Evidence from functional neuroimaging of a compensatory prefrontal network in Alzheimer's disease

Abstract

Previous experiments have found that individuals with Alzheimer's disease (AD) show increased activity in prefrontal regions compared with healthy age-matched controls during cognitive tasks. This has been interpreted as compensatory reallocation of cognitive resources, but direct evidence for a facilitating effect on performance has been lacking. To address this we measured neural activity during semantic and episodic memory tasks in mildly demented AD patients and healthy elderly controls. Controls recruited a left hemisphere network of regions, including prefrontal and temporal cortices in both the semantic and episodic tasks. Patients engaged a unique network involving bilateral dorsolateral prefrontal and posterior cortices. Critically, activity in this network of regions was correlated with better performance on both the semantic and episodic tasks in the patients. This provides the most direct evidence to date that AD patients can use additional neural resources in prefrontal cortex, presumably those mediating executive functions, to compensate for losses attributable to the degenerative process of the disease.

Fig. 1.

Scatter plots of performance on the semantic and recognition tasks. Task accuracy below chance performance (50%) in some patients was caused by failures to respond to some items.Sem, Semantic task; Rec, recognition task; Obj, object.

Fig. 2.

Changes in brain activity related to task for controls and AD patients. The images in A (LV1;p < 0.001) and C (LV2;p = 0.002) show the active areas on a standard magnetic resonance imaging scan in which the right side of the brain is shown on the right side of the image. The brain slices begin at −28 mm relative to the anterior commissure–posterior commissure line (top left image) and end at +28 mm (bottom right image) with a 4 mm slice separation. Thegraphs in B and D show the mean brain scores for controls and AD patients on the LVs. Positive mean brain scores were found in those conditions in which activity was increased in the brain regions shown in red andyellow (i.e., those with positive salience on the LV). Negative mean brain scores were found in those conditions in which activity was increased in the brain regions shown inblue (those with negative salience on the LV).Arrows point to the regions of left VLPFC and extrastriate cortex used in subsequent analyses. Maxima of regions with increased activity during the semantic and recognition tasks (salience/SE ≥ 3.0) are shown in Table 2. Base, Baseline task; Sem, semantic task; Rec, recognition task.

Fig. 3.

Functional connectivity of left VLPFC and GOs. A, Connectivity in the control group;B,connectivity in the AD patients. The VLPFC voxel in both groups was x −36, y 28, andz 4, and for the extrastriate region the voxel used wasx −34, Y −72, and z 28 (indicated bywhite arrows). Positive correlations are shown inyellow and red, and negative correlations are shown in blue. Maxima of regions with positive correlations for the controls (salience/SE ≥ 3.0) are given in Results, and maximum regions of positive correlation for the AD patients are shown in Table 4.