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September 20, 1995

Decreased Brain Choline Uptake in Older Adults: An In Vivo Proton Magnetic Resonance Spectroscopy Study

Author Affiliations

From the Brain Imaging Center, McLean Hospital, Belmont, Mass (Drs Cohen, Renshaw, Stoll, and Yurgelun-Todd and Ms Babb); Department of Psychiatry, Harvard Medical School, Boston, Mass (Drs Cohen, Renshaw, Stoll, and Yurgelun-Todd); the Clinical Research Center (Drs Cohen, Renshaw, and Wurtman) and Department of Brain and Cognitive Sciences (Dr Wurtman), Massachusetts Institute of Technology, Cambridge; and the Psychopharmacology Unit, Brigham and Women's Hospital, Boston (Dr Stoll).

JAMA. 1995;274(11):902-907. doi:10.1001/jama.1995.03530110064037

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 on1H-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.(JAMA. 1995;274:902-907)