Age-related changes in the default mode network are more advanced in Alzheimer disease.

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 ε4 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.