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An In Vivo Proton Magnetic Resonance Spectroscopy Study

Felix Beacher, BA, MSc; Andy Simmons, BSc, MSc, PhD; Eileen Daly, BA; Verinder Prasher, PhD; Claire Adams, RNMH, Dip NS; Maria Luisa Margallo-Lana, MRCPsych, MD; Robin Morris, MA, MSc, PhD; Simon Lovestone, MRCPsych, PhD; Kieran Murphy, MRCPsych, PhD; Declan G. M. Murphy, MRCPsych, MD

Arch Gen Psychiatry. 2005;62:1360-1365.

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 (P = .006), and within people with DS, increased myo-inositol concentration was significantly negatively correlated with overall cognitive ability (P = .04).

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.

Author Affiliations: Section of Brain Maturation, Department of Psychological Medicine (Mr Beacher, Drs K. Murphy and D. G. M. Murphy, and Ms Daly), Neuroimaging Research Group (Dr Simmons), and Departments of Psychology (Dr Morris) and Old Age Psychiatry and Neuroscience (Dr Lovestone), Institute of Psychiatry, London, England (Mr Beacher, Drs Simmons, Morris, Lovestone, K. Murphy, and D. G. M. Murphy, and Ms Daly); Institute for Ageing and Health, Wolfson Research Unit, Newcastle General Hospital, Newcastle upon Tyne, England (Dr Margallo-Lana); Greenfields Monyhull Hospital, Kings Norton, Birmingham, England (Dr Prasher and Ms Adams); College of Surgeons, Dublin, Ireland (Dr K. Murphy).

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