Cortical atrophy in presymptomatic Alzheimer's disease presenilin 1 mutation carriers
- Yakeel T Quiroz1,2,
- Chantal E Stern1,3,
- Eric M Reiman4,
- Michael Brickhouse5,
- Adriana Ruiz2,
- Reisa A Sperling3,6,7,
- Francisco Lopera2,
- Bradford C Dickerson3,5,7
- 1Psychology Department, Center for Memory and Brain, Boston University, Boston, Massachusetts, USA
- 2Grupo de Neurociencias, Universidad de Antioquia, Medellín, Colombia
- 3Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA
- 4Banner Alzheimer's Institute, Phoenix, Arizona, USA
- 5Department of Neurology, Frontotemporal Dementia Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA
- 6Department of Neurology, Center for Alzheimer Research and Treatment, Brigham & Women's Hospital, Boston, Massachusetts, USA
- 7Department of Neurology, Massachusetts Alzheimer's Disease Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA
- Correspondence to Dr Brad Dickerson, Massachusetts General Hospital Frontotemporal Dementia Unit, 149 13th Street, Suite 2691, Charlestown, MA 02129, USA;
- Received 24 May 2012
- Revised 4 October 2012
- Accepted 11 October 2012
- Published Online First 7 November 2012
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.