Beta-amyloid deposition, a hallmark of Alzheimer's disease, is also common in cognitively normal older adults. Using Pittsburgh compound-B PET imaging, the study found that greater beta-amyloid burden in normal controls is associated with altered functional connectivity within the default mode network during rest. Connectivity decreased in regions critical for episodic memory, including posteromedial cortex, ventral medial prefrontal cortex, and angular gyrus, while increases appeared in dorsal and anterior medial prefrontal and lateral temporal cortices. The decreases align with known vulnerability of memory-related areas in Alzheimer's disease, and the increases may reflect compensatory mechanisms.
In cognitively normal older adults, β-amyloid (Aβ) buildup in the default mode network impairs learning independently of tau, but higher dopamine synthesis capacity in the dorsolateral striatum can recover that learning performance. Aβ-positive individuals show reduced default mode network activity in response to error feedback, which relates to poorer learning. Computational modeling indicates that Aβ disinhibits the default mode network during error processing, and dopamine synthesis capacity in the dorsolateral striatum rebalances effective connectivity between the default mode network and frontostriatal network, counteracting Aβ-related disruption. These findings suggest that dopaminergic function can partially compensate for Aβ-related learning deficits through network rebalancing, offering a candidate mechanism for cognitive resilience in preclinical Alzheimer's disease.