We're unable to sign you in at this time. Please try again in a few minutes.
We were able to sign you in, but your subscription(s) could not be found. Please try again in a few minutes.
There may be a problem with your account. Please contact the AMA Service Center to resolve this issue.
Contact the AMA Service Center:
Telephone: 1 (800) 262-2350 or 1 (312) 670-7827  *   Email: subscriptions@jamanetwork.com
Error Message ......
Article |

Apolipoprotein E Genotype and Rate of Decline in Probable Alzheimer's Disease

Gloria Dal Forno, MD; D. Xeno Rasmusson, PhD; Jason Brandt, PhD; Kathryn A. Carson; Ronald Brookmeyer, PhD; Juan Troncoso, MD; Claudia H. Kawas, MD
Arch Neurol. 1996;53(4):345-350. doi:10.1001/archneur.1996.00550040085017.
Text Size: A A A
Published online


Background:  The risk of Alzheimer's disease (AD) appears to increase, and the age at onset to decrease, with the number of ϵ4 alleles. If this relationship is due to increased rate of pathophysiological change, the presence of ϵ4 would be expected to influence progression of disease, predicting a more rapid decline with increasing number of ϵ4 alleles.

Objective:  To determine if the frequency of the ϵ4 allele of the apolipoprotein E (ApoE) gene affects the rate of clinical progression in AD.

Setting:  Alzheimer's Disease Research Center. Subjects: One hundred one subjects meeting criteria of the National Institute of Neurological Disorders and Stroke for probable AD or of the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) for definite AD; 78 of these subjects met the additional criterion of having a Mini-Mental State Examination score of at least 10 for analysis of rate of decline.

Measurements:  The subjects' characteristics and a neuropsychological battery, including the Mini-Mental State Examination, Spatial Delayed Recognition Span, Boston Naming Test, Category Fluency Test, and the Physical Capacity Subscale of the Psychogeriatric Dependency Rating Scale.

Design:  The subjects were followed up longitudinally for approximately one decade. Medical histories were taken and physical and neurologic examinations and neuropsychological testing were performed every 6 months. Three and a half years of data were available for most tests and 5.5 for the Psychogeriatric Dependency Rating Scale; thereafter, patients were no longer testable. A general linear model analysis of variance was used to assess the influence of ApoE on demographic characteristics and baseline performances on neuropsychological measures. A random-effects regression model was used to predict change over time associated with presence of ϵ4 on clinical and cognitive measures.

Results:  The age at onset was greatest for the ϵ4-heterozygous subjects and least for the ϵ4-negative subjects. The heterozygous subjects declined more rapidly on the Mini-Mental State Examination and the Category Fluency Test than the subjects without the ϵ4 allele or with ϵ4 homozygosity. The homozygous subjects declined faster on only one subscale: the Physical Capacity subscale of the Psychogeriatric Dependency Rating Scale. Covarying for age at onset did not affect the results.

Conclusions:  The ApoE genotype does not strongly influence the rate of decline in AD, implying that ϵ4 might predispose to the development of the disease without accelerating its pathogenesis or progression. The effects of ϵ4 on both age at onset and rate of decline need to be further investigated.


Sign in

Purchase Options

• Buy this article
• Subscribe to the journal
• Rent this article ?





Also Meets CME requirements for:
Browse CME for all U.S. States
Accreditation Information
The American Medical Association is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The AMA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM per course. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Physicians who complete the CME course and score at least 80% correct on the quiz are eligible for AMA PRA Category 1 CreditTM.
Note: You must get at least of the answers correct to pass this quiz.
Please click the checkbox indicating that you have read the full article in order to submit your answers.
Your answers have been saved for later.
You have not filled in all the answers to complete this quiz
The following questions were not answered:
Sorry, you have unsuccessfully completed this CME quiz with a score of
The following questions were not answered correctly:
Commitment to Change (optional):
Indicate what change(s) you will implement in your practice, if any, based on this CME course.
Your quiz results:
The filled radio buttons indicate your responses. The preferred responses are highlighted
For CME Course: A Proposed Model for Initial Assessment and Management of Acute Heart Failure Syndromes
Indicate what changes(s) you will implement in your practice, if any, based on this CME course.


Some tools below are only available to our subscribers or users with an online account.

0 Citations

Sign in

Purchase Options

• Buy this article
• Subscribe to the journal
• Rent this article ?

Related Content

Customize your page view by dragging & repositioning the boxes below.