Risperidone in the Treatment of Patients With Alzheimer's Disease With Negative Symptoms

2000 ◽  
Vol 12 (4) ◽  
pp. 527-536 ◽  
Author(s):  
Arnaldo E. Negrón ◽  
William E. Reichman
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Negative Symptoms ◽  
Emotional Reactivity ◽  
Rating Scales ◽  
Behavioral Assessment ◽  
Cognitive Status ◽  
Day Range ◽  
Clinically Significant ◽  
Positive And Negative Symptoms

Introduction: Negative symptoms such as diminished initiative, drive, motivation, and emotional reactivity have been described in patients with Alzheimer's disease (AD). The purpose of this study was to retrospectively analyze the efficacy and tolerability of risperidone for the treatment of clinically significant positive and negative symptoms in AD. Methods: We reviewed the charts of 50 community-residing AD patients who had been treated in a specialized university-based dementia management clinic. Clinical data comparing baseline and 12 weeks of treatment were obtained by reviewing a series of rating scales that were recorded as part of a comprehensive behavioral assessment. Results: Reviewed subjects had a mean age of 79.7±6 years and a mean of 12±3.6 years of school. Seventy percent of the subjects were female and the majority was White. The mean dose of risperidone prescribed was 1.3±0.6 mg per day (range from 0.5 mg to 3.0 mg). After 12 weeks of treatment, the severity of positive and negative symptoms was significantly reduced. Importantly, improvement in negative symptoms with the use of risperidone appeared to be independent of a positive treatment effect on positive symptoms. Risperidone had insignificant effects on both cognitive status and the emergence of extrapyramidal symptoms. Conclusion: This retrospective study demonstrates that risperidone appears to be efficacious in the treatment of clinically significant positive and negative symptoms in patients with AD.

scholarly journals Depression as a Risk Factor for Alzheimer’s Disease: A Systematic Review of Longitudinal Meta-Analyses

2021 ◽  
Vol 10 (9) ◽  
pp. 1809
Author(s):  
Olalla Sáiz-Vázquez ◽  
Patricia Gracia-García ◽  
Silvia Ubillos-Landa ◽  
Alicia Puente-Martínez ◽  
Silvia Casado-Yusta ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Risk Factor ◽  
Rating Scales ◽  
Rating Scale ◽  
Symptoms Of Depression ◽  
Clinically Significant ◽  
Criteria For Diagnosis ◽  
Meta Analyses ◽  
Clinical Measures

Alzheimer’s disease (AD) is the most frequent cause of dementia, linked to morbidity and mortality among elderly patients. Recently, several clinical studies suggested that depression is a potential risk factor for cognitive decline and AD. A review of meta-analyses was performed, calculating pooled odds ratios to estimate the risk of AD in people with a prior diagnosis (or clinically significant symptoms) of depression. A total of six meta-analyses which represented 28 individual studies were analyzed. A significant association between depression and AD was found (OR = 1.54, 95% CI [1.02–2.31]; p = 0.038). The results showed that heterogeneity across studies was substantial. We found a significant positive effect size for clinical measures of depression, but not for symptomatic rating scales, in the association of depression with risk of AD. The type of rating scale used to assess depression and the cut-off criteria selected also moderated the relationship between depression and AD risk. We found that studies that used clinically significant criteria for diagnosis of depression had more consistent and significant results than studies that used symptomatic scales.

scholarly journals Validity Evidence for the Research Category, “Cognitively Unimpaired – Declining,” as a Risk Marker for Mild Cognitive Impairment and Alzheimer’s Disease

2021 ◽  
Vol 13 ◽  
Author(s):  
Rebecca Langhough Koscik ◽  
Bruce P. Hermann ◽  
Samantha Allison ◽  
Lindsay R. Clark ◽  
Erin M. Jonaitis ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Cognitive Decline ◽  
Operational Definition ◽  
Cognitive Status ◽  
Validity Evidence ◽  
Positron Emission ◽  
Clinically Significant

While clinically significant cognitive impairment is the key feature of the symptomatic stages of the Alzheimer’s disease (AD) continuum, subtle cognitive decline is now known to occur years before a clinical diagnosis of mild cognitive impairment (MCI) or dementia due to AD is made. The primary aim of this study was to examine criterion validity evidence for an operational definition of “cognitively unimpaired-declining” (CU-D) in the Wisconsin Registry for Alzheimer’s Prevention (WRAP), a longitudinal cohort study following cognition and risk factors from mid-life and on. Cognitive status was determined for each visit using a consensus review process that incorporated internal norms and published norms; a multi-disciplinary panel reviewed cases first to determine whether MCI or dementia was present, and subsequently whether CU-D was present, The CU-D group differed from CU-stable (CU-S) and MCI on concurrent measures of cognition, demonstrating concurrent validity. Participants who changed from CU-S to CU-D at the next study visit demonstrated greater declines than those who stayed CU-S. In addition, those who were CU-D were more likely to progress to MCI or dementia than those who were CU-S (predictive validity). In a subsample with positron emission tomography (PET) imaging, the CU-D group also differed from the CU-S and MCI/Dementia groups on measures of amyloid and tau burden, indicating that biomarker evidence of AD was elevated in those showing sub-clinical (CU-D) decline. Together, the results corroborate other studies showing that cognitive decline begins long before a dementia diagnosis and indicate that operational criteria can detect subclinical decline that may signal AD or other dementia risk.

Case Studies in Dementia-Related Anxiety

GeroPsych ◽  
2020 ◽  
pp. 1-6
Author(s):  
Molly Maxfield ◽  
Jennifer R. Roberts ◽  
JoAnna Dieker
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Social Withdrawal ◽  
Cognitive Status ◽  
Generalized Anxiety ◽  
Neurocognitive Disorder ◽  
High Genetic Risk ◽  
Disease Case ◽  
Negative Perceptions

Abstract. Two clients seeking neuropsychological assessment reported anxiety about their cognitive status. We review the cases to increase our understanding of factors contributing to dementia-related anxiety. Case 1 met the criteria for mild neurocognitive disorder; the client’s memory was impaired, and she had a high genetic risk for Alzheimer’s disease. The client reported anxiety about negative perceptions of quality of life among individuals diagnosed with Alzheimer’s disease. Case 2 did not meet the criteria for a neurocognitive disorder. Anxiety about this client’s cognitive status appeared attributable to generalized anxiety disorder, given his anxiety about diverse topics. Both clients reported embarrassment about forgetfulness and social withdrawal. Dementia-related anxiety is believed to be relatively common, to exist on a continuum, to have unique social implications, and to stem from various sources, necessitating differing interventions.

scholarly journals Remote monitoring technologies in Alzheimer’s disease: design of the RADAR-AD study

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Marijn Muurling ◽  
◽  
Casper de Boer ◽  
Rouba Kozak ◽  
Dorota Religa ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Remote Monitoring ◽  
Rating Scales ◽  
Functional Decline ◽  
Cognitive Domain ◽  
Subjective Rating ◽  
Functional Domain ◽  
Smartphone Applications ◽  
Monitoring Technologies

Abstract Background Functional decline in Alzheimer’s disease (AD) is typically measured using single-time point subjective rating scales, which rely on direct observation or (caregiver) recall. Remote monitoring technologies (RMTs), such as smartphone applications, wearables, and home-based sensors, can change these periodic subjective assessments to more frequent, or even continuous, objective monitoring. The aim of the RADAR-AD study is to assess the accuracy and validity of RMTs in measuring functional decline in a real-world environment across preclinical-to-moderate stages of AD compared to standard clinical rating scales. Methods This study includes three tiers. For the main study, we will include participants (n = 220) with preclinical AD, prodromal AD, mild-to-moderate AD, and healthy controls, classified by MMSE and CDR score, from clinical sites equally distributed over 13 European countries. Participants will undergo extensive neuropsychological testing and physical examination. The RMT assessments, performed over an 8-week period, include walk tests, financial management tasks, an augmented reality game, two activity trackers, and two smartphone applications installed on the participants’ phone. In the first sub-study, fixed sensors will be installed in the homes of a representative sub-sample of 40 participants. In the second sub-study, 10 participants will stay in a smart home for 1 week. The primary outcome of this study is the difference in functional domain profiles assessed using RMTs between the four study groups. The four participant groups will be compared for each RMT outcome measure separately. Each RMT outcome will be compared to a standard clinical test which measures the same functional or cognitive domain. Finally, multivariate prediction models will be developed. Data collection and privacy are important aspects of the project, which will be managed using the RADAR-base data platform running on specifically designed biomedical research computing infrastructure. Results First results are expected to be disseminated in 2022. Conclusion Our study is well placed to evaluate the clinical utility of RMT assessments. Leveraging modern-day technology may deliver new and improved methods for accurately monitoring functional decline in all stages of AD. It is greatly anticipated that these methods could lead to objective and real-life functional endpoints with increased sensitivity to pharmacological agent signal detection.

scholarly journals Differential effects of chronic immunosuppression on behavioral, epigenetic, and Alzheimer’s disease-associated markers in 3xTg-AD mice

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Minesh Kapadia ◽  
M. Firoz Mian ◽  
Donglai Ma ◽  
Craig P. Hutton ◽  
Amber Azam ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Emotional Reactivity ◽  
Histone Variant ◽  
In Vivo Model ◽  
Adult Males ◽  
Bdnf Expression ◽  
Systemic Autoimmunity ◽  
Circulating Autoantibodies

Abstract Background Circulating autoantibodies and sex-dependent discrepancy in prevalence are unexplained phenomena of Alzheimer’s disease (AD). Using the 3xTg-AD mouse model, we reported that adult males show early manifestations of systemic autoimmunity, increased emotional reactivity, enhanced expression of the histone variant macroH2A1 in the cerebral cortex, and loss of plaque/tangle pathology. Conversely, adult females display less severe autoimmunity and retain their AD-like phenotype. This study examines the link between immunity and other traits of the current 3xTg-AD model. Methods Young 3xTg-AD and wild-type mice drank a sucrose-laced 0.4 mg/ml solution of the immunosuppressant cyclophosphamide on weekends for 5 months. After behavioral phenotyping at 2 and 6 months of age, we assessed organ mass, serologic markers of autoimmunity, molecular markers of early AD pathology, and expression of genes associated with neurodegeneration. Results Chronic immunosuppression prevented hematocrit drop and reduced soluble Aβ in 3xTg-AD males while normalizing the expression of histone variant macroH2A1 in 3xTg-AD females. This treatment also reduced hepatosplenomegaly, lowered autoantibody levels, and increased the effector T cell population while decreasing the proportion of regulatory T cells in both sexes. Exposure to cyclophosphamide, however, neither prevented reduced brain mass and BDNF expression nor normalized increased tau and anxiety-related behaviors. Conclusion The results suggest that systemic autoimmunity increases soluble Aβ production and affects transcriptional regulation of macroH2A1 in a sex-related manner. Despite the complexity of multisystem interactions, 3xTg-AD mice can be a useful in vivo model for exploring the regulatory role of autoimmunity in the etiology of AD-like neurodegenerative disorders.

scholarly journals RESTING HEART RATE MODERATES THE RELATIONSHIP BETWEEN NEUROPSYCHIATRIC SYMPTOMS, MCI, AND ALZHEIMER’S DISEASE

2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S641-S641
Author(s):  
Shanna L Burke
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Heart Rate ◽  
Relative Risk ◽  
Neuropsychiatric Symptoms ◽  
Cognitive Status ◽  
Resting Heart Rate ◽  
Data Set ◽  
Increased Risk ◽  
The Relationship

Abstract Little is known about how resting heart rate moderates the relationship between neuropsychiatric symptoms and cognitive status. This study examined the relative risk of NPS on increasingly severe cognitive statuses and examined the extent to which resting heart rate moderates this relationship. A secondary analysis of the National Alzheimer’s Coordinating Center Uniform Data Set was undertaken, using observations from participants with normal cognition at baseline (13,470). The relative risk of diagnosis with a more severe cognitive status at a future visit was examined using log-binomial regression for each neuropsychiatric symptom. The moderating effect of resting heart rate among those who are later diagnosed with mild cognitive impairment (MCI) or Alzheimer’s disease (AD) was assessed. Delusions, hallucinations, agitation, depression, anxiety, elation, apathy, disinhibition, irritability, motor disturbance, nighttime behaviors, and appetite disturbance were all significantly associated (p<.001) with an increased risk of AD, and a reduced risk of MCI. Resting heart rate increased the risk of AD but reduced the relative risk of MCI. Depression significantly interacted with resting heart rate to increase the relative risk of MCI (RR: 1.07 (95% CI: 1.00-1.01), p<.001), but not AD. Neuropsychiatric symptoms increase the relative risk of AD but not MCI, which may mean that the deleterious effect of NPS is delayed until later and more severe stages of the disease course. Resting heart rate increases the relative risk of MCI among those with depression. Practitioners considering early intervention in neuropsychiatric symptomology may consider the downstream benefits of treatment considering the long-term effects of NPS.

Prospective longitudinal study of depression and anosognosia in Alzheimer's disease

1997 ◽  
Vol 171 (1) ◽  
pp. 47-52 ◽  
Author(s):  
Sergio E. Starkstein ◽  
Erán Chemerinski ◽  
Liliana Sabe ◽  
Gabriela Kuzis ◽  
Gustavo Petracca ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Major Depression ◽  
Cognitive Status ◽  
Initial Evaluation ◽  
Consecutive Series ◽  
Psychiatric Interview ◽  
Prospective Longitudinal Study ◽  
Prospective Longitudinal

BackgroundThe aim was to examine the longitudinal evolution of depression and anosognosia in patients with probable Alzheimer's disease (AD).MethodSixty-two of a consecutive series of 116 AD patients that were examined with a structured psychiatric interview had a follow-up evaluation between one and two years after the initial evaluation.ResultsAt the initial evaluation 19% of the 62 patients had major depression, 34% had dysthymia, and 47% were not depressed. After a mean follow-up of 16 months, 58% of patients with major depression at the initial evaluation were still depressed, whereas only 28% of patients with initial dysthymia and 21% of the non-depressed patients were depressed at follow-up. During the follow-up period, all three groups showed similar declines in cognitive status and activities of daily living. At the initial evaluation, 39% of the patients had anosognosia, and there was a significant increment of anosognosia during the follow-up period.ConclusionsWhile dysthymia in AD is a brief emotional disorder, major depression is a longer-lasting mood change. Anosognosia is another prevalent disorder among AD patients, and increases with the progression of the illness.

Influence of Educational Attainment on Cognition-Based Intervention Programs for Persons with Mild Alzheimer’s Disease

2016 ◽  
Vol 22 (5) ◽  
pp. 577-582 ◽  
Author(s):  
Israel Contador ◽  
Bernardino Fernández-Calvo ◽  
Francisco Ramos ◽  
Javier Olazarán
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Decline ◽  
Effect Size ◽  
Study Groups ◽  
Total Sample ◽  
Cognitive Intervention ◽  
Potential Effect ◽  
Cognitive Status ◽  
Disease Assessment

AbstractObjectives: This research retrospectively analyzed the effect of education on cognitive interventions carried out in patients with mild Alzheimer’s disease (AD). Methods: The total sample consisted of 75 patients with mild AD receiving treatment with cholinesterase inhibitors. The participants were divided into two groups: cognitive intervention (IG; n=45) and waiting list (WLG; n=30). Patients in the IG received either the Big Brain Academy (n=15) or the Integrated Psychostimulation Program (n=30) during 12 weeks. The influence of education on intervention effect was analyzed comparing mean change scores of the two study groups in the cognitive subscale of the Alzheimer’s Disease Assessment Scale (ADAS-cog), stratified by educational level. The potential effect of age, sex, cognitive status, and type of intervention was examined using post hoc stratification analyses. Results: Higher education was associated with faster cognitive decline in the WLG (effect size=0.51; p<.01). However, cognitive evolution was not influenced by education in the IG (effect size=0.12; p=.42). Conclusions: Our results suggest that cognitive intervention might delay accelerated cognitive decline in higher educated individuals with mild AD. (JINS, 2016, 23, 1–6)

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