Robert Goldman

Pfizer Inc., New York City, New York, United States

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Publications (42)330.27 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: A magnetic resonance imaging (MRI) study was conducted as part of an intervention study in subjects with amnestic mild cognitive impairment (aMCI) to assess donepezil's treatment effect on brain atrophy. Adults with aMCI were randomly assigned to double-blind treatment with 10 mg/day donepezil hydrochloride or placebo for 48 weeks. Brain MRI scans were acquired at baseline and endpoint. The primary outcome measure was annualized percentage change (APC) in hippocampal volume; the main secondary outcome measure was APC in whole brain volumes. An analysis of variance (ANOVA) model including terms for treatment, site, and age was used to compare the treatment groups. APCs for hippocampal volumes were not significantly different between treatment groups. There were significant differences favoring the donepezil group for total (p = 0.001), ventricular region (p = 0.0002), and cortical region (p = 0.003) whole brain volumes. Although the primary MRI outcome measure was negative, the main secondary MRI outcome measure showed a positive result. These findings suggest a treatment effect of donepezil on brain atrophy in aMCI.
    Neurobiology of aging 12/2011; 32(12):2318.e31-41. DOI:10.1016/j.neurobiolaging.2010.04.005 · 4.85 Impact Factor
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    ABSTRACT: Amnestic mild cognitive impairment (aMCI), characterized by episodic memory impairment in the absence of clinical dementia, often represents a transitional stage between normal aging and Alzheimer's disease (AD). It is not known if non-expert primary-care physicians (PCPs) can differentiate individuals with no cognitive impairment (NCI), aMCI and mild AD in a primary-care practice setting. This study develops an approach to this question, which is necessary for aMCI to become a treatment target. Fourteen experts assessed subjects with memory complaints in terms of their laboratory test results, magnetic resonance imaging findings and scores on the Mini-Mental State Examination, adapted Clinical Dementia Rating Scale and Alzheimer's Disease Assessment Scale-cognitive subscale Delayed Word Recall before designating each subject as having NCI, aMCI or AD. Subjects agreed upon by a consensus committee were assigned to non-expert PCPs who, following brief training, assessed them using the same clinical information and utilizing the same assessment instruments. The chance-corrected inter-rater reliability (expert versus non-expert) measure κ, based on binary outcome (aMCI/not-aMCI), was estimated. The study recruited 119 evaluable subjects (50 aMCI, 27 mild AD and 42 NCI) and demonstrated fair to moderate agreement (κ = 0.423) between experts and non-experts in designation of aMCI. The percent agreement was 72.3%, sensitivity 62.0% and specificity 79.7%. Overall, non-experts under-rated the level of impairment compared with experts. This study established the feasibility of making the aMCI designation in the community and identified some likely sources of error. The results suggest that when drugs with clear benefit for aMCI patients are developed, community-based PCPs, with additional, more optimized training, will be able to accurately identify those patients who should receive treatment.
    Clinical Drug Investigation 07/2011; 31(7):483-91. DOI:10.2165/11588810-000000000-00000 · 1.70 Impact Factor
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    ABSTRACT: In this article, we review the literature on practice effects in schizophrenia, an underappreciated confound in interpreting cognitive improvement in clinical trials. We first examine claims regarding first- and second-generation antipsychotic medications as cognitive enhancers, and follow it with a discussion of recent studies demonstrating how practice or placebo effects may drive 'positive' findings. Thus, this review suggests that many previous findings can be reinterpreted in this light. Critically, we also make several suggestions about test construction, study design, and statistical analyses that the field might use to overcome this potential confound. Our suggestions may also have implications for drug discovery and regulatory approval of cognitive-enhancing adjunctive agents, in terms of study design and/or test psychometric characteristics, including the development of tests that are relatively insensitive to practice-related changes. Such advances might be important for improving the methodology involved in the assessment of cognitive change in treatment studies.
    Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology 04/2010; 35(5):1053-62. DOI:10.1038/npp.2009.211 · 7.83 Impact Factor
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    ABSTRACT: Following a 48-week, double-blind, randomized, placebo-controlled trial of donepezil in 821 patients with amnestic mild cognitive impairment (aMCI), safety and tolerability of donepezil (10 mg) were further evaluated in a 28-week extension study. Of 499 participants who completed the double-blind phase, 145 enrolled in the open-label study. Adverse events (AEs) were recorded throughout. Overall, 57.4% of participants in the donepezil/donepezil group and 62.3% in the placebo/donepezil group experienced an AE, with the most frequent treatment-emergent AEs being diarrhea, muscle spasms, insomnia, and nausea. Most were mild to moderate in severity and were more common in the first several weeks after treatment initiation. More participants in the placebo/donepezil group (22.1%) discontinued donepezil due to an AE compared with the donepezil/donepezil group (10.3%). These findings support the safety of donepezil in patients with aMCI. When compared with other studies, however, the data suggest that patients with Alzheimer's tolerate donepezil better than patients with MCI.
    American Journal of Alzheimer s Disease and Other Dementias 11/2009; 25(2):155-9. DOI:10.1177/1533317509352334 · 1.43 Impact Factor
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    ABSTRACT: This study assessed the relationship between duration of untreated psychosis (DUP) and cognitive measures in order to assess if longer DUP was associated with worse performance. One hundred two patients with first episode schizophrenia or schizoaffective disorder were assessed on cognitive measures of speed of processing, episodic memory, executive function, and visual spatial processing at baseline (when patients were drug naive and after 16 weeks of olanzapine or risperidone treatment), so that a change score could be derived. DUP was defined by the emergence of psychiatric symptoms and the emergence of psychotic symptoms. Data were analyzed correlationally, parametrically (after the group was divided into long and short DUP by median split), and by regression. We found that DUP for psychotic symptoms in this group of patients was long, with a median of 46 weeks. Neither correlational, parametric analyses in which DUP served as a class variable, nor multiple regression indicated that longer DUP was associated with worse cognition at baseline or smaller magnitude of improvement in cognition. Our results suggest that while early intervention may be critical for symptom amelioration by shortening DUP, early intervention for treatment of psychiatric symptoms may have little or no impact on cognitive function. Furthermore, assuming that cognition is a core symptom of schizophrenia, the notion that ongoing psychosis is somehow toxic for a variety of information processing domains appears questionable.
    Schizophrenia Research 12/2008; 107(2-3):262-6. DOI:10.1016/j.schres.2008.11.003 · 4.43 Impact Factor
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    ABSTRACT: Objective: To identify factors associated with substance misuse in first-episode patients with schizophrenia or schizoaffective disorder.Method: Twenty-seven patients with a past or current history of substance misuse were compared with 91 patients with no history of misuse on demographic and psychopathological measures before being treated for their first episode of psychosis, and on cognitive measures after 6 months of treatment.Results: There were no statistically significant differences between groups for sex, schizophrenia subtype, marital status, education, family history of schizophrenia, course of illness, age of onset, baseline symptoms, time to treatment response, medication side effects, attention span, memory and executive functioning. However, dual diagnosis patients were found to have a higher parental social class, better premorbid cognitive functioning, higher IQ and better language skills.Conclusion: First-episode patients with a history of substance misuse have higher intellectual functioning, which may be associated with higher premorbid socioeconomic status and cognitive functioning.
    Acta Psychiatrica Scandinavica 07/2008; 104(5):367 - 374. DOI:10.1111/j.1600-0447.2001.00452.x · 5.55 Impact Factor
  • Alzheimer's and Dementia 07/2008; 4(4). DOI:10.1016/j.jalz.2008.05.775 · 17.47 Impact Factor
  • Alzheimer's and Dementia 07/2008; 4(4). DOI:10.1016/j.jalz.2008.05.2575 · 17.47 Impact Factor
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    ABSTRACT: Altered expression of central muscarinic and nicotinic acetylcholine receptors in hippocampal and cortical regions may contribute to the cognitive impairment exhibited in patients with schizophrenia. Increasing cholinergic activity through the use of a cholinesterase inhibitor (ChEI) therefore represents a possible strategy for cognitive augmentation in schizophrenia. We examined the efficacy and safety of the ChEI donepezil as cotreatment for mild to moderate cognitive impairment in schizophrenia or schizoaffective disorder in a prospective, 12-week, placebo-controlled, double-blind, parallel-group study. In total, 250 patients (18-55 years) with schizophrenia or schizoaffective disorder who were clinically stabilized on risperidone, olanzapine, quetiapine, ziprasidone, or aripiprazole, alone or in combination, were enrolled at 38 outpatient psychiatric clinics in the United States. Patients were randomized to donepezil 5 mg q.d. for 6 weeks then 10 mg q.d. for 6 weeks, or placebo administered as oral tablets. The primary outcome measure was the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) neurocognitive battery composite score. In the intent-to-treat sample (donepezil, n=121; placebo, n=124), both treatments showed improvement in the composite score from baseline to week 12. At week 12, cognitive improvement with donepezil was similar to that with placebo (last-observation-carried-forward effect size, 0.277 vs 0.411; p=0.1182) and statistically significantly inferior for the observed-cases analysis (0.257 vs 0.450; p=0.044). There was statistically significant improvement in the Positive and Negative Syndrome Assessment Scale negative symptoms score for placebo compared with donepezil, while total and positive symptom scores were similar between both treatments. Statistically significant improvements in positive symptoms score and Clinical Global Impression-Improvement for donepezil compared with placebo were noted at Week 6. Treatment-emergent adverse events (AEs) were observed for 54.5% of donepezil- and 61.3% of placebo-treated patients; most AEs were rated as mild to moderate in severity. Donepezil was safe and well-tolerated but was not effective compared with placebo as a cotreatment for the improvement of cognitive impairment in this patient population. A significant and surprisingly large placebo/practice effect was observed among placebo-treated patients, and is a serious consideration in future clinical trial study designs for potential cognitive enhancing compounds in schizophrenia.
    Neuropsychopharmacology 06/2008; 33(6):1217-28. DOI:10.1038/sj.npp.1301499 · 7.83 Impact Factor
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    ABSTRACT: Cognitive impairment in schizophrenia is frequent, involves multiple domains, and is enduring. Numerous recent clinical trials have suggested that second-generation antipsychotic medications significantly enhance cognition in schizophrenia. However, none of these studies included healthy controls undergoing repeated testing to assess the possibility that improvements might reflect simple practice effects. To report the results on cognition of a randomized comparison of 2 widely prescribed second-generation antipsychotic medications, olanzapine and risperidone, in patients with first-episode schizophrenia and a healthy control group. Randomized clinical trial. Hospital-based research units. Patients A total of 104 participants with first-episode schizophrenia and 84 healthy controls. Cognitive assessment of all study participants occurred at baseline, 6 weeks later, and 16 weeks later. Neurocognitive tests included measures of working memory and attention, speed, motor function, episodic memory, and executive function. No differential drug effects were observed. Of 16 cognitive measures, 9 demonstrated improvement over time and only 2 demonstrated greater rates of change than those observed in the healthy control group undergoing repeated assessment. The composite effect size for cognitive change was 0.33 in the healthy control group (attributed to practice) and 0.36 in the patients with first-episode schizophrenia. Improvements in cognition in the first-episode schizophrenia group could not be accounted for by medication dose, demographic variables, or intellectual level. The cognitive improvements observed in the trial were consistent in magnitude with practice effects observed in healthy controls, suggesting that some of the improvements in cognition in the first-episode schizophrenia group may have been due to practice effects (ie, exposure, familiarity, and/or procedural learning). Our results also indicated that differential medication effects on cognition were small. We believe that these findings have important implications for drug discovery and the design of registration trials that attempt to demonstrate cognitive enhancement.
    Archives of General Psychiatry 11/2007; 64(10):1115-22. DOI:10.1001/archpsyc.64.10.1115 · 13.75 Impact Factor
  • Thomas S Ehmann · Robert Goldman · Jodi Yager · Yikang Xu · G W MacEwan
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    ABSTRACT: This study examined the reliability and validity of a brief, face-valid self-report measure designed to assess subjective judgments of functioning. The Patient Perception of Functioning Scale (PPFS) is a 6-item scale with ratings for both community functioning and cognition. Sixty-eight subjects with psychotic disorders were recruited to complete the PPFS on 2 occasions and to complete a battery of neurocognitive tests. Objective ratings of overall illness severity (Clinical Global Impression), illness severity (Global Assessment of Functioning), and functioning (Social and Occupational Functioning Assessment Scale and Role Functioning Scale) were also obtained. The internal consistency and test-retest correlation coefficients revealed that the PPFS possesses good reliability characteristics. The PPFS did not show relationships to demographic, historical, or illness-related variables such as diagnosis or length of illness. The PPFS did show significant associations with several dimensions of community functioning. However, no significant associations were found with neurocognitive measures or clinical status. In populations with psychotic disorders, self-reported ratings of community function and cognition may converge less with objective cognitive measures than with objective ratings of everyday functioning. Several factors inherent to self-report methodology may have contributed to the poor convergent validity results. Theoretical underpinnings and operationalization of the underlying constructs of some neuropsychological instruments may not closely match how patients conceptualize those constructs.
    Comprehensive Psychiatry 11/2007; 48(6):597-604. DOI:10.1016/j.comppsych.2007.05.017 · 2.26 Impact Factor
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    ABSTRACT: Despite consensus that schizophrenia is a neurodevelopmental disorder characterized by cognitive deficits, objective data documenting the course of cognitive development remain sparse. We conducted a follow-back study of patients ascertained at the time of their initial episode of schizophrenia or schizoaffective disorder, and a group of demographically matched healthy volunteers. We obtained school records containing standardized achievement test scores from the 1st through 12th grades, and scholastic aptitude test results from the 11th and 12th grades, and examined the developmental trajectories of cognitive performance with respect to prospective examinations conducted following participants' enrollment in our study. We found significant differences in academic achievement tests as early as the first grade, with scores from participants who would later develop schizophrenia lagging behind their peers by 0.8 to 1.1 grade equivalents. This gap widened resulting in a difference between groups of 1.5 to 1.8 grade equivalents by the 12th grade. In the subset of patients for whom SAT scores were available, we found that WAIS-R Full Scale IQ was 11.5 points lower than predicted from earlier SAT scores, suggesting a substantial decline in cognitive ability accompanying the initial episode of illness. These findings suggest that schizophrenia is marked by substantial cognitive deficits in the first grade, that there may be additional subtle decline preceding the overt onset of psychotic symptoms, and that the initial episode of illness is marked by additional decline. These observations may help advance concepts of premorbid cognitive ability in the schizophrenia syndrome and constrain models of pathophysiology.
    Journal of Clinical and Experimental Neuropsychology 03/2006; 28(2):270-82. DOI:10.1080/13803390500360554 · 2.16 Impact Factor
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    ABSTRACT: The purpose of this investigation was to evaluate the effects of clozapine and risperidone on spatial working memory in patients with schizophrenia. Spatial working memory performance was evaluated at baseline and after 17 and 29 weeks in 97 patients with schizophrenia participating in a multisite trial. Compared with baseline performance while receiving conventional antipsychotic medication, risperidone improved, and clozapine worsened, spatial working memory performance. The differential effects of these medications on spatial working memory may be due to the anticholinergic effects of clozapine and prefrontal dopamine-enhancing effects of risperidone.
    American Journal of Psychiatry 06/2005; 162(5):1013-6. DOI:10.1176/appi.ajp.162.5.1013 · 13.56 Impact Factor
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    ABSTRACT: Functional neuroimaging studies have identified a role for the cerebellum in the neuropsychology of schizophrenia. Few studies, however, have examined the relationship between cerebellar size and neuropsychological functioning in schizophrenia. The authors' goal was to examine this relationship in patients and healthy comparison subjects. Total cerebellar volume was computed from magnetic resonance images in 48 male and 33 female patients experiencing a first episode of schizophrenia and in 14 male and nine female healthy comparison subjects. Patients and comparison subjects completed a comprehensive neuropsychological assessment encompassing six domains of functioning: executive, motor, language, visuospatial, memory, and attention. A global domain of functioning was computed as the mean of these six domains. Larger cerebellar volume correlated significantly with better global functioning in healthy subjects but not among patients with schizophrenia; this relationship was significantly stronger in healthy subjects than in patients. Additional analyses revealed significant associations between cerebellar volume and visuospatial, executive, and memory functions in healthy volunteers but not among patients. The cerebellum plays a role in higher cognitive functions in healthy individuals, and normal associations between cerebellar size and function are absent in patients experiencing a first episode of schizophrenia. These findings are consistent with neurobiological models implicating the cerebellum in the pathogenesis of schizophrenia.
    American Journal of Psychiatry 11/2003; 160(10):1884-7. DOI:10.1176/appi.ajp.160.10.1884 · 13.56 Impact Factor
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    ABSTRACT: Deficits in working memory (WM) have been reported in patients with schizophrenia, but WM is a complex construct dependent on several subprocesses, including input representation (perceptual competency) and holding stimuli on-line (maintenance). A visual delayed match-to-sample task (DMST) was developed to isolate perceptual competency from maintenance during delays. It was hypothesized that patients in the first episode of schizophrenia would exhibit dissociable deficits in both WM domains. Performance on the DMST was assessed in 57 patients in the first episode of schizophrenia or schizoaffective disorder and 22 healthy comparison subjects. In phase 1 of the DMST, a complex visual stimulus (target) was followed immediately by a forced choice between 2 test stimuli, and item difficulty (differences between the test stimuli) was titrated until each subject achieved a consistent accuracy (80%-90%) in this no-delay condition. In phase 2, a delay of 4 or 8 seconds with a mask of randomly illuminated pixels was introduced between target and test stimuli; test stimuli were fixed in difficulty level based on phase 1 titration. Main outcome measures were mean item difficulty attained in the no-delay condition and mean accuracy in matching after delay. Compared with controls, patients attained a lower level of difficulty in the no-delay condition (P =.001) and significantly lower accuracy with delay (P =.002). Deficits in both domains of WM suggest abnormality in the posterior and prefrontal cortexes. These deficits can be observed in a task involving complex visual pattern stimuli using only a brief delay and are present even in unmedicated patients in the first episode of illness.
    Archives of General Psychiatry 04/2003; 60(3):238-43. DOI:10.1001/archpsyc.60.3.238 · 13.75 Impact Factor
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    9th International Congress on Schizophrenia Research; 03/2003
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    ABSTRACT: Neurocognitive deficits are recognized as a cardinal feature of schizophrenia, but the determinants of these deficits remain unknown. Recent reports have suggested that a functional polymorphism, Val(158)Met in exon III of the catechol-O-methyltransferase gene, shares approximately 4% variance with performance on the Wisconsin Card Sorting Test. These findings led to suggestions that the catechol-O-methyltransferase polymorphism may exert its effects by modulating prefrontal dopamine function, but few other neurocognitive measures have been examined, leaving open questions about phenotypic specificity. We examined the effects of the catechol-O-methyltransferase Val(158)Met polymorphism in 58 individuals with chronic schizophrenia who completed a battery of 15 neurocognitive tests, which were reduced to four reliable neurocognitive domain scores. We examined the effects of genotype on these four domains and on global neurocognitive ability. The Met allele was associated with better performance in the Processing Speed and Attention domain, but not with other domain scores measuring executive and visuoperceptual functions, declarative verbal learning and memory, simple motor ability, or global neurocognitive function. Genotype shared approximately 11% of variance with Processing Speed and Attention scores, and approximately 2% of variance with Wisconsin Card Sorting Test scores. The findings provide independent support for the hypothesis that the catechol-O-methyltransferase Val(158)Met polymorphism influences neurocognitive function in schizophrenia, and suggest that the functional effects may be expressed on measures of Processing Speed and Attention. This information may prompt reconsideration of the "prefrontal dopamine" hypothesis and invites examination of a broader range of effects in efforts to refine the neurocognitive phenotype that is most relevant to variation in catechol-O-methyltransferase expression.
    Biological Psychiatry 11/2002; 52(7):701-7. DOI:10.1016/S0006-3223(02)01416-6 · 10.25 Impact Factor
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    ABSTRACT: Newer antipsychotic drugs have shown promise in ameliorating neurocognitive deficits in patients with schizophrenia, but few studies have compared newer antipsychotic drugs with both clozapine and conventional agents, particularly in patients who have had suboptimal response to prior treatments. The authors examined the effects of clozapine, olanzapine, risperidone, and haloperidol on 16 measures of neurocognitive functioning in a double-blind, 14-week trial involving 101 patients. A global score was computed along with scores in four neurocognitive domains: memory, attention, motor function, and general executive and perceptual organization. Global neurocognitive function improved with olanzapine and risperidone treatment, and these improvements were superior to those seen with haloperidol. Patients treated with olanzapine exhibited improvement in the general and attention domains but not more than that observed with other treatments. Patients treated with risperidone exhibited improvement in memory that was superior to that of both clozapine and haloperidol. Clozapine yielded improvement in motor function but not more than in other groups. Average effect sizes for change were in the small to medium range. More than half of the patients treated with olanzapine and risperidone experienced "clinically significant" improvement (changes in score of at least one-half standard deviation relative to baseline). These findings did not appear to be mediated by changes in symptoms, side effects, or blood levels of medications. Patients with a history of suboptimal response to conventional treatments may show cognitive benefits from newer antipsychotic drugs, and there may be differences between atypical antipsychotic drugs in their patterns of cognitive effects.
    American Journal of Psychiatry 07/2002; 159(6):1018-28. DOI:10.1176/appi.ajp.159.6.1018 · 13.56 Impact Factor
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    ABSTRACT: Despite evidence for hippocampal structural abnormalities in patients with schizophrenia, their functional correlates remain largely unknown. This study investigated the neuropsychological correlates of hippocampal volume in 43 men and 32 women experiencing a first episode of schizophrenia. Posterior and anterior hippocampal volumes were computed from contiguous 3.1-mm magnetic resonance images and examined in relationship to six domains of neuropsychological functioning. Significant structure-function associations were investigated by examining the correlations between functioning and individual hippocampal slice volumes across the long axis of the hippocampus after interpolation to 10 equally spaced slice positions. Among men, worse executive and motor functioning correlated significantly with smaller anterior, but not posterior, hippocampal volume. The relationship between executive and motor functioning and hippocampal volume was not linear, however, when examined across the long axis of the hippocampus. Anterior hippocampal volume was more strongly correlated with both executive and motor functioning than with either memory or language functioning in men. None of the correlations between either posterior or anterior hippocampal volumes and the neuropsychological domains was significant among women. Anterior hippocampal volume was more strongly correlated with motor functioning in men than in women. Anterior hippocampal abnormalities associated with deficits on tests considered sensitive to frontal lobe functions implicate a defect in the integrated system linking frontal and mesiotemporal lobe regions. These findings further suggest that there are sex differences in structure-function relations in schizophrenia such that men may have more pronounced frontolimbic system abnormalities.
    American Journal of Psychiatry 03/2002; 159(2):217-26. DOI:10.1176/appi.ajp.159.2.217 · 13.56 Impact Factor
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    ABSTRACT: To identify factors associated with substance misuse in first-episode patients with schizophrenia or schizoaffective disorder. Twenty-seven patients with a past or current history of substance misuse were compared with 91 patients with no history of misuse on demographic and psychopathological measures before being treated for their first episode of psychosis, and on cognitive measures after 6 months of treatment. There were no statistically significant differences between groups for sex, schizophrenia subtype, marital status, education, family history of schizophrenia, course of illness, age of onset, baseline symptoms, time to treatment response, medication side effects, attention span, memory and executive functioning. However, dual diagnosis patients were found to have a higher parental social class, better premorbid cognitive functioning, higher IQ and better language skills. First-episode patients with a history of substance misuse have higher intellectual functioning, which may be associated with higher premorbid socioeconomic status and cognitive functioning.
    Acta Psychiatrica Scandinavica 12/2001; 104(5):367-74. DOI:10.1034/j.1600-0447.2001.00452.x · 5.55 Impact Factor

Publication Stats

3k Citations
330.27 Total Impact Points


  • 2006–2011
    • Pfizer Inc.
      New York City, New York, United States
  • 1999–2008
    • Albert Einstein College of Medicine
      • Department of Radiology
      New York, New York, United States
  • 2005
    • University of California, Davis
      • Department of Psychology
      Davis, California, United States
  • 2000–2003
    • North Shore-Long Island Jewish Health System
      • • Department of Psychiatry
      • • Department of Psychiatry Research
      New York City, New York, United States
    • North Shore-LIJ Health System
      Manhasset, New York, United States
  • 1998–2003
    • University of North Carolina at Chapel Hill
      North Carolina, United States
  • 2002
    • Nathan Kline Institute
      Orangeburg, New York, United States