Decreased brain choline uptake in older adults. An in vivo proton magnetic resonance spectroscopy study.

OBJECTIVE: To test the hypothesis that uptake of circulating choline into the brain decreases with age, because alterations in metabolism of choline may be a factor contributing to age-related degenerative changes in the brain. DESIGN: Cohort comparison in younger and older adults. PARTICIPANTS: Subjects were chosen consecutively from lists of healthy volunteers screened by medical and psychiatric interviews and laboratory tests. Younger adults (n = 12) were between the ages of 20 and 40 years (mean age, 32 years), and older adults (n = 16) were between the ages of 60 and 85 years (mean age, 73 years). INTERVENTIONS: After fasting overnight, subjects received choline, as the bitartrate, to yield free choline equal to 50 mg/kg of body weight. Blood was drawn for determination of plasma choline concentration by high-performance liquid chromatography, and proton magnetic resonance spectroscopy (1H-MRS) was performed to determine the relative concentration of cytosolic choline-containing compounds in the brain at baseline and after ingestion of choline. MAIN OUTCOME MEASURES: Plasma choline and cytosolic choline-containing compounds in the brain, estimated as the ratio of the choline resonance to the creatine resonance on 1H-MRS scans of the basal ganglia, were compared following blinded analyses of data from subject cohorts studied at baseline and 3 hours after choline ingestion. RESULTS: Levels of plasma choline and cytosolic choline-containing compounds in brain were similar at baseline in younger and older subjects. Following ingestion of choline, plasma choline concentration increased by similar proportions (76% and 80%) in both younger and older subjects. Brain cytosolic choline--containing compounds increased substantially in younger subjects (mean increase, 60%; P < .001 vs baseline). Older subjects showed a much smaller increase in brain choline-containing compounds (mean, 16%; P < .001 vs the increase in younger subjects). CONCLUSION: Uptake of circulating choline into the brain decreases with age. Given the key role of choline in neuronal structure and function, this change may be a contributing factor in onset in late life of neurodegenerative, particularly dementing, illnesses in which cholinergic neurons show particular susceptibility to loss.