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January 14, 2015

“Noncognitive” symptoms of early Alzheimer disease
A longitudinal analysis

February 10, 2015 issue
84 (6) 617-622

Abstract

Objectives:

To observe the natural time course of noncognitive symptoms before the onset of symptomatic Alzheimer disease dementia.

Methods:

Using the National Alzheimer's Coordinating Center Uniform Data Set from September 2005 to March 2013, data from cognitively normal individuals who were aged 50 years or older at first visit and had subsequent follow-up were analyzed. Survival analyses were used to examine the development of particular symptoms relative to each other on the Neuropsychiatric Inventory Questionnaire (NPI-Q), Functional Activities Questionnaire, and Geriatric Depression Scale, and to compare the development of individual symptoms for persons who did and did not receive a Clinical Dementia Rating (CDR) >0 (indicating abnormal cognition) during the follow-up period.

Results:

The order of symptom occurrence on the NPI-Q was similar for participants who remained at CDR 0 and for those who received a CDR >0 over the follow-up period, although the time to most NPI-Q symptoms was faster for participants who received a CDR >0 (p < 0.001). With the exception of memory, Geriatric Depression Scale symptoms reported by both CDR groups were similar.

Conclusions:

We found a significantly earlier presence of positive symptoms on the NPI-Q in cognitively normal patients who subsequently developed CDR >0. Among participants with no depression symptoms at baseline, results suggest that depressive symptoms may increase with aging regardless of incipient dementia. Such findings begin to delineate the noncognitive course of Alzheimer disease dementia in the preclinical stages. Future research must further elucidate the correlation between noncognitive changes and distinct dementia subtypes.

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Information & Authors

Information

Published In

Neurology®
Volume 84Number 6February 10, 2015
Pages: 617-622
PubMed: 25589671

Publication History

Received: June 16, 2014
Accepted: October 10, 2014
Published online: January 14, 2015
Published in print: February 10, 2015

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Disclosure

M. Masters reports no disclosures relevant to the manuscript. J. Morris reports disclosures: Neither Dr. Morris nor his family owns stock or has equity interest (outside of mutual funds or other externally directed accounts) in any pharmaceutical or biotechnology company. Dr. Morris has participated or is currently participating in clinical trials of antidementia drugs sponsored by Janssen Immunotherapy and Pfizer. Dr. Morris has served as a consultant for the following companies: Eisai, Esteve, Janssen Alzheimer Immunotherapy Program, GlaxoSmithKline, Novartis, and Pfizer. He receives research support from Eli Lilly/Avid Radiopharmaceuticals and is funded by NIH grants P50AG005681, P01AG003991, P01AG026276, and U19AG032438. C. Roe reports no disclosures relevant to the manuscript. Go to Neurology.org for full disclosures.

Study Funding

Funding for this study was provided by the Longer Life Foundation, the National Institute on Aging (NIA) (P50 AG005681, P01 AG003991, and P01 AG026276), Fred Simmons and Olga Mohan, the Farrell Family Research Fund, and the Charles and Joanne Knight Alzheimer's Research Initiative of the Washington University Knight Alzheimer's Disease Research Center (ADRC). The NACC database is funded by NIA grant U01 AG016976.

Authors

Affiliations & Disclosures

Mary Clare Masters, MD
From the Departments of Neurology (J.C.M., C.M.R.), Pathology and Immunology (J.C.M.), Physical Therapy (J.C.M.), and Occupational Therapy (J.C.M.), and Knight Alzheimer's Disease Research Center (J.C.M., C.M.R.), Washington University School of Medicine (M.C.M., J.C.M., C.M.R.), St. Louis, MO.
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.
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
John C. Morris, MD
From the Departments of Neurology (J.C.M., C.M.R.), Pathology and Immunology (J.C.M.), Physical Therapy (J.C.M.), and Occupational Therapy (J.C.M.), and Knight Alzheimer's Disease Research Center (J.C.M., C.M.R.), Washington University School of Medicine (M.C.M., J.C.M., C.M.R.), St. Louis, MO.
Disclosure
Scientific Advisory Boards:
1.
Lilly USA
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
Serves on the editorial advisory board of JAMA Neurology
Patents:
1.
NONE
Publishing Royalties:
1.
1. Blackwell Publishing, 2009, for Burns J and Morris JC, “Mild Cognitive Impairment and Early Alzheimer's Disease”, copyright 2008 by John Wiley and Sons, Ltd 2. Taylor & Francis 2008; “Handbook of Dementing Illnesses, 2 Ed”, Morris JC, Galvin JE, Holtzman DM, Eds, copyright 2006
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.
Receives research support from Eli Lilly/Avid Radiopharmaceuticals
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
Catherine M. Roe, PhD
From the Departments of Neurology (J.C.M., C.M.R.), Pathology and Immunology (J.C.M.), Physical Therapy (J.C.M.), and Occupational Therapy (J.C.M.), and Knight Alzheimer's Disease Research Center (J.C.M., C.M.R.), Washington University School of Medicine (M.C.M., J.C.M., C.M.R.), St. Louis, MO.
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.
Salary support from NIH/NIA (R01 AG04343401, R01 AG15928- 02, P50-AG05681, P50-AG0568129 and P01- AG03991), the Longer Life Foundation, from the Charles and Joanne Knight Alzheimer Research Initiative of the Knight Alzheimer?s Disease Research Center, The Farrell Family Research Fund, and The generous support of F Simmons and O Mohan.
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.
Salary support from NIH/NIA (R01 AG04343401, R01 AG15928- 02, P50-AG05681, P50-AG0568129 and P01- AG03991),
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
The Charles and Joanne Knight Alzheimer Research Initiative of the Knight Alzheimer?s Disease Research Center, the Longer Life Foundation, The Farrell Family Research Fund, and The generous support of F Simmons and O Mohan
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. Roe: [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

Ms. Masters: study concept and design, data analysis and interpretation, drafting and critical revision of manuscript. Dr. Morris: data analysis and interpretation, critical revision of manuscript, study supervision. Dr. Roe: study concept and design, data analysis and interpretation, drafting and critical revision of manuscript.

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