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

Synapse. 2010 Feb;64(2):146-51. doi: 10.1002/syn.20708.

Abstract

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-[(11)C]-methylphenidate (MP, a marker of DAT) and [(11)C]-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 [(11)C]-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 [(11)C]-DTBZ. In contrast, [(11)C]-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 [(11)C]-MP on PPB could be observed according to age group. There was a positive relation between the PPB and [(11)C]-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.

MeSH terms

  • Adult
  • Aged
  • Aging / physiology*
  • Brain / diagnostic imaging*
  • Brain / physiology*
  • Carbon Radioisotopes
  • Caudate Nucleus / diagnostic imaging
  • Caudate Nucleus / physiology
  • Dopamine Plasma Membrane Transport Proteins / metabolism*
  • Female
  • Humans
  • Male
  • Methylphenidate
  • Middle Aged
  • Motor Activity / physiology*
  • Neuropsychological Tests
  • Positron-Emission Tomography
  • Putamen / diagnostic imaging
  • Putamen / physiology
  • Tetrabenazine / analogs & derivatives

Substances

  • Carbon Radioisotopes
  • Dopamine Plasma Membrane Transport Proteins
  • Methylphenidate
  • dihydrotetrabenazine
  • Tetrabenazine