A trial of buspirone for anxiety in Parkinson's disease: Safety and tolerability

IntroductionIn Parkinson's disease (PD), anxiety is common, associated with lower health-related quality of life, and undertreated. The primary objective of this study was to determine the tolerability of buspirone for the treatment of anxiety in PD.MethodsIndividuals with PD and clinically significant anxiety were randomized 4:1 to flexible dosage buspirone or placebo for 12 weeks. Treatment was initiated at 7.5 mg twice daily and titrated based on response and tolerability to an optimal dosage (maximum 30 mg twice daily). The primary outcome was the proportion of participants who failed to complete the study on study drug. Secondary outcomes included adverse events, dosage reductions, motor function, dyskinesias, and anxiety.ResultsA total of 21 participants enrolled, 4 were randomized to placebo and 17 to buspirone (mean (SD) age 65.5 (9.8), 76.5% male, 88% on concomitant antidepressant or anxiolytic). In the buspirone group, 7 (41%) failed to complete the study on drug, 5 due to intolerability. The median buspirone dosage was 7.5 mg twice daily. No serious adverse events occurred. A total of 9 (53%) buspirone participants experienced adverse events consistent with worsened motor function. In the buspirone group, mean (SD) improvement from baseline to week 12 in Hamilton Anxiety Rating Scale was −3.9 (3.8) and Parkinson Anxiety Scale −7.1 (6.4).ConclusionTolerability concerns do not support moving immediately forward with a large-scale efficacy trial. However, concomitant anxiolytics may have affected tolerability and a signal of efficacy was seen suggesting that future studies of buspirone monotherapy be considered.     

Zidovudine treatment of the AIDS dementia complex: Results of a placebo-controlled trial

The efficacy of two doses of zidovudine was examined for the treatment of the acquired immunodeficiency syndrome (AIDS) dementia complex in a randomized, double-blinded, placebo-controlled trial conducted at nine study centers. For the initial 16 weeks, 40 subjects with mild to moderate AIDS dementia complex were randomized to one of three treatment arms: 400 mg of zidovudine five times daily, 200 mg of zidovudine five times daily, or placebo five times daily. After week 16, patients initially randomized to the placebo group were rerandomized to one of the two zidovudine treatment arms. The primary efficacy end point was improvement in performance on a battery of seven neuropsychological tests; the secondary end point was improvement on a protocol neurological evaluation directed at the cardinal features of the AIDS dementia complex. For the initial 16-week period, average z scores based on the neuropsychological test battery revealed a significant improvement in the combined treatment groups compared to the placebo group; however, when the two treatment groups were compared separately to the placebo group, only the group receiving the higher zidovudine dose exhibited significant improvement. After rerandomization of the placebo patients to one of the two treatment arms at week 16, this group also showed significant improvement in the average neuropsychological z score by week 32. These results extend previous observations that indicate a therapeutic benefit of zidovudine for the treatment of AIDS dementia complex.     

Low Dose Lithium Treatment of Behavioral Complications in Alzheimer's Disease: Lit-AD Randomized Clinical Trial

BackgroundA case series suggested efficacy for lithium to treat agitation in dementia, but no placebo-controlled trials have been conducted.ObjectivesTo evaluate low-dose lithium treatment of agitation in Alzheimer's disease (AD).MethodIn a four-site trial, patients with AD and agitation/aggression score ≥4 on the Neuropsychiatric Inventory (NPI) were randomized, double-blind, to lithium carbonate 150–600 mg daily or placebo for 12 weeks. Primary efficacy outcome was change in NPI agitation/aggression; secondary efficacy outcome was treatment response (30% reduction in NPI score for agitation/aggression plus psychosis and a Clinical Global Impression (CGI) score of much or very much improved). Safety profile of lithium was assessed.ResultsFifty-eight of 77 patients (75.3%) completed the trial. In linear mixed effects model analyses, lithium was not significantly superior to placebo for agitation/aggression. Proportion of responders was 31.6% on lithium and 17.9% on placebo (χ²=1.26, p = 0.26). Moderate or marked improvement (CGI) was greater on lithium (10/38=36.8%) than placebo (0/39=0%, Fisher's exact test p <0.001). In exploratory analyses, improvement on lithium was greater than placebo on NPI delusions and irritability/lability (p's<0.05). Lithium showed greater reduction than placebo in patients with high Young Mania Rating Scale scores (β=5.06; 95%CI,1.18 to 8.94, p = 0.01). Oral dose and serum levels demonstrated similar associations with efficacy outcomes. Lithium did not differ significantly from placebo on safety outcomes.ConclusionsLow-dose lithium was not efficacious in treating agitation but was associated with global clinical improvement and excellent safety. A larger trial may be warranted of likely lithium-responsive behavioral symptoms that overlap with mania.     

Ginkgo biloba and donepezil: a comparison in the treatment of Alzheimer's dementia in a randomized placebo-controlled double-blind study

The Ginkgo biloba special extract EGb 761 seems to produce neuroprotective effects in neurodegenerative diseases of multifactorial origin. There is still debate about the efficacy of Ginkgo biloba special extract EGb 761 compared with second‐generation cholinesterase inhibitors in the treatment of mild to moderate Alzheimer's dementia. Our aim is to assess the efficacy of the Ginkgo biloba special extract E.S. in patients with dementia of the Alzheimer type in slowing down the disease's degenerative progression and the patients' cognitive impairment compared with donepezil and placebo. The trial was designed as a 24‐week randomized, placebo‐controlled, double‐blind study. Patients aged 50–80 years, suffering from mild to moderate dementia, were allocated into one of the three treatments: Ginkgo biloba (160 mg daily dose), donepezil (5 mg daily dose), or placebo group. The degree of severity of dementia was assessed by the Syndrom Kurz test and the Mini‐Mental State Examination. Clinical Global Impression score was recorded to assess the change in the patients’ conditions and the therapeutic efficacy of tested medications. Our results confirm the clinical efficacy of Ginkgo biloba E.S. (Flavogin) in the dementia of the Alzheimer type, comparable with donepezil clinical efficacy. There are few published trials that have directly compared a cholinesterase inhibitor with Ginkgo for dementia. This study directly compares a cholinesterase inhibitor with Ginkgo biloba for dementia of the Alzheimer type and could be a valid contribution in this debate. Our study suggests that there is no evidence of relevant differences in the efficacy of EGb 761 and donepezil in the treatment of mild to moderate Alzheimer's dementia, so the use of both substances can be justified. In addition, this study contributes to establish the efficacy and tolerability of the Ginkgo biloba special extract E.S. in the dementia of the Alzheimer type with special respect to moderately severe stages.     

Twice‐daily,low‐dose pramipexole in early Parkinson's disease: A randomized,placebo‐controlled trial

To compare the safety and efficacy of low dosages of pramipexole given twice daily (bid) in early Parkinson's disease (PD) with those of a standard 3 times daily (tid) regimen in a randomized, double‐blind, placebo controlled trial involving 311 early PD patients not receiving dopaminergic treatment. Subjects were randomly assigned and followed on assigned treatment for 12 weeks with pramipexole at dosages of 0.5 mg bid, 0.75 mg bid, or 0.5 mg tid, or matching placebo. All subjects were dosed 3 times daily, with placebo if necessary, to maintain blinding. The primary outcome was the change from baseline to Week 12 in the Unified Parkinson Disease Rating Scale (UPDRS) total score (Parts I–III). All active dosages had similar antiparkinson efficacy showing reductions of 4–5 UPDRS points relative to placebo (p < 0.0001) for each comparison. Somnolence, fatigue, nausea, constipation, and peripheral edema were more common in the active treatment groups than in the placebo group, but their frequency did not vary by dosage. In this fixed dosage, randomized study pramipexole administered twice daily at a total daily dosage of 1.0–1.5 mg daily was of comparable efficacy and tolerability to a dosage of 0.5 mg tid over a 12‐week treatment period in early PD. © 2010 Movement Disorder Society     

CARBAMAZEPINE USE IN AGGRESSIVE BEHAVIOUR ASSOCIATED WITH SENILE DEMENTIA

In a randomized placebo crossover controlled study, six patients meeting DSM-III-R criteria for Alzheimer's disease and exhibiting significantly aggressive behaviour were administered carbamazepine (in doses up to 600 mg daily) and placebo, with each treatment period lasting 8 weeks. Levels of aggression as measured by the RAGE scale were significantly reduced compared with placebo (p<0.05). The results suggest that carbamazepine is an effective anti-aggressive agent in patients with dementia. Recommendations for further studies are made.     

A double-blind,placebo controlled,multicentre study of tacrine for alzheimer's disease

The present study was designed to determine whether oral tacrine (tetrahydraminoacridine, THA) improves the symptoms of patients with mild to moderate Alzheimer's disease. The study was a multicentre, randomized double-blind, placebo controlled, parallel group study with individual determination of maximum tolerated dose over a period of 12 weeks. One hundred and fifty-four patients (93 women) aged 44–92 years (mean 75) were selected as having probable Alzheimer's disease as defined by NINCDS–ADRDA workgroup classification and a Mini-Mental State Examination score of 10 or more. Most patients were titrated to 80 mg of tacrine per day. Tacrine improved patients in clinicians‘ global ratings and the relatives’ global rating compared to placebo (p < 0.05). Tacrine did not significantly improve the Mini-Mental State Examination score, although as with other scores the trend favoured tacrine. There was a substantial variation in response among patients. Twelve patients in the tacrine and four in the placebo group were withdrawn from the study due to raised LFTs or adverse events. No serious sequelae resulted from these. One patient in the placebo group and two in the tacrine group died from causes which were considered unrelated to the treatment.     

A pilot placebo-controlled study of trazodone and buspirone in alzheimer's disease

The pharmacological management of behavioural symptoms in Alzheimer's disease is limited by the dearth of effective agents in this area. The purpose of this study was to determine whether trazodone or buspirone are helpful in the treatment of behavioural disturbance in AD. Ten patients meeting NINCDS criteria for AD with behavioural complications were administered trazodone (up to 50 mg tid), buspirone (10 mg tid), and placeboin a 12-week double-blind, crossover design. Outcome measures were the Brief Psychiatric Rating Scale (BPRS), the Dementia Mood Assessment Scale (DMAS), and the Buschke Selective Reminding Task. The data were analysed by ANOVA. Compared to placebo, trazodone produced a small but significant reduction in BPRS and DMAS scores (p<0.05), indicating improvement in behaviour but no change in cognitive measures. In contrast, buspirone has no significant effect on either behavioural or cognitive measures compared to placebo. The results of this pilot study suggest a beneficial role for trazodone, but not buspirone, in the treatment of behavioural disturbance in AD. Further studies using a wider range of doses of trazodone in more behaviourally disturbed AD patients should now be initiated in an attempt to replicate and expand on this preliminary finding.     

Efficacy and withdrawal of clobazam, lorazepam and buspirone in the treatment of anxiety disorders

This multicentre study was conducted to evaluate the efficacy and consequences of progressive or abrupt withdrawal of clobazam in the treatment of Generalized Anxiety Disorder in a double blind study in comparison to lorazepam and buspirone. 128 outpatients suffering from Generalized Anxiety Disorder according to DMS III criteria were included in the study and treated for three weeks. They were randomly divided into 4 groups: group 1: 32 patients receiving clobazam, abruptly withdrawn and replaced by a placebo; group 2: 29 patients receiving clobazam with progressive withdrawal over 3 weeks, clobazam being replaced by a placebo; group 3: 33 patients receiving lorazepam with progressive withdrawal over 3 weeks, lorazepam being replaced by a placebo; group 4: 34 patients receiving buspirone, abruptly withdrawn and replaced by a placebo. The dosages were increased progressively during the first week of treatment. At the end of this time, the patients received either 30 mg clobazam or 30 mg buspirone or 3 mg lorazepam daily. After the first week, the Hamilton Anxiety Rating Scale (HARS) showed a significant improvement in clobazam and lorazepam groups but not in buspirone group. All the drugs were equally effective after three weeks of treatment. The anti-anxiety activity persisted after withdrawal of the studied drug in the 4 groups, without any signs of rebound anxiety or withdrawal syndrome. No clinically relevant differences were found between the 4 groups regarding safety. The side-effects reported were mainly drowsiness in clobazam and lorazepam groups, nausea and headache in buspirone group. In conclusion, clobazam like lorazepam improved anxiety more quickly than buspirone; after 3 weeks of therapy, efficacy was comparable with the 3 drugs and persisted after treatment discontinuation.     

Efficacy of a high dosage of donepezil for Alzheimer's disease as examined by single‐photon emission computed tomography imaging

Background: The efficacy of donepezil 10 mg/day against Alzheimer's disease (AD) was examined, with a primary focus on changes in cerebral blood flow (CBF) as determined by single‐photon emission computed tomography imaging. Methods: The subjects were 24 outpatients who had been diagnosed with probable AD, which had progressed to advanced AD. Mini‐Mental State Examination and Alzheimer's Disease Assessment Scale (ADAS) scores were determined before and after the donepezil dosage increase. ^99mTc‐ethylcysteinate dimer single‐photon emission computed tomography was performed to evaluate changes in CBF. Then, a comparative study evaluated changes after the donepezil dosage increased. Results: After the donepezil dosage increase, adverse effects associated with gastrointestinal symptoms were observed in one patient, and irritability was observed in three. The average Mini‐Mental State Examination score changed from15.25 ± 6.24 to 14.67 ± 6.07; significant changes were not observed. Seventeen subjects were evaluated with the Alzheimer's Disease Assessment Scale‐cognitive subscale. After the dosage increase, the average subscale score decreased from 24.52 ± 13.39 to 21.56 ± 9.14, and significant improvement was observed (P= 0.021). With respect to changes in the CBF, the values of all three indicators decreased after the higher dosage increased CBF. However, no significant differences were observed in CBF. Analysis performed after the donepezil dosage increase revealed significant increases in CBF in the right occipital and temporal lobes, left temporal lobe, right parietal lobe, and both parts of the posterior cerebellum. Conclusion: Increasing the donepezil dosage from 5 mg/day to 10 mg/day is effective for the treatment of AD.     

Determinants of disability in alzheimer's disease

The aim of the study is to evaluate risk factors of disability in a population of 64 patients affected by Alzheimer's disease. The subjects were consecutively recruited at the day hospital service of an Alzheimer's dementia care unit. The associations between activities of daily living and age, cognitive status, affective status, cognitive symptoms duration and number of diseases were evaluated within a multidimensional assessment programme. Cognitive performance, as detected by the Mini-Mental Status Examination, was the main independent predictor of disability; other independent predictors of disability were age and cognitive disease duration. Number of diseases—physical and mental–and self-rated depression scores were not independently associated with disability. It is concluded that, in a population of Alzheimer's patients, cognitive impairment has a high impact on the aetiology of disability, but other variables such as age and disease duration should be taken into account. It is also suggested that cognitive performance is the most important indicator of performance in activities of daily living.     

Metabolic reduction in the posterior cingulate cortex in very early Alzheimer's disease

This study investigated cerebral glucose metabolism in very early Alzheimer's disease, before a clinical diagnosis of probable Alzheimer's disease is possible, using [¹⁸F]fluorodeoxyglucose positron emission tomography. First, 66 patients with probable Alzheimer's disease with a spectrum of dementia severity (Mini-Mental State Examination score, 0–23) were recruited and studied. Cortical metabolic activity was analyzed topographically using three-dimensional stereotactic surface projections. Regression analysis was performed for each brain pixel to predict metabolic patterns of very early disease. Predictions were tested prospectively in a group of 8 patients who complained only of memory impairment without general cognitive decline (Mini-Mental State Examination score, 25 · 1) at the time of scanning but whose condition later progressed to probable Alzheimer's disease. Both results were compared to cerebral metabolic activity in 22 age-similar normal control subjects. Prediction and analysis of actual patients consistently indicated marked metabolic reduction (21–22%) in the posterior cingulate cortex and cinguloparietal transitional area in patients with very early Alzheimer's disease. Mean metabolic reduction in the posterior cingulate cortex was significantly greater than that in the lateral neocortices or parahippocampal cortex. The result suggests a functional importance for the posterior cingulate cortex in impairment of learning and memory, which is a feature of very early Alzheimer's disease.     

Mianserin,a 5-HT2 receptor antagonist,in the treatment of delirium: an open study

To determine the role of the serotonin system at the 5-HT₂ receptors on delirium in the aged, we assessed the effects of mianserin, a relatively selective 5-HT₂ receptor antagonist, in such patients. Twenty-six delirious patients [four without dementia, nine with Alzheimer's disease (AD), 13 with ischemic vascular dementia (IVD)] were included in the open study. After the dose titration period, the mean dose of mianserin administrated was 31.2 mg in delirious patients without dementia, 25.0 mg in delirious patient with AD and 25.9 mg in delirious patients with IVD. The average total score of each patient group on a symptom rating scale was reduced significantly within 24 h (p < 0.05). A complete elimination of symptoms was noted in all four delirious patients without dementia. In the nine delirious patients with AD, marked improvement was noted in four patients (44.4%), moderate improvement in four (44.4%) and no improvement in one (11.1%). In the 13 delirious patients with IVD marked improvement was noted in seven (53.8%), moderate improvement in five (38.5%) and no improvement in one (7.7%). The rapidity of the improvement may be attributable to mianserin's antagonism at the 5-HT₂ receptors, and such serotonin antagonism at the 5-HT₂ receptors may be important in treating delirium.-     

Olfactory dysfunction in dementia of Alzheimer's type and vascular dementia

Background: Olfactory function in vascular dementia has not been extensively investigated to date. We studied olfactory function in vascular dementia (VD) and dementia of Alzheimer's type (DAT). Methods: We studied olfactory functioning in 12 patients suffering from dementia of Alzheimer's type, 11 patients with vascular dementia and 30 normal subjects. For these subjects we examined a 12‐item version of the Pennsylvania smell identification test and mini‐mental state examinations. These three groups were matched for age, sex and educational level. Results: Although the dementia scores were comparable in the DAT and VD groups, the smell identifications were low in DAT patients compared with VD patients and normal control subjects. Conclusions: These results suggest that the smell identification test may be useful in differential diagnosis between DAT and VD patients     

Phase II safety,tolerability, and dose selection study of isradipine as a potential disease‐modifying intervention in early Parkinson's disease (STEADY‐PD)

Isradipine, a dihydropyridine calcium channel antagonist, has been shown to be neuroprotective in animal models of Parkinson's disease (PD). To establish a dosage of isradipine controlled‐release (CR) that is tolerable and demonstrates preliminary efficacy for use in a future pivotal efficacy trial a Phase 2, randomized, double‐blind, parallel group trial (Safety, Tolerability and Efficacy Assessment of Dynacirc CR in Parkinson Disease [STEADY‐PD]) was undertaken in subjects with early PD not requiring dopaminergic therapy (dopamine agonists or levodopa) randomized 1:1:1:1 to 5, 10, or 20 mg of isradipine CR or matching placebo daily. The primary outcome was tolerability defined as no more than a 30% difference in the proportion of patients completing the study on the originally assigned dosage between an active and placebo group. If more than one isradipine dosage was tolerable, then a 3‐point difference in total Unified Parkinson's Disease Rating Scale (UPDRS) change between baseline and week 52 (or time to sufficient disability to require dopaminergic therapy) was taken as a criterion for selection of the most desirable dosage for future study. STEADY‐PD enrolled 99 subjects. The tolerability of isradipine was dose dependent: placebo, 25 of 26 patients (96%); 5 mg, 19 of 23 patients (83%); 10 mg 19 of 26 patients (73%); and 20 mg 9 of 24 patients (37%). There was no difference in change in UPDRS among dosages. The most common adverse events were peripheral edema (30) and dizziness (24). Isradipine 10 mg daily was the maximal tolerable dosage in this study of early PD. A large placebo‐controlled trial will be necessary and is planned to assess efficacy of isradipine 10 mg daily to slow progression of PD disability. © 2013 International Parkinson and Movement Disorder Society.     

Donepezil in Parkinson's disease dementia: A randomized,double‐blind efficacy and safety study

Parkinson's disease dementia (PDD) is associated with cholinergic deficits. This report presents an efficacy and safety study of the acetylcholinesterase inhibitor donepezil hydrochloride in PDD. PDD patients (n = 550) were randomized to donepezil (5 or 10 mg) or placebo for 24 weeks. Coprimary end points were the Alzheimer's Disease Assessment Scale–cognitive subscale (ADAS‐cog) and Clinician's Interview‐Based Impression of Change plus caregiver input (CIBIC+; global function). Secondary end points measured executive function, attention, activities of daily living (ADLs), and behavioral symptoms. Safety and tolerability were assessed. ADAS‐cog mean changes from baseline to week 24 (end point) were not significant for donepezil in the intent‐to‐treat population by the predefined statistical model (difference from placebo: ?1.45, P = .050, for 5 mg; ?1.45, P = .076, for 10 mg). Alternative ADAS‐cog analysis, removing the treatment‐by‐country interaction term from the model, revealed significant, dose‐dependent benefit with donepezil (difference from placebo: ?2.08, P = .002, for 5 mg; ?3.31, P < .001, for 10 mg). The 10‐mg group, but not the 5‐mg group, had significantly better CIBIC+ scores compared with placebo (3.7 vs 3.9, P = .113, for 5 mg; 3.6 vs 3.9, P = .040, for 10 mg). Secondary end points—Mini–Mental State Exam; Delis–Kaplan Executive Function System; Brief Test of Attention, representing cognitive functions particularly relevant to PDD—showed significant benefit for both donepezil doses (P ≤ .007). There were no significant differences in ADLs or behavior. Adverse events were more common with donepezil but mostly mild/moderate in severity. Although the study did not achieve its predefined primary end points, it presents evidence suggesting that donepezil can improve cognition, executive function, and global status in PDD. Tolerability was consistent with the known safety profile of donepezil. © 2012 Movement Disorder Society     

Effects of rivastigmine in patients with and without visual hallucinations in dementia associated with Parkinson's disease

We aimed to determine prospectively whether rivastigmine, an inhibitor of acetylcholinesterase and butyrylcholinesterase, provided benefits in patients with and without visual hallucinations in a population with dementia associated with Parkinson's disease (PDD). This was a 24‐week double‐blind placebo‐controlled study. Primary efficacy measures were the Alzheimer's Disease Assessment Scale cognitive subscale (ADAS‐cog) and Alzheimer's Disease Cooperative Study–Clinician's Global Impression of Change (ADCS‐CGIC). Secondary efficacy measures included activities of daily living, behavioral symptoms, and executive and attentional functions. Patients were stratified according to the presence of visual hallucinations at baseline. The study included 188 visual hallucinators (118 on rivastigmine, 70 on placebo) and 348 nonvisual hallucinators (239 on rivastigmine, 109 on placebo). Rivastigmine provided benefits in both visual hallucinators and nonvisual hallucinators. Absolute responses to rivastigmine on the ADAS‐cog were comparable over 6 months, although rivastigmine–placebo differences tended to be larger in visual hallucinators (4.27; P = 0.002) than in nonhallucinators (2.09; P = 0.015). On the ADCS‐CGIC, differences between rivastigmine and placebo were 0.5 in visual hallucinators (P = 0.030) and 0.3 in nonhallucinators (P = 0.111). Rivastigmine provided benefits on all secondary efficacy measures, and placebo declines and treatment differences were more marked in visual hallucinators. Adverse events were reported more frequently by rivastigmine‐treated patients, although this difference was less marked in visual hallucinators. Visual hallucinations appear to predict more rapid decline and possibly greater therapeutic benefit from rivastigmine treatment in PDD. © 2006 Movement Disorder Society     

Risk factors in clinically diagnosed Alzheimer's disease: A retrospective hospital-based case control study in Warrington

The objective of the study was to assess risk factors for Alzheimer's disease, previously reported in cases control studies from other countries. It was conducted in a psychiatric of unit for the elderly in Warrington, a town in the northwest of England. A retrospective hospital-based, case control method was used comparing 198 cases of Alzheimer's disease (ADRDANINCDS diagnostic criteria) to selected controls (164 other dementias and 176 non-dementing group) in respect of their family, medical and personal histories.The subjects included all patients referred to and seen by the author during a two-year study period. Fifty-eight of 198 Alzheimer's cases reported family history of dementia, compared with 35 of 340 controls (OR=3.27 95% CI 1.89–5.39), p <0.01. The Odds ratio for smoking was 0.68; significant only in men (0.45, p <0.05). The odds ratio for having a history of head injury was 1.52 (0.98–2.35), also significant only in male patients (OR=2.1, p <0.05). The study confirms a family history of dementia in first-degree relatives as a risk factor for Alzheimer's disease. No cases with either Down's syndrome or having family history of it were reported in the study sample. Previously reported head injury as a risk factor appears to apply to all dementias and was not confined to Alzheimer's disease. The inverse relationship with smoking was evident, but significant only in men.     

Prazepam in anxiety: A controlled clinical trial

Prazepam, a benzodiazepine derivative similar in chemical structure and biological activity to diazepam and chlordiazepoxide, has been reported in the literature to possess antianxiety properties in daily doses of up to 80 mg/day. Shaffer et al.¹ found 40–80 mg/day prazepam more effective than placebo but not chlordiazepoxide, in relief of postwithdrawal anxiety in alcoholics. Studies with anxious outpatient psychoneurotics have shown prazepam to be more effective than placebo and equally effective to chlordiazepoxide. For example Silver et al.² found prazepam 30–60 mg superior to chlordiazepoxide and placebo in overall efficacy at 4 weeks but not at 2 weeks, while Dunlop and Weisberg³ reported similar results with 30–60 mg at an endpoint of 4 or 6 weeks.The present 4 week double-blind study was undertaken to help determine the optimum daily dosage of prazepam. To this end the study was designed not only to test the efficacy of 2 daily dosage regimens of prazepam, i.e., 40 and 60 mg, but also to make use of its relatively long half-life by administering it once daily at bedtime.     

Differences in olfactory test performance between normal aged,Alzheimer and vascular type dementia individuals

A comparison was made between 3 groups of elderly subjects — normal controls aged 69–79 years, patients with vascular dementia aged 64–84 years and patients with probable senile dementia of Alzheimer type (SDAT) aged 70–90 years — by means of several tests of olfactory functions. Significant group differences were found at all levels assessed — olfactory thresholds, smell recognition, smell identification, naming of smells — with the normal aged performing best and the SDAT group scoring lowest throughout. The differences were most pronounced with regard to smell recognition and smell identification where minimal or no overlap at all between controls and SDAT patients was found. Differences in age and severity of dementia did not fully account for the findings, suggesting that differential diagnosis of Alzheimer - type dementia could be facilitated and improved by the use of olfactory tasks. Neurophysiological and - pathological findings support a close association or even identity of brain structures involved in olfaction and affected in Alzheimer's disease.