Analysis of top-down control and spatial attention in mild cognitive impairment and Alzheimer's disease: relationship to ApoE4 genotype

Accumulating evidence suggests that deficits of visual selective attention may already occur at early stages of dementia like the prodromal phase of Mild Cognitive Impairment (MCI). Methods: For the attentional assessment in patients with MCI and probable Alzheimer's disease (AD), we used partial report of brief letter arrays in combination with Bundesen's theory of visual attention (Bundesen, 1990). On the basis of performance in this task TVA provides two mathematically independent and quantitative parameter estimates: task-related weighting for prioritizing relevant visual objects (top-down control), and the spatial distribution of attentional weights across the left and right hemi-field. Results: Compared to an age-, gender- and education-matched healthy control group, AD patients showed significantly reduced top-down control functions whereas MCI patients were unimpaired. In contrast, spatial attentional weighting was already highly significantly unbalanced across hemifields in MCI. While the majority of patients were lateralized to the left hemifield, a rightward attentional bias was also found in a few patients. In the AD stage the bias was even more pronounced. Controls showed balanced spatial weighting across both hemi-fields. Analysis of the effects of ApoE4 genotype (positive versus negative) and age (65 years) on spatial attentional weighting in a combined patient group suggests that especially in young, ApoE4-positive patients a pathological leftward spatial bias prevails. For both partial report parameters correlations with clinical criteria like e.g. the Clinical Dementia Rating Scale (CDR; Morris, 1993) rating the overall severity of cognitive deficits and the neurological status according to The Consortium to Establish a Registry for Alzheimer's Disease (CERAD; Thalmann al., 1997) were found. Conclusions: In conclusion, already the early MCI stage in the neurodegenerative progression to dementia seems to be characterized by pathologically unbiased spatial weighing. At the AD stage, reduced selectivity of top-down control appears to emerge additionally. Probable underlying genetic ApoE4 pathology seems to be related with spatial attention, irrespective of disease stage. Consequently, these results emphasise the necessity of the application of sensitive tools for the assessment of task-related and spatial attentional selection in Alzheimer's disease