For Gene Carriers, Age 60 Is Key

By Sullivan, Michele G. | Clinical Psychiatry News, March 2008 | Go to article overview

For Gene Carriers, Age 60 Is Key

Sullivan, Michele G., Clinical Psychiatry News

Age 60 seems to be the defining year for many homozygous carriers of the apolipoprotein [epsilon]4 gene--the time when age-related changes in cognition focus more on memory and begin a steeper decline into mild cognitive impairment and, eventually Alzheimer's disease, according to new unpublished observations from a longitudinal study of apo [epsilon]4 carriers and normal controls.

"We saw normal age-related patterns of memory loss that occurred before age 60, but during this period, we didn't see any significant cognitive differences between the apo [epsilon]4 homozygotes, heterozygotes, and noncarriers," said Dr. Richard Caselli, a lead investigator for the Arizona Apo[epsilon]4 Cohort Longitudinal Study of Cognitively Normal Individuals. "But our latest information shows that at around age 60, a separation begins and continues for as long as we have been able to follow our subjects. There is a particular pattern of decline in apo [epsilon]4 homozygotes that tends to precede any diagnosis of mild cognitive impairment [MCI] or anything that can be seen with routine clinical brain imaging," he said in an interview.

This pattern suggests that pathologic changes could be occurring earlier in homozygous [epsilon]4 carriers, although the exact nature of these changes, and their triggers, remain speculative, said Dr. Caselli, chairman of the department of neurology at the Mayo Clinic, Scottsdale, Ariz., and a member of the Arizona Alzheimer's Disease Consortium.

The Arizona cohort was initiated in 1994, and now includes more than 600 people, enrolled at ages 20-90 years, who have at least one first-degree relative with Alzheimer's disease. The subjects are all genotyped for the apo [epsilon]4 allele, and undergo extensive neuropsychological testing every 2 years.

Dr. Caselli's recent substudy focuses on 214 of these subjects aged 50-69 years. Almost half are apo [epsilon]4 carriers--43 homozygous and 59 heterozygous.

The study set out to characterize the effect of apo [epsilon]4 status on the development of presymptomatic cognitive changes. It's well known that the gene has a dose-response effect on the age at AD diagnosis: 80%-90% of homozygotes will develop the disease, at a mean age of 68 years. About 30% of heterozygotes will develop AD and will do so at a mean age of 73, while 9% of noncarriers will develop the disease and are usually diagnosed around age 80.

As in the larger cohort, subjects in the substudy took the battery of neuropsychological tests every 2 years. The battery consists of four tests in each of five domains: executive, memory, language, spatial, and behavioral. Significant decline was defined as a drop of two standard deviations beyond that of the entire cohort in one or more domain test scores. Subjects were judged to have cognitive domain decline if their scores were lower on at least two tests in any single domain.

"We found that there was really no difference between the genetic subgroups in patterns of decline in the younger group of patients, aged 50-59 years," Dr. Caselli said. "Some had no decline, some showed improvement, and some had domain decline, but there were no statistically significant differences."

Significant differences did emerge in the group of 60- to 69-year-olds, however. Homozygotes had the highest proportion of cognitive decline, with 40% showing domain decline, compared with 8% of heterozygotes and noncarriers. None of the older noncarriers or heterozygotes experienced a decline in two or more domains, while this occurred in 20% of the homozygous subjects.

Dr. Caselli has additional data on 97 subjects who have been tested again in the years following their initial decline. "We saw that it was those who initially declined on memory who tended to continue to decline significantly in other areas, and if that subsequent decline was in the memory domain, it was even more pronounced."

Seven subjects developed MCI or AD during the study; five of these were apo [epsilon]4 homozygotes, one was an apo [epsilon]4 heterozygote, and one was a noncarrier. …

The rest of this article is only available to active members of Questia

Already a member? Log in now.

Notes for this article

Add a new note
If you are trying to select text to create highlights or citations, remember that you must now click or tap on the first word, and then click or tap on the last word.
One moment ...
Default project is now your active project.
Project items

Items saved from this article

This article has been saved
Highlights (0)
Some of your highlights are legacy items.

Highlights saved before July 30, 2012 will not be displayed on their respective source pages.

You can easily re-create the highlights by opening the book page or article, selecting the text, and clicking “Highlight.”

Citations (0)
Some of your citations are legacy items.

Any citation created before July 30, 2012 will labeled as a “Cited page.” New citations will be saved as cited passages, pages or articles.

We also added the ability to view new citations from your projects or the book or article where you created them.

Notes (0)
Bookmarks (0)

You have no saved items from this article

Project items include:
  • Saved book/article
  • Highlights
  • Quotes/citations
  • Notes
  • Bookmarks
Cite this article

Cited article

Citations are available only to our active members.
Buy instant access to cite pages or passages in MLA, APA and Chicago citation styles.

(Einhorn, 1992, p. 25)

(Einhorn 25)

1. Lois J. Einhorn, Abraham Lincoln, the Orator: Penetrating the Lincoln Legend (Westport, CT: Greenwood Press, 1992), 25,

Note: primary sources have slightly different requirements for citation. Please see these guidelines for more information.

Cited article

For Gene Carriers, Age 60 Is Key


Text size Smaller Larger Reset View mode
Search within

Search within this article

Look up

Look up a word

  • Dictionary
  • Thesaurus
Please submit a word or phrase above.
Print this page

Print this page

Why can't I print more than one page at a time?

Full screen

matching results for page

    Questia reader help

    How to highlight and cite specific passages

    1. Click or tap the first word you want to select.
    2. Click or tap the last word you want to select, and you’ll see everything in between get selected.
    3. You’ll then get a menu of options like creating a highlight or a citation from that passage of text.

    OK, got it!

    Cited passage

    Citations are available only to our active members.
    Buy instant access to cite pages or passages in MLA, APA and Chicago citation styles.

    "Portraying himself as an honest, ordinary person helped Lincoln identify with his audiences." (Einhorn, 1992, p. 25).

    "Portraying himself as an honest, ordinary person helped Lincoln identify with his audiences." (Einhorn 25)

    "Portraying himself as an honest, ordinary person helped Lincoln identify with his audiences."1

    1. Lois J. Einhorn, Abraham Lincoln, the Orator: Penetrating the Lincoln Legend (Westport, CT: Greenwood Press, 1992), 25,

    New feature

    It is estimated that 1 in 10 people have dyslexia, and in an effort to make Questia easier to use for those people, we have added a new choice of font to the Reader. That font is called OpenDyslexic, and has been designed to help with some of the symptoms of dyslexia. For more information on this font, please visit

    To use OpenDyslexic, choose it from the Typeface list in Font settings.

    OK, got it!

    Cited passage

    Thanks for trying Questia!

    Please continue trying out our research tools, but please note, full functionality is available only to our active members.

    Your work will be lost once you leave this Web page.

    Buy instant access to save your work.

    Already a member? Log in now.

    Author Advanced search


    An unknown error has occurred. Please click the button below to reload the page. If the problem persists, please try again in a little while.