Objectives: Parietal lobe dysfunction is an important characteristic of early Alzheimer disease (AD). Functional studies have shown conflicting parietal activation patterns indicative of either compensatory or dysfunctional mechanisms. This study aimed at examining activation differences in early AD using a visuospatial task. We focused on functional characteristics of the parietal lobe and examined compensation or disconnection mechanisms by combining a fMRI task with effective connectivity measures from Granger causality mapping (GCM).Methods: Eighteen male patients with amnestic mild cognitive impairment (aMCI) and 18 male cognitively healthy older individuals were given a mental rotation task with different rotation angles.Results: There were no behavioral group differences on the fMRI task. Separate measurements at each angle revealed widespread activation group differences. More temporal and parietal activation in the higher angle condition was observed in patients with aMCI. The parametric modulation, which identifies regions associated with increasing angle, confirmed these results. The GCM showed increased connectivity within the parietal lobe and between parietal and temporal regions in patients with aMCI. Decreased connectivity was found between the inferior parietal lobule and posterior cingulate gyrus. Connectivity patterns correlated with memory performance scores in patients with aMCI.Conclusions: Our results demonstrate increased effective temporoparietal connectivity in patients with aMCI, while maintaining intact behavioral performance. This might be a compensational mechanism to counteract a parietal-posterior cingulate gyrus disconnection. These findings highlight the importance of connectivity changes in the pathophysiology of AD. In addition, effective connectivity may be a promising method for evaluating interventions aimed at the promotion of compensatory mechanisms. Neurology ® 2012;78:352-360 GLOSSARY AD ϭ Alzheimer disease; aMCI ϭ amnestic mild cognitive impairment; CDR ϭ Clinical Dementia Rating; CSTE ϭ Cluster-level Statistical Threshold Estimator; DMN ϭ default mode network; FA ϭ flip angle; FOV ϭ field of view; GCM ϭ Granger causality mapping; MCI ϭ mild cognitive impairment; MTL ϭ medial temporal lobe; MUMC؉ ϭ Memory Clinic of the Maastricht University Medical Center; ROI ϭ region of interest; RT ϭ reaction time; TE ϭ echo time; TR ϭ repetition time.Parietal lobe dysfunction in early Alzheimer disease (AD) has been shown abundantly in both postmortem 1,2 and neuroimaging 3,4 studies. fMRI studies in early AD have shown indications for either compensation or functional loss. [5][6][7][8] Compensatory mechanisms have been observed in medial temporal but also in parietal areas. 5,7,9 Early AD has been associated with a disconnection between lobes with increased intralobe connectivity, 10 although some studies have reported interlobe disconnection. 10,11 Compensation reflects increased activation in one or more regions in order to maintain behavioral performance, while disconn...