Treatment effects of therapeutic cholinesterase inhibitors on visuospatial processing in Alzheimer's disease: a longitudinal functional MRI study.

BACKGROUND/AIMS: Visuospatial impairments are known to occur in Alzheimer's disease (AD). We hypothesised that functional magnetic resonance imaging (fMRI) response in task-related brain regions would be impaired in patients with AD during the task and that treatment with acetyl cholinesterase inhibitors would enhance activations in brain regions concerned with this visual perceptual processing. METHOD: Ten AD subjects were neuropsychologically assessed and underwent fMRI imaging whilst performing a series of visuospatial perception tasks, before and after treatment with acetyl cholinesterase inhibitors. Eleven healthy elderly comparison subjects were also scanned twice. RESULTS: Regions of increased brain activation in AD included the left precuneus, left cuneus, left supramarginal gyrus, right parieto-temporal cortex and right inferior parietal lobule. Further, increased activation in the left precuneus was found to correlate significantly with improved functioning of activities of daily living. CONCLUSIONS: We believe this to be the first fMRI study that, after controlling for the confound of repeat scanning, demonstrates altered patterns of brain activation associated with visuospatial processing following treatment in patients with AD. The treatment-related improvement of visual perception in AD may rely on enhanced attentional mechanisms, thereby possibly supporting independent living through improvement on activities of daily living.

The neural basis of visuospatial perception in Alzheimer's disease and healthy elderly comparison subjects: an fMRI study.

The neural basis of visuospatial deficits in Alzheimer's disease is unclear. We wished to investigate the neural basis of visuospatial perception in patients with Alzheimer's disease compared with healthy elderly comparison subjects using functional magnetic resonance imaging (fMRI). Twelve patients with AD and thirteen elderly comparison subjects were investigated. The patients were recruited from the local clinic and comparison subjects were from spouses and community. All participants underwent fMRI whilst viewing visuospatial stimuli and structural MRI, and findings were analysed using voxel-based morphometry. The comparison group activated V5, superior parietal lobe, parieto-occipital cortex and premotor cortices. The AD group demonstrated hypoactivation in the above regions and instead showed greater activation in inferior parietal lobule and activated additional areas. There was no structural atrophy above and beyond that found globally in patients in the identified regions of BOLD activation. To our knowledge, this is the first study to explore the neuroanatomy of perception of depth and motion in Alzheimer's disease. These specific functional deficits in AD provide evidence for an underlying patho-physiological basis for the clinically important symptom of visuospatial disorientation in patients with AD.