Age- and sex-related effects on the neuroanatomy of healthy elderly pdf

Age- and sex-related effects on the neuroanatomy of healthy elderly

Herve´ Lemaıˆtre,a Fabrice Crivello,a Blandine Grassiot,a Annick Alpe´rovitch,b

Christophe Tzourio,b and Bernard Mazoyera,c,d,

T

a

Groupe d’Imagerie Neurofonctionnelle, UMR 6194, CNRS, CEA, Universite´s de Caen et Paris 5, GIP Cyceron, BP5229, F-14074 Caen, France b

INSERM U360, Hoˆ pital Pitie´-Salpeˆtrie`re, 75013 Paris, France c

Unite´ IRM, CHU de Caen, 14000 Caen, France d

Institut Universitaire de France, 75005 Paris, France

Received 16 December 2004; revised 4 February 2005; accepted 24 February 2005

Available online 13 April 2005

Effects of age and sex, and their interaction on the structural brain

anatomy of healthy elderly were assessed thanks to a cross-sectional

study of a cohort of 662 subjects aged from 63 to 75 years. T1- and T2-

weighted MRI scans were acquired in each subject and further

processed using a voxel-based approach that was optimized for the

identification of the cerebrospinal fluid (CSF) compartment. Analysis

of covariance revealed a classical neuroanatomy sexual dimorphism,

men exhibiting larger gray matter (GM), white matter (WM), and CSF

compartment volumes, together with larger WM and CSF fractions,

whereas women showed larger GM fraction. GM and WM were found

to significantly decrease with age, while CSF volume significantly

increased. Tissue probability map analysis showed that the highest

rates of GM atrophy in this age range were localized in primary

cortices, the angular and superior parietal gyri, the orbital part of the

prefrontal cortex, and in the hippocampal region. There was no

significant interaction between bSexQ and bAgeQ for any of the tissue

volumes, as well as for any of the tissue probability maps. These

findings indicate that brain atrophy during the seventh and eighth

decades of life is ubiquitous and proceeds at a rate that is not

modulated by bSexQ.

D 2005 Elsevier Inc. All rights reserved.

Keywords: Brain; Aging; Sex; Voxel-based morphometry; MRI

Introduction

The increase of life expectancy during the last century has led

to a growing number of dementia cases in the aging population.

Prevalence studies suggested that, in 2000, the number of persons

with Alzheimer’s disease in the United States was 4.5 million and

predicted to rise to 13.2 million by 2050 (Hebert et al., 2003). This

dementia incidence upsurge has reinforced the importance of

characterizing the mechanisms of the human brain aging during the

seventh and eighth decades of life. Indeed, a better understanding

of the normal neuroanatomical aging could be of high interest for

dissociating processes specifically associated with pathologic brain

changes from those associated to normal changes.

During the past two decades, several studies have investigated

the effect of aging on the human brain. More often than not, these

studies investigated cerebral changes over life span (from 20 up to

80 years). Their findings have led to a large consensus regarding

the global morphological changes due to aging. First, postmortem

studies have described, starting at the fourth decade, a decrease of

the brain weight and an increase of the cerebrospinal fluid volume

(CSF) (Dekaban, 1978). Then, studies using Magnetic Resonance

Imaging (MRI) have confirmed and refined these findings by

showing that the gray matter (GM) volume starts to decrease earlier

in the life (at the end of the first decade), whereas the white matter

(WM) volume starts to decrease at the fourth decade (Courchesne

et al., 2000; Pfefferbaum et al., 1994).

There seems to exist, however, a large variability in the way the

different brain areas are reacting to aging. These selective age￾related neuroanatomical changes could be explained by several

aging theories. One of them is based on brain ontogeny and

phylogeny and states that the age-related changes of the various

cerebral regions follow a time pattern that is the reverse sequence

of their maturation during development (Braak et al., 1999; Raz et

al., 1997). According to this model, late maturating unimodal or

high-order heteromodal associative cortices are the first and the

most age-sensitive, while early maturating primary areas are

subject to later and smaller age-related changes. In agreement

with this model, several studies have specifically focused on

associative cortices and have shown a preferential atrophy of the

regions belonging to the prefrontal cortex (Coffey et al., 1992;

Jernigan et al., 2001; Salat et al., 2001). Other studies have

reported focal atrophy localized into the temporal lobe (Bigler et

al., 2002) including the hippocampus (Raz et al., 2004b; Tisserand

et al., 2000). However, other aging hypotheses based on the

dysfunction of the principal neurotransmitter systems could also

explain the affliction of these cerebral regions in healthy elderly

1053-8119/$ - see front matter D 2005 Elsevier Inc. All rights reserved.

doi:10.1016/j.neuroimage.2005.02.042

T Corresponding author. Groupe d’ Imagerie Neurofonctionnelle

UMR6194, CNRS, CEA, Universite´s de Caen et Paris 5, GIP Cyceron,

BP5229, F-14074 Caen, France. Fax: +33 231 470 271.

E-mail address: [email protected] (B. Mazoyer).

Available online on ScienceDirect (www.sciencedirect.com).

www.elsevier.com/locate/ynimg

NeuroImage 26 (2005) 900 – 911