Journal
NEUROLOGY
Volume 77, Issue 16, Pages 1524-1531Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1212/WNL.0b013e318233b33d
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Funding
- NIH [R01-AG11378, P50-AG16574, U01-AG06786]
- Mayo Foundation, USA
- Opus building [NIH C06-RR018898]
- Robert H. Smith Family Foundation
- NIH/NIA-University of Pittsburgh Alzheimer Disease Research Center
- Elan/Janssen AI
- Baxter International Inc.
- Forest Laboratories, Inc.
- Cephalon, Inc.
- Allon Therapeutics, Inc.
- NIH/NIA
- Alzheimer's Association
- Mangurian Foundation
- Pfizer Inc
- Mayo Foundation
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Objective: To investigate age-related default mode network (DMN) connectivity in a large cognitively normal elderly cohort and in patients with Alzheimer disease (AD) compared with age-, gender-, and education-matched controls. Methods: We analyzed task-free-fMRI data with both independent component analysis and seed-based analysis to identify anterior and posterior DMNs. We investigated age-related changes in connectivity in a sample of 341 cognitively normal subjects. We then compared 28 patients with AD with 56 cognitively normal noncarriers of the APOE epsilon 4 allele matched for age, education, and gender. Results: The anterior DMN shows age-associated increases and decreases in fontal lobe connectivity, whereas the posterior DMN shows mainly age-associated declines in connectivity throughout. Relative to matched cognitively normal controls, subjects with AD display an accelerated pattern of the age-associated changes described above, except that the declines in frontal lobe connectivity did not reach statistical significance. These changes survive atrophy correction and are correlated with cognitive performance. Conclusions: The results of this study indicate that the DMN abnormalities observed in patients with AD represent an accelerated aging pattern of connectivity compared with matched controls. Neurology (R) 2011;77:1524-1531
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