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Abstract
Objective: To determine whether, and to what degree, preclinical Alzheimer disease (AD) confounds studies of healthy aging where “healthy” is based on cognitive normality alone.
Methods: We examined the effects of preclinical AD in cognitively normal older individuals using resting-state functional connectivity MRI. We investigated 2 groups of cognitively normal participants: one group with evidence of preclinical AD as assessed by CSF markers of AD and the other group with normal CSF biomarkers.
Results: There were significant interactions between age and biomarker status in the default-mode, dorsal attention, and salience resting-state networks. In the group with evidence of preclinical AD, there were dramatic changes in functional connectivity with age. In the group without evidence of preclinical AD, those changes were greatly attenuated. In most regions with significant interactions of age and biomarker status, the age-related change in functional connectivity in the normal biomarker group was indistinguishable from zero.
Conclusions: These results suggest that preclinical AD accounts for a substantial portion of the reported effects of aging in the extant functional connectivity literature.
GLOSSARY
- Aβ42=
- β-amyloid 1–42;
- AD=
- Alzheimer disease;
- CDR=
- Clinical Dementia Rating;
- CON=
- control network;
- DAN=
- dorsal attention network;
- DMN=
- default mode network;
- GSR=
- global signal regression;
- PCC=
- posterior cingulate cortex;
- PiB=
- Pittsburgh compound B;
- ROI=
- region of interest;
- rs-fcMRI=
- resting-state functional connectivity MRI;
- RSN=
- resting-state network;
- SAL=
- salience network;
- SMN=
- sensorimotor network
Footnotes
Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
Supplemental data at Neurology.org
- Received February 7, 2014.
- Accepted in final form July 28, 2014.
- © 2014 American Academy of Neurology
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