Only a few reports exist of plasma amino acid profiles in the oldest-old, and none exist of the oldest-old with cognitive problems. Therefore, we measured fasting plasma amino acid concentrations in twenty-three healthy community-dwellers aged 90-103 years (group A); eighteen community-dwellers with mild cognitive impairment without dementia aged 91-104 years (group B); thirty-three patients with dementia aged 96-100 years (group C); and sixty healthy young controls aged 20-50 years. Biochemical and anthropometric parameters, and the basic activities of daily living (ADL) were also measured. Independent of cognitive status, in all oldest-old groups, essential:non essential amino acids (EAA:NEAA) was lower than in young controls and positively associated with body muscle mass. Patients with dementia were further characterized by a negative association between EAA:NEAA and the number of dependent ADL. All oldest-old groups had higher values of tyrosine:other large neutral amino acids (LNAA) than young controls. Groups B and C also had a higher phenylalanine:other LNAA. These data show that abnormalities in plasma amino acid profile are common in oldest-old individuals independent of their cognitive status, but that, in oldest-old patients with dementia, they are associated with functional disability. The abnormalities in phenylalanine and tyrosine plasma availability could contribute to the cause or aggravation of concurrent cognitive problems because these amino acids are neurotransmitter precursors and compete with other LNAA for transport into the brain.