Hypofrontality and negative symptoms in patients with dementia of Alzheimer type

Objective: The purpose of the current study was to examine the relation bet ween regional cerebral blood flow (rCBF) and negative symptoms (NS) in pati ents with dementia of Alzheimer type (DAT). Background: Negative symptoms i n neuropsychiatric disorders were associated with altered rCBF in frontal c ortex. Methods: Twenty-five subjects with a diagnosis of DAT were administe red the Scale for the Assessment of Negative Symptoms (SANS), the Positive and Negative Symptom Scale, the Hamilton Rating Scale for Depression, and t he Mini-Mental State Examination. The subjects were divided into two groups by means of a median split with regard to NS severity thigh NS group, N = 12; low NS group, N = 13). Each patient underwent a single photon emission tomography scan using Tc-99m-HMPAO at rest. Cortical and subcortical region s of interest were symmetrically defined in each hemisphere. Cortical-to-ce rebellar perfusion ratios were established quantitatively using ADAC softwa re. Results: High NS group subjects had a significantly lower rCBF than low NS group subjects in the frontal cortex and cingulate gyrus (MANOVA: p = 0 .022) as a result of differences in the dorsolateral prefrontal cortex bila terally (right: F = 12.12, p = 0.002; left: F = 6.55, p = 0.02) and in the frontal cortex, mainly in the right hemisphere (right: F = 6.33, p = 0.02; left: F = 3.26, p = 0.08). For all the subjects (N = 25), there were negati ve correlations between the SANS total score and rCBF, most prominently in the dorsolateral prefrontal cortex bilaterally (right: r = -0.48, p <0.01; left: r = -0.49, p = 0.01). No significant correlation was found between rC BF in any of the regions of interest and either the Mini-Mental State Exami nation or the Hamilton Rating Scale for Depression scores. Conclusions: Thi s study indicates that decreased perfusion in the frontal cortex is associa ted with NS severity but not with measures of cognitive impairment or depre ssive symptoms in DAT patients. These results support the hypothesis that t he frontal lobes may be involved in the cause of NS in DAT, and they unders core the importance of NS evaluation in neuroimaging studies.