A positron emission tomography (PET) investigation of the role of striatal dopamine (D2) receptor availability in spatial cognition

Abstract

The functional significance of age-related changes in regional brain dopamine (DA) function is poorly understood in health. Two recent studies have reported positive linear associations between measures of striatal DA (D2) receptor availability (binding potential) and specific aspects of motor and cognitive performance, after controlling for the effects of age [(Volkow, N.D., Gur, R.C., Wang, G.-J., Fowler, J.S., Moberg, P.J., Ding, Y.-S., Hitzemann, R., Smith, G., Logan, J., 1998. Association between decline in brain dopamine activity with age and cognitive and motor impairment in healthy individuals. Am. J. Psychiatry 155 (3), 344–349; Backman, L., Ginovart, N., Dixon, R.A., Wahlin, T.-B.R., Wahlin, A., Halldin, C., Farde, L., 2000. Age-related cognitive deficits mediated by changes in the striatal dopamine system. Am. J. Psychiatry 157 (4), 635–637)]. We investigated the relationship between measures of striatal DA (D2) receptor availability and visuo-spatial cognitive performance in thirty healthy post-menopausal women aged 58–90 years. [11C] Raclopride (RAC) positron emission tomography (PET) was used to assess dopamine (D2) receptor availability. The CANTAB neuropsychological test battery was used to assess spatial span, spatial working memory (SWM) and planning ability. Age showed significant linear correlations with several of the CANTAB performance measures. After controlling for age effects, DA (D2) receptor measures in left-sided striatal regions (caudate and putamen) were significantly and positively correlated with ‘perfect solution’ scores—the measure of performance accuracy—on the Tower of London (TOL) test of spatial planning. When this relationship was examined in relation to task difficulty, only perfect scores for the most ‘difficult’ (4-move) problems were significantly correlated with BP measures in all striatal regions, most notably the right and left caudate nuclei. Paradoxically, individuals with higher DA (D2) receptor measures in the right caudate performed less accurately on the SWM task, exhibiting a higher number of errors within each search sequence. The relative contribution of striatal DA (D2) receptor availability to specific aspects of cognitive performance needs to be evaluated in larger mixed-sex samples to facilitate the meaningful investigation of the potential therapeutic benefits of DA (D2) agonists in later life.