Dopamine transporter PET in normal aging: Dopamine transporter decline and its possible role in preservation of motor function

Objectives: To determine the impact of age-related decline in dopamine transporter (DAT) expression on motor function in the elderly. Methods: About 33 normal individuals of a wide age range were scanned with PET employing d-threo-[11C]-methylphenidate (MP, a marker of DAT) and [11C]-dihydrotetrabenazine (DTBZ, that binds to the vesicular monoamine transporter Type 2). Motor function was assessed using the Purdue Pegboard Test (PPB). We analyzed the relationship between [11C]-MP and motor performance. Results: Age ranged from 27- to 77-year old (mean ± SD, 54.75 ± 14.14). There was no age-related decline in binding potentials (BP) for [11C]-DTBZ. In contrast, [11C]-MP BP was inversely related to age in all striatal regions analyzed (caudate: reduction of 11.2% per decade, P < 0.0001, r = −0.86; putamen: reduction of 10.5% per decade, P < 0.0001, r = −0.80). A differential effect of [11C]-MP on PPB could be observed according to age group. There was a positive relation between the PPB and [11C]-MP in young individuals (coefficient = 13.56), whereas in individuals greater than 57 years this relationship was negative (coefficient = −19.53, P = 0.031). Conclusions: Our findings confirm prior observations of age-related DAT decline and suggest that this phenomenon is independent of changes in VMAT2. After the fifth decade of life, this reduction in DAT binding is associated with a motor performance comparable to mid-adult life. These findings imply that biochemical processes associated with healthy aging may offset the naturaldecline in motor function observed in the elderly. Synapse 64:146–151, 2010. © 2009 Wiley-Liss, Inc.