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Articles
March 5, 2014
Letter to the Editor

Contribution of Alzheimer disease to mortality in the United States

March 25, 2014 issue
82 (12) 1045-1050

Abstract

Objective:

To assess the burden of mortality attributable to Alzheimer disease (AD) dementia in the United States.

Methods:

Data came from 2,566 persons aged 65 years and older (mean 78.1 years) without dementia at baseline from 2 cohort studies of aging with identical annual diagnostic assessments of dementia. Because both studies require organ donation, ascertainment of mortality was complete and dates of death accurate. Mortality hazard ratios (HRs) after incident AD dementia were estimated per 10-year age strata from proportional hazards models. Population attributable risk percentage was derived to estimate excess mortality after a diagnosis of AD dementia. The number of excess deaths attributable to AD dementia in the United States was then estimated.

Results:

Over an average of 8 years, 559 participants (21.8%) without dementia at baseline developed AD dementia and 1,090 (42.4%) died. Median time from AD dementia diagnosis to death was 3.8 years. The mortality HR for AD dementia was 4.30 (confidence interval = 3.33, 5.58) for ages 75–84 years and 2.77 (confidence interval = 2.37, 3.23) for ages 85 years and older (too few deaths after AD dementia in ages 65–74 were available to estimate HR). Population attributable risk percentage was 37.0% for ages 75–84 and 35.8% for ages 85 and older. An estimated 503,400 deaths in Americans aged 75 years and older were attributable to AD dementia in 2010.

Conclusions:

A larger number of deaths are attributable to AD dementia in the United States each year than the number (<84,000 in 2010) reported on death certificates.

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Letters to the Editor
24 March 2014
Response from authors
Bryan D. James, Assistant professor
Bryan James, Sue Leurgans, David Bennett; Chicago, IL

We appreciate Dr. Campbell-Taylor???s feedback and regret any confusion. We appreciate the distinction between "immediate" and "underlying" causes of death, and it is up to the CDC to decide how US death certificates are to be completed. Our goal was to estimate excess deaths due to Alzheimer's disease (AD) regardless of the immediate or secondary causes of death. Therefore, we prospectively followed older persons without dementia, accurately counted who developed AD, and the excess deaths associated with having AD. This approach is agnostic to the exact series of events that lead to death. It strongly implicates AD as an underlying cause in many more deaths than reported. Our crude estimate of 500,000+ excess deaths in the US is likely valid, although it will be important to see results from other cohort studies. We introduced the concept of "mixed mortality" to reflect how many chronic conditions contribute to death in old age. Trying to identify a single cause of death may not accurately reflect the process of dying for most older persons. Overall, our study suggests that developing AD markedly increases one's risk of death and contributes to more than half a million deaths in the US each year.

For disclosures, please contact the editorial office at [email protected].

12 March 2014
Confusion over Alzheimer Deaths
Irene Campbell-Taylor, Clinical Neurologist
New Waterford, NS

I read the article by James et al. and would like to comment on some of the authors' confusing statements. The authors stated: "Death certificates often list the immediate cause of death, such as pneumonia, rather than listing dementia as an underlying cause." [1] It's not an "instead of" issue. Immediate cause and underlying cause are two different things. Immediate cause is usually something like pneumonia, the event that caused the heart and lungs to stop. This is the reason that physicians are instructed never to put "cardiopulmonary arrest" as the immediate cause as everybody dies of cardiopulmonary arrest. Under that line on the certificate are two words "due to" in small print and this is where the underlying, actual cause of death is listed. However, the misdiagnosis rate for Alzheimer disease (AD) is at least 50% so that the cause of death as AD is also possibly incorrect. The authors contend that AD was confirmed through autopsy for about 90 percent of those who were clinically diagnosed. That is 90% of 21% of the total. It was not - probably could not- have been verified in the total. The article is based on the inability of physicians to accurately complete certificates of death thereby causing serious doubt as to the actual numbers of persons whose cause of death is anything because the underlying and antecedent cause is not given. A valid certificate might read pneumonia due to congestive heat failure due to COPD. Cause of death: COPD. Apparently we should be spending more time teaching physicians how to fill in death certificates to obtain valid numbers. This is a confusing and confused article.

1. James BD, Leurgans SE, Hebert LE, Scherr PA, Yaffe K, Bennett DA. Contribution of Alzheimer disease to mortality in the United States. Neurology 2014; 0: WNL.0000000000000240v1-101212000.

For disclosures, please contact the editorial office at [email protected].

Information & Authors

Information

Published In

Neurology®
Volume 82Number 12March 25, 2014
Pages: 1045-1050
PubMed: 24598707

Publication History

Received: June 12, 2013
Accepted: December 11, 2013
Published online: March 5, 2014
Published in print: March 25, 2014

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Disclosure

B. James is funded by National Institute on Aging (NIA) grants R01AG17917, R01AG033678, and P30 AG10161. Dr. James is a consultant for the Alzheimer's Association and Partner's Health Care System. S. Leurgans is supported by grants from the NIH (R01AG017917, P30AG010161, RC2AG036547, R01AG042210, P20MD006886, R01NS078009, R01AG036042, P01AG014449, P01AG009466, R01NS028127, and R21AG030346) and the Illinois Department of Public Health (contract 23282007). Dr. Leurgans served as a paid faculty member for a Parkinson's Disease Foundation Learning Institute. L. Hebert is/has been supported by NIH grants NR010211, AG303544, AG011101, AG036650, and AG009966. Dr. Hebert reports no disclosures. P. Scherr is supported as a consultant to the Rush Institute of Healthy Aging. Dr. Scherr reports no disclosures. K. Yaffe is supported by NIA K24 AG031155. Dr. Yaffe reports research support from the NIH (NIA R01 AG05401, NIMH R01 MH086498, NIA R01 AG026720, NIDDK R01 DK069406, NIA P50 AG023501, and NIA 2P01 AG019724), the Alzheimer's Association, Department of Defense, California Department of Public Health, and the Bright Focus Foundation. She serves on data safety monitoring boards for Takeda, Inc. and a study sponsored by the NIH and has served as a consultant for Novartis, Inc. D. Bennett is supported by grants from the NIH (R01AG017917, P30AG010161, R01AG015819, U01AG46152, and R01AG036042), and Nutricia, Inc. Dr. Bennett serves on the editorial board of Neurology, Current Alzheimer Research, and Neuroepidemiology; has received honoraria for nonindustry-sponsored lectures; serves on data safety monitoring boards for Takeda, Inc., and has served as a consultant to Nutricia, Inc., Eli Lilly, Inc., Gerson Lehrman Group, Double Helix, and Enzymotic, Ltd. Go to Neurology.org for full disclosures.

Study Funding

Directly supported by the National Institute on Aging (P30 AG10161, R01AG15819, R01AG17917, K24AG031155), and the Illinois Department of Public Health (contract 23282007).

Authors

Affiliations & Disclosures

Bryan D. James, PhD
From the Rush Alzheimer's Disease Center (B.D.J., S.E.L., D.A.B.), Chicago; Departments of Internal Medicine (B.D.J.) and Neurological Sciences (S.E.L., D.A.B.), and Rush Institute on Healthy Aging (L.E.H., P.A.S.), Rush University Medical Center, Chicago, IL; Departments of Psychiatry, Neurology, and Epidemiology (K.Y.), University of California, San Francisco; and San Francisco Veterans Affairs Medical Center (K.Y.), San Francisco, CA.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
(1) Alzheimer's Association (2) Partners Healthcare
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Sue E. Leurgans, PhD
From the Rush Alzheimer's Disease Center (B.D.J., S.E.L., D.A.B.), Chicago; Departments of Internal Medicine (B.D.J.) and Neurological Sciences (S.E.L., D.A.B.), and Rush Institute on Healthy Aging (L.E.H., P.A.S.), Rush University Medical Center, Chicago, IL; Departments of Psychiatry, Neurology, and Epidemiology (K.Y.), University of California, San Francisco; and San Francisco Veterans Affairs Medical Center (K.Y.), San Francisco, CA.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
(1) NIH: P30AG010161 (ADC), core Leader and statistician, 2007-ongoing (2) NIH: RC2AG036547, statistician (3) NIH: R01 AG017917, statistician, 2008-present (4) NIH: P01 AG014449, Core leader, 2001-present (5) NIH: P01 AG009466, Core Leader, 2000-present (6) NIH: R01NS028127, statistician, 2006-present (7) NIH: R01 AG024480, statistician, 2007-present (8) NIH: R01 AG033678, statistician, 2008-present
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Liesi E. Hebert, ScD
From the Rush Alzheimer's Disease Center (B.D.J., S.E.L., D.A.B.), Chicago; Departments of Internal Medicine (B.D.J.) and Neurological Sciences (S.E.L., D.A.B.), and Rush Institute on Healthy Aging (L.E.H., P.A.S.), Rush University Medical Center, Chicago, IL; Departments of Psychiatry, Neurology, and Epidemiology (K.Y.), University of California, San Francisco; and San Francisco Veterans Affairs Medical Center (K.Y.), San Francisco, CA.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NIH R01NR010211 PI 2009-2012 NIH R01AG030544 biostatistician 2008-2011 NIH R01AG009966 biostatistician 2008-2010 NIH RO1AG011101 epidemiologist 2009-2011 NIH RC2AG036650 biostatistician 2009-2011
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
a contract with the Alzheimer's Association to cover some of the costs of calculating projections of numbers of people with AD in the US
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Paul A. Scherr, PhD, ScD
From the Rush Alzheimer's Disease Center (B.D.J., S.E.L., D.A.B.), Chicago; Departments of Internal Medicine (B.D.J.) and Neurological Sciences (S.E.L., D.A.B.), and Rush Institute on Healthy Aging (L.E.H., P.A.S.), Rush University Medical Center, Chicago, IL; Departments of Psychiatry, Neurology, and Epidemiology (K.Y.), University of California, San Francisco; and San Francisco Veterans Affairs Medical Center (K.Y.), San Francisco, CA.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
Rush Institute for Healthy Aging
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
Employee of Centers for Disease Control and Prevention (CDC)
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Kristine Yaffe, MD
From the Rush Alzheimer's Disease Center (B.D.J., S.E.L., D.A.B.), Chicago; Departments of Internal Medicine (B.D.J.) and Neurological Sciences (S.E.L., D.A.B.), and Rush Institute on Healthy Aging (L.E.H., P.A.S.), Rush University Medical Center, Chicago, IL; Departments of Psychiatry, Neurology, and Epidemiology (K.Y.), University of California, San Francisco; and San Francisco Veterans Affairs Medical Center (K.Y.), San Francisco, CA.
Disclosure
Scientific Advisory Boards:
1.
-Novartis, Inc. - Pfizer -DSMB for Takeda, Inc -DSMB for NIH trials - Beeson Advisory Scientific Committee
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
-Associate Editor, 2011-, International Review of Psychiatry -Associate Editor 2012-, Journal of Gerontology: Medical Sciences
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NIH, NIA, NIDDK, NIMH, Department of Defense, California Department of Public Health
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
Bright Focus Foundation and Alzheimer Association's
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
David A. Bennett, MD
From the Rush Alzheimer's Disease Center (B.D.J., S.E.L., D.A.B.), Chicago; Departments of Internal Medicine (B.D.J.) and Neurological Sciences (S.E.L., D.A.B.), and Rush Institute on Healthy Aging (L.E.H., P.A.S.), Rush University Medical Center, Chicago, IL; Departments of Psychiatry, Neurology, and Epidemiology (K.Y.), University of California, San Francisco; and San Francisco Veterans Affairs Medical Center (K.Y.), San Francisco, CA.
Disclosure
Scientific Advisory Boards:
1.
1) Vigorous Minds, Scientific Advisory Board
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
Nutricia, paid for travel to scientific meeting
Editorial Boards:
1.
(1) Neurology, Editorial Board; (2) Current Alzheimer Research, Editorial Board; (3) Neuroepidemiology, Editorial Board
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
(1) Nutricia, Inc., (2) Eli Lilly, Inc., (3) the Gerson Lehrman Group, (4) Enzymotec Ltd., (5) Double Helix, (6) Takeda Pharmaceuticals USA, Inc
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
(1) Nutricia Inc., PI
Research Support, Government Entities:
1.
NIH: P30AG10161, PI; R01AG15819, PI; R01AG17917, PI; R01AG36042, PI; U01AG32984, Co-I; R01AG22018, Co-I; R01AG33678, Co-I; R01AG36836, Co-I; R01AG41797, Co-I; R01AG42210, Co-I; and Illinois Department Public Health
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE

Notes

Correspondence to Dr. James: [email protected]
Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

Author Contributions

Dr. Bryan D. James is the primary author of this manuscript. He was responsible for the study concept and design, interpretation of data, and drafting the manuscript. Dr. Sue E. Leurgans conducted the analysis for this study and contributed to the study concept and design and interpretation of data. Dr. Liesi E. Hebert, Dr. Paul A. Scherr, and Dr. Kristine Yaffe contributed to the study design and interpretation of data. Dr. David A. Bennett is the senior author of this manuscript. He is responsible for the initial concept of the study, study supervision, contribution to interpretation of data, and obtaining funding for the cohort studies.

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