THE INTEGRATED ALZHEIMER’S DISEASE RATING SCALE (IADRS) FINDINGS FROM THE EXPEDITION3 TRIAL

2018 ◽  
pp. 1-3
Author(s):  
A.M. Wessels ◽  
S.W. Andersen ◽  
S.A. Dowsett ◽  
E.R. Siemers
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Active Drug ◽  
Rating Scale ◽  
Controlled Study ◽  
Measurement Tool ◽  
Phase 3 ◽  
Cognitive Subscale ◽  
Significant Difference ◽  
Disease Rating

The Integrated Alzheimer’s Disease (AD) Rating Scale (iADRS) is a composite tool that combines scores from the AD Assessment Scale-Cognitive subscale (ADAS-Cog) and the AD Cooperative Study – instrumental Activities of Daily Living (ADCS-iADL). It demonstrates acceptable psychometric properties, and is effective in capturing both disease progression and separation of placebo and active drug effect. We assessed the performance of iADRS in the solanezumab EXPEDITION3 study, an 80-week, placebo-controlled study of individuals with mild AD dementia. A statistically significant difference between placebo and active drug was observed for iADRS score change from baseline at Week 28 (p=0.028) through Week 80 (p=0.015). Across the Phase 3 solanezumab trials, iADRS was the only tool that consistently differentiated between solanezumab and placebo groups. These findings suggest that the iADRS is a useful integrated measurement tool for treatment trials of individuals with mild AD dementia.

DELAYED-START ANALYSES IN THE PHASE 3 SOLANEZUMAB EXPEDITION3 STUDY IN MILD ALZHEIMER’S DISEASE

2018 ◽  
pp. 1-7
Author(s):  
H. Liu-Seifert ◽  
M.G. Case ◽  
S.W. Andersen ◽  
K.C. Holdridge ◽  
P.S. Aisen ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Phase 3 ◽  
Significant Treatment ◽  
Treatment Difference ◽  
Significant Difference ◽  
Efficacy Measures ◽  
Modifying Effect ◽  
Disease Modifying ◽  
Significant Treatment Difference

OBJECTIVE: A delayed-start design has been proposed to assess a potential disease-modifying effect in investigational drugs for Alzheimer’s disease that target the underlying disease process. We extended this methodology to recently obtained data from the EXPEDITION3. METHODS: EXPEDITION3 was a Phase 3, double-blind study with participants randomized to solanezumab (400 mg) or placebo every 4 weeks for 80 weeks, with an optional extension of active treatment. The delayed-start analysis was designed to determine if a statistically significant treatment difference established during the placebo-controlled period is maintained (at predefined level) during the delayed-start period, which would suggest the active drug has a disease-modifying effect. The delayed-start analysis was assessed across multiple efficacy measures, and includes data from baseline in the placebo-controlled period and up to 9 months in the delayed-start period. RESULTS: No significant difference was observed between the placebo and solanezumab treatment groups at the end of the placebo-controlled period for the Alzheimer’s Disease Assessment Scale-Cognitive 14-item subscale. A significant treatment difference was observed at the end of the placebo-controlled period for the Alzheimer’s Disease Cooperative Study-Activities of Daily Living instrumental items, an effect also seen at 6 months in the delayed-start period, and the noninferiority criterion was met. No other efficacy measures met these criteria. CONCLUSIONS: Delayed-start statistical methodology was used to understand the longitudinal outcomes in EXPEDITION3 and its extension. The small treatment differences observed at the end of the placebo-controlled phase prevented adequate assessment of any putative disease modifying effect.

A Double-Blind, Placebo-Controlled Study of Fluoxetine in Depressed Patients With Alzheimer's Disease

2001 ◽  
Vol 13 (2) ◽  
pp. 233-240 ◽  
Author(s):  
Gustavo M. Petracca ◽  
Eran Chemerinski ◽  
Sergio E. Starkstein
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Rating Scale ◽  
Functional Independence ◽  
Controlled Study ◽  
Consecutive Series ◽  
Hamilton Depression Scale ◽  
Double Blind ◽  
Treatment Of Depression ◽  
Efficacy Measures

Objective: To examine the efficacy of fluoxetine in the treatment of depression in patients with probable Alzheimer's disease (AD). Methods: This double-blind, parallel-design study included a consecutive series of 41 AD subjects meeting DSM-IV criteria for major or minor depression who were randomized to receive fluoxetine (up to 40 mg/day) or identical-appearing placebo. All patients received biweekly evaluations consisting of the Hamilton Depression Scale (HAM-D) and the Clinical Global Impression as primary efficacy measures, and the Mini-Mental State Exam, Hamilton Rating Scale for Anxiety, and the Functional Independence Measure as secondary efficacy measures. Results: Complete remission of depression was found in 47% of subjects treated with fluoxetine and in 33% of subjects treated with placebo. Both the fluoxetine and the placebo groups showed a significant decline in HAM-D scores over time, but the magnitude of mood improvement was similar for both groups. Fluoxetine was well tolerated, and most side effects were mild. Conclusion: Fluoxetine treatment for depression in AD did not differ significantly from treatment with placebo. Our study also confirms the presence of a placebo effect in the treatment of depression in AD.

Serotonin 5-HT2A Receptor Binding in Platelets From Patients With Alzheimer's Disease or Vascular Dementia

2000 ◽  
Vol 12 (4) ◽  
pp. 537-545 ◽  
Author(s):  
Olav Spigset ◽  
Christer Wilhelmsson ◽  
Tom Mjörndal ◽  
Sture Eriksson
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Vascular Dementia ◽  
Receptor Binding ◽  
Rating Scale ◽  
Control Group ◽  
Receptor Status ◽  
Serotonin System ◽  
Significant Difference ◽  
Scale Scores

It is well known that abnormalities in the brain serotonin system exist in patients with dementia. The present study was performed in order to investigate whether a peripheral serotonin system marker, the platelet 5-HT2A receptor, is affected in dementia. Thirty-eight patients with Alzheimer's disease (AD), 13 patients with vascular dementia, and 40 healthy controls were included in the study. There were no significant differences in receptor density for 5-HT2A receptor binding between the groups. Affinity of the radioligand to the receptor was significantly lower in AD than in vascular dementia and in the controls (p = .006 and p = .003, respectively), whereas there was no significant difference between the vascular dementia group and the control group. In 12 patients, treatment with citalopram was started due to depression or agitation. This treatment significantly reduced the Behavioral Pathology in Alzheimer's Disease Rating Scale scores (p = .001), but did not affect the platelet 5-HT2A receptor status. There was no correlation between 5-HT2A receptor status before treatment and the therapeutic effect of citalopram. The study indicates that platelet 5-HT2A receptor status is of limited value as a peripheral marker in dementia.

scholarly journals Use of Fast Gamma Magnetic Stimulation Over the Left Prefrontal Dorsolateral Cortex for the Treatment of MCI and Mild Alzheimer's Disease: A Double-Blind, Randomized, Sham-Controlled, Pilot Study

2021 ◽  
Vol 12 ◽  
Author(s):  
Alberto José Mimenza-Alvarado ◽  
Sara Gloria Aguilar-Navarro ◽  
Francisco M. Martinez-Carrillo ◽  
Alma E. Ríos-Ponce ◽  
Gabriel Villafuerte
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Adverse Effects ◽  
Magnetic Stimulation ◽  
Controlled Study ◽  
Magnetic Pulse ◽  
Double Blind ◽  
Clinical Trial Registration ◽  
Significant Difference ◽  
Dorsolateral Cortex

Background: Alzheimer's disease (AD) animal models have shown a reduced gamma power in several brain areas, and induction of these oscillations by non-invasive methods has been shown to modify several pathogenic mechanisms of AD. In humans, the application of low-intensity magnetic fields has shown to be able to produce neural entrainment at the magnetic pulse frequency, making it useful to induce gamma frequencies.Objective: The aim of this study was to assess if the application of fast gamma magnetic stimulation (FGMS) over the left prefrontal dorsolateral cortex would be a safe and well-tolerated intervention that could potentially improve cognitive scores in subjects with mild cognitive impairment and mild AD.Methods: In these randomized, double-blind, sham-controlled study, participants were assigned to either receive daily sessions two times a day of active or sham FGMS for 6 months. Afterward, measurements of adverse effects, cognition, functionality, and depression were taken.Results: Thirty-four patients, 17 in each group, were analyzed for the primary outcome. FGMS was adequately tolerated by most of the subjects. Only four patients from the active FGMS group (23.52%) and one patient from the sham FGMS group (5.88%) presented any kind of adverse effects, showing no significant difference between groups. Nevertheless, FGMS did not significantly change cognitive, functionality, or depressive evaluations.Conclusion: FGMS over the left prefrontal dorsolateral cortex applied twice a day for 6 months resulted to be a viable intervention that can be applied safely directly from home without supervision of a healthcare provider. However, no statistically significant changes in cognitive, functionality, or depression scores compared to sham stimulation were observed.Clinical Trial Registration:www.ClinicalTrials.gov, Identifier: NCT03983655, URL: https://clinicaltrials.gov/ct2/show/NCT03983655.

Behavioral Pathology in Alzheimer’s Disease Rating Scale

1987 ◽  
Author(s):  
Barry Reisberg ◽  
Jeffrey Borenstein ◽  
Emile Franssen ◽  
Stacy Salob ◽  
Gertrude Steinberg ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Rating Scale ◽  
Disease Rating ◽  
Behavioral Pathology

P4-002: A Phase 3, 26-Week, Double-Blind, Randomized, Placebo-Controlled Study of AC-1204 in Mild-to-Moderate Alzheimer's Disease: Study Design and Progress

2016 ◽  
Vol 12 ◽  
pp. P1014-P1014
Author(s):  
Martin R. Farlow ◽  
Michael Gold ◽  
Samuel Henderson ◽  
Sabrina Greer ◽  
Janet Vogel ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Study Design ◽  
Controlled Study ◽  
Phase 3 ◽  
Double Blind ◽  
Disease Study

Assessment of Behavioral and Affective Symptoms in Alzheimer's Disease

1990 ◽  
Vol 3 (1) ◽  
pp. 21-30 ◽  
Author(s):  
Marian B. Patterson ◽  
Audrey H. Schnell ◽  
Richard J. Martin ◽  
Mario F. Mendez ◽  
Kathleen A. Smyth ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Rating Scale ◽  
Signs And Symptoms ◽  
Behavioral Symptoms ◽  
Symptoms Of Depression ◽  
Patient Interviews ◽  
Affective Symptoms ◽  
Disease Rating ◽  
State Examination

Noncognitive behavioral symptoms occurring during the prior week were studied in 34 Alzheimer's disease (AD) patients and 21 spousal control subjects via caregiver and patient interviews using the Behavioral Pathology in Alzheimer's Disease Rating Scale and the Cornell Scale for Depression in Dementia. Delusional or paranoid features were reported in 13 subjects (38%) and hallucinations in six (18%); patients with these psychoticlike symptoms had lower scores on the Folstein's Mini-Mental State Examination. Other behavioral symptoms reported in AD patients included anxiety (50%) and activity disturbances (44%). Six AD subjects (18%) and two controls (10%) showed mild to moderate symptoms of depression ; AD subjects were more likely than controls to show behavioral signs and symptoms of depression, but the two groups did not differ in terms of mood-related, cyclical, or physical signs and symptoms. (J Geriatr Psychiatry Neurol 1990;3:21-30).

The Empirical Behavioral Pathology in Alzheimer's Disease (E-BEHAVE-AD) Rating Scale

1996 ◽  
Vol 8 (2) ◽  
pp. 247-266 ◽  
Author(s):  
Stefanie R. Auer ◽  
Isabel M. Monteiro ◽  
Barry Reisberg
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Interrater Reliability ◽  
Rating Scale ◽  
Behavioral Assessment ◽  
Reliability Study ◽  
Dementia Patients ◽  
Rating Instrument ◽  
Disease Rating ◽  
Behavioral Pathology

A clinician should not rely entirely upon a caregiver's report regarding behavioral pathology when planning a treatment strategy. Direct observational evaluation instruments as well as caregiver-based assessments are necessary. A new scale for the empirical (observational) evaluation of behavioral symptoms in Alzheimer's disease (AD) and related dementias, the Empirical Behavioral Pathology in Alzheimer's Disease Rating Scale (E-BEHAVEAD) was developed. Interrater reliability of this new assessment instrument was examined. Additionally, the relationship between the observed occurrence of behavioral symptomatology on this new rating instrument was compared with the occurrence using a similarly designed, caregiver-based instrument. The interrater reliability study consisted of two raters who simultaneously evaluated 20 dementia patients. The comparative study employed a cross-sectional design (N = 49). Individuals were evaluated in an outpatient clinic setting. The study population consisted of cognitively normal individuals and dementia patients. Evaluations included the new, observationally based behavioral assessment (the E-BEHAVE-AD), a caregiver-based behavioral assessment (the Behavioral Pathology in Alzheimer's Disease Rating Scale; BEHAVE-AD), a clinical global measure (the Global Deterioration Scale), and a mental status assessment (the Mini-Mental State Examination). The interrater reliability study revealed an intraclass correlation coefficient of .97 (p < .01) for total scores on the new E-BEHAVE-AD rating scale. The correlation coefficient for the amount of agreement on the presence of symptoms in six symptomatic categories between caregiver-based information about the patient's behavioral pathology assessed on the BEHAVE-AD and the clinician's observations assessed with the new E-BEHAVE-AD rating instrument was .51 (p < .01). The New E-BEHAVE-AD rating instrument showed excellent interrater reliability. Furthermore, there was a statistically significant relationship between clinician observation of the occurrence of behavioral pathology assessed using the E-BEHAVE-AD and caregive-reported pathology assessed with the BEHAVE-AD. However the magnitude of the correlation between these measures indicated that the majority of variance was independent and nonoverlapping. Consequently, these data support theoretical models suggesting that the assessment of behavioral pathology in dementia might ideally encompass both direct observational and caregiver-report approaches, using measures such as the E-BEHAVE-AD as well as measures such as the BEHAVE-AD.

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