Vasavan Nair

Tetrahydroaminoacridine-lecithin combination treatment in patients with intermediate-stage Alzheimer's disease. Results of a Canadian double-blind, crossover, multicenter study.

We studied the efficacy and safety of oral tetrahydroaminoacridine (THA) combined with lecithin in 52 patients with Alzheimers disease. The maximal tolerated dose of THA (up to 100 mg per day) was determined during an eight-week titration period, after which the tolerated dose of THA or placebo was given during two sequential randomized periods of treatment lasting eight weeks each. Highly purified lecithin (4.7 g per day) was administered during all phases of the study. Efficacy was expressed in terms of scores on the Mini-Mental State (MMS) test, the modified MMS test, the Hierarchic Dementia Scale, the Rapid Disability Rating Scale-II, and the behavioral scale of Reisberg et al. Safety was assessed by careful clinical monitoring as well as serial measurements of liver aminotransferases. Forty-six patients completed the titration period, and 39 completed the double-blind period, during which only the MMS score showed a small but significant increase (P less than 0.05) after four weeks of treatment with THA. Autonomic side effects of THA were common but mild. Reversible elevations of serum aspartate and alanine aminotransferase levels to three or more times the upper limit of normal occurred in 17 percent of patients; most of the patients affected were women. A liver biopsy performed in one patient showed resolving focal liver-cell necrosis. These studies fail to demonstrate a significant clinical benefit of THA given orally in a maximal dose of 100 mg per day over a period of eight weeks in combination with lecithin.

Prevalence of bipolar disorder in a psychogeriatric population

Bipolar affective disorder arising for the first time in old age (60 years and over) has not been extensively studied. The authors present a prevalence study of mania arising after age 60. Of 217 patients admitted to our unit in a 2-year period, 10 (4.7%) showed symptoms of mania, using the DSM-III criteria. This constitutes 9.3% of 108 affective disorder patients admitted during the same period. An important factor in the precipitation of these attacks was marital discord, leading, in several cases, to separation, even in this age group.

Tardive dyskinesia and the primary psychiatric diagnosis.

Abstract Over 300 patients were assessed for the presence of tardive dyskinesia in relation to the primary psychiatric diagnosis. Patients with organic mental syndrome or bipolar disorder showed a significantly (P

Tardive dyskinesia: a two-year follow-up study.

Abstract Eighty patients whose tardive dyskinesia (TD) had been assessed two years previously were reevaluated. The majority (66%) showed no change in their TD. An almost equal number improved (18%) and worsened (16%). Patients whose TD improved were younger (P

Early versus Late Onset Psychosis and Tardive Dyskinesia

Patients with late-onset psychosis (defined as psychosis requiring hospitalization at age 45 or more, n = 20) were compared with early-onset psychosis patients (defined as psychosis requiring hospitalization at age 25 or less, n = 56) for the prevalence of tardive dyskinesia (TD). Late-onset psychosis patients were found to have significantly more TD (p less than 0.01), which was more severe (p less than 0.05) and developed in a relatively shorter period of neuroleptic treatment (p less than 0.001), than patients with early-onset psychosis. In addition, TD patients (irrespective of early or late onset of neuroleptic treatment) were found to show a preponderance of drug-free periods (p less than 0.01) in their past neuroleptic history, more so than non-TD patients. Our findings indicate that late-onset psychosis should be considered to be a risk factor for the development of TD.

The association of tardive dyskinesia and pseudoparkinsonism.

1. A survey of 315 chronic inpatients for the presence of extrapyramidal side effects indicates that 58.7% of the patients had no evidence of extrapyramidal side effects, 28.6% had tardive dyskinesia (TD) alone, 8.9% had pseudoparkinsonism and 3.8% had a combination of both. 2. Women seemed to exhibit more side effects. 3. Aging was another factor associated with a higher risk for the appearance of extrapyramidal side effects. 4. Affective disorder patients carried more risk than patients with schizophrenia. 5. The low prevalence of the combined TD and pseudoparkinsonism may be related to several factors. The possible explanations are explored and discussed. These patients present a therapeutic dilemma.

Incidence of tardive dyskinesia in an outpatient population.

Abstract Among 108 primarily psychiatric outpatients surveyed for tardive dyskinesia (TD), eight (7.4%) developed the disorder by the end of a two-year prospective study. A comparison between the TD patients and a control group (matched for age, sex, duration of neuroleptic treatment, and diagnosis) yielded no confirmed predisposing factor differentiating the two populations. However, age, especially in women, may be important in the development of TD.

Prophylaxis and the lithium ratio in bipolar patients

Thirty-five bipolar outpatients treated with lithium carbonate were followed for up to 5 years with the aim of studying the relation of the lithium ratio (LR) and its predictive value. Only male responders were found to have higher LR than male nonresponders. No difference was found between the mean LR of men and women, as a group. Aging also had no effect on LR. Positive family history of affective disorders was correlated with high LR, irrespective of response.

Anosognosia predicts default mode network hypometabolism and clinical progression to dementia

Objective To identify the pathophysiologic mechanisms and clinical significance of anosognosia for cognitive decline in mild cognitive impairment. Methods We stratified 468 patients with amnestic mild cognitive impairment into intact and impaired awareness groups, determined by the discrepancy between the patient and the informant score on the Everyday Cognition questionnaire. Voxel-based linear regression models evaluated the associations between self-awareness status and baseline β-amyloid load, measured by [18F]florbetapir, and the relationships between awareness status and regional brain glucose metabolism measured by [18F]fluorodeoxyglucose at baseline and at 24-month follow-up. Multivariate logistic regression tested the association of awareness status with conversion from amnestic mild cognitive impairment to dementia. Results We found that participants with impaired awareness had lower [18F]fluorodeoxyglucose uptake and increased [18F]florbetapir uptake in the posterior cingulate cortex at baseline. In addition, impaired awareness in mild cognitive impairment predicted [18F]fluorodeoxyglucose hypometabolism in the posterior cingulate cortex, left basal forebrain, bilateral medial temporal lobes, and right lateral temporal lobe over 24 months. Furthermore, participants with impaired awareness had a nearly 3-fold increase in likelihood of conversion to dementia within a 2-year time frame. Conclusions Our results suggest that anosognosia is linked to Alzheimer disease pathophysiology in vulnerable structures, and predicts subsequent hypometabolism in the default mode network, accompanied by an increased risk of progression to dementia. This highlights the importance of assessing awareness of cognitive decline in the clinical evaluation and management of individuals with amnestic mild cognitive impairment.

A possible indication for red cell lithium determinations: a case report.

The recommended prophylactic lithium levels in the treatment of manic depressive patients differ from study to study. In this paper, we present a patient who was maintained euthymic on lower plasma levels than those recommended. However, we theorize that the reason for this may be due to the fact that she had a high RBC/plasma ratio. We recommend that in those patients whose plasma lithium levels are consistently low, this point should be kept in mind before considering them as noncompliant.