Original ArticlesThe relation between global and limbic brain volumes on MRI and cognitive performance in healthy individuals across the age range
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.
References (41)
- et al.
Frequency of hippocampal formation atrophy in normal aging and Alzheimer’s disease
Neurobiol Aging
(1997) - et al.
Cerebral structure on MRI, part Ilocalization of age-related changes
Biol Psychiatry
(1991) - et al.
In vivo quantification of the limbic system using MRIeffects of normal aging
Psychiatry Res
(1990) - et al.
Age-related decline in MRI volumes of temporal lobe gray matter but not hippocampus
Neurobiol Aging
(1995) - et al.
History, concepts, and theory in the psychology of aging
- et al.
Quantitative volumetric analysis of brain MRnormative database spanning 5 decades of life
Am J Neuroradiol
(1995) - et al.
Learning and retrieval rate of words presented auditorily and visually
J Gen Psychol
(1985) - et al.
Cognitive correlates of ventricular enlargement and cerebral white matter lesions on magnetic resonance imaging. The Rotterdam Study
Stroke
(1994) - et al.
Mamillary body atrophy in Wernicke’s encephalopathyantemortem identification using magnetic resonance imaging
Ann Neurol
(1987) - et al.
Sex differences in brain aginga quantitative magnetic resonance imaging study
Arch Neurol
(1998)
Relation of education to brain size in normal agingimplications for the reserve hypothesis [In Process Citation]
Neurology
Quantitative cerebral anatomy of the aging human braina cross-sectional study using magnetic resonance imaging
Neurology
The human brainsurface, three-dimensional sectional anatomy and MRI
Interrelations of age, self-reported health, speed, and memory
Psychol Aging
Hippocampal athrophy in normal agingan association with recent memory impairment
Arch Neurol
Hippocampal formation size predicts declining memory performance in normal aging
Neurology
Hippocampal formation size in normal human aginga correlate of delayed secondary memory performance
Learn Memory
The mismeasure of man
Stroop interferenceaging effects assessed with the Stroop Color-Word Test
Exp Aging Res
MR-based hippocampal volumetry in the diagnosis of Alzheimer’s disease
Neurology
Cited by (126)
Identifying brain changes related to cognitive aging using VBM and visual rating scales
2019, NeuroImage: ClinicalRelationships between default-mode network connectivity, medial temporal lobe structure, and age-related memory deficits
2015, Neurobiology of AgingCitation Excerpt :Disruptions in the default-mode network have also been associated with age-related memory performance deficits (Hampson et al., 2006; Ranganath et al., 2005; Sala-Llonch et al., 2012; Wang et al., 2010). Several models propose that age-related memory deficits are mediated by declines in hippocampus (Chen et al., 2010; Head et al., 2008; Tisserand et al., 2000; Walhovd et al., 2004), entorhinal cortex (Tisserand et al., 2000), and the default-mode network (Miller et al., 2008; Sambataro et al., 2010; Wang et al., 2010). Although hippocampus volume, entorhinal cortex thickness, and default-network connectivity have each individually been linked to age-related memory deficits, the shared and independent contributions of these imaging markers are less clear (Salthouse, 2011).
Sex differences in volume and structural covariance of the anterior and posterior hippocampus
2014, NeuroImageCitation Excerpt :Given these sex differences in performance and evidence of distinct neural correlates of these memory systems within the HC (Kühn and Gallinat, 2013), regionally varying sex differences in HC volume might also be expected. When considering overall HC volume, sex differences have sometimes been reported, suggesting a larger hippocampus in women than in men after correcting for total intracranial volume (Filipek et al., 1994; Giedd et al., 1996; Murphy et al., 1996), but a large number of studies report no difference in volume (Bueller et al., 2006; Jack et al., 1989; Lange et al., 1997; Mu et al., 1999; Pruessner et al., 2001; Tisserand et al., 2000). Sex differences in functional lateralization in the hippocampus could be expected considering the sex difference in episodic and spatial memory — functions that sometimes show hippocampal lateralization (e.g. Burgess et al., 2002; e.g. Golby et al., 2001).
Cardiovascular symptoms and longitudinal declines in processing speed differentially predict cerebral white matter lesions in older adults
2018, Archives of Gerontology and Geriatrics