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Article ; Online: Pimavanserin Treatment for Psychosis in Patients with Dementia with Lewy Bodies: A Case Series.

Rothenberg, Kasia Gustaw / McRae, Sharon G / Dominguez-Colman, Liza M / Shutes-David, Andrew / Tsuang, Debby W

2023 Volume 24, Page(s) e939806

Abstract: BACKGROUND Many patients with dementia with Lewy bodies (DLB) experience cholinesterase inhibitor- and antipsychotic-resistant psychosis. The new second-generation antipsychotic pimavanserin has been used with some success in the treatment of psychosis ... ...

Abstract	BACKGROUND Many patients with dementia with Lewy bodies (DLB) experience cholinesterase inhibitor- and antipsychotic-resistant psychosis. The new second-generation antipsychotic pimavanserin has been used with some success in the treatment of psychosis in other forms of dementia, including Alzheimer disease and Parkinson disease dementia. It is possible that pimavanserin may also be useful in the treatment of psychosis in DLB. We sought to describe the disease course and treatment of psychosis in 4 patients with DLB who were prescribed pimavanserin after other medications failed to reduce the frequency or severity of hallucinations and delusions. CASE REPORT This is a case series of 4 male patients (ages 56 to 74 at the beginning of the reports) who developed DLB and psychosis (eg, visual illusions, visual and olfactory hallucinations, and paranoid delusions). All 4 patients were prescribed cholinesterase inhibitors (eg, donepezil or rivastigmine) prior to pimavanserin, and only 1 patient experienced improved psychosis while on cholinesterase inhibitors. All 3 patients who were prescribed first-generation antipsychotics (eg, haloperidol) or traditional second-generation antipsychotics (eg, olanzapine, risperidone, or quetiapine) experienced initial or lasting side effects with no improvement of psychosis. Conversely, all 4 patients tolerated pimavanserin well, and 3 of the 4 patients experienced significant improvement of psychosis (eg, fewer hallucinations, fewer delusions, reduced paranoia, and/or reduced distress or agitation related to hallucinations and delusions) when prescribed pimavanserin. CONCLUSIONS This case series suggests that pimavanserin is tolerable in older males with DLB and that it may be useful for the reduction of distressful hallucinations, delusions, and paranoia in patients with DLB.
MeSH term(s)	Humans ; Male ; Aged ; Antipsychotic Agents/therapeutic use ; Lewy Body Disease/complications ; Lewy Body Disease/drug therapy ; Lewy Body Disease/chemically induced ; Dementia ; Cholinesterase Inhibitors/therapeutic use ; Parkinson Disease/complications ; Psychotic Disorders/drug therapy ; Psychotic Disorders/etiology ; Hallucinations/drug therapy ; Hallucinations/etiology ; Piperidines ; Urea/analogs & derivatives
Chemical Substances	Antipsychotic Agents ; pimavanserin (JZ963P0DIK) ; Cholinesterase Inhibitors ; Piperidines ; Urea (8W8T17847W)
Language	English
Publishing date	2023-09-30
Publishing country	United States
Document type	Case Reports ; Journal Article
ZDB-ID	2517183-5
ISSN	1941-5923 ; 1941-5923
ISSN (online)	1941-5923
ISSN	1941-5923
DOI	10.12659/AJCR.939806
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Endophenotypes in Schizophrenia: Digging Deeper to Identify Genetic Mechanisms.

Greenwood, Tiffany A / Shutes-David, Andrew / Tsuang, Debby W

Journal of psychiatry and brain science

2019 Volume 4, Issue 2

Abstract: Schizophrenia (SZ) is a severe psychotic disorder that is highly heritable and common in the general population. The genetic heterogeneity of SZ is substantial, with contributions from common, rare, ... ...

Abstract	Schizophrenia (SZ) is a severe psychotic disorder that is highly heritable and common in the general population. The genetic heterogeneity of SZ is substantial, with contributions from common, rare, and
Language	English
Publishing date	2019-03-13
Publishing country	England
Document type	Journal Article
ISSN	2398-385X
ISSN (online)	2398-385X
DOI	10.20900/jpbs.20190005
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Genetic factors in neurodegenerative diseases.

Tsuang, Debby W / Bird, Thomas D

American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics

2016 Volume 174, Issue 1, Page(s) 3–4

MeSH term(s)	Animals ; Humans ; Neurodegenerative Diseases/etiology ; Neurodegenerative Diseases/genetics
Language	English
Publishing date	2016-10-22
Publishing country	United States
Document type	Editorial ; Introductory Journal Article ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2143866-3
ISSN	1552-485X ; 1552-4841
ISSN (online)	1552-485X
ISSN	1552-4841
DOI	10.1002/ajmg.b.32504
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Article ; Online: Mild COVID-19 Disease Course With Protracted Delirium in a Cognitively Impaired Patient Over the Age of 85 Years.

Payne, Sarah / Jankowski, Adrienne / Shutes-David, Andrew / Ritchey, Katherine / Tsuang, Debby W

The primary care companion for CNS disorders

2020 Volume 22, Issue 4

MeSH term(s)	Aged, 80 and over ; COVID-19 ; Cognitive Dysfunction/complications ; Cognitive Dysfunction/virology ; Coronavirus Infections/complications ; Coronavirus Infections/diagnosis ; Coronavirus Infections/psychology ; Delirium/etiology ; Delirium/virology ; Humans ; Pandemics ; Pneumonia, Viral/complications ; Pneumonia, Viral/diagnosis ; Pneumonia, Viral/psychology
Keywords	covid19
Language	English
Publishing date	2020-08-06
Publishing country	United States
Document type	Case Reports ; Journal Article
ZDB-ID	2675414-9
ISSN	2155-7780 ; 2155-7772
ISSN (online)	2155-7780
ISSN	2155-7772
DOI	10.4088/PCC.20l02721
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Article ; Online: Alzheimer's Disease and Alzheimer's Disease-Related Dementias in Older African American and White Veterans.

Cheng, Yan / Ahmed, Ali / Zamrini, Edward / Tsuang, Debby W / Sheriff, Helen M / Zeng-Treitler, Qing

Journal of Alzheimer's disease : JAD

2020 Volume 75, Issue 1, Page(s) 311–320

Abstract: Background: Racial disparity in the epidemiology of Alzheimer's disease and Alzheimer's disease-related dementias (AD/ADRD) has been reported. However, less is known about this disparity among Veterans.: Objective: To estimate the racial disparity in ...

Abstract	Background: Racial disparity in the epidemiology of Alzheimer's disease and Alzheimer's disease-related dementias (AD/ADRD) has been reported. However, less is known about this disparity among Veterans. Objective: To estimate the racial disparity in AD/ADRD among the Veterans. Methods: Of the 5,413,418 Veterans≥65 years receiving care at the Veterans Health Administration (1999-2016), 4,045,269 were free of prevalent AD/ADRD, schizophrenia, or bipolar disorder at baseline. Of these, 432,469 were African American. Race was self-identified and incident AD/ADRD during 20 (median 6.7) years of follow-up was ascertained using International Classification of Diseases codes. Results: Patients had a mean age of 70.4 (±6.6) years and 97.8% were men. Age-sex-adjusted incidence of AD/ADRD per 1,000 person-year was 19.3 and 10.8 for African American and white Veterans, respectively (age-sex-adjusted hazard ratio associated with African American race, 1.77; 95% confidence interval, 1.75-1.79; p < 0.0001). This association remained essentially unchanged after multivariable adjustment (hazard ratio, 1.67; 95% confidence interval, 1.65-1.69; p < 0.0001). Among the key baseline characteristics that were significant predictors of AD/ADRD in both races, stroke was a significantly stronger predictor among African Americans, and Hispanic ethnicity and depression among whites (p-value for all interaction,<0.0001). Conclusion: The findings of a higher incidence of AD/ADRD among African American Veterans is consistent with the findings in the general population reported in the literature, although the overall incidence appears to be lower than that in the general population. Future studies need to examine this disparity in incidence as well as the between-race heterogeneity in AD/ADRD risk.
MeSH term(s)	African Americans/statistics & numerical data ; Aged ; Alzheimer Disease/epidemiology ; Dementia/epidemiology ; European Continental Ancestry Group/statistics & numerical data ; Female ; Health Status Disparities ; Humans ; Incidence ; Male ; Middle Aged ; Prevalence ; Veterans/statistics & numerical data
Language	English
Publishing date	2020-03-10
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	1440127-7
ISSN	1875-8908 ; 1387-2877
ISSN (online)	1875-8908
ISSN	1387-2877
DOI	10.3233/JAD-191188
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bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
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Article: Identifying probable dementia in undiagnosed Black and White Americans using machine learning in Veterans Health Administration electronic health records.

Shao, Yijun / Todd, Kaitlin / Shutes-David, Andrew / Millard, Steven P / Brown, Karl / Thomas, Amy / Chen, Kathryn / Wilson, Katherine / Zeng, Qing T / Tsuang, Debby W

medRxiv : the preprint server for health sciences

2023

Abstract: The application of machine learning (ML) tools in electronic health records (EHRs) can help reduce the underdiagnosis of dementia, but models that are not designed to reflect minority population may perpetuate that underdiagnosis. To address the ... ...

Abstract	The application of machine learning (ML) tools in electronic health records (EHRs) can help reduce the underdiagnosis of dementia, but models that are not designed to reflect minority population may perpetuate that underdiagnosis. To address the underdiagnosis of dementia in both Black Americans (BAs) and white Americans (WAs), we sought to develop and validate ML models that assign race-specific risk scores. These scores were used to identify undiagnosed dementia in BA and WA Veterans in EHRs. More specifically, risk scores were generated separately for BAs (n=10K) and WAs (n=10K) in training samples of cases and controls by performing ML, equivalence mapping, topic modeling, and a support vector-machine (SVM) in structured and unstructured EHR data. Scores were validated via blinded manual chart reviews (n=1.2K) of controls from a separate sample (n=20K). AUCs and negative and positive predictive values (NPVs and PPVs) were calculated to evaluate the models. There was a strong positive relationship between SVM-generated risk scores and undiagnosed dementia. BAs were more likely than WAs to have undiagnosed dementia per chart review, both overall (15.3% vs 9.5%) and among Veterans with >90
Language	English
Publishing date	2023-02-14
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.02.08.23285540
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Book: Genetics of mental disorders

Faraone, Stephen V. / Tsuang, Ming T. / Tsuang, Debby W.

a guide for students, clinicians, and researchers

1999

Author's details	Stephen V. Faraone ; Ming T. Tsuang ; Debby W. Tsuang
Keywords	Genetic Predisposition to Disease / genetics ; Hereditary Diseases / genetics ; Mental Disorders / genetics ; Psychiatry / methods
Language	English
Size	XVI, 272 S. : Ill., graph. Darst.
Publisher	The Guilford Press
Publishing place	New York u.a.
Publishing country	United States
Document type	Book
HBZ-ID	HT011125973
ISBN	1-57230-479-0 ; 978-1-57230-479-6
Database	Catalogue ZB MED Medicine, Health

In stock of ZB MED Cologne/Königswinter

Shelf mark	Loan status	Location
1999 A 6766	order for loan	Magazin

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Article: Mild COVID-19 Disease Course With Protracted Delirium in a Cognitively Impaired Patient Over the Age of 85 Years

Payne, Sarah / Jankowski, Adrienne / Shutes-David, Andrew / Ritchey, Katherine / Tsuang, Debby W

Prim. care companion CNS disord. (Online)

Keywords	covid19
Publisher	WHO
Document type	Article
Note	WHO #Covidence: #696452
Database	COVID19

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Article ; Online: Homozygous CADPS2 Mutations Cause Neurodegenerative Disease with Lewy Body-like Pathology in Parrots.

Lorenzo-Betancor, Oswaldo / Galosi, Livio / Bonfili, Laura / Eleuteri, Anna Maria / Cecarini, Valentina / Verin, Ranieri / Dini, Fabrizio / Attili, Anna-Rita / Berardi, Sara / Biagini, Lucia / Robino, Patrizia / Stella, Maria Cristina / Yearout, Dora / Dorschner, Michael O / Tsuang, Debby W / Rossi, Giacomo / Zabetian, Cyrus P

Movement disorders : official journal of the Movement Disorder Society

2022 Volume 37, Issue 12, Page(s) 2345–2354

Abstract: Background: Several genetic models that recapitulate neurodegenerative features of Parkinson's disease (PD) exist, which have been largely based on genes discovered in monogenic PD families. However, spontaneous genetic mutations have not been linked to ...

Abstract	Background: Several genetic models that recapitulate neurodegenerative features of Parkinson's disease (PD) exist, which have been largely based on genes discovered in monogenic PD families. However, spontaneous genetic mutations have not been linked to the pathological hallmarks of PD in non-human vertebrates. Objective: To describe the genetic and pathological findings of three Yellow-crowned parrot (Amazona ochrocepahala) siblings with a severe and rapidly progressive neurological phenotype. Methods: The phenotype of the three parrots included severe ataxia, rigidity, and tremor, while their parents were phenotypically normal. Tests to identify avian viral infections and brain imaging studies were all negative. Due to their severe impairment, they were all euthanized at age 3 months and their brains underwent neuropathological examination and proteasome activity assays. Whole genome sequencing (WGS) was performed on the three affected parrots and their parents. Results: The brains of affected parrots exhibited neuronal loss, spongiosis, and widespread Lewy body-like inclusions in many regions including the midbrain, basal ganglia, and neocortex. Proteasome activity was significantly reduced in these animals compared to a control (P < 0.05). WGS identified a single homozygous missense mutation (p.V559L) in a highly conserved amino acid within the pleckstrin homology (PH) domain of the calcium-dependent secretion activator 2 (CADPS2) gene. Conclusions: Our data suggest that a homozygous mutation in the CADPS2 gene causes a severe neurodegenerative phenotype with Lewy body-like pathology in parrots. Although CADPS2 variants have not been reported to cause PD, further investigation of the gene might provide important insights into the pathophysiology of Lewy body disorders. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.
MeSH term(s)	Animals ; Lewy Bodies/pathology ; Neurodegenerative Diseases/genetics ; Parrots/genetics ; Parrots/metabolism ; Proteasome Endopeptidase Complex/genetics ; Proteasome Endopeptidase Complex/metabolism ; Parkinson Disease/genetics ; Parkinson Disease/pathology ; Mutation/genetics ; Carrier Proteins/genetics ; alpha-Synuclein/genetics ; alpha-Synuclein/metabolism
Chemical Substances	Proteasome Endopeptidase Complex (EC 3.4.25.1) ; Carrier Proteins ; alpha-Synuclein
Language	English
Publishing date	2022-09-10
Publishing country	United States
Document type	Journal Article ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	607633-6
ISSN	1531-8257 ; 0885-3185
ISSN (online)	1531-8257
ISSN	0885-3185
DOI	10.1002/mds.29211
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Zs.MO 238: Show issues

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Article ; Online: Detection of probable dementia cases in undiagnosed patients using structured and unstructured electronic health records.

Shao, Yijun / Zeng, Qing T / Chen, Kathryn K / Shutes-David, Andrew / Thielke, Stephen M / Tsuang, Debby W

BMC medical informatics and decision making

2019 Volume 19, Issue 1, Page(s) 128

Abstract: Background: Dementia is underdiagnosed in both the general population and among Veterans. This underdiagnosis decreases quality of life, reduces opportunities for interventions, and increases health-care costs. New approaches are therefore necessary to ... ...

Abstract	Background: Dementia is underdiagnosed in both the general population and among Veterans. This underdiagnosis decreases quality of life, reduces opportunities for interventions, and increases health-care costs. New approaches are therefore necessary to facilitate the timely detection of dementia. This study seeks to identify cases of undiagnosed dementia by developing and validating a weakly supervised machine-learning approach that incorporates the analysis of both structured and unstructured electronic health record (EHR) data. Methods: A topic modeling approach that included latent Dirichlet allocation, stable topic extraction, and random sampling was applied to VHA EHRs. Topic features from unstructured data and features from structured data were compared between Veterans with (n = 1861) and without (n = 9305) ICD-9 dementia codes. A logistic regression model was used to develop dementia prediction scores, and manual reviews were conducted to validate the machine-learning results. Results: A total of 853 features were identified (290 topics, 174 non-dementia ICD codes, 159 CPT codes, 59 medications, and 171 note types) for the development of logistic regression prediction scores. These scores were validated in a subset of Veterans without ICD-9 dementia codes (n = 120) by experts in dementia who performed manual record reviews and achieved a high level of inter-rater agreement. The manual reviews were used to develop a receiver of characteristic (ROC) curve with different thresholds for case detection, including a threshold of 0.061, which produced an optimal sensitivity (0.825) and specificity (0.832). Conclusions: Dementia is underdiagnosed, and thus, ICD codes alone cannot serve as a gold standard for diagnosis. However, this study suggests that imperfect data (e.g., ICD codes in combination with other EHR features) can serve as a silver standard to develop a risk model, apply that model to patients without dementia codes, and then select a case-detection threshold. The study is one of the first to utilize both structured and unstructured EHRs to develop risk scores for the diagnosis of dementia.
MeSH term(s)	Aged ; Aged, 80 and over ; Delayed Diagnosis ; Dementia/diagnosis ; Electronic Health Records ; Female ; Humans ; International Classification of Diseases ; Machine Learning ; Male ; Veterans
Language	English
Publishing date	2019-07-09
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
ISSN	1472-6947
ISSN (online)	1472-6947
DOI	10.1186/s12911-019-0846-4
Database	MEDical Literature Analysis and Retrieval System OnLINE

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