Frontoparietal Cognitive Control of Verbal Memory Recall in Alzheimer's Disease

Objective: Episodic memory retrieval is reliant upon cognitive control systems, of which 2 have been identified with functional neuroimaging: a cingulo-opercular salience network (SN) and a frontoparietal executive network (EN). In Alzheimer's disease (AD), pathology is distributed throughout higher-order cortices. The hypotheses were that this frontoparietal pathology would impair activity associated with verbal memory recall; and that central cholinesterase inhibition (ChI) would modulate this, improving memory recall. Methods: Functional magnetic resonance imaging was used to study normal participants and 2 patient groups: mild cognitive impairment (MCI) and AD. Activity within the EN and SN was observed during free recall of previously heard sentences, and related to measures of recall accuracy. Results: In normal subjects, trials with reduced recall were associated with greater activity in both the SN and EN. Better recall was associated with greater activity in medial regions of the default mode network. By comparison, AD patients showed attenuated responses in both the SN and EN compared with either controls or MCI patients, even after recall performance was matched between groups. Following ChI, AD patients showed no modulation of activity within the SN, but increased activity within the EN. There was also enhanced activity within regions associated with episodic and semantic memory during less successful recall, requiring greater cognitive control. Interpretation: The results indicate that in AD, impaired responses of cognitive control networks during verbal memory recall are partly responsible for reduced recall performance. One action of symptom-modifying treatment is partially to reverse the abnormal function of frontoparietal cognitive control and temporal lobe memory networks.