Alzheimer Disease: Tractenberg RE

Singer C, Tractenberg RE, Kaye J, Schafer K, Gamst A, Grundman M, Thomas R, Thal LJ, Anonymous00015. · Department of Psychiatry, Oregon Health & Science University, Portland, USA. · Sleep. · Pubmed #14655926 No free full text.

Abstract: OBJECTIVES: To determine the safety and efficacy of 2 dose formulations of melatonin for the treatment of insomnia in patients with Alzheimer's disease. DESIGN: A multicenter, randomized, placebo-controlled clinical trial of 2 dose formulations of oral melatonin coordinated by the National Institute of Aging-funded Alzheimer's Disease Cooperative Study. Subjects with Alzheimer's disease and nighttime sleep disturbance were randomly assigned to 1 of 3 treatment groups: placebo, 2.5-mg slow-release melatonin, or 10-mg melatonin. SETTING: Private homes and long-term care facilities. PARTICIPANTS: 157 individuals were recruited by 36 Alzheimer's disease research centers. Subjects with a diagnosis of Alzheimer's disease were eligible if they averaged less than 7 hours of sleep per night (as documented by wrist actigraphy) and had 2 or more episodes per week of nighttime awakenings reported by the caregiver. MEASUREMENTS: Nocturnal total sleep time, sleep efficiency, wake-time after sleep onset, and day-night sleep ratio during 2- to 3-week baseline and 2-month treatment periods. Sleep was defined by an automated algorithmic analysis of wrist actigraph data. RESULTS: No statistically significant differences in objective sleep measures were seen between baseline and treatment periods for the any of the 3 groups. Nonsignificant trends for increased nocturnal total sleep time and decreased wake after sleep onset were observed in the melatonin groups relative to placebo. Trends for a greater percentage of subjects having more than a 30-minute increase in nocturnal total sleep time in the 10-mg melatonin group and for a decline in the day-night sleep ratio in the 2.5-mg sustained-release melatonin group, compared to placebo, were also seen. On subjective measures, caregiver ratings of sleep quality showed improvement in the 2.5-mg sustained-release melatonin group relative to placebo. There were no significant differences in the number or seriousness of adverse events between the placebo and melatonin groups. CONCLUSIONS: Based on actigraphy as an objective measure of sleep time, melatonin is not an effective soporific agent in people with Alzheimer's disease.

Weiner MF, Tractenberg RE, Sano M, Logsdon R, Teri L, Galasko D, Gamst A, Thomas R, Thal LJ. · Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, USA. · J Geriatr Psychiatry Neurol. · Pubmed #12083600 No free full text.

Abstract: Th determine if teaching caregivers behavior management techniques (BMTs) reduces long-term psychotropic use in Alzheimer's disease (AD) patients, we examined 12-month follow-up data from a 4-month randomized study comparing placebo, BMTs, trazodone, and haloperidol for the treatment of agitated behaviors in persons with AD. After 4 months, treatment was allowed with any agent. Between 42.8% and 51% of AD patients received additional psychotropics between 4 and 12 months. The relative risk of being prescribed any psychotropic drug after the 4-month trial was at or about 1.0 for subjects in each drug arm or placebo arm versus BMTs. We concluded that teaching caregivers BMTs did not diminish long-term prescription of psychotropic drugs.

Tractenberg RE, Weiner MF, Thal LJ. · Alzheimer's Disease Cooperative Study, Department of Neurosciences, University of California, San Diego, La Jolla 92093-0949, USA. · J Neuropsychiatry Clin Neurosci. · Pubmed #11884649 links to  free full text

Abstract: To estimate the prevalence of, and develop norms for, significant agitation in community-dwelling persons with Alzheimer's disease (AD), the authors applied three different criteria to persons with AD (n=235) and normal elderly control subjects (NEC; n=64). The criteria were used to identify the minimum total score on the Cohen-Mansfield Agitation Inventory (CMAI) that represents significant or "excessive" agitation and to estimate its prevalence. The "ultraliberal" criterion resulted in 99.1% of persons with AD and 56.6% of NEC being classified as "excessively" disturbed. The "liberal" and "conservative" criteria classified 66.7% and 68.2% of persons with AD, and no NEC, as "excessively" disturbed. The authors conclude that the best estimate of prevalence of excessive agitation in this population is 67.5%, and that individuals with CMAI scores of 0 to 14 probably should not be considered to have excessive agitation.

Teri L, Logsdon RG, Peskind E, Raskind M, Weiner MF, Tractenberg RE, Foster NL, Schneider LS, Sano M, Whitehouse P, Tariot P, Mellow AM, Auchus AP, Grundman M, Thomas RG, Schafer K, Thal LJ, Anonymous00040. · University of Washington, Department of Psychosocial and Community Health, Seattle 98195-7263, USA. · Neurology. · Pubmed #11087767 No free full text.

Abstract: BACKGROUND: Treatment of agitation is a crucial problem in the care of patients with AD. Although antipsychotic and antidepressant medications and behavior management techniques (BMT) have each been used to treat agitation, clinical trials of these treatments have been characterized by small sample sizes and uncontrolled treatment designs. OBJECTIVE: To compare haloperidol, trazodone, and BMT with placebo in the treatment of agitation in AD outpatients. METHODS: A total of 149 patients with AD and their caregivers participated in a randomized, placebo-controlled, multicenter trial. Blind assessment was conducted at baseline and after 16 weeks of treatment. The three active treatments were haloperidol, trazodone, and BMT. The Alzheimer's Disease Cooperative Study Clinical Global Impression of Change was the primary outcome measure. Secondary outcomes included patient agitation, cognition, and function, and caregiver burden. RESULTS: Thirty-four percent of subjects improved relative to baseline. No significant differences on outcome were obtained between haloperidol (mean dose, 1.8 mg/d), trazodone (mean dose, 200 mg/d), BMT, or placebo. Significantly fewer adverse events of bradykinesia and parkinsonian gait were evident in the BMT arm. No other significant difference in adverse events was seen. Symptoms did not respond differentially to the different treatments. CONCLUSIONS: Comparable modest reductions in agitation occurred in patients receiving haloperidol, trazodone, BMT, and placebo. More effective pharmacologic, nonpharmacologic, and combination treatments are needed.

Tractenberg RE, Aisen PS. · Departments of Neurology, Biostatistics, Bioinformatics and Biomathematics, and Psychiatry, Georgetown University School of Medicine, Washington, D.C. 20057, USA. · Dement Geriatr Cogn Disord. · Pubmed #19293567 No free full text.

Abstract: AIMS: To estimate agreement among scores on three common assessments of cognitive function. METHOD: Baseline responses on the Alzheimer's Disease Assessment Scale - Cognitive, Clinical Dementia Rating, and the Mini-Mental State Examination were obtained from two clinical trials (n = 138 and n = 351). A graphical method of examining agreement, the means-difference or Bland-Altman plot, was followed by Levene's test of the equality of variance corrected for multiple comparison within each sample. RESULTS: 70-78% of variability was shared by one factor, suggesting that all three instruments reflect cognitive impairment. However, agreement among tests was significantly worse for individuals with greater-than-average, relative to individuals with less-than-average, cognitive impairment. CONCLUSIONS: Worse agreement between tests, as a function of increasing cognitive impairment, implies that interpretation of these tests and selection of coprimary cognitive impairment outcomes may depend on impairment level.

Tractenberg RE, Singer CM, Kaye JA. · Departments of Biostatistics, Biomathematics & Bioinformatics and Psychiatry, Georgetown University School of Medicine, Washington, DC, USA. · J Sleep Res. · Pubmed #16490008 No free full text.

Abstract: We retrospectively analyzed sleep disturbance symptoms and estimated time in bed from the intake interviews of 399 healthy, non-demented elderly (NDE) and 263 persons with a diagnosis of possible (n = 53) or probable (n = 210) Alzheimer's disease (AD). Our primary objective was to identify what symptoms might underlie an individual's perception of 'sleep problems' and to determine if these were consistent within, and across, our two cohorts. We stratified each cohort according to whether or not they (or their caregiver) indicated that they had a 'sleep problem', and compared the frequency and endorsement rates of each of 21 sleep disturbance symptoms across those who did or did not endorse 'sleep problem'. For less than half of the symptoms in persons with AD, and a quarter of those in NDE, endorsement rates were significantly different depending on whether the reporter (or their sleep partner) did or did not report a sleep problem. Differences in mean frequency ratings between individuals reporting sleep problems relative to those not reporting were observed on 10 symptoms in both cohorts; six of these were the same symptom for both cohorts. When persons with subjective sleep problems in the AD and NDE cohorts were compared, only four of 21 symptoms were endorsed in one and not the other; two symptoms were significantly more frequent in one cohort than the other. Thus, within cohorts, the differences between persons with and without 'sleep problems' were relatively pronounced while the main differences in specific sleep-related symptoms between AD and NDE were not. Observed between-cohort differences appear to be driven by who is reporting, and the high prevalence of daytime sleeping in AD. Within-cohort differences reflect a clear distinction between persons with and without sleep problems, regardless of the reporter.

Cummings JL, Tractenberg RE, Gamst A, Teri L, Masterman D, Thal LJ. · Department of Neurology, UCLA School of Medicine, Los Angeles, CA 90095-1769, USA. · Curr Alzheimer Res. · Pubmed #15975061 No free full text.

Abstract: Effective drug development depends on understanding and optimizing results from controlled clinical trials. A recent double-blind, randomized, controlled trial of the treatment of agitation in patients with Alzheimer's disease (AD) found no difference among the four arms of the study: haloperidol, trazodone, behavioral therapy, placebo. The current analysis was undertaken to further investigate the issues bearing on this outcome and to identify better means of detecting psychotropic effects in trials involving patients with AD. This was post hoc analysis of a clinical trial data set. Patients in the placebo group were divided into responders (25% reduction in symptoms), worseners (25% worsening in baseline agitation scores), and those without a change in symptoms. Analysis of the trial outcomes demonstrated that the reduction observed in the placebo group was of the same magnitude as predicted by regression to the mean. Patients exhibiting greater improvement had more severe baseline behavioral disturbances. The relatively modest severity of agitation and the low medication doses achieved in the study may have further contributed to the failure to distinguish among treatment groups. Research design adjustments such as collection of both screening and baseline measures to determine eligibility may limit the effects of regression to the mean on trial outcomes and reduce this challenge to clinical trials.

Tractenberg RE, Singer CM, Kaye JA. · Department of Biomathematics and Biostatistics, Georgetown University School of Medicine, Georgetown University Hospital, Washington, DC 20007, USA. · J Sleep Res. · Pubmed #15910515 No free full text.

Abstract: We retrospectively analyzed sleep time and sleep disturbance symptoms in 399 healthy, non-demented elderly (NDE) and 263 persons with a diagnosis of possible (n = 53) or probable (n = 210) Alzheimer's disease (AD). Our primary objective was to determine differences in subjective sleep disturbance between these samples. Secondary objectives were to determine if subjects with time in bed (TIB) < or =6 h per night reported more sleep disturbance and whether sleep complaints were associated with more severe cognitive and/or functional impairment. The prevalence of 'sleep problems' (a single item) was significantly lower in NDE (18.3%) than AD (27.6%), and the proportions of each cohort reporting TIB < or =6 h per night were very low (NDE: 6.0%; AD: 3.5%) and not significantly different. Less TIB was correlated with better cognitive function for AD (P < 0.01), and cognition and function were significantly worse for AD subjects with estimates of >6 h of TIB compared with those with estimates of < or =6 h (P < 0.05). Greater sleep disturbance was correlated with greater functional impairment in both cohorts; but only in AD did greater estimated TIB also correlate with greater functional impairment (all P < 0.05). In general, estimated TIB was not associated with mood in either cohort; however, in both cohorts depression was significantly associated with sleep disturbance symptoms and was significantly worse in those who reported having 'sleep problems'. There was no association between subjective perception of 'sleep problems', the number and frequency of sleep disturbance symptoms, and estimated TIB in either group.

Tractenberg RE, Weiner MF, Cummings JL, Patterson MB, Thal LJ. · Department of Biomathematics and Biostatistics, Georgetown University School of Medicine, 7 East Main, M702, Georgetown University Hospital, 3800 Reservoir Rd, NW, Washington, DC 20007, USA. · J Neuropsychiatry Clin Neurosci. · Pubmed #15746483 links to  free full text

Abstract: The authors' main objective was to investigate the relationship between changes in psychopathological, cognitive and activity of daily living (ADL) instrument scores over 12 months in community-dwelling persons with Alzheimer's disease (AD). A secondary objective was to evaluate the validity of dividing the Clinical Dementia Rating (CDR), a global dementia staging instrument into cognitive and functional subscores. Changes in measures of psychopathology, cognition and function between the baseline and 12-month visits were entered into these post hoc analyses of data from a one-year clinical trial to evaluate behavioral, cognitive and functional assessment instruments for use in clinical trials with AD patients. Exploratory factor analysis was used to determine whether there was independence between changes in any of these three domains of interest for this disease population; participants were a cohort of 187 well-characterized, community-dwelling persons with AD. One-year change in the behavioral symptoms of this cohort of persons with AD was statistically independent from changes in scores on cognitive and functional measures. Some evidence of independence of 12 month changes in cognitive and functional measures was found. Cognitive and functional subscores for the CDR were supported. These findings suggest that changes in behavior and cognition in dementia may have distinct pathophysiologies.

Schafer KA, Tractenberg RE, Sano M, Mackell JA, Thomas RG, Gamst A, Thal LJ, Morris JC, Anonymous00016. · Department of Neurosciences, University of California, San Diego, CA, USA. · Alzheimer Dis Assoc Disord. · Pubmed #15592134 No free full text.

Abstract: CONTEXT: The Clinical Dementia Rating (CDR) is quickly becoming a criterion standard in multicenter clinical trials in Alzheimer disease. An abbreviated version, with formal monitoring for consistency across sites and raters, is currently used in the Alzheimer's Disease Cooperative Study (ADCS). OBJECTIVE: To demonstrate the degree of agreement on CDR scoring of clinical monitors working independently from ADCS-CDR worksheets. DESIGN: Three members of the ADCS who are experienced and highly trained with respect to the CDR independently reviewed the ADCS-CDR worksheets of 15 subjects, assigning box and global CDR scores according to the prescribed algorithm. SETTING: The ratings were assigned during a single, 3-hour session in a closed room. PARTICIPANTS: Two clinical monitors and one project director/clinical monitor supervisor. MAIN OUTCOME MEASURES: Percent agreement, Kendall's tau-b, and Cohen's kappa were used to assess the degree of agreement of the raters with the previously established gold standard assessment on global and box scores for the 15 subjects. RESULTS: Raters, blinded to patient groupings, were in agreement with the Gold Standard global CDR assessment on 87% of ratings. Kappa values indicated good (kappa = 0.66, orientation and judgment & problem solving boxes) to excellent (kappa = 0.83, global CDR) agreement. CONCLUSIONS: The ADCS-CDR worksheets were reliably and consistently scored by clinical monitors, who may be considered proxy gold standards for CDR assessment.

Tractenberg RE, Weinstein M, Weiner MF, Aisen PS, Fuh JL, Goldman N, Chuang YL. · Department of Biomathematics and Biostatistics, Georgetown University School of Medicine, Washington, DC 20008, USA. · Neuroepidemiology. · Pubmed #15492486 No free full text.

Abstract: Orientation questions are readily incorporated into longitudinal population surveys, but their value as a screening tool for cognitive impairment is uncertain. We evaluated the screening value of four orientation-to-time items (TTO) from the Mini-Mental State Examination (MMSE) by determining their association with full-scale MMSE scores. Data collected under protocols with strict eligibility criteria in the US (64 normal elderly, 242 persons with probable Alzheimer's disease) and Taiwan (241 persons with probable Alzheimer's disease) were analyzed. The TTO and full-scale MMSE scores were significantly correlated (p < 0.05) in persons with a Clinical Dementia Rating (CDR) score of 0 or 1; this was not significant in persons with a CDR of >1 (p > 0.05). Both TTO and MMSE were significantly associated with education in persons with 0-7 years of education; some MMSE items, but none of the TTO items, were associated with education in persons with more than 7 years of education. TTO may be a useful component of cognitive screening efforts.

Swanberg MM, Tractenberg RE, Mohs R, Thal LJ, Cummings JL. · Department of Neurology, David Geffen School of Medicine at UCLA, 90095-1769, USA. · Arch Neurol. · Pubmed #15096405 links to  free full text

Abstract: BACKGROUND: Executive dysfunction (EDF) is common in Alzheimer disease (AD); however, its relationship to other symptoms is difficult to assess in patients with AD. OBJECTIVES: To determine the prevalence of EDF and study its relationship to cognitive, functional, and neuropsychiatric symptoms in patients with AD. DESIGN, SETTING, AND PATIENTS: A retrospective analysis of data from participants in the English Instruments Protocol of the Alzheimer's Disease Cooperative Study. Subjects were drawn from a sample of patients evaluated at tertiary referral centers. RESULTS: A total of 64% of AD patients were classified as having EDF. Patients with EDF performed worse on tests of cognition (P <.001), dementia severity (P <.001), and activities of daily living (P =.01) and had more frequent symptoms of psychosis (P =.03) with greater emergence during the 12-month interval (P =.03) compared with patients with normal executive function. Less than 30% of the variance in executive function performance was explained by cognitive measures. CONCLUSION: These findings support the assessment of executive function in persons with AD and the importance of frontal lobe dysfunction in AD.

Tractenberg RE, Singer CM, Cummings JL, Thal LJ. · Department of Biomathematics and Biostatistics, Georgetown University School of Medicine, Washington, DC 20057, USA. · J Sleep Res. · Pubmed #14633245 No free full text.

Abstract: The Sleep Disorders Inventory (SDI) is an expanded version of one item of the Neuropsychiatric Inventory (NPI). It describes the frequency, severity, and caregiver burden of sleep-disturbed behaviors during a period prior to its administration. We carried out post hoc analyses on baseline responses to the SDI in 104 persons with Alzheimer's disease (AD) and live-in caregivers who had been recruited for a trial of melatonin in the treatment of sleep disturbance. These patient-participants averaged <7 h of sleep per night, measured by actigraph (sleep disturbance), for the 2-3-week period prior to administration of SDI. Data were from the 2 weeks prior to the baseline visit (SDI, NPI) including actigraph-derived sleep variables and 2 weeks' worth of sleep quality ratings (SQR) kept in a diary by caregivers, plus Mini-Mental State Examination and activities of daily living assessment at baseline. The prevalence of sleep disorder symptoms ranged from 34% (waking up at night thinking it is daytime) and 82% (getting up during the night). Worse SDI scores were associated with worse cognitive, functional, and behavioral status, but not with sex, age, education or duration of dementia. SDI scores were significantly worse in individuals meeting independently established criteria for a diagnosis of 'sleep disturbance' (<6 h total sleep time per night) whereas demographic variables and scores reflecting cognition and function were not significantly different across this grouping. The SDI covers a wide range of sleep behaviors and provides information independent of sleep time and SQR.

Tractenberg RE, Weiner MF, Patterson MB, Teri L, Thal LJ. · Center for Population and Health, Georgetown University, Washington, DC 20057-1197, USA. · J Geriatr Psychiatry Neurol. · Pubmed #12801159 No free full text.

Abstract: In this post hoc analysis of baseline responses to the CERAD Behavior Rating Scale for Dementia in a clinical trial of interventions for agitation in Alzheimer's disease (AD), the authors investigated the distribution of, and relationships between, agitation, depression, and psychosis in 148 individuals with AD. Prevalence of depressive symptoms was highest (78.4%), followed by agitation (77.6%) and psychotic symptoms (69.3%); 51.1% of the sample had symptoms in all 3 domains. Cross-sectionally, psychotic symptoms were most closely associated with Mini-Mental State Examination (MMSE) scores, while agitation was less so. Depressive symptoms were relatively consistently prevalent across MMSE levels. After controlling for the presence of agitated symptoms, psychosis and depression were significantly associated, but neither symptoms of psychosis nor of depression were associated with agitation when depression or psychosis, respectively, was controlled for. Significant psychopathological comorbidity should be considered in the design of clinical trials targeting particular psychopathology in this disease population.

Tractenberg RE, Gamst A, Thomas RG, Patterson M, Schneider LS, Thal LJ. · Alzheimer's Disease Cooperative Study, Department of Neurosciences, University of California, San Diego 92093-0949, USA. · J Neuropsychiatry Clin Neurosci. · Pubmed #12154155 links to  free full text

Abstract: These retrospective analyses represent a pilot study of a potential new outcome, expected emergence. The Behavior Rating Scale for Dementia (BRSD) was administered at the baseline and 12-month visits of a multicenter study. The authors computed the rates at which each BRSD symptom emerged over 12 months in normal elderly control subjects (n=64). These normal rates were then applied as the expected emergent rate (EER) to a population of individuals with Alzheimer's disease (n=235). The comparison of expected emergence to observed emergence in Alzheimer's disease showed interpretable differences. EER assesses whether treatments limit emergence in the target, relative to the standard, population. The ratio of expected to observed emergence provides an intuitively appealing quantification of treatment efficacy and can be used with any instrument that uses categorical or frequency ratings.

Tractenberg RE, Weiner MF, Patterson MB, Gamst A, Thal LJ. · Department of Neurosciences, University of California, San Diego, La Jolla 92093-0949, USA. · J Geriatr Psychiatry Neurol. · Pubmed #12083593 No free full text.

Abstract: In a large, well-characterized population of community-dwelling persons with Alzheimer's disease (AD), we investigated the emergence of behavioral symptomatology and its association with changes in cognitive, global-clinical, and functional status. Behavioral Rating Scale for Dementia (BRSD) item responses from 235 AD patients with varying levels of dementia severity and without significant behavioral disturbance were taken from the baseline and 12-month visits in a study of cognitive and behavioral instruments. Item-level analysis revealed new symptoms at every dementia severity level. The symptoms that emerged in the greatest proportion of patients were change in weight, change in appetite, diurnal confusion, uncooperativeness, restlessness, clingy behavior, loss of initiative, and change in sleeping pattern. Changes in cognitive status over the 12 months were associated with changes in functional status and not with the emergence of behavioral symptomatology; however, change in the latter two domains tended to be associated. The findings support the hypothesis that increasing behavioral disturbance is not strongly associated with decreasing cognitive status and that, except for psychotic symptoms, a previously observed association between dementia severity and behavioral status may have been mediated partly by changes in functional abilities.

Weiner MF, Tractenberg RE, Jin S, Gamst A, Thomas RG, Koss E, Thal LJ. · Departments of Psychiatry and Neurology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390-9070, USA. · J Psychiatr Res. · Pubmed #11755457 No free full text.

Abstract: We explored the applicability of the standard scoring of the Cohen-Mansfield Agitation Inventory (CMAI), a widely used nursing-home derived instrument, to community-dwelling persons with Alzheimer's disease (AD). Item responses to the CMAI were gathered from participants in two large clinical studies, one of which specifically included patients with behavioral disturbances. Confirmatory factor analysis in these two groups of well-characterized AD patients suggested that conventional CMAI subscoring did not adequately describe the responses of these two groups. Exploratory factor analysis indicated that the four CMAI subscores, based on a verbal-physical and aggressive-non-aggressive conceptualization of behavioral disturbance, did not fit community dwelling persons with AD. Based on cross-sectional and longitudinal analyses, there was suggestive evidence for three behavioral clusters, but these clusters did not achieve statistical significance Overall, the CMAI seemed best suited to describe the overall level rather than the specific subtypes of behavioral dyscontrol in community-dwelling persons with AD.

Tractenberg RE, Gamst A, Weiner MF, Koss E, Thomas RG, Teri L, Thal L. · Alzheimer's Disease Cooperative Study and Department of Neurosciences, University of California, San Diego 92093-0949, USA. · Int J Geriatr Psychiatry. · Pubmed #11571769 No free full text.

Abstract: This study describes two well-characterized groups of Alzheimer's disease (AD) patients with similar levels of cognitive functioning, but with different overall behavioral disturbance levels. We sought to determine the nature of this difference-whether AD patients with higher levels of behavioral disturbance (n = 148) differ from less disturbed AD patients (n = 235) in terms of (a) the range of symptoms exhibited, (b) the frequency of occurrence of these symptoms, or (c) both of these. We defined and operationalized 'diversity of behaviors' and 'frequency' with respect to the item-level responses on the Cohen-Mansfield agitation inventory (CMAI). We found that, in these two samples of AD patients, differences occurred in the frequency of 10 out of 21 behaviors, rather than in a variety of endorsed behaviors. These 10 behaviors, observed at different frequencies in both groups, may be useful for monitoring change in studies of drugs or behavioral interventions for behavioral disturbance in persons with AD.

Tractenberg RE, Jin S, Patterson M, Schneider LS, Gamst A, Thomas RG, Thal LJ. · Alzheimer's Disease Cooperative Study, Department of Neurosciences, University of California, San Diego, La Jolla 92093-0949, USA. · J Am Geriatr Soc. · Pubmed #11083327 No free full text.

Abstract: OBJECTIVES: To identify clinically meaningful change in longitudinal assessment. DESIGN: A novel approach that qualifies item-level change over time by the degree to which it is clinically meaningful. SETTING: The classification method was tested by applying it to changes over 12 months in the frequency ratings of the items of a behavioral assessment instrument that is used commonly in clinical trials with Alzheimer's disease (AD) patients. PARTICIPANTS: Responses from a cohort of 235 well characterized, community-dwelling subjects with AD were analyzed by this method. MEASUREMENTS: The approach allowed us to describe the proportions of items that emerged, ceased, worsened, and improved between the baseline and 12-month visits. RESULTS AND CONCLUSIONS: One-year change in the behavioral symptoms of persons with AD was used to exemplify the methodology. This approach can be used in other populations and with other measurements and was designed for analyses of clinical trial data. This method uses item-level changes to generate global impressions of clinically meaningful change; it also facilitates the definition of change that can be used in the clinical setting.

Tractenberg RE, Patterson M, Weiner MF, Teri L, Grundman M, Thomas RG, Thal LJ. · Department of Neurosciences, University of California, San Diego 92093-0949, USA. · J Neuropsychiatry Clin Neurosci. · Pubmed #11083164 links to  free full text

Abstract: The authors sought to define "abnormal" levels for total scores on the CERAD Behavioral Rating Scale for Dementia (BRSD) and for 37 BRSD items by comparing 242 patients with Alzheimer's disease (AD) and 64 normal elderly control subjects (NEC). BRSD total scores for NEC ranged as high as 52 (out of a maximum 167), and although item prevalence rates were higher for AD patients, not all of these differences were significant. Many symptoms were observed in < or = 10% of AD subjects. Lower Mini-Mental State Examination scores were not consistently associated with lower or higher levels of endorsement across all items. Over 6 and 12 months, endorsement rates were relatively stable for both groups. The authors conclude that assessment of behavior in long-term studies will be needed to quantify "abnormal" levels, and that item-level BRSD information could be important in clinical trials.