Original Investigation |

Reduced Prevalence of Cognitive Impairment in Families With Exceptional Longevity

Stephanie Cosentino, PhD1,2,3; Nicole Schupf, PhD1,2,4; Kaare Christensen, PhD5; Stacy L. Andersen, MA6; Anne Newman, PhD7; Richard Mayeux, MD1,2,3,4
[+] Author Affiliations
1Gertrude H. Sergievsky Center, Columbia University, New York, New York
2Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, Columbia University, New York, New York
3Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, New York
4Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, New York
5The Danish Aging Research Center, University of Southern Denmark and Departments of Clinical Genetics and Clinical Biochemistry and Pharmacology, Odense University Hospital, Odense C, Denmark
6Geriatrics Section, School of Medicine, Boston University and Boston Medical Center, Boston, Massachusetts
7Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania
JAMA Neurol. 2013;70(7):867-874. doi:10.1001/jamaneurol.2013.1959.
Text Size: A A A
Published online

Importance  Family studies of centenarians and long-lived persons have found substantial familial aggregation of survival to extreme ages; however, the extent to which such familial longevity is characterized by cognitively intact survival is not established.

Objective  To determine whether families with exceptional longevity are protected against cognitive impairment consistent with Alzheimer disease.

Design  Cross-sectional analysis.

Setting  Multisite study in New York, Massachusetts, Pennsylvania, and Denmark.

Participants  A total of 1870 individuals (1510 family members and 360 spouse controls) recruited through the Long Life Family Study.

Main Outcome and Measure  Prevalence of cognitive impairment based on a diagnostic algorithm validated using the National Alzheimer’s Coordinating Center data set.

Results  The cognitive algorithm classified 546 individuals (38.5%) as having cognitive impairment consistent with Alzheimer disease. Long Life Family Study probands had a slightly but not statistically significant reduced risk of cognitive impairment compared with spouse controls (121 of 232 for probands vs 45 of 103 for spouse controls; odds ratio = 0.7; 95% CI, 0.4-1.4), whereas Long Life Family Study sons and daughters had a clearly reduced risk of cognitive impairment (11 of 213 for sons and daughters vs 28 of 216 for spouse controls; odds ratio = 0.4; 95% CI, 0.2-0.9). Restriction to nieces and nephews in the offspring generation attenuated this effect (37 of 328 for nieces and nephews vs 28 of 216 for spouse controls; odds ratio = 0.8; 95% CI, 0.4-1.4).

Conclusions and Relevance  Rates of cognitive impairment characteristic of Alzheimer disease were relatively high. In the proband generation, rates were comparable across family members and spouse controls, whereas sons and daughters of probands had significantly lower rates than spouse controls. Results suggest a delayed onset of cognitive impairment in families with exceptional longevity, but assessment of age-specific incidence rates is required to confirm this hypothesis.

Figures in this Article

Sign In to Access Full Content

Don't have Access?

Register and get free email Table of Contents alerts, saved searches, PowerPoint downloads, CME quizzes, and more

Subscribe for full-text access to content from 1998 forward and a host of useful features

Activate your current subscription (AMA members and current subscribers)

Purchase Online Access to this article for 24 hours


Place holder to copy figure label and caption
Cognitively Intact Survival in Long Life Family Study (Llfs) Family Members and Controls

Percentage of cognitively intact survival in Long Life Family Study (LLFS) family members and controls.

Graphic Jump Location




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.
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.
Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s "Cited By" API will populate this tab (http://www.crossref.org/citedby.html).
Submit a Comment


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

Sign In to Access Full Content

Related Content

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

Articles Related By Topic
Related Topics