Original Article

Alzheimer disease family history impacts resting state functional connectivity

  1. Liang Wang MD1,
  2. Catherine M. Roe PhD1,2,
  3. Abraham Z. Snyder MD, PhD1,3,
  4. Matthew R. Brier BS1,
  5. Jewell B. Thomas BA1,
  6. Chengjie Xiong PhD2,4,
  7. Tammie L. Benzinger MD, PhD2,3,
  8. John C. Morris MD1,2,
  9. Beau M. Ances MD, PhD1,*

Article first published online: 29 OCT 2012

DOI: 10.1002/ana.23643

Issue

Annals of Neurology

Annals of Neurology

Volume 72, Issue 4, pages 571–577, October 2012

Additional Information

How to Cite

Wang, L., Roe, C. M., Snyder, A. Z., Brier, M. R., Thomas, J. B., Xiong, C., Benzinger, T. L., Morris, J. C. and Ances, B. M. (2012), Alzheimer disease family history impacts resting state functional connectivity. Ann Neurol., 72: 571–577. doi: 10.1002/ana.23643

Author Information

  1. 1

    Department of NeurologyWashington University in Saint Louis, Saint Louis, MO

  2. 2

    Charles F. and Joanne Knight Alzheimer's Disease Research CenterWashington University in Saint Louis, Saint Louis, MO

  3. 3

    Department of RadiologyWashington University in Saint Louis, Saint Louis, MO

  4. 4

    Division of Biostatistics, Washington University in Saint Louis, Saint Louis, MO

*Box 8111, 660 South Euclid Ave, Saint Louis, MO 63110

Publication History

  1. Issue published online: 29 OCT 2012
  2. Article first published online: 29 OCT 2012
  3. Accepted manuscript online: 9 MAY 2012 06:23AM EST
  4. Manuscript Accepted: 4 MAY 2012
  5. Manuscript Revised: 10 APR 2012
  6. Manuscript Received: 11 JAN 2012

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Abstract

Objective:

Offspring whose parents have Alzheimer disease (AD) are at increased risk for developing dementia. Patients with AD typically exhibit disruptions in the default mode network (DMN). The aim of this study was to investigate the effect of a family history of late onset AD on DMN integrity in cognitively normal individuals. In particular, we determined whether a family history effect is detectable in apolipoprotein E (APOE) ε4 allele noncarriers.

Methods:

We studied a cohort of 348 cognitively normal participants with or without family history of late onset AD. DMN integrity was assessed by resting state functional connectivity magnetic resonance imaging.

Results:

A family history of late onset AD was associated with reduced resting state functional connectivity between particular nodes of the DMN, namely the posterior cingulate and medial temporal cortex. The observed functional connectivity reduction was not attributable to medial temporal structural atrophy. Importantly, we detected a family history effect on DMN functional connectivity in APOE ε4 allele noncarriers.

Interpretation:

Unknown genetic factors, embodied in a family history of late onset AD, may affect DMN integrity prior to cognitive impairment. ANN NEUROL 2012;72:571–577

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