The World Health Organization’s international Global Burden of Disease 2016 study1 noted a decrease in rates of age-standardized neurological disorder death from 1990 to 2015, with a significant increase in disease burden due to aging populations and population growth. Considerable US health care system investments into cardiovascular disease and cancer research have resulted in dramatic increases in overall health and survival while potentially increasing neurological diseases’ relative burden.2,3 We estimate neurological disease mortality rate trends at a population scale from January 1999 to December 2017 while investigating regionalized differences within the US.
We calculated age-adjusted mortality rates (AAMRs) per 100 000 using the US Centers for Disease Control and Prevention Wide-ranging Online Data for Epidemiologic Research (WONDER) database4 from January 1999 to December 2017. AAMR values per 100 000 were standardized to the 2000 US population and were calculated for overall neurological diseases and in the following categories by International Statistical Classification of Diseases and Related Health Problems, Tenth Revision code: cerebrovascular (I60-I69), neurodegenerative (G30-G32), neoplastic (C70-C72, D32-D33, and D42-D43), and other (G00-G29, G35-G37, G40-G47, G50-G59, G60-G65, G70-G73, G80-G83, and G89-G99). AAMRs per 100 000 were calculated for all neurological diseases and for each category by census region (Northeast, Midwest, South, and West). Regional differences were assessed with 1-way analysis of variance using the Northeast region as the reference in January 1999 and December 2017.
Rates of change were determined using linear regression. Significance was set at a P value less than .05, and all P values were 2-tailed. The Joinpoint regression program version 4.7.0.0 (National Cancer Institute) was used to identify inflection points, and rates of change over time with 95% CIs were calculated using linear regression.5
Overall, AAMRs per 100 000 from neurological disease exhibited a sharp decline from 98.6 (95% CI, 98.2 to 99.0) in 1999 to 84.2 (95% CI, 83.9 to 84.5) in 2013, a decrease in AAMR per 100 000 of 1.2 (95% CI, −1.4 to −1.0) per year (Table). However, by 2017, the AAMR per 100 000 rose back to 98.6 (95% CI, 98.3 to 99.0), an increase of 4.1 (95% CI, 2.8 to 5.5) per year (Figure). There was a significant average decline in cerebrovascular AAMRs per 100 000 from 61.6 (95% CI, 61.3 to 61.9) in 1999 to 37.6 (95% CI, 37.4 to 37.8) in 2017, despite a plateau from 2012 to 2017 (β = 0.3; 95% CI, −0.01 to 0.5). This decline was mirrored by an increased AAMR per 100 000 from neurodegenerative disorders (1999: 16.9; 95% CI, 16.7 to 17.0; 2017: 36.8; 95% CI, 36.6 to 36.9) driven by increases from 1999 to 2005 (β = 1.3; 95% CI, 0.9 to 1.7) and 2013 to 2017 (β = 2.8; 95% CI, 2.1 to 3.6).
In 1999, the regional AAMR per 100 000 for cerebrovascular disease was highest in the South region at 65.9 (95% CI, 65.3 to 66.4) and remained the highest there in 2017 at 42.1 (95% CI, 41.7 to 42.4) compared with the Northeast region (29.4; 95% CI, 29.0 to 29.7), Midwest region (38.3; 95% CI, 37.9 to 38.8), and West region (36.6; 95% CI, 36.1 to 37.0). The South region was also the only region to have an increased total neurological disease AAMR per 100 000 (1999: 103.0; 95% CI, 102.4 to 103.7; 2017: 109.3; 95% CI, 108.7 to 109.8) over the study period.
A U-shaped trend in US neurological disease mortality is evident from 1999 to 2017, attributable to declining cerebrovascular mortality and escalating mortality from Alzheimer dementia and other neurodegenerative disorders. This trend of increasing deaths from neurological disease will likely accelerate with an aging population and rising neurodegenerative disorder prevalence.3 The Southern region in the US also showed less cerebrovascular mortality improvement while worsening in overall neurological mortality rates. Further studies examining neurological disease prevalence, access to care, and racial/ethnic and socioeconomic disparities are needed to determine if they are causing these regional differences. Study weaknesses include International Statistical Classification of Diseases and Related Health Problems, Tenth Revision coding limitations, death certificate mortality tracking, and lack of morbidity results.
Population-level survival gains from treating and preventing cerebrovascular disease have already been overtaken by rising neurodegenerative disease rates. Neurological disorders provide an imminent, and growing, threat to public health.
Accepted for Publication: February 27, 2020.
Corresponding Author: Eric Karl Oermann, MD, Department of Neurological Surgery, Mount Sinai Health System, One Gustave L. Levy Place, Annenberg Building, 8th Floor, New York, NY 10029 (eric.oermann@mountsinai.org).
Published Online: June 22, 2020. doi:10.1001/jamaneurol.2020.1878
Author Contributions: Mr Neifert and Dr Oermann had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.
Study concept and design: Neifert, McNeill, Caridi, Mocco, Oermann.
Acquisition, analysis, or interpretation of data: Neifert, Rothrock, Mocco, Oermann.
Drafting of the manuscript: Neifert, Mocco, Oermann.
Critical revision of the manuscript for important intellectual content: All authors.
Statistical analysis: Neifert, Mocco, Oermann.
Administrative, technical, or material support: Rothrock, Caridi, Mocco, Oermann.
Study supervision: McNeill, Caridi, Mocco, Oermann.
Conflict of Interest Disclosures: Dr Caridi reports receiving consulting fees from Zimmer Biomet. Dr Mocco reports receiving research support from Stryker, Penumbra, Medtronic, and Microvention and is a consultant for Imperative Care, Cerebrotech, Viseon, Endostream, Rebound Therapeutics, and Vastrax. Dr Oermann reports owning equity in MedAugur and Whiteboard Coordinator, receiving consulting fees from Google, and being employed at Merck. No other disclosures were reported.