Cerebrovascular risk factors and preclinical memory decline in healthy APOE ε4 homozygotes
Citation Manager Formats
Make Comment
See Comments
This article requires a subscription to view the full text. If you have a subscription you may use the login form below to view the article. Access to this article can also be purchased.
Objective: To characterize the effects of cerebrovascular (CV) risk factors on preclinical memory decline in cognitively normal individuals at 3 levels of genetic risk for Alzheimer disease (AD) based on APOE genotype.
Methods: We performed longitudinal neuropsychological testing on an APOE ε4 enriched cohort, ages 21–97. The long-term memory (LTM) score of the Auditory Verbal Learning Test (AVLT) was the primary outcome measure. Any of 4 CV risk factors (CVany), including hypercholesterolemia (CHOL), prior cigarette use (CIG), diabetes mellitus (DM), and hypertension (HTN), was treated as a dichotomized variable. We estimated the longitudinal effect of age using statistical models that simultaneously modeled the cross-sectional and longitudinal effects of age on AVLT LTM by APOE genotype, CVany, and the interaction between the two.
Results: A total of 74 APOE ε4 homozygotes (HMZ), 239 ε4 heterozygotes (HTZ), and 494 ε4 noncarriers were included. APOE ε4 carrier status showed a significant quadratic effect with age-related LTM decline in all models as previously reported. CVany was associated with further longitudinal AVLT LTM decline in APOE ε4 carriers (p = 0.02), but had no effect in noncarriers. When ε4 HTZ and HMZ were considered separately, there was a striking effect in HMZ (p < 0.001) but not in HTZ. In exploratory analyses, significant deleterious effects were found for CIG (p = 0.001), DM (p = 0.03), and HTN (p = 0.05) in APOE ε4 carriers only that remained significant only for CIG after correction for multiple comparisons.
Conclusion: CV risk factors influence age-related memory decline in APOE ε4 HMZ.
Footnotes
-
Study funding: Supported by the National Institute on Aging (P30-AG19610 and R01-AG031581), the National Institute of Mental Health (R01-MH057899), the Alzheimer's Association (IIRG-98-078), the Arizona Alzheimer's Consortium, the State of Arizona, and with resources from Southern Arizona VA Health Care System.
-
- AD
- Alzheimer disease
- AVLT
- Auditory Verbal Learning Test
- CHOL
- hypercholesterolemia
- CI
- confidence interval
- CIG
- cigarette use
- CV
- cerebrovascular
- CVany
- any of 4 cerebrovascular risk factors
- DM
- diabetes mellitus
- DSM-III-R
- Diagnostic and Statistical Manual of Mental Disorders, 3rd edition, revised
- FAQ
- Functional Activities Questionnaire
- Ham-D
- Hamilton Depression Rating Scale
- HMZ
- homozygotes
- HTN
- hypertension
- HTZ
- heterozygote
- IADL
- Instrumental Activities of Daily Living
- LTM
- long-term memory
- MCI
- mild cognitive impairment
- MMSE
- Mini-Mental State Examination
-
Supplemental data at www.neurology.org
- Received September 2, 2010.
- Accepted November 18, 2010.
- Copyright © 2011 by AAN Enterprises, Inc.
AAN Members
We have changed the login procedure to improve access between AAN.com and the Neurology journals. If you are experiencing issues, please log out of AAN.com and clear history and cookies. (For instructions by browser, please click the instruction pages below). After clearing, choose preferred Journal and select login for AAN Members. You will be redirected to a login page where you can log in with your AAN ID number and password. When you are returned to the Journal, your name should appear at the top right of the page.
AAN Non-Member Subscribers
Purchase access
For assistance, please contact:
AAN Members (800) 879-1960 or (612) 928-6000 (International)
Non-AAN Member subscribers (800) 638-3030 or (301) 223-2300 option 3, select 1 (international)
Sign Up
Information on how to subscribe to Neurology and Neurology: Clinical Practice can be found here
Purchase
Individual access to articles is available through the Add to Cart option on the article page. Access for 1 day (from the computer you are currently using) is US$ 39.00. Pay-per-view content is for the use of the payee only, and content may not be further distributed by print or electronic means. The payee may view, download, and/or print the article for his/her personal, scholarly, research, and educational use. Distributing copies (electronic or otherwise) of the article is not allowed.
Letters: Rapid online correspondence
REQUIREMENTS
You must ensure that your Disclosures have been updated within the previous six months. Please go to our Submission Site to add or update your Disclosure information.
Your co-authors must send a completed Publishing Agreement Form to Neurology Staff (not necessary for the lead/corresponding author as the form below will suffice) before you upload your comment.
If you are responding to a comment that was written about an article you originally authored:
You (and co-authors) do not need to fill out forms or check disclosures as author forms are still valid
and apply to letter.
Submission specifications:
- Submissions must be < 200 words with < 5 references. Reference 1 must be the article on which you are commenting.
- Submissions should not have more than 5 authors. (Exception: original author replies can include all original authors of the article)
- Submit only on articles published within 6 months of issue date.
- Do not be redundant. Read any comments already posted on the article prior to submission.
- Submitted comments are subject to editing and editor review prior to posting.
You May Also be Interested in
Dr. Deborah Friedman and Dr. Stacy Smith
► Watch
Topics Discussed
Alert Me
Recommended articles
-
Articles
Longitudinal modeling of frontal cognition in APOE ε4 homozygotes, heterozygotes, and noncarriersR.J. Caselli, A.C. Dueck, D.E.C. Locke et al.Neurology, April 18, 2011 -
Article
APOE ε4, white matter hyperintensities, and cognition in Alzheimer and Lewy body dementiaSaira Saeed Mirza, Usman Saeed, Jo Knight et al.Neurology, October 01, 2019 -
Articles
APOE modifies the association between Aβ load and cognition in cognitively normal older adultsK. Kantarci, V. Lowe, S.A. Przybelski et al.Neurology, December 21, 2011 -
Article
APOE polymorphisms and cognitive functions in patients with brain tumorsDenise D. Correa, Jaya Satagopan, Raymond E. Baser et al.Neurology, June 18, 2014