Michael E. Mahler

A double-blind comparison of trazodone and haloperidol for treatment of agitation in patients with dementia

The authors compared the efficacy and side effects of trazodone and haloperidol for treating agitated behaviors associated with dementia. Twenty-eight elderly patients with dementia and agitated behaviors were randomly assigned to double-blind treatment with either trazodone (50-250 mg/day) or haloperidol (1-5 mg/day) for 9 weeks. There was no significant difference in improvement between the medication groups. Adverse effects, however, were more common in the group treated with haloperidol. Improvement in individual areas suggested that repetitive, verbally aggressive, and oppositional behaviors responded preferentially to trazodone, whereas symptoms of excessive motor activity and unwarranted accusations responded preferentially to haloperidol. These results indicate that moderate doses of trazodone and haloperidol are equally effective for treatment of overall agitated behaviors in patients with dementia, but specific symptoms may respond preferentially to a particular agent.

Assessment of cognitive, psychiatric, and behavioral disturbances in patients with dementia: the Neurobehavioral Rating Scale.

To assess the validity of the Neurobehavioral Rating Scale (NRS) in patients with Alzheimers disease (AD) or multi‐infarct dementia (MID) and to characterize the cognitive, psychiatric, and behavioral disturbances that occur in these patients.

Clinical Features and Treatment Outcomes of Necrotizing Autoimmune Myopathy

IMPORTANCE Necrotizing autoimmune myopathy (NAM) is characterized pathologically by necrotic muscle fibers with absent or minimal inflammation. It is often accompanied by statin therapy, connective tissue diseases, cancer, and autoantibodies specific for signal recognition particle (SRP) or 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR). Data are limited concerning differences among etiologic subgroups and treatment outcomes in NAM. OBJECTIVES To describe the clinical, serologic, and electrophysiologic characteristics of NAM, compare patient subgroups, and determine clinical outcome predictors. DESIGN, SETTING, AND PARTICIPANTS We conducted a retrospective review of medical records for 63 adult Mayo Clinic patients assigned the clinical and histopathologic diagnosis of NAM from January 1, 2004, through December 31, 2013. Patients were stratified by presumed cause and autoantibody status. MAIN OUTCOMES AND MEASURES Clinical, electrophysiologic, and pathologic characteristics were collected and compared among patient subgroups. Predictors of response to treatment were identified by univariate logistic regression. RESULTS Lower extremity weakness predominated (46 [73%]). Distal weakness (26 [41%]), dysphagia (22 [35%]), and dyspnea (23 [37%]) were common. Twenty-two patients (35%) were receiving a statin medication at onset, 6 had cancer, and 3 had a connective tissue disease. The median creatine kinase level was 5326 U/L. In 13 patients (24%), SRP-IgG was detected, and in 17 patients (34%), HMGCR-IgG was detected (one-third of whom had not received statin medication). One patient was dual seropositive. Facial weakness was more common in SRP-IgG-positive patients. Myotonic discharges were more common in statin-associated NAM. Prednisone monotherapy was insufficient to control disease in most patients; 30 (90%) of 32 patients required 2 or more immunotherapeutic agents. Relapse occurred in 16 (55%) of 29 patients during immunosuppressant taper or discontinuation. Predictors of favorable outcome were male sex and use of 2 or more immunotherapeutic agents within 3 months of onset. CONCLUSIONS AND RELEVANCE Necrotizing autoimmune myopathy was idiopathic in half of this cohort with clinical and histopathologically defined disease. In the remainder, NAM was associated with statin medication, cancer, or connective tissue disease. One in 4 patients was SRP-IgG positive, and 1 in 3 was HMGCR-IgG positive. The disease was usually not controlled by corticosteroid monotherapy. Presentation, course, and outcomes did not differ significantly in seropositive, seronegative, and statin-associated cases. Early aggressive immunosuppressant therapy improved outcomes, and risk of relapse was high during medication dose reduction or withdrawal.

Alzheimer disease and the dementia of Parkinson disease : comparative investigations

Intellectual abnormalities are common in Parkinson disease (PD), occurring in a majority of patients and exhibiting a spectrum of severity from mild to severe. Alzheimer disease (AD) has been posited as the cause of dementia in PD. Comparative neuropsychological studies, however, show differences in memory, language, and frontal lobe functions between AD and PD patients even when the two groups have comparably severe dementia syndromes. The AD-type neuropathology occurs in 10–60% of PD patients, and dementia is usually overt when AD pathology is identified at autopsy. The AD changes are less frequent than intellecutal deterioration in PD, and dementia has been observed in PD patients without AD pathology. Therefore, concurrent AD cannot be the cause of all cases of dementia in PD. Cholinergic deficits occur in some PD patients, but cholinergic deficits have been described in patients without dementia and dementia has been documented in patients without cholinergic system abnormalities. Dopaminergic disturbances contribute to the dementia of PD. Differences in neuropeptide concentrations, electrophysiologic responses, and cerebral metabolism also support patholphysiologic distinctions between AD and the dementia of PD. Genetic investigations suggest a role for heredity in AD, whereas PD appears to be an acquired, nongenetic disorder. These studies indicate that despite areas of overlap in clinical symptoms and neuropathology, AD and the dementia of PD are largely distinct.

Does Behavioral Improvement with Haloperidol or Trazodone Treatment Depend on Psychosis or Mood Symptoms in Patients with Dementia

Several previous studies have examined the effects of pharmacological interventions for agitated behavior in patients with dementia. However, the choice of medication in clinical practice continues to be directed largely by local pharmacotherapy culture rather than empirical treatment guidelines. We examined the relationship between behavioral improvement and co‐occurring delusions and mood symptoms in patients with dementia who were treated with haloperidol, an antipsychotic medication, or trazodone, a serotonergic antidepressant.

Behavioral neurology of multi-infarct dementia

Multi-infarct dementia (MID) is a heterogeneous entity in which a variety of cerebrovascular disorders leads to intellectual impairment. A variety of patterns of behavioral changes may be observed in MID, depression, psychosis, and personality change are common. The neurobehavioral syndromes of MID are determined by the specific arteries involved and the location and extent of tissue infarction.

Regional Metabolie Dependency in Obstructive Sleep Apnea

Abnormalities of oxygen use occur in obstructive sleep apnea, as do impaired cerebral perfusion and alterations of cerebral function. In this case study, the authors quantitated the local cerebral glucose metabolic rate in two patients with obstructive sleep apnea (one with and one without oxygen supply dependency) and assessed cerebral glucose use by increasing oxygen delivery through passive leg elevation. Obstructive sleep apnea was confirmed by visual analysis of nocturnal pulse oximetry traces in two patients and its severity assessed from the respiratory disturbance index and minimum oxygen saturation. Awake local cerebral glucose metabolic rate (μM/min/100 g) was determined by positron-emission tomography using [18 F]-2-Fluoro-2-Deoxy-D-Glucose at baseline and on the following day during passive leg elevation. Conditions otherwise were unchanged. The patient with global oxygen supply dependency exhibited a significant increase in the local cerebral glucose metabolic rate. In contrast, the patient without global supply dependency had no change in the local cerebral glucose metabolic rate. These case studies demonstrate the first evidence of improvement in regional metabolic consumption in response to increased oxygen delivery and in the presence of global oxygen supply dependency.

Diffusion in an elliptical cylinder, and a numerical method for calculating time-varying diffusant sink rates, with special reference to diffusion of oxygen in the frog sartorius muscle

Abstract For a substance whose distribution F ( x, y, t ) within an elliptical cylinder is governed by the diffusion equation, a formal description of the time course of this distribution following a step change at the boundary was given by McLachlan in 1945; it is a doubly infinite series of exponentials. Computer programs have been written to evaluate these terms, each of which requires frequent evaluation of the standard and modified Mathieu functions. The exponent of the leading term, together with measurements of F ( x,y,t ) at a given ( x 0 , y 0 , t ), allows the determination of the diffusion coefficient D . These exponents are tabulated for boundaries spanning the range from a cylinder to a sheet. If the diffusant is produced or consumed at uniformly distributed sites, at the rate Q ( t ), evaluation of the above solution allows the computation of Q ( t ) from F ( x 0 , y 0 , t ). This was investigated in detail for conditions chosen to simulate the diffusion and consumption of oxygen in the frog sartorius muscle. Ten terms of the solution, when used with a convergence-speeding routine, were sufficient for an accurate approximation to Q ( t ).

Control of Respiration in Intact Muscle

We believe that the hydrolysis of ATP provides the free energy for all cell function, and we know that the ultimate source of almost all ATP produced in muscle is oxidative metabolism (Fig. 1). We’d like to know, in as much detail as possible, the mechanism coupling these two fundamental processes, whereby a change in the rate of ATP utilization leads to a change in the rate of oxidative phosphorylation. That brings me to my second reason for choosing the first figure. In what can be thought of as perhaps the first attempt to model the control of respiration in muscle, Chance and Connelly’ used a scheme little more complicated than this. Having determined the responses of isolated mitochondria to limiting concentrations of ADP or inorganic phosphate (Pi), they assumed that the rest of the cell could be represented simply as an ATPase. I mention this not to impugn or embarass two distinguished scientists, but to illustrate the point that, in general, workers in this field have shown a surprising lack of awareness of, or concern for, events occurring outside the mitochondrial inner membrane. To the extent that this audience shares that attitude, I hope to correct it. Fig. 2 shows a current, schematic description of the reactions believed to couple oxidative phosphorylation to ATP hydrolysis, which I hope will meet with everyone’s approval.