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Down Syndrome Abstract
of the Month: Jan 2006

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Hippocampal myo-inositol and cognitive ability in adults with Down syndrome: an in vivo proton magnetic resonance spectroscopy study.

Beacher F, Simmons A, Daly E, Prasher V, Adams C, Margallo-Lana ML, Morris R, Lovestone S, Murphy K, Murphy DG.
Arch Gen Psychiatry. 2005 Dec;62(12):1360-5.

Section of Brain Maturation, Department of Psychological Medicine, Neuroimaging Research Group, Institute of Psychiatry, De Crespigny Park, Denmark Hill, London, England.

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Abstract:

CONTEXT: Down syndrome (DS) is the most common genetic cause of mental retardation. However, the biological determinants of this are poorly understood. The serum sodium/myo-inositol cotransporter gene is located on chromosome 21, and myo-inositol affects neuronal survival and function. Nevertheless, few in vivo studies have examined the role of myo-inositol in DS. OBJECTIVE: To determine if people with DS have significant differences in brain myo-inositol concentration from controls and if, within people with DS, this is related to cognitive ability. DESIGN: A case-control study. SETTING: Outpatient. PARTICIPANTS: The sample was composed of 38 adults with DS without dementia (age range, 18-66 years) and 42 healthy controls (age range, 19-66 years). The DS and control groups did not differ significantly in age, sex, ethnic origin, apolipoprotein E status, or handedness. MAIN OUTCOME MEASURES: Hippocampal myo-inositol concentration and cognitive performance, as measured by the Cambridge Cognitive Examination. RESULTS: Hippocampal myo-inositol concentration was significantly higher in people with DS than in controls, and within people with DS, increased myo-inositol concentration was significantly negatively correlated with overall cognitive ability. CONCLUSIONS: Adults with DS have a significantly increased brain concentration of myo-inositol, and this is associated with reduced cognitive ability. Future studies are required to relate myo-inositol concentration in people with DS to brain development and increased risk for developing Alzheimer disease.

My comments:

Inositol is a cyclic compound that is found in cell membranes, especially in the nervous system. Myo-inositol is the major active form of inositol, and is involved in neuronal development and survival, cell membrane metabolism and amyloid production. There were a few previous small studies that found higher levels than normal of this substance in the brains of adults with DS (it shows up pretty well on scans by "proton magnetic resonance spectroscopy"). The inositol appeared to be higher in the area of the brain called the hippocampus which is associated with learning. So the present study was designed to test a larger number of adults with DS and to see if it affected cognitive processes.

While this is an impressive study, there are a few caveats to point out. This is a small sample of people with DS and a larger scale study would be needed to confirm the findings, on the order of several hundred adults. And this study just shows an association between the high myo-inositol amounts and reduced cognitive ability, and does not prove a cause-effect relationship. If this does prove to be the case, then a drug that limits production of inositol or breaks down the already present inositol, may be very useful. There is some research that indicates that the anticonvulsant valproate inhibits inositol synthesis, and that lithium may deplete inositol that is present in the brain, but more human research is needed.

 
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