Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Neural compensation in older people with brain amyloid-β deposition


Recruitment of extra neural resources may allow people to maintain normal cognition despite amyloid-β (Aβ) plaques. Previous fMRI studies have reported such hyperactivation, but it is unclear whether increases represent compensation or aberrant overexcitation. We found that older adults with Aβ deposition had reduced deactivations in task-negative regions, but increased activation in task-positive regions related to more detailed memory encoding. The association between higher activity and more detailed memories suggests that Aβ-related hyperactivation is compensatory.

This is a preview of subscription content

Access options

Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Figure 1: Group imaging results.
Figure 2: Age and Aβ effects on parametric encoding activity for details.


  1. Jack, C.R. et al. Lancet Neurol. 12, 207–216 (2013).

    CAS  Article  Google Scholar 

  2. Bennett, D.A. et al. Neurology 66, 1837–1844 (2006).

    CAS  Article  Google Scholar 

  3. Morris, J.C. et al. Ann. Neurol. 67, 122–131 (2010).

    CAS  Article  Google Scholar 

  4. Aizenstein, H.J. et al. Arch. Neurol. 65, 1509–1517 (2008).

    Article  Google Scholar 

  5. Sperling, R.A. et al. Alzheimers Dement. 7, 280–292 (2011).

    Article  Google Scholar 

  6. Sperling, R.A. et al. Neuron 63, 178–188 (2009).

    CAS  Article  Google Scholar 

  7. Mormino, E.C. et al. Cereb. Cortex 22, 1813–1823 (2012).

    Article  Google Scholar 

  8. Dickerson, B.C. et al. Ann. Neurol. 56, 27–35 (2004).

    Article  Google Scholar 

  9. Qin, S., van Marle, H.J.F., Hermans, E.J. & Fernández, G. J. Neurosci. 31, 8920–8927 (2011).

    CAS  Article  Google Scholar 

  10. Naghavi, H.R. & Nyberg, L. Conscious. Cogn. 14, 390–425 (2005).

    Article  Google Scholar 

  11. Raichle, M.E. et al. Proc. Natl. Acad. Sci. USA 98, 676–682 (2001).

    CAS  Article  Google Scholar 

  12. Walsh, D.M. et al. Nature 416, 535–539 (2002).

    CAS  Article  Google Scholar 

  13. Palop, J.J. & Mucke, L. Nat. Neurosci. 13, 812–818 (2010).

    CAS  Article  Google Scholar 

  14. Oh, H. & Jagust, W.J. J. Neurosci. 33, 18425–18437 (2013).

    CAS  Article  Google Scholar 

  15. Morcom, A.M., Li, J. & Rugg, M.D. Cereb. Cortex 17, 2491–2506 (2007).

    Article  Google Scholar 

  16. Spreng, R.N., Wojtowicz, M. & Grady, C.L. Neurosci. Biobehav. Rev. 34, 1178–1194 (2010).

    Article  Google Scholar 

  17. Bakker, A. et al. Neuron 74, 467–474 (2012).

    CAS  Article  Google Scholar 

  18. O'Brien, J.L. et al. Neurology 74, 1969–1976 (2010).

    CAS  Article  Google Scholar 

  19. Cirrito, J.R. et al. Neuron 48, 913–922 (2005).

    CAS  Article  Google Scholar 

  20. Jagust, W.J. & Mormino, E.C. Trends Cogn. Sci. 15, 520–526 (2011).

    Article  Google Scholar 

  21. Oh, H., Habeck, C., Madison, C. & Jagust, W. Hum. Brain Mapp. 35, 297–308 (2014).

    Article  Google Scholar 

  22. Agosta, F. et al. Proc. Natl. Acad. Sci. USA 106, 2018–2022 (2009).

    CAS  Article  Google Scholar 

  23. Rabinovici, G.D. et al. Neurology 68, 1205–1212 (2007).

    CAS  Article  Google Scholar 

  24. Friston, K.J., Ashburner, J.T., Kiebel, S.J., Nichols, T.E. & Penny, W.D. Statistical Parametric Mapping: The Analysis of Functional Brain Images (Academic, 2011).

  25. Logan, J. et al. J. Cereb. Blood Flow Metab. 16, 834–840 (1996).

    CAS  Article  Google Scholar 

  26. Price, J.C. et al. J. Cereb. Blood Flow Metab. 25, 1528–1547 (2005).

    CAS  Article  Google Scholar 

  27. Dale, A.M., Fischl, B. & Sereno, M.I. Neuroimage 9, 179–194 (1999).

    CAS  Article  Google Scholar 

  28. Jenkinson, M., Beckmann, C.F., Behrens, T.E.J., Woolrich, M.W. & Smith, S.M. NeuroImage 62, 782–790 (2012).

    Article  Google Scholar 

  29. Casanova, R. et al. Neuroimage 34, 137–143 (2007).

    Article  Google Scholar 

  30. Yang, X., Beason-Held, L., Resnick, S.M. & Landman, B.A. Neuroimage 57, 423–430 (2011).

    Article  Google Scholar 

  31. Van Essen, D.C. Neuroimage 28, 635–662 (2005).

    Article  Google Scholar 

Download references


We thank S. Qin for task stimuli and W. Huijbers for discussion. Supported by US National Institutes of Health grant AG034570.

Author information

Authors and Affiliations



J.A.E., H.O. and W.J.J. designed the study; J.P.O. synthesized the [11C]PIB; J.W.V. performed neuropsychological testing; S.C. performed PET acquisition; J.A.E. and H.O. performed MRI acquisition; S.L.B., C.M.M. and S.M.M. processed PET data; J.A.E., H.O. and C.M.M. processed MRI data; J.A.E. and H.O. analyzed data; J.A.E., H.O. and W.J.J. prepared the manuscript. J.A.E. and H.O. contributed equally to the study. All authors discussed results and commented on the manuscript.

Corresponding authors

Correspondence to Jeremy A Elman or William J Jagust.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Integrated supplementary information

Supplementary Figure 1 Task paradigm and behavioral results.

A scanned encoding session was followed by an approximately 15 minute delay and 2 unscanned memory tasks. a.) During the scanned fMRI encoding session, subjects studied 150 pictures of scenes. b.) In the unscanned gist task, subjects judged whether written descriptions corresponded to scenes studied during encoding. c.) In the details task, subjects determined whether 6 written details were true or false about each of the previously studied scenes.

Supplementary Figure 2 Encoding activity for gist.

Activity for hits versus baseline was assessed for age and PIB effects. To distinguish between relative increases and decreases from baseline, tests of age (panel a) and PIB (panel e) were masked by task positive and negative networks (defined by contrasting hits with baseline, averaged across all groups). Plots displaying mean z-scores of significant clusters accompany masked results to better visualize underlying patterns of activity in the voxelwise analysis. Error bars represent s.e.m. a.) Greater activity for remembered gist in young compared to old PIB– subjects (warm colors). b.) Task positive regions show greater activation in young than PIB– subjects (warm colors). c.) Task negative regions show reduced deactivation in young compared to PIB– subjects (cool colors). d.) Aβ effects revealed greater activity for hits in old PIB+ compared to PIB– subjects (warm colors). e.) Task positive regions indicate greater activity in old PIB+ than PIB– subjects (warm colors). f.) Task negative regions indicate reduced deactivation in old PIB+ compared to PIB– subjects (cool colors). Results are thresholded at p<0.05, cluster corrected for multiple comparisons.

Supplementary Figure 3 Hits compared to misses in the gist task.

Activity for hits versus misses was assessed for age and PIB effects. a.) Age effects revealed greater activity for hits compared to misses in young compared to old PIB– subjects (warm colors) in lateral posterior and inferior regions. There was greater activity for hits compared to misses in old PIB– compared to young subjects (cool colors) in prefrontal cortex and mid-line structures. b.) Aβ effects revealed greater activity for hits compared to misses in old PIB– compared to PIB+ subjects (warm colors). Results are thresholded at p<0.05, cluster corrected for multiple comparisons. The PIB effect when comparing hits versus misses appears to be inconsistent with results from the comparison of hits to baseline. It should be noted that the above results are primarily driven by group differences on miss trials, suggesting that this condition serves as an incomparable baseline by which to compare activity for hits.

Supplementary Figure 4 Parametric activity for details related to PIB as a continuous measure.

The relationship between linear increases of activity across detail level and PIB Index was tested on a voxelwise basis in all older subjects controlling for age, hit rate and gray matter. Results are thresholded at p<0.05, cluster corrected for multiple comparisons. Greater parametric increases were positively related to the amount of amyloid deposition as measure by PIB Index (warm colors). The results are similar to those when subjects were dichotomized into PIB+ and PIB– groups.

Supplementary Figure 5 Relationship between PIB Index and detail activity in PIB+ subjects.

To explore whether parametric increases in activity vary with the amount of amyloid deposition, linear contrast values were extracted from regions in the task positive network demonstrating significant PIB effects (clusters displayed in Fig. 2e). These values were regressed against the PIB Index of PIB+ subjects, controlling for age, hit rate and gray matter. There is a negative relationship [B=–1.89, t(11)=–2.413, p= 0.034] such that parametric increases are reduced at high levels of amyloid accumulation. Contrast values of the old PIB– group are displayed on the left for comparison purposes. It should be noted that the linear contrast values of subjects with a high PIB Index are still greater than much of the PIB– group.

Supplementary information

Supplementary Text and Figures

Supplementary Figures 1–5 and Supplementary Tables 1–6 (PDF 2149 kb)

Supplementary Methods Checklist (PDF 384 kb)

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Elman, J., Oh, H., Madison, C. et al. Neural compensation in older people with brain amyloid-β deposition. Nat Neurosci 17, 1316–1318 (2014).

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI:

Further reading


Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing