Elsevier

Neurobiology of Aging

Volume 21, Issue 4, July–August 2000, Pages 569-576
Neurobiology of Aging

Original Articles
The relation between global and limbic brain volumes on MRI and cognitive performance in healthy individuals across the age range

https://doi.org/10.1016/S0197-4580(00)00133-0Get rights and content

Abstract

The present study investigated the range of age-related changes in brain morphology and the relation with performance on memory and other cognitive tests in a healthy population. A group of 61 subjects (21 to 81 years old, mean = 55.7), free from cognitive and medical deficits, underwent MRI scanning and neuropsychological assessment encompassing memory and other cognitive tests. Volumetry of the hippocampus, parahippocampal gyrus, mamillary bodies, third ventricle, and total brain matter was performed. The results indicate that in healthy individuals increases in ventricular volume and volume decreases in total brain matter, hippocampus and parahippocampal gyrus, but not mamillary bodies, are clearly apparent with increasing age. However, no relation could be established between the brain volumes and test performance when controlling for the effects of age. To conclude, variations in total and limbic brain volumes do not seem predictive for cognitive performance independent of age.

Introduction

Because the proportion of elderly people has increased considerably during the last century, there is growing interest in normal and pathological changes associated with the aging process. Neuroimaging techniques such as computed tomography (CT) and magnetic resonance imaging (MRI) have substantiated the findings from postmortem studies (see [34], for a review) that nonpathological aging is associated with considerable morphological brain changes. Widening of the ventricular and sulcal liquor spaces is clearly evident in elderly persons [2], [6], [8], [21], [22], [27], and studies that directly measured brain volume have found age-related reductions in total and gray (but not white) matter volumes [8], [21], [30], [31]. This atrophy seems to occur particularly in the frontal and temporal lobes [8], [31], and also in subcortical regions [20].

With respect to cognitive functioning, especially speed of mental processing and the ability to learn and retrieve new information tend to decrease with advancing age [1], [23]. Because cognitive processes are dependent upon the integrity of the brain, it seems probable that changes in brain morphology (partly) account for these decreases in cognitive functioning. Studies examining patients with neurodegenerative disorders (e.g. Alzheimer’s disease and Korsakoff’s syndrome) have demonstrated that damage to specific brain structures is indeed related to deterioration of cognitive functions. In these studies memory impairment is often associated with atrophy of limbic structures (including hippocampus, parahippocampal gyrus [17], thalamus [38], or third ventricle [39], and mamillary bodies [36]), whereas global cognitive deficits such as slower mental processing is related to more general cerebral atrophy [33], [35].

Despite a considerable number of patient studies, relatively few studies with healthy volunteers have examined the relation between age-related changes in brain structures and neuropsychological test performance. No clear associations have emerged, which might be caused by a lack of adequate image analysis methods. For instance, several studies have relied only on global atrophy measures such as ventricular dilatation [4], [22], whereas others focused on specific brain regions but used qualitative rating scales to assess severity of atrophy [9], [12]. Only two studies have investigated the relation between regional brain atrophy and cognitive deterioration using quantitative (i.e. volumetric) analysis methods in a large sample [14], [32]. A relation was found between limbic structures and memory in subjects over 55 years of age.

In the present study a group of healthy subjects with a wide age-range was examined using both MRI and a number of neuropsychological tests. The aim of this research was twofold. First, we wanted to establish the range of nonpathological changes in brain regions known to be involved in memory across the adult age spectrum. Volumetry of the hippocampus, parahippocampal gyrus, mamillary bodies, third ventricle, and total brain matter was performed. Secondly, we investigated whether normal age-related cognitive decline can be explained by volume changes. The general hypothesis was that volume reductions in limbic structures (hippocampus, parahippocampal gyrus and mamillary bodies; and dorsomedial thalamus as indexed by the third ventricle [19]) are especially related to lower scores on memory tests, whereas decreases in total brain volume are related to slower performance on speed tasks. Furthermore, although advancing age is accompanied by decreases both in brain volumes and in test performance, it was expected that the volume-performance associations were only partially mediated by age.

Section snippets

Subjects

The study sample comprised 61 healthy and cognitively normal persons, aged 21 to 81 years (mean ± SD = 55.7 ± 16.1). The group consisted of 35 men (mean ± SD = 53.5 ± 2.7) and 26 women (mean ± SD = 58.6 ± 3.1). Mean educational level, as measured on a five-point scale (1 = primary school, 5 = university degree), was 2.6 (SD = 1.1). Subjects were rigorously screened and excluded if there was a history of cerebrovascular (e.g. stroke) or chronic neurological disease (e.g. dementia, epilepsy, head

Relations between VOIs and age

Men had significantly larger intracranial volumes than women (1071 versus 957 cm3, P < 0.001). Because of this difference, and because brain structures and intracranial size are related [15] all VOIs were adjusted for intracranial volume. In none of the cases did either gender or education add significantly to the model, so these variables were not considered any further. Associations between the adjusted brain volumes and age were assessed in hierarchical regression analyses. A summary of the

Discussion

The main hypothesis of the present study was that smaller brain volumes and larger ventricular volumes are related to reductions in neuropsychological test performance. Indeed, a relation was found between most regions of interest and various processing speed and memory tests. However, it was expected that this effect would still hold when controlling the effects of age, but this was not the case. Although higher age is clearly associated with larger ventricular volumes and smaller total brain

Acknowledgments

Aknowledgments

We thank Dr E. Gronenschild for his technical support.

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