Decreased volumes of both the caudate and putamen were found in PD brains compared to healthy controls. This study provides the first 3-tesla evidence of caudate atrophy in PD brains, using manual tracing methods. The present findings contrast with prior studies utilising fewer patients and in which, reduced putamen volumes but not caudate volumes were reported [2–5, 7, 8]. A possible source of variation in the findings across previous studies is variation in imaging parameters, including magnet strength, scanning sequence, slice thickness and inter-slice gap. The present study has the advantage of enhanced image resolution offered by acquisition at 3-tesla compared to 1.5-tesla, and 1 mm-thick slices with no inter slice gap, enabling the full extent of the regions of interest to be viewed. Another potential source of variation may be the boundaries used to delineate each structure. Although the putamen and caudate have well-defined boundaries due to the surrounding white matter and lateral ventricles, these structures fuse anteriorly with the ventral striatum. Unfortunately, most previous studies do not give detailed descriptions of the boundaries used.
A volume reduction in the putamen has previously been accepted due to the reduced dopaminergic activity in the nucleus in early disease stages [3, 4, 7], but little attention has been given to potential mechanisms of such a reduction. Although MRI is not able to directly inform us on such mechanisms, post-mortem studies provide some insight. A reduction in the dendritic spine density and a shortening of dendritic length in the medium spiny neurons of the striatum [25, 26], and frank loss of striatal cells  have been described in post-mortem tissue. Such changes may contribute to a volume reduction and could significantly influence the functionality of the vast cortical projections to the striatum, which synapse on the medium spiny neuron dendritic arbour. Whether these events occur as a direct result of dopamine loss is unclear.
The volume reduction in the caudate was greatest in the head of the nucleus with non-significant volume changes in the body. The head of the caudate is more involved in cognitive function than the body, which is primarily involved in oculomotor function. However, our results do not suggest that the volume loss in the caudate is associated with cognitive status, as we also observed reduced caudate volume when comparing the cognitively unimpaired PD participants to healthy controls and no significant changes in volume between the PD cognitive groups. Whether caudate volume loss contributes to an increased susceptibility to later cognitive decline remains unknown.
Aside from Ghaemi et al. all earlier studies from which we were able to calculate effect sizes indicated the putamen and caudate volumes to be smaller in PD brains compared to control brains (Table 1). The effect size for the caudate volume decrease in the study by Geng et al. was of a reasonable size, but no significant reduction in PD volume was reported, suggesting that the study may have been underpowered to detect the difference in this measurement. Given the consistency in direction of effect sizes across previous studies, and the large sample used in our study, we believe our results reflect true changes in striatal volume in PD.
The absence of an effect of laterality of symptoms (whether side of initial onset or currently most affected side) upon striatal volume is consistent with previous studies . The lack of association between striatal volumes and disease stage indicates that continued loss of volume over time due to disease processes may be of a relatively small magnitude and unable to be teased apart from the losses associated with increasing age. This is in contrast to the previously reported negative association between putamen volume and H & Y stage . Since H & Y stage was significantly correlated with age in this current study, and the correlation between H & Y stage and volumes was not present after correcting for age, the association reported previously may have been, at least in part, due to age rather than more advanced stages of PD. Further investigation into the relationship between disease stage and striatal volume would require greater numbers of younger people with more advanced symptoms. Nigro-striatal neuronal loss is approximately 60% by the time of symptom onset  with rates of loss greater in earlier rather than late stages of the disease. Thus, it should not be surprising that we observed a significant reduction in striatal volumes in patients with normal cognition and no significant change with advancing disease (as measured by H & Y stage).
A limitation to the study is the unbalanced sample sizes in the cognitive sub-groups. Increased numbers of MCI and dementia PD participants would strengthen the analysis based on cognitive status. Also, improved delineation of the sub-regions of the caudate may be achieved in the future with the utilisation of diffusion tensor imaging tractography.
In summary, we have provided evidence at 3-tesla, that the caudate and putamen undergo volume loss in Parkinson’s disease, even early in the disease course. These new data, in conjunction with the existing literature, confirm the presence of atrophy in the striatum in PD brains over and above the influence of natural aging, although not with declining cognitive function and increasing motor impairment. Given the overlap in volumes across groups, such measures would not be useful as a diagnostic tool, however, knowledge of such volume reductions is important for understanding disease effects on the brain.