Clozapine for treatment-resistant agitation in dementia.

Few studies have examined the potential role of clozapine in treatment of agitation in dementia patients who have previously failed to respond to standard pharmacotherapy. We conducted a systematic chart review of all elderly patients admitted to our inpatient unit between 2001 and 2004. Of them, 16 dementia patients were treated with clozapine for treatment-resistant agitation, and their charts were blindly rated by 3 clinicians on the Clinical Global Impression (CGI) Scale, Brief Agitation Rating Scale (BARS), and the Cohen-Mansfield Agitation Inventory-Short Form (CMAI-SF). Overall, clozapine therapy seemed beneficial in treatment-resistant agitation in dementia patients.

Genetic associations between neuregulin-1 SNPs and neurocognitive function in multigenerational, multiplex schizophrenia families.

OBJECTIVES: Recent work shows promising associations between schizophrenia and polymorphisms in neuregulin-1 (NRG1) and a large literature also finds strong familial relationships between schizophrenia and cognitive deficits. Given the role of NRG1 in glutamate regulation and glutamate's effect on cognition, we hypothesized that cognitive deficits may be related to variation within NRG1, providing a possible mechanism to increase risk for schizophrenia. METHODS: This study examined the associations between NRG1, cognition, and schizophrenia using a multigenerational multiplex family sample (total N=419, 40 families), including 58 affected participants (schizophrenia or schizoaffective disorder-depressed type) and their 361 unaffected relatives. Participants were genotyped for 40 NRG1 single nucleotide polymorphisms (SNPs), chosen largely based on previous associations with schizophrenia. All participants completed structured diagnostic interviews and a computerized neurocognitive battery assessing eight cognitive domains. Variance component quantitative trait analyses tested for associations between individual NRG1 SNPs and cognitive performance in the total sample, a subsample of healthy participants with no Diagnostic and Statistical Manual of Mental Disorders diagnosis, and using general intelligence as a covariate. RESULTS: Effect sizes (within-family ß coefficients) ranged from 0.08 to 0.73, and 61 of these associations were nominally significant (P≤0.05), with 12 associations at P≤0.01, although none achieved the modified Bonferroni significance threshold of P<0.0003. Attention was the most frequently nominally associated domain and rs10503929, a nonsynonymous SNP, was the most frequently nominally associated SNP. CONCLUSION: Although not significant experiment-wise, these findings suggest that further study of the associations between variation in NRG1 and cognition may be productive.

Level of cognitive impairment predicts mortality in high-risk community samples: the memory and medical care study.

Over the course of 3 years, the authors investigated the relationship between severity of cognitive impairment and mortality in a community sample of 498 elders at high risk for cognitive impairment. Subjects were classified as having no cognitive disorder, mild cognitive impairment, or dementia, based on a validated battery of four neuropsychological tests. Severity of impairment was based on Mini-Mental State Examination scores. Additional data were obtained from subjects' knowledgeable informants and Medicare records. Kaplan-Meier survival estimates and Cox hazard proportion analysis of the sample revealed that presence of cognitive impairment increases mortality in a fashion that parallels the severity of the impairment.