Hypofrontality and negative symptoms in patients with dementia of Alzheimer type.

OBJECTIVE: The purpose of the current study was to examine the relation between regional cerebral blood flow (rCBF) and negative symptoms (NS) in patients with dementia of Alzheimer type (DAT). BACKGROUND: Negative symptoms in neuropsychiatric disorders were associated with altered rCBF in frontal cortex. METHODS: Twenty-five subjects with a diagnosis of DAT were administered the Scale for the Assessment of Negative Symptoms (SANS), the Positive and Negative Symptom Scale, the Hamilton Rating Scale for Depression, and the Mini-Mental State Examination. The subjects were divided into two groups by means of a median split with regard to NS severity (high NS group, N = 12; low NS group, N = 13). Each patient underwent a single photon emission tomography scan using 99mTc-HMPAO at rest. Cortical and subcortical regions of interest were symmetrically defined in each hemisphere. Cortical-to-cerebellar perfusion ratios were established quantitatively using ADAC software. 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 bilaterally (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 negative 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 rCBF in any of the regions of interest and either the Mini-Mental State Examination or the Hamilton Rating Scale for Depression scores. CONCLUSIONS: This study indicates that decreased perfusion in the frontal cortex is associated with NS severity but not with measures of cognitive impairment or depressive symptoms in DAT patients. These results support the hypothesis that the frontal lobes may be involved in the cause of NS in DAT, and they underscore the importance of NS evaluation in neuroimaging studies.

Methylphenidate treatment of negative symptoms in patients with dementia.

This pilot study evaluated response of negative symptoms (NS) to methylphenidate in patients with dementia and relationships between NS, depression, and cognitive deficits in these patients. Consecutively admitted patients with NS and dementia--12 with dementia of Alzheimer's type and 15 with vascular dementia--were rated on severity of NS (SANS and PANSS-N scales), depressive symptoms (Ham-D), and cognitive impairment (MMSE) before and after treatment with methylphenidate. NS decreased significantly, and cognitive scores increased. A decrease in depression scores was nonsignificant after all variance attributable to NS was removed. NS, depression, and cognitive scores were not significantly intercorrelated. Results were similar for Alzheimer's and vascular dementia patients. Negative symptoms in dementia patients appear responsive to methylphenidate treatment. This effect may underlie putative changes in symptoms of depression observed by other researchers.