Frontotemporal Network Connectivity during Memory Encoding Is Increased with Aging and Disrupted by Beta-Amyloid

Approximately 30% of cognitively normal older adults harbor brain beta-amyloid (A beta), a prominent feature of Alzheimer's disease associated with neural alterations and episodic memory decline. We examined how aging and A beta deposition affect neural function during memory encoding of visual scenes using functional magnetic resonance imaging (fMRI) in humans. Thirty-six cognitively normal older people underwent fMRI scanning, and positron emission tomography with [C-11] Pittsburgh compound B to measure fibrillar brain A beta; 15 young subjects were studied with fMRI. Older adults without A beta deposition showed reduced regional brain activation (compared with young subjects) with decreased task-independent functional connectivity between parahippocampal gyrus and prefrontal cortex. In this network, task-related connectivity was increased compared with young subjects, and the degree of connectivity was related to memory performance. In contrast, older individuals with A beta deposition showed no such increased task-related network connectivity, but did display increased regional activity unassociated with performance. These findings suggest that network connectivity plays a significant role in compensating for reduced regional activity during successful memory encoding in aging without A beta deposition, while in those with A beta this network compensation fails and is accompanied by inefficient regional hyperactivation.