R.D. Jewart

Donepezil HCl (E2020) maintains functional brain activity in patients with Alzheimer disease: Results of a 24-week, double-blind, placebo-controlled study

OBJECTIVE The authors evaluated the effects of donepezil (10 mg/day) versus placebo on brain glucose metabolism. METHODS This was a randomized, double-blind, parallel-group, 24-week pilot study in 28 patients with mild-to-moderate Alzheimer disease (AD). Functional brain activity was quantified by measuring average glucose metabolism in an axial brain slice and regional brain glucose metabolism using positron emission tomography. RESULTS At Week 24, relative to the pons metabolic rate, mean brain glucose metabolism in an axial slice at the level of the striatum was maintained within 0.5% of mean baseline levels for donepezil-treated patients, whereas it declined by an average of 10.4% in placebo-treated patients. This observation was confirmed by an analysis of differences in the mean slopes of glucose metabolism in the striatal slice in donepezil- and placebo-treated patients during the 24-week period. Significant treatment differences at Week 24 favoring donepezil for the mean percentage change from baseline in regional brain glucose metabolism were observed in four predefined regions of interest: the right parietal lobe 1, left temporal lobe 2, right frontal lobe 2, and left frontal lobe 2. CONCLUSION Placebo-treated patients with AD show a decline in functional brain activity, relative to the pons, in several regions, and treatment with donepezil may slow this decline.

Quetiapine improves psychotic symptoms and cognition in Parkinson's disease

Twenty‐nine elderly patients who failed treatment with clozapine, risperidone, or olanzapine entered this 24‐week, single‐center, open‐label trial to assess the efficacy of quetiapine (12.5–400 mg/day) for psychosis in patients with Parkinsons disease (PD). Psychiatric, motor, and cognitive assessments were administered at baseline and at periodic intervals for 24 weeks. These included the Brief Psychiatric Rating Scale (BPRS), Neuropsychiatric Inventory (NPI), Unified Parkinsons Disease Rating Scale (UPDRS) and tests of intellectual functioning, attention, and memory. Repeated measures statistical analysis was used to assess change from baseline. The results revealed significant improvements in the 24‐week BPRS total score and NPI psychosis subscale scores, with no decline in UPDRS total or motor subscale scores. There was also significant improvement in recall scores on cognitive measures. These results indicate that quetiapine may treat psychotic symptoms and improve cognition without worsening motor function in patients with PD, suggesting that quetiapine is an effective and well‐tolerated antipsychotic in this population.

Cognitive, Behavioral, and Physiological Changes in Alzheimer Disease Patients as a Function of Incontinence Medications

OBJECTIVE Authors evaluated the cognitive, neurophysiologic, and behavioral effects of incontinence medications in patients with Alzheimer disease (AD). METHODS Nine patients were evaluated, both on and off incontinence medication, for cognitive status, neuropsychiatric status, activities of daily living, and serum anticholinergic level. Caregivers were interviewed to evaluate behavioral status and caregiver burden. RESULTS Patients showed better performance on specific measures of cognition and behavior when not taking medication for incontinence. A significant, inverse correlation was found between mental status and anticholinergic level. CONCLUSION Although the sample size was small, the findings suggest that, in patients with AD, incontinence medications with anticholinergic properties may have detrimental effects on mental status and behavior.

Natural killer cell activity in schizophrenia and schizoaffective disorder : a pilot study

Natural killer cell activity was prospectively studied in 15 patients with chronic schizophrenia and in seven patients with schizoaffective disorder, depressed type. These patients were compared to individually matched normal controls. No mean differences in natural killer cell activity between the patient groups and their controls were observed.

An Association between Increased Concentrations of Cerebrospinal Fluid Dopamine Sulfate and Higher Negative Symptom Scores in Patients with Schizophrenia and Schizoaffective Disorder

There has been much speculation as to the role of dopamine in the etiology and/or manifestation of positive and negative symptoms. Traditionally, cerebrospinal fluid (CSP) concentrations of homovanillic acid (HVA) has been used as an index of central dopaminergic activity. Relea~l dopamine is metabolized to HVA, by catechol-O-methyltransferase (COMT) and monoamine oxidase (MAO) (Cooper et al 1991). A review of the CSF HVA literature, however, reveals no consistent correlations between HVA and schizophrenic symptomatoiogy (reviewed by Pickax et al ! 9907. Yet there is sufficient data to suggest that dopamine activity is abnormal in schizophrenia (Davis et al 19917. Therefore the evaluation of other putative measures of dopamine release or metabolism seems warranted. Released dopamine is also converted to dopamine sulfate (DASO47 by the enzyme phenolsulphotransferase (PST7 (Jenner and Rose, 1973). in the brain, it appears that the sulfoconjugation of dopamine occurs primarily outside of dopaminergic neurons (Tyce et al 1988). Therefore CSF DASO~ concentrations may reflect an important alternate route of dopamine metabolism. Assessment of PST-dependent DASO4 independently, or in re-