Alzheimer's disease research has largely concentrated on the study of cognitive decline, but the associated behavioural and neuropsychiatric symptoms are of equal importance in the clinical profile of the disease. There is emerging evidence that regional differences in brain atrophy may align with variant disease presentations. The objective of this study was to identify the regions of decreased grey matter (GM) volume which were associated with specific neuropsychiatric behaviours in patients with mild Alzheimer's disease. Voxel-based morphometry was used to correlate GM derived from T(1)-weighted MRI images of 31 patients with mild Alzheimer's disease and specific neuropsychiatric symptoms and behaviours measured by the Neuropsychiatric Inventory. Delusions were associated with decreased GM density in the left frontal lobe, in the right frontoparietal cortex and in the left claustrum. Apathy was associated with GM density loss in the anterior cingulate and frontal cortex bilaterally, the head of the left caudate nucleus and in bilateral putamen. Agitation was associated with decreased GM values in the left insula, and in anterior cingulate cortex bilaterally. Neuropsychiatric symptoms of Alzheimer's disease seem to associate with neurodegeneration of specific neural networks supporting personal memory, reality monitoring, processing of reward, interoceptive sensations and subjective emotional experience. The study of neurodegenerative disorders such as Alzheimer's disease using voxel-based morphometry and other imaging modalities may further the understanding of the neural structures that mediate the genesis of abnormal behaviours.

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Twenty seven patients with mild AD were enrolled in a prospective open label controlled study of rivastigmine. Assessments included a range of neuropsychiatric and behavioural measures and rCBF using HMPAO SPECTat baseline, three and six months. Significant enhancement of frontal, parietal and temporal brain blood flow with related psychometric improvement was observed in twelve of the treated patients. A pattern of reduced rCBF and cognitive performance was observed in four unresponsive and eleven untreated patients. The results suggest that alterations in the clinical and cognitive status of patients receiving a cholinesterase inhibitor are paralleled by changes in rCBF. Longitudinal assessment with repeated imaging offers a method of better understanding the effects of cholinesterase inhibition on the AD brain.

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The accurate distinction of premorbid dementia syndromes from benign non-progressive memory problems. Studies of treatment options for people with benign non-progressive memory problems and longer-term follow-up to determine which patients develop chronic problems.

Cross-sectional comparisons indicated that mild-moderate AD patients produced more word-finding delays (WFDs) and empty and indefinite phrases, while producing fewer pictorial themes, repairing fewer errors, responding to fewer WFDs, produce shorter and less complex phrases and produce speech with less intonational contour than controls. However, the two groups could not be distinguished on the basis of phonological paraphasias. Longitudinal follow-up, however, suggested that phonological processing deteriorates over time, where the prevalence of phonological errors increased over 12 months. Discussion Consistent with findings from neuropsychological, neuropathological and neuroimaging studies, the language deterioration shown by the AD patients shows a pattern of impairment dominated by semantic errors, which is later joined by a disruption in the phonological aspects of speech.