The Douglas Hospital Longitudinal Study of Normal and Pathological Aging: summary of findings

The Douglas Hospital Longitudinal Study of Normal and Pathological Aging: summary of findings

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J Psychiatry Neurosci 2006;30(5):328-334

Sonia J. Lupien, PhD; Georges Schwartz, MSc; Ying Kin Ng, PhD; Alexandra Fiocco, MSc; Nathalie Wan, MSc; Jens C. Pruessner, PhD; Michael J. Meaney, PhD; N.P. Vasavan Nair, MD

Douglas Hospital Research Centre, Borough of Verdun, and Department of Psychiatry, McGill University, Montréal, Que.

Abstract

In 1988, our group initiated the Douglas Hospital Longitudinal Study of Normal and Pathological Aging to assess the association between secretion of the stress hormone cortisol and cognitive performance in a group of 51 older adults. In this paper, we summarize the data obtained in this study to date. We have found that long-term exposure to high endogenous levels of cortisol is associated with both memory impairments and a 14% smaller volume of the hippocampus. We also report on studies showing that in older adults with moderate levels of cortisol over time, memory performance can be acutely modulated by pharmacologic manipulations of cortisol. We describe one participant who was included in the group of older adults presenting with increased cortisol levels over time, memory impairments and reduced hippocampal volume and in whom major depression, followed by Alzheimer’s disease, developed during the course of the study. Together, the results of the Douglas Hospital Longitudinal Study of Normal and Pathological Aging show that increased secretion of cortisol in the older human population is significantly associated with impairment of cognitive function during aging.

Résumé

En 1988, notre groupe a lancé l’Étude longitudinale de l’Hôpital Douglas sur le vieillissement normal et pathologique afin d’évaluer le lien entre la sécrétion du cortisol, hormone du stress, et la performance cognitive dans un groupe de 51 adultes âgés. Dans ce document, nous résumons les données réunies par l’étude jusqu’à maintenant. Nous avons constaté qu’on établit un lien entre l’exposition à long terme à des concentrations endogènes élevées de cortisol et des déficits de la mémoire, ainsi qu’une réduction de 14 % du volume de l’hippocampe. Nous présentons aussi un rapport sur des études indiquant que chez des adultes âgés exposés à des concentrations moyennes de cortisol au fil du temps, il est possible de moduler activement la performance de la mémoire en manipulant pharmacologiquement le cortisol. Nous décrivons un participant du groupe des adultes âgés qui a présenté des concentrations accrues de cortisol au fil du temps, des déficits de la mémoire et une réduction du volume de l’hippocampe et chez qui une dépression majeure, suivie de la maladie d’Alzheimer, a fait son apparition pendant l’étude. Globalement, les résultats de l’Étude longitudinale de l’Hôpital Douglas sur le vieillissement normal et pathologique montrent qu’il y a un lien important entre la sécrétion accrue de cortisol chez les êtres humains âgés et un déficit de la fonction cognitive au cours du vieillissement.


Medical subject headings: glucocorticoids; stress; aging; memory; cognition; longitudinal studies.

Submitted Feb. 1, 2005; Revised July 27, 2005; Accepted July 27, 2005

Acknowledgements: The Douglas Hospital Longitudinal Study of Normal and Pathological Aging has been supported by a grant from the Canadian Institutes of Health Research (CIHR grant 15000) to S.J. Lupien, a grant from the Alzheimer Society of Canada to S.J. Lupien and N.P.V. Nair and a Research Scholar Award from the E.J.L.B. Foundation to S.J. Lupien. Dr. Lupien’s work is also supported by an Investigator Award from the CIHR Institute of Aging.

Competing interests: None declared.

Contributors: All authors contributed substantially to drafting and revising the article, and each gave final approval for the article to be published.

Correspondence to: Dr. Sonia J. Lupien, Laboratory of Human Stress Research, Douglas Hospital Research Centre, 6875 Lasalle Blvd., Borough of Verdun, Montréal QC H4H 1R3; fax 514 888-4064; sonia.lupien@mcgill.ca