Age-related decline in striatal volume in monkeys as measured by magnetic resonance imaging

Abstract

Age-related declines in striatal markers for the dopamine system have been demonstrated in several species. The current study investigated structural changes during aging in the rhesus monkey striatum. Male monkeys were studied using a volumetric spoiled gradient recall (SPGR) magnetic resonance imaging protocol. The caudate nucleus and putamen were segmented by manual tracing using landmarks made in the orthogonal planes. The whole brain volume (defined as volume of gray and white matter plus cerebrospinal fluid in ventricles and sulci) was measured using a semi-automated algorithm. There was no correlation between age and whole brain volume. There were age-related declines in normalized (i.e. brain region/whole brain volume) caudate nucleus and putamen volumes. Monkeys in the young group (n = 7, 39–45 months old) had larger volumes of both the caudate nucleus and putamen than animals in the middle-age (n = 5, 120–180 months) or old (n = 7, 291–360 months) groups. The current results provide normative data to assess potential interventions (e.g. caloric restriction) in the aging process.

Introduction

Decline in the function (or in indices) of dopaminergic neurotransmission is a characteristic feature of the aging mammalian brain [8], [23]. Age-related declines in various striatal markers for the dopamine system have been demonstrated in several species. For example, in vivo imaging using positron emission tomography (PET) or single photon emission computed tomography has been used to assess potential loss of striatal dopamine receptor binding with age. Several imaging studies have shown a decline in dopamine D₂ receptor binding in the human striatum with increasing age [1], [6], [21], [26], [27], [28]. Our laboratory has provided in vivo evidence using PET [17] of an age-dependent loss of D₂ binding in the striatum of a nonhuman primate. However, the rate of decline of D₂ binding in our study using the rhesus monkey [17] was smaller than the rate measured in humans, possibly due to our correction for partial volume error to account for age-related differences in the volume of the brain regions that were measured. The human PET imaging studies did not correct for potential errors of measurement in the striatum due to partial volume effects.

The estimation of neurochemical changes that occur during aging could be confounded by structural changes (e.g. neuronal cell loss) that may accompany them. Because PET measurements of tracer concentration in objects, which are small relative to the spatial resolution of the PET scanner, are biased by spillover and tissue inhomogeneity, object size or changes in object size must be taken into account for accurate quantification. Several imaging studies have indicated that the size or volume of the human striatum declines with age [4], [9], [10], [16], [18], [20]. Although the striatum is larger in humans than in nonhuman primates and is consequently less prone to partial volume effects, some measurement error is likely. To assess the extent to which structural changes might influence neurochemical assays in the rhesus monkey, we addressed the question of whether there were age-related differences in striatal volume. High-resolution volumetric magnetic resonance imaging (MRI) was used to measure the volume of the caudate nucleus and putamen in monkeys over a wide age range.