Abstract
This study estimates neurological disease mortality rate trends in the US population from 1999 to 2017 as well as regionalized differences within the US.
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.
Methods
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
Results
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).
Table. Age-Adjusted Mortality Rates (AAMRs) per 100 000 From Neurological Diseases in the US by Region From 1999 to 2017 and Rates of Change by Disease Category and Inflection Point.
| Region | AAMR per 100 000 (SE) | Difference from 1999 to 2017 (95% CI) | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| 1999 | 2001 | 2003 | 2005 | 2007 | 2009 | 2011 | 2013 | 2015 | 2017 | ||
| Total mortality | 98.6 (0.2) | 98.6 (0.2) | 98.3 (0.2) | 94.0 (0.2) | 89.7 (0.2) | 86.3 (0.2) | 85.8 (0.2) | 84.2 (0.2) | 94.3 (0.2) | 98.6 (0.2) | 0 |
| Trend perioda | 1999 to 2013 | 2013 to 2017 | NA | ||||||||
| Rate of change, β (95% CI)b | −1.2 (−1.4 to −1.0) | 4.1 (2.8 to 5.5) | NA | ||||||||
| P value | <.001 | <.001 | NA | ||||||||
| Northeast | 81.0 (0.4) | 81.7 (0.4) | 78.9 (0.4) | 76.0 (0.3) | 72.4 (0.3) | 70.1 (0.3) | 69.6 (0.3) | 67.5 (0.3) | 72.7 (0.3) | 73.6 (0.3) | −7.4 |
| Midwestc,d | 103.8 (0.4) | 102.0 (0.4) | 101.5 (0.4) | 98.1 (0.4) | 93.3 (0.4) | 90.1 (0.3) | 90.8 (0.3) | 88.8 (0.3) | 94.9 (0.3) | 101.0 (0.3) | −2.8 |
| Southc,d | 103.0 (0.3) | 105.0 (0.3) | 104.8 (0.3) | 100.8 (0.3) | 96.8 (0.3) | 92.4 (0.3) | 90.6 (0.3) | 88.8 (0.3) | 104.2 (0.3) | 109.3 (0.3) | 6.3 |
| Westc,d | 103.8 (0.4) | 102.0 (0.4) | 103.9 (0.4) | 96.1 (0.4) | 90.7 (0.4) | 87.7 (0.4) | 87.9 (0.4) | 87.0 (0.3) | 96.6 (0.3) | 101.0 (0.3) | −2.8 |
| Cerebrovascular mortality | 61.6 (0.1) | 58.4 (0.1) | 54.6 (0.1) | 48.0 (0.1) | 43.5 (0.1) | 39.6 (0.1) | 37.9 (0.1) | 36.2 (0.1) | 37.6 (0.1) | 37.6 (0.1) | 24.0 |
| Trend perioda | 1999 to 2002 | 2002 to 2006 | 2006 to 2012 | 2012 to 2017 | NA | ||||||
| Rate of change, β (95% CI)b | −1.4 (−2.3 to −0.5) | −3.1 (−3.8 to −2.5) | −1.4 (−1.7 to −1.1) | 0.3 (−0.01 to 0.5) | NA | ||||||
| P value | .02 | <.001 | <.001 | .09 | NA | ||||||
| Northeast | 49.5 (0.3) | 47.2 (0.3) | 43.9 (0.3) | 38.8 (0.2) | 35.5 (0.2) | 32.9 (0.2) | 32.1 (0.2) | 30.5 (0.2) | 30.8 (0.2) | 29.4 (0.2) | −20.1 |
| Midwestc,d | 64.1 (0.3) | 59.4 (0.3) | 55.2 (0.3) | 49.3 (0.3) | 44.6 (0.2) | 40.5 (0.2) | 39.5 (0.2) | 37.4 (0.2) | 37.8 (0.2) | 38.3 (0.2) | −25.8 |
| Southc,d | 65.9 (0.3) | 63.0 (0.3) | 59.2 (0.2) | 52.4 (0.2) | 48.2 (0.2) | 43.7 (0.2) | 41.1 (0.2) | 39.5 (0.2) | 42.4 (0.2) | 42.1 (0.2) | −23.8 |
| Westc,d | 64.1 (0.3) | 60.9 (0.3) | 57.1 (0.3) | 48.1 (0.3) | 42.2 (0.3) | 38.0 (0.2) | 36.0 (0.2) | 34.3 (0.2) | 35.4 (0.2) | 36.6 (0.2) | −27.5 |
| Neurodegenerative mortality | 16.9 (0.1) | 19.8 (0.1) | 22.6 (0.1) | 24.6 (0.1) | 24.9 (0.1) | 25.4 (0.1) | 26.1 (0.1) | 25.5 (0.1) | 33.2 (0.1) | 36.8 (0.1) | 19.9 |
| Trend perioda | 1999 to 2005 | 2005 to 2013 | 2013 to 2017 | NA | |||||||
| Rate of change, β (95% CI)b | 1.3 (0.9 to 1.7) | 0.1 (−0.2 to 0.5) | 2.8 (2.1 to 3.6) | NA | |||||||
| P value | <.001 | .39 | <.001 | NA | |||||||
| Northeast | 12.7 (0.1) | 15.4 (0.2) | 16.1 (0.2) | 17.5 (0.2) | 17.4 (0.2) | 17.6 (0.2) | 17.7 (0.2) | 16.7 (0.2) | 20.6 (0.2) | 22.3 (0.2) | 9.6 |
| Midwestc,d | 17.9 (0.2) | 20.2 (0.2) | 23.0 (0.2) | 25.3 (0.2) | 25.5 (0.2) | 26.1 (0.2) | 27.1 (0.2) | 26.4 (0.2) | 31.3 (0.2) | 36.0 (0.2) | 18.1 |
| Southc,d | 17.3 (0.1) | 21.2 (0.1) | 24.4 (0.2) | 27.0 (0.2) | 27.2 (0.1) | 27.0 (0.2) | 27.3 (0.2) | 26.1 (0.2) | 37.6 (0.2) | 41.9 (0.2) | 24.6 |
| Westc,d | 19.7 (0.2) | 21.6 (0.2) | 26.0 (0.2) | 27.2 (0.2) | 28.3 (0.2) | 29.9 (0.2) | 31.4 (0.2) | 31.8 (0.2) | 39.5 (0.2) | 42.1 (0.2) | 22.4 |
| Other mortality | 14.0 (0.1) | 14.7 (0.1) | 15.4 (0.1) | 15.8 (0.1) | 15.8 (0.1) | 15.9 (0.1) | 16.6 (0.1) | 17.3 (0.1) | 18.1 (0.1) | 19.1 (0.1) | 5.1 |
| Trend perioda | 1999 to 2012 | 2012 to 2017 | NA | ||||||||
| Rate of change, β (95% CI)b | 0.2 (0.2 to 0.2) | 0.5 (0.3 to 0.6) | NA | ||||||||
| P value | <.001 | <.001 | NA | ||||||||
| Northeast | 12.7 (0.1) | 13.5 (0.2) | 13.5 (0.2) | 14.2 (0.2) | 14.3 (0.2) | 14.4 (0.2) | 14.8 (0.2) | 15.3 (0.2) | 16.0 (0.2) | 16.7 (0.2) | 4.0 |
| Midwestc,d | 15.6 (0.2) | 16.2 (0.2) | 17.2 (0.2) | 17.8 (0.2) | 17.5 (0.2) | 17.7 (0.2) | 18.6 (0.2) | 19.3 (0.2) | 20.1 (0.2) | 21.2 (0.2) | 5.6 |
| Southc,d | 13.9 (0.1) | 14.8 (0.1) | 15.4 (0.1) | 15.8 (0.1) | 16.2 (0.1) | 16.3 (0.1) | 17.0 (0.1) | 17.9 (0.1) | 18.9 (0.1) | 20.2 (0.1) | 6.3 |
| Westc,e | 13.9 (0.2) | 13.9 (0.2) | 15.1 (0.2) | 15.2 (0.2) | 14.9 (0.2) | 14.7 (0.1) | 15.4 (0.1) | 15.8 (0.1) | 16.6 (0.1) | 17.4 (0.1) | 3.5 |
| Neoplasms | 6.1 (0) | 5.9 (0) | 5.8 (0) | 5.6 (0) | 5.4 (0) | 5.4 (0) | 5.3 (0) | 5.3 (0) | 5.3 (0) | 5.1 (0) | −1.0 |
| Trend perioda | 1999 to 2007 | 2007 to 2017 | NA | ||||||||
| Rate of change, β (95% CI)b | −0.1 (−0.1 to −0.1) | −0.02 (−0.03 to −0.02) | NA | ||||||||
| P value | <.001 | .01 | NA | ||||||||
| Northeast | 6.1 (0.1) | 5.6 (0.1) | 5.4 (0.1) | 5.5 (0.1) | 5.3 (0.1) | 5.3 (0.1) | 5.0 (0.1) | 5.0 (0.1) | 5.3 (0.1) | 5.2 (0.1) | −0.9 |
| Midwest | 6.4 (0.1) | 6.1 (0.1) | 6.1 (0.1) | 5.7 (0.1) | 5.7 (0.1) | 5.7 (0.1) | 5.6 (0.1) | 5.6 (0.1) | 5.7 (0.1) | 5.4 (0.1) | −1.0 |
| Southf | 5.9 (0.1) | 5.9 (0.1) | 5.9 (0.1) | 5.7 (0.1) | 5.4 (0.1) | 5.3 (0.1) | 5.2 (0.1) | 5.3 (0.1) | 5.3 (0.1) | 5.1 (0.1) | −0.8 |
| West | 6.0 (0.1) | 5.6 (0.1) | 5.6 (0.1) | 5.6 (0.1) | 5.3 (0.1) | 5.2 (0.1) | 5.2 (0.1) | 5.1 (0.1) | 5.1 (0.1) | 5.0 (0.1) | −1.0 |
Abbreviation: NA, not applicable.
Separated based on inflection points determined with Joinpoint software (National Cancer Institute) by examining changes in slopes of trend lines.
Rate of change presented as the regression estimate (β value) with 95% CIs and P values.
Analysis of variance P < .001 for difference in means with Northeast as the reference group in 1999.
Analysis of variance P < .001 for difference in means with Northeast as the reference group in 2017.
Analysis of variance P <.05 for difference in means with Northeast as the reference group in 1999.
Analysis of variance P < .05 for difference in means with Northeast as the reference group in 2017.
Figure. Trends in Total and Disease-Specific Neurological Disease Age-Adjusted Mortality Rates per 100 000 in the US From 1999 to 2017.
Error bars indicate 95% CIs.
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.
Discussion
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.
References
- 1.GBD 2016 Neurology Collaborators Global, regional, and national burden of neurological disorders, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol. 2019;18(5):459-480. doi: 10.1016/S1474-4422(18)30499-X [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Shah NS, Lloyd-Jones DM, O’Flaherty M, et al. Trends in cardiometabolic mortality in the United States, 1999-2017. JAMA. 2019;322(8):780-782. doi: 10.1001/jama.2019.9161 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Gooch CL, Pracht E, Borenstein AR. The burden of neurological disease in the United States: a summary report and call to action. Ann Neurol. 2017;81(4):479-484. doi: 10.1002/ana.24897 [DOI] [PubMed] [Google Scholar]
- 4.US Centers for Disease Control and Prevention About underlying cause of death, 1999-2018. Accessed December 3, 2019. https://wonder.cdc.gov/ucd-icd10.html
- 5.National Cancer Institute Division of Cancer Control and Population Sciences Joinpoint trend analysis software. Accessed February 12, 2020. https://surveillance.cancer.gov/joinpoint/