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.