | 1.72 | 5.20 | 202.33 | 4.44* (3.16–5.74) | 4.16 | 11.25 | 170.43 | 3.96* (2.15–5.81) | ||
| Other | NA | 4.75 | NA | NA | 12.38 | NA | ||||
| AAMRs (/1,00,000) | Total | 1.65 | 5.53 | 235.15 | 4.90* (3.23–6.60) | 4.12 | 13.31 | 223.06 | 4.70* (2.89–6.55) | |
| Census Region | Northeast | 1.28 | 3.21 | 150.78 | 3.55* (1.82–5.30) | 3.13 | 6.12 | 95.53 | 2.46* (0.94–4.00) | |
| Midwest | 2.21 | 6.16 | 178.73 | 4.74* (2.83–6.68) | 4.97 | 14.70 | 195.77 | 4.30* (2.55–6.09) | ||
| South | 1.55 | 5.36 | 245.81 | 5.03* (3.36–6.72) | 4.58 | 11.92 | 160.26 | 3.97* (2.29–5.67) | ||
| West | 1.45 | 7.20 | 396.55 | 7.16* (5.24–9.11) | 3.29 | 20.44 | 521.28 | 7.78* (5.30–10.31) | ||
| Race | Hispanic or Latino | NA | 7.02 | NA | 2.90 | 19.65 | 577.59 | 8.71* (6.08–11.40) | ||
| Black or African American | 1.19 | 3.57 | 200.00 | 4.91* (3.89–5.95) | 5.03 | 14.14 | 181.11 | 4.76* (3.07–6.49) | ||
| White | 1.71 | 5.66 | 230.99 | 4.83* (3.52–6.16) | 4.14 | 12.49 | 201.69 | 4.47* (3.05–5.91) | ||
| Other | NA | 5.30 | NA | NA | 13.99 | NA | ||||
AAMRs are per 1,00,000 population, standardized to the 2000 US standard population. Crude mortality rates are per 1,00,000 population.
NA indicates data suppressed or unreliable per CDC WONDER standards.
AAMR = age-adjusted mortality rate, AAPC = average annual percentage change, AD = Alzheimer’s Disease, CDC = Centers for Disease Control and Prevention, CI = confidence interval, PD = Parkinson’s Disease, T2DM = type 2 diabetes mellitus, WONDER = Wide-ranging Online Data for Epidemiologic Research.
P < .05.
3.2. Demographic and geographic disparities
Variations in mortality were observed across population subgroups. Geographically, the Western census region had the highest AAPCs across all mortality indicators for both conditions. Regarding race and ethnicity, the Hispanic/Latino population showed the highest AAPCs in number of deaths for both T2DM with PD (AAPC = 11.96%) and T2DM with AD (AAPC = 13.80%). Mortality increased across all census regions and racial/ethnic groups (Table 1).
3.3. Sex-stratified mortality patterns
Mortality patterns differed by sex (Fig. 1; Table 2). For T2DM with PD, males had higher death counts and AAMRs than females, and this difference widened over time, as reflected by a higher AAPC in males (4.96% vs 4.38%). For T2DM with AD, death counts were higher in females, but the AAPC was higher in males (4.99% vs 4.64%). Joinpoint regression indicated different temporal patterns: males with T2DM and PD showed a biphasic growth pattern, while females with T2DM and AD maintained a consistent growth rate throughout the study period.
Figure 1.
Number of deaths and age-adjusted mortality rates (AAMRs) for type 2 diabetes mellitus (T2DM) with Parkinson’s disease (PD) and T2DM with Alzheimer’s disease (AD) by sex in the United States, 1999–2023. (A, B) Number of deaths for T2DM with PD and T2DM with AD, stratified by sex. (C, D) Corresponding AAMRs for T2DM with PD and T2DM with AD, stratified by sex. AAMR = age-adjusted mortality rate, AD = Alzheimer’s disease, PD = Parkinson’s disease, T2DM = type 2 diabetes mellitus.
Table 2.
Temporal trends in AAMRs for T2DM with PD and T2DM with AD by sex in the United States, 1999–2023.
| Period | APC (%, 95% CI) | AAPC (%, 95% CI) | ||
|---|---|---|---|---|
| T2DM with PD | Male | 1999–2002 | 10.42* (3.02–18.34) | 4.96* (3.37–6.57) |
| 2002–2014 | 0.89 (−0.05 to 1.84) | |||
| 2014–2021 | 12.05* (9.45–14.70) | |||
| 2021–2023 | −1.88 (−14.58 to 12.71) | |||
| Female | 1999–2006 | 6.62* (3.67–9.66) | 4.38* (2.10–6.72) | |
| 2006–2015 | −0.76 (−3.02 to 1.54) | |||
| 2015–2021 | 12.82* (7.64–18.26) | |||
| 2021–2023 | −3.64 (−21.93 to 18.93) | |||
| T2DM with AD | Male | 1999–2005 | 11.14* (8.63–13.71) | 4.99* (3.67–6.33) |
| 2005–2014 | −0.01 (−1.47 to 1.48) | |||
| 2014–2020 | 10.39* (7.10–13.77) | |||
| 2020–2023 | −1.90 (−8.31 to 4.96) | |||
| Female | 1999–2005 | 10.25* (6.74–13.88) | 4.64* (2.58–6.73) | |
| 2005–2014 | 0.37 (−1.70 to 2.49) | |||
| 2014–2021 | 9.17* (5.70–12.77) | |||
| 2021–2023 | −7.05 (−23.25 to 12.57) | |||
AAMRs are per 1,00,000 population.
AAMR = age-adjusted mortality rate, AAPC = average annual percentage change, AD = Alzheimer’s disease, APC = annual percentage change, CI = confidence interval, PD = Parkinson’s disease, T2DM = type 2 diabetes mellitus.
P <.05.
3.4. Age-stratified mortality patterns
Mortality distributions differed by age group (Fig. 2; Table 3). For T2DM with PD, mortality was highest in the 75 to 84 age group. For T2DM with AD, both death counts and age-specific mortality rates increased with age. The AAPC for T2DM with PD decreased with age, whereas for T2DM with AD, it followed a “V”-shaped pattern across age groups. An increase in mortality was observed among the 65 to 74 age group with T2DM and PD from 2014 to 2023 (APC = 11.75%), which was higher than the APC for T2DM with AD in the same age group.
Figure 2.
Number of deaths and age-specific mortality rates for type 2 diabetes mellitus (T2DM) with Parkinson’s disease (PD) and T2DM with Alzheimer’s disease (AD) by age group in the United States, 1999–2023. (A, B) Number of deaths for T2DM with PD and T2DM with AD across different age groups. (C, D) Age-specific mortality rates for T2DM with PD and T2DM with AD across different age groups. AD = Alzheimer’s disease, PD = Parkinson’s disease, T2DM = type 2 diabetes mellitus.
Table 3.
Temporal trends in age-specific mortality rates for T2DM with PD and T2DM with AD in the United States, 1999–2023.
| Period | APC (%, 95% CI) | AAPC (%, 95%CI) | ||
|---|---|---|---|---|
| T2DM with PD | 65–74 yr | 1999–2014 | 1.69* (0.07–3.34) | 5.35* (3.74–7.00) |
| 2014–2023 | 11.75* (7.93–15.70) | |||
| 75–84 yr | 1999–2004 | 7.50* (3.76–11.38) | 5.05 (3.30–6.83) | |
| 2004–2015 | 1.09 (−0.15 to 2.34) | |||
| 2015–2021 | 13.20* (9.26–17.29) | |||
| 2021–2023 | −2.10 (−16.44 to 14.71) | |||
| 85+ yr | 1999–2015 | 2.65* (1.59–3.72) | 4.75* (3.58–5.94) | |
| 2015–2023 | 9.09* (5.92–12.35) | |||
| T2DM with AD | 65–74 yr | 1999–2002 | 18.38 (−0.87 to 41.37) | 5.00* (2.31–7.77) |
| 2002–2014 | 0.22 (−2.15 to 2.65) | |||
| 2014–2023 | 7.36* (3.94–10.89) | |||
| 75–84 yr | 1999–2005 | 9.70* (6.91–12.56) | 4.31* (2.67–5.97) | |
| 2005–2014 | 0.10 (−1.55 to 1.78) | |||
| 2014–2021 | 8.33* (5.57–11.16) | |||
| 2021–2023 | −5.47 (−18.83 to 10.09) | |||
| 85+ yr | 1999–2005 | 11.51* (8.54–14.55) | 5.24* (3.68–6.82) | |
| 2005–2014 | 0.50 (−1.23 to 2.26) | |||
| 2014–2020 | 10.88* (7.00–14.89) | |||
| 2020–2023 | −3.05 (−10.47 to 4.98) | |||
Rates are per 1,00,000 population within the specified age group.
AAPC = average annual percentage change, AD = Alzheimer’s disease, APC = annual percentage change, CI = confidence interval, PD = Parkinson’s disease, T2DM = type 2 diabetes mellitus.
P < .05.
3.5. Trends in place of death
From 1999 to 2023, the place of death for both conditions shifted from institutional settings to the home (Table 4). Although nursing homes and long-term care facilities remained the most common locations, their proportion decreased (from 49.70% to 36.32% for T2DM with PD; from 63.07% to 45.54% for T2DM with AD). Inpatient deaths also decreased. Home-based deaths increased, rising by 96.47% for T2DM with PD and by 161.69% for T2DM with AD when comparing the 2019–2023 period to 1999–2003.
Table 4.
Distribution of primary place of death for T2DM with PD and T2DM with AD in the United States, 1999–2023.
| 1999–2003 | 2004–2008 | 2009–2013 | 2013–2018 | 2019–2023 | ||
|---|---|---|---|---|---|---|
| Inpatient | PD with T2DM | 852 (24.39%) | 979 (20.67%) | 848 (16.10%) | 990 (13.09%) | 1911 (14.03%) |
| AD with T2DM | 1709 (17.71%) | 2145 (14.43%) | 1861 (10.61%) | 1813 (7.69%) | 2749 (7.77%) | |
| Outpatient or Emergency Room | PD with T2DM | 126 (3.61%) | 143 (3.02%) | 185 (3.51%) | 257 (3.40%) | 379 (2.78%) |
| AD with T2DM | 269 (2.79%) | 369 (2.48%) | 447 (2.55%) | 511 (2.17%) | 694 (1.96%) | |
| Decedent’s home | PD with T2DM | 643 (18.41%) | 1052 (22.21%) | 1428 (27.11%) | 2330 (30.81%) | 4925 (36.17%) |
| AD with T2DM | 1201 (12.45%) | 2344 (15.77%) | 3579 (20.41%) | 6093 (25.85%) | 11,533 (32.58%) | |
| Hospice facility | PD with T2DM | NA | NA | 184 (3.49%) | 318 (4.20%) | 667 (4.90%) |
| AD with T2DM | NA | NA | 435 (2.48%) | 883 (3.75%) | 1496 (4.23%) | |
| Nursing home/long-term care | PD with T2DM | 1736 (49.70%) | 2304 (48.65%) | 2362 (44.85%) | 3309 (43.75%) | 4945 (36.32%) |
| AD with T2DM | 6086 (63.07%) | 9144 (61.52%) | 10,113 (57.67%) | 12,671 (53.76%) | 16,121 (45.54%) | |
Data are presented as number of deaths and corresponding percentage of total deaths for each condition within the specified time period.
NA indicates data suppressed or unavailable per CDC WONDER standards.
AD = Alzheimer’s disease, CDC = Centers for Disease Control and Prevention, PD = Parkinson’s disease, T2DM = type 2 diabetes mellitus, WONDER = Wide-ranging Online Data for Epidemiologic Research.
3.6. Mortality projections to 2030
Projections indicate that AAMRs for both conditions are expected to increase through 2030 (Fig. 3). The AAMR is projected to reach 6.66 per 1,00,000 for T2DM with PD and 15.99 per 1,00,000 for T2DM with AD, representing an increase of >20% from 2023 levels and a nearly 4-fold increase since 1999. The difference in mortality between sexes for T2DM with PD is projected to widen. The steepest increases in age-specific rates are projected in the ≥85 years age group, followed by the 75 to 84 years group.
Figure 3.
Projected mortality rates for type 2 diabetes mellitus (T2DM) with Parkinson’s disease (PD) and T2DM with Alzheimer’s disease (AD) in the United States through 2030. (A, B) Projected total age-adjusted mortality rates (AAMRs) for T2DM with PD and T2DM with AD. (C, D) Projected AAMRs by sex for T2DM with PD and T2DM with AD. (E, F) Projected age-specific mortality rates for T2DM with PD and T2DM with AD. AAMR = age-adjusted mortality rate, AD = Alzheimer’s disease, PD = Parkinson’s disease, T2DM = type 2 diabetes mellitus.
4. Discussion
This nationwide study characterizes a substantial and sustained rise in mortality among older US adults with T2DM concurrently diagnosed with PD or AD over a 25-year period. The findings delineate distinct epidemiological patterns and divergent future trajectories for these comorbidities. Projections indicate a continuing escalation in mortality burden, underscoring an urgent need for targeted public health action. These pronounced increases are likely driven by a confluence of aging demographics,[12,16] rising T2DM prevalence,[17] and heightened clinical recognition of neurodegenerative comorbidities.[18-20] While the absolute mortality burden for T2DM with AD remains higher, the faster relative growth observed for T2DM with PD may indicate a changing epidemiological pattern. This differential growth could be explained, in part, by the fact that T2DM interacts with PD and AD through both shared and distinct pathological mechanisms, as suggested by prior research.[21-23.
The marked disparities identified herein underscore the critical role of social determinants of health. The accelerated mortality growth among Hispanic/Latino populations for both conditions was a key finding in our data. In the literature, such disparities have been attributed to a confluence of factors, including a higher prevalence of metabolic risk factors, such as obesity and diabetes,[17,24] structural barriers to healthcare access,[25,26] and, particularly for PD, occupational environmental exposures.[27-30] These factors may contribute synergistically to the elevated risk observed in this population. Additionally, unmeasured genetic, sociocultural, or environmental determinants specific to this population may also play a role. The concentration of higher mortality rates and growth in the Western United States likely reflects regional heterogeneity in healthcare infrastructure, insurance coverage, and public health resource allocation.[31-33]
Distinct sex and age patterns further elucidate the differential interaction between T2DM and each neurodegenerative disease. The male predominance in T2DM with PD mortality aligns with the established sex bias in PD.[34,35] It has been hypothesized that diabetes-related pathology could exacerbate this preexisting disparity.[30] For T2DM with AD, the converging mortality rates between sexes, driven by a steeper rise among men, could be consistent with the hypothesis that diabetes attenuates the relative neuroprotective advantage often observed in males.[36,37] One proposed mechanism for this is the aggravation of cerebrovascular disease.[36,37] Alternatively, this pattern could reflect sex differences in the management of cardiometabolic risk factors, healthcare utilization, or the expression of comorbid conditions unrelated to a specific neuroprotective pathway. The concentration of T2DM with PD mortality in the 75 to 84 age group contrasts with the continuous age-related rise in T2DM with AD mortality, reflecting differing underlying age-risk profiles. The sharp increase in T2DM with PD mortality in the younger-old cohort (65–74 years) is particularly concerning, indicating a trend toward earlier disease impact with significant implications for healthcare planning.
The significant transition from institutional to home-based deaths mirrors broader societal trends favoring “aging in place,” influenced by rising long-term care costs and improvements in home-based palliative support. This shift, especially pronounced for T2DM with AD, places increasing demands on family caregivers and necessitates that healthcare systems adapt by strengthening home-care infrastructure and caregiver support programs.
Our findings necessitate stratified, evidence-informed strategies. Integrating routine cognitive and motor symptom screening into the standard management of older adults with T2DM is warranted, with particular vigilance for younger cohorts regarding PD risk and for Hispanic/Latino populations regarding both conditions. Public health programs must be developed to address the specific drivers of excess risk in high-burden groups, such as enhancing primary care access in underserved regions. Furthermore, fostering integrated care models that bridge endocrinology, neurology, and geriatrics is crucial for the holistic management of these complex comorbidities. Care planning must also account for the observed shift toward home death by ensuring adequate palliative resources in community settings.
Several limitations merit consideration. First, the reliance on death certificate data subjects the analysis to potential misclassification bias, including diagnostic overlap between PD, AD, and other dementias. Second, although ICD-10 codes remained stable, diagnostic practices and disease awareness have evolved over the 25-year span, potentially influencing trend interpretation. Third, our mortality projections, particularly for demographic subgroups, are subject to increased uncertainty. The ARIMA models require complete historical time-series data for stable forecasting; however, for some subgroups (e.g., smaller racial/ethnic populations in specific regions or years), data suppression rules resulted in missing or unstable data points due to low death counts. This data incompleteness may affect the precision of the subgroup-specific forecasts, and these results should therefore be interpreted with caution. Fourth, the absence of individual-level clinical data precludes causal inference regarding treatment effects or specific comorbidities. Additionally, broad racial/ethnic categories limit insights into heterogeneity within these groups. Finally, our projections assume the continuation of historical trends and do not account for future therapeutic breakthroughs. Results are specific to US adults aged ≥65 years and may not be generalizable to younger populations or healthcare systems in other countries.
5. Conclusion
In conclusion, this study delineates the escalating and distinct mortality burdens of T2DM when comorbid with PD versus AD in the older US population. The disparities observed across racial/ethnic, geographic, sex, and age groups identify populations in need of prioritized intervention. The projected rise in mortality underscores the necessity for timely, coordinated, and precise public health and clinical strategies that address both the shared metabolic origins and the unique pathological trajectories of these debilitating conditions.
Acknowledgments
We would like to thank all the participants involved in the survey.
Author contributions
Conceptualization: Huafeng Yang.
Data curation: Ting Zhang.
Formal analysis: Ting Zhang.
Funding acquisition: Xin Hong.
Methodology: Qiaoyu Huang.
Project administration: Huafeng Yang.
Resources: Guoliang Ma.
Software: Weiwei Wang.
Supervision: Weiwei Wang.
Validation: Guoliang Ma.
Visualization: Qiaoyu Huang, Simeng Sun.
Writing – original draft: Ting Zhang.
Writing – review & editing: Ting Zhang, Huafeng Yang.
Abbreviations:
- AAMR
- age-adjusted mortality rate
- AAPC
- average annual percentage change
- AD
- Alzheimer’s disease
- APC
- annual percentage change
- ARIMA
- autoregressive integrated moving average
- CDC
- Centers for Disease Control and Prevention
- ICD-10
- International Classification of Diseases, 10th Revision
- PD
- Parkinson’s disease
- T2DM
- type 2 diabetes mellitus.
This study was funded by grants from the Nanjing Municipal Medical Science and Technique Development Foundation (ZKX18049) and the Nanjing Key Medical Department (of Chronic NonCommunicable Disease Prevention and Control).
The authors have no conflicts of interest to disclose.
The datasets generated during and/or analyzed during the current study are publicly available.
How to cite this article: Zhang T, Ma G, Wang W, Huang Q, Sun S, Yang H, Hong X. Mortality trends and projections for type 2 diabetes with concomitant Parkinson’s versus Alzheimer’s disease among older United States adults, 1999–2023: A retrospective cohort study. Medicine 2026;105:27(e49321).
Contributor Information
Ting Zhang, Email: ztt2030405274@163.com.
Guoliang Ma, Email: 2750260520@qq.com.
Weiwei Wang, Email: 1715556404@qq.com.
Qiaoyu Huang, Email: 2030405274@qq.com.
Simeng Sun, Email: 2770642783@qq.com.
Huafeng Yang, Email: 13913832172@126.com.
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