The Relationship Between the Striatal Dopaminergic Neuronal and Cognitive Function With Aging

Abstract

Both cognitive function and striatal dopamine function decline by normal aging. However, the relationship among these three factors remains unclear. The aim of this study was to elucidate the association among age-related changes in the striatal dopamine transporter (DAT) and cognitive function in healthy subjects. The 30 healthy volunteers were enrolled in this research, the age ranged from 41 to 82 (64.5 ± 11.5, mean ± SD). All subjects were scanned with both T1-weighted magnetic resonance imaging (MRI) and ¹²³I-FP-CIT single-photon emission computed tomography (SPECT) images. The Wechsler Adult Intelligence Scale-Third Edition (WAIS-III) was used to evaluate cognitive function. Six spherical regions of interest (ROI) using 10 mm in diameter on the caudate nucleus, anterior putamen and posterior putamen were manually drawn on MRI image which was applied onto SPECT image. The relationship between striatal occipital ratio (SOR) values and WAIS-III subscore were analyzed by multiple regression analysis. Subscores which was significant were further analyzed by path analyses. Full intelligence quotient (IQ), verbal IQ, verbal comprehension were all positively correlated with age-adjusted striatal DAT binding (P < 0.01). Multiple regression analyses revealed that the coding digit symbol correlated with all striatal regions except for the left caudate (P < 0.04). Picture completion and right caudate, similarities and left caudate also showed a positive correlation (P < 0.04). Path analysis found that the right caudate and picture completion; the left caudate and similarities were correlated independently from age, whereas the models of coding digit symbol were not significant. These results suggest that age-based individual diversity of striatal DAT binding was associated with verbal function, and the caudate nucleus plays an important role in this association.

Keywords: SPECT; Wechsler Adult Intelligence Scale; aging; cognitive function; dopamine transporter; verbal function.

Figure 1

Representative image of regions of interest (ROIs) in dopamine transporter (DAT) image. Circular ROIs were manually placed 10 mm in diameter, in each hemisphere on the structural MRI for the caudate nucleus (CN), anterior putamen (AP) and posterior putamen (PP) and 8 on the occipital cortex as the reference region. Calculating each specific activity with DAT binding is estimated by the striatal-to-occipital ratio, defined as (striatum—occipital)/occipital counts. (A) Axial section of structural MRI (3-dimensional T1 weight image). (B) ROIs placed on an axial slice of MRI. (C) [¹²³I]FP-CIT SPECT image overlaid onto the coregistered MRI.

Figure 2

The relationship between the intelligence quotient (IQ) and dopamine transporter (DAT) binding. The scatter plot showing the age-adjusted intellectual score and age-adjusted right and left averaged striatal specific binding ratio (SBR) of [¹²³I]-FP-CIT SPECT in 30 healthy subjects. (A) The full IQ, (B) Verbal IQ (VIQ) and (D) verbal comprehension were positively correlated with the striatal DAT binding. (C) Performance IQ (PIQ), working memory, perceptual organization and processing speed (see text) did not show any correlation. The dotted line represents the 95% confidence interval.

Figure 3

The relationship among the striatal DAT binding, Wechsler Adult Intelligence Scale—third edition (WAIS-III) subscores and age. Two models remarked significantly by path analysis. (A) DAT binding value of right caudate was directly associated with the WAIS-III subscores of picture completion (c’). (B) Left caudate was directly associated with the WAIS-III subscores of similarities (c’). The indirect path was significant (a path) in both models. In this model, the direct and indirect relationships between aging, striatal DAT binding and cognition, the standardized path coefficients (β) are listed as a, b and c’, where a and b are part of the indirect path and c’ is the direct path adjusted for the indirect path.