Introduction: Alzheimer's disease and anemia are both common among older adults in the United States and are linked to increased morbidity and mortality, particularly when paired. Anemia may accelerate cognitive decline by inducing neuronal hypoxia, disrupting neurotransmitter synthesis and myelination through nutrient deficiencies (e.g., B12, folate, iron), and promoting oxidative stress and systemic inflammation. Observational studies report that anemic individuals have a 41% greater risk of developing dementia over 11 years compared to those without anemia. Demographic and geographically stratified mortality trend analyses concerning Alzheimer's disease and anemia amongst the elderly in the United States are limited. This study examines national mortality trends in adults aged ≥ 65 years with Alzheimer's disease and anemia from 1999 to 2023.

Methods: The CDC WONDER Multiple Cause-of-Death dataset (1999-2023) was used to analyze mortality trends in adults aged ≥ 65 years using ICD-10 codes for Alzheimer's disease (G30) and anemia (D55-D59, D60-D64). Results were stratified by place of death, year, sex, age group, race, census region, state, and urbanization. Age-adjusted mortality rates (AAMRs) were quantified per 100,000 persons by standardizing crude mortality rates (CMRs) with 95% confidence intervals (95%CI). Annual percent change (APC) and average annual percent change (AAPC) were calculated using Joinpoint regression software. Statistical significance was defined as a P value < 0.05.

Results: A total of 51,506 Alzheimer's disease and anemia-related deaths occurred in adults ≥ 65 years in the United States from 1999 to 2023. Most of the deaths occurred in nursing homes/long-term care facilities (61.57%), followed by the decedent's home (16.14%), medical facilities (14.05%), other/place of death unknown (5.52%), and hospices (2.72%). Overall AAMRs increased from 4.43 in 1999 to 5.88 in 2003 (APC: 7.20; 95%CI: 1.69 to 19.02), but declined to 3.88 in 2023 (APC: -1.98; 95%CI: -2.61 to -1.52). This culminated in an overall period of statistically stable AAMRs from 1999- 2023. Women had a higher average AAMR (5.23) compared to men (4.00). Women had statistically stable AAMRs spanning the study duration, while men saw their AAMR decline (AAPC men: -0.90; 95%CI: -1.4 to -0.37). Average CMRs increased with age, as adults ≥ 85 years had the highest average CMR (26.15),

followed by 75-84 year olds (3.96), and 65-74 year olds (0.35). Adults aged 65-74 years had their AAMR increase (AAPC: 0.93; 95%CI: 0.11 to 2.35), while adults aged 75-84 years had their AAMR decrease (AAPC: -1.17; 95%CI: -2.19 to -0.16). Adults ≥ 85 years had statistically stable AAMRs. Racially, non-Hispanic (NH) Black/African Americans had the highest average AAMR (6.44), followed by NH Whites (4.70) and Hispanic/Latinos (4.24). NH Black/African Americans and NH Whites had decreasing AAMRs (AAPC NH Black/African American: -1.02; 95%CI: -1.70 to -0.13; AAPC NH White: -0.67; 95%CI: -1.22 to -0.05), while Hispanic/Latinos had stable AAMRs. Amongst census regions, the West had the highest average AAMR (5.23), followed by the South (5.12), the Midwest (4.96), and the Northeast (3.58). The Northeast saw the highest rate of decline in AAMRs, followed by the South and the Midwest (AAPC Northeast: -1.74; 95%CI: -2.95 to -0.73; AAPC South: -1.09; 95%CI: -1.84 to -0.41; AAPC Midwest: -0.84; 95%CI: -1.57 to -0.15). In contrast, the West had stable AAMRs. State-wise, California had the greatest number of deaths at 7,728, accounting for 15.00% of deaths. From 1999-2020, rural areas had a higher average AAMR (5.70) compared to urban areas (4.73). Rural areas had increasing AAMRs (AAPC: 0.69; 95%CI: 0.18 to 1.24), while urban areas had stable rates.

Conclusion: National Alzheimers and anemia-related mortality rates in the elderly have largely remained stable from 1999 to 2023, with interspersed periods of increase and decrease.

Crucial disparities among demographic and geographical stratifications were illustrated. Further research into the interplay between Alzheimer's disease and anemia and its associated mortality is of great importance to address these disparities. The formulation of public health programs to address at-risk populations is critical to ameliorate health outcomes related to Alzheimers disease and anemia.

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2025
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