High Brain myo-Inositol Levels in the Predementia Phase of Alzheimer’s Disease in Adults With Down’s Syndrome: A ¹H MRS Study

OBJECTIVE: An extra portion of chromosome 21 in Down’s syndrome leads to a dementia in later life that is phenotypically similar to Alzheimer’s disease. Down’s syndrome therefore represents a model for studying preclinical stages of Alzheimer’s disease. Markers that have been investigated in symptomatic Alzheimer’s disease are myo-inositol and N-acetylaspartate. The authors investigated whether abnormal brain levels of myo-inositol and other metabolites occur in the preclinical stages of Alzheimer’s disease associated with Down’s syndrome. METHOD: The authors used ¹H magnetic resonance spectroscopy (MRS) with external standards to measure absolute brain metabolite concentrations in 19 nondemented adults with Down’s syndrome and 17 age- and sex-matched healthy comparison subjects. RESULTS: Concentrations of myo-inositol and choline-containing compounds were significantly higher in the occipital and parietal regions of the adults with Down’s syndrome than in the comparison subjects. Within the Down’s syndrome group, older subjects (42–62 years, N=11) had higher myo-inositol levels than younger subjects (28–39 years, N=8). Older subjects in both groups had lower N-acetylaspartate levels than the respective younger subjects, although this old-young difference was not greater in the Down’s syndrome group. CONCLUSIONS: The approximately 50% higher level of myo-inositol in Down’s syndrome suggests a gene dose effect of the extra chromosome 21, where the human osmoregulatory sodium/myo-inositol cotransporter gene is located. The even higher myo-inositol level in older adults with Down’s syndrome extends to the predementia phase earlier findings of high myo-inositol levels in symptomatic Alzheimer’s disease.