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J Neurol Neurosurg Psychiatry 84:556-561 doi:10.1136/jnnp-2012-303299
  • Neurodegeneration
  • Research paper

Cortical atrophy in presymptomatic Alzheimer's disease presenilin 1 mutation carriers

  1. Bradford C Dickerson3,5,7
  1. 1Psychology Department, Center for Memory and Brain, Boston University, Boston, Massachusetts, USA
  2. 2Grupo de Neurociencias, Universidad de Antioquia, Medellín, Colombia
  3. 3Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA
  4. 4Banner Alzheimer's Institute, Phoenix, Arizona, USA
  5. 5Department of Neurology, Frontotemporal Dementia Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA
  6. 6Department of Neurology, Center for Alzheimer Research and Treatment, Brigham & Women's Hospital, Boston, Massachusetts, USA
  7. 7Department of Neurology, Massachusetts Alzheimer's Disease Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA
  1. Correspondence to Dr Brad Dickerson, Massachusetts General Hospital Frontotemporal Dementia Unit, 149 13th Street, Suite 2691, Charlestown, MA 02129, USA; bradd{at}nmr.mgh.harvard.edu
  • Received 24 May 2012
  • Revised 4 October 2012
  • Accepted 11 October 2012
  • Published Online First 7 November 2012

Abstract

Background Sporadic late-onset Alzheimer's disease (AD) dementia has been associated with a ‘signature’ of cortical atrophy in paralimbic and heteromodal association regions measured with MRI.

Objective To investigate whether a similar pattern of cortical atrophy is present in presymptomatic presenilin 1 E280A mutation carriers an average of 6 years before clinical symptom onset.

Methods 40 cognitively normal volunteers from a Colombian population with familial AD were included; 18 were positive for the AD-associated presenilin 1 mutation (carriers, mean age=38) whereas 22 were non-carriers. T1-weighted volumetric MRI images were acquired and cortical thickness was measured. A priori regions of interest from our previous work were used to obtain thickness from AD-signature regions.

Results Compared to non-carriers, presymptomatic presenilin 1 mutation carriers exhibited thinner cortex within the AD-signature summary measure (p<0.008). Analyses of individual regions demonstrated thinner angular gyrus, precuneus and superior parietal lobule in carriers compared to non-carriers, with trend-level effects in the medial temporal lobe.

Conclusion Results demonstrate that cognitively normal individuals genetically determined to develop AD have a thinner cerebral cortex than non-carriers in regions known to be affected by typical late-onset sporadic AD. These findings provide further support for the hypothesis that cortical atrophy is present in preclinical AD more than 5 years prior to symptom onset. Further research is needed to determine whether this method could be used to characterise the age-dependent trajectory of cortical atrophy in presymptomatic stages of AD.

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