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 i nto the brain decreases with age, because alterations in metabolism of choline may be a factor contributing to age-related degenerative chan ges in the brain. Design.-Cohort comparison in younger and older adult s. Participants.-Subjects were chosen consecutively from lists of heal thy volunteers screened by medical and psychiatric interviews and labo ratory 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 fas ting overnight, subjects received choline, as the bitartrate, to yield free choline equal to 50 mg/kg of body weight. Blood was drawn for de termination of plasma choline concentration by high-performance liquid chromatography, and proton magnetic resonance spectroscopy (H-1-MRS) was performed to determine the relative concentration of cytosolic cho line-containing compounds in the brain at baseline and after ingestion of choline. Main Outcome Measures.-Plasma choline and cytosolic choli ne-containing compounds in the brain, estimated as the ratio of the ch oline resonance to the creatine resonance on H-1-MRS scans of the basa l ganglia, were compared following blinded analyses of data from subje ct cohorts studied at baseline and 3 hours after choline ingestion. Re sults.-Levels of plasma choline and cytosolic choline-containing compo unds 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 subjec ts. Brain cytosolic choline-containing compounds increased substantial ly in younger subjects (mean increase, 60%; P<.001 vs baseline). Older subjects showed a much smaller increase in brain choline-containing c ompounds (mean, 16%, P<.001 vs the increase in younger subjects). Conc lusion.-Uptake of circulating choline into the brain decreases with ag e. Given the key role of choline in neuronal structure and function, t his change may be a contributing factor in onset in late life of neuro degenerative, particularly dementing, illnesses in which cholinergic n eurons show particular susceptibility to loss.