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

J Neurol Neurosurg Psychiatry. 2013 May;84(5):556-61. doi: 10.1136/jnnp-2012-303299. Epub 2012 Nov 7.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alzheimer Disease / genetics*
  • Alzheimer Disease / pathology*
  • Atrophy
  • Cerebral Cortex / pathology*
  • DNA / genetics
  • Female
  • Heterozygote*
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Memory / physiology
  • Mental Recall / physiology
  • Mutation / genetics*
  • Neuropsychological Tests
  • Presenilin-1 / genetics*
  • Recognition, Psychology / physiology
  • Socioeconomic Factors
  • Verbal Behavior / physiology

Substances

  • Presenilin-1
  • DNA