Examining the association between genetic liability for schizophrenia and psychotic symptoms in Alzheimer’s disease

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Abstract

Psychosis (delusions or hallucinations) in Alzheimer’s disease (AD + P) occurs in up to 50% of individuals and is associated with significantly worse clinical outcomes. Atypical antipsychotics, first developed for schizophrenia, are commonly used in AD + P, suggesting shared mechanisms. Despite this implication, little empirical research has been conducted to examine whether there are mechanistic similarities between AD + P and schizophrenia. In this study, we tested whether polygenic risk score (PRS) for schizophrenia was associated with AD + P. Schizophrenia PRS was calculated using Psychiatric Genomics Consortium data at ten GWAS p value thresholds ( P _T) in 3111 AD cases from 11 cohort studies characterized for psychosis using validated, standardized tools. Association between PRS and AD + P status was tested by logistic regression in each cohort individually and the results meta-analyzed. The schizophrenia PRS was associated with AD + P at an optimum P _T of 0.01. The strongest association was for delusions where a one standard deviation increase in PRS was associated with a 1.18-fold increased risk (95% CI: 1.06–1.3; p = 0.001). These new findings point towards psychosis in AD—and particularly delusions—sharing some genetic liability with schizophrenia and support a transdiagnostic view of psychotic symptoms across the lifespan.

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Most cited references 36

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With the increasing life expectancy in developed countries, the incidence of Alzheimer's disease (AD) and thus its socioeconomic impact are growing. Increasing knowledge over the last years about the pathomechanisms involved in AD allow for the development of specific treatment strategies aimed at slowing down or even preventing neuronal death in AD. However, this requires also that (1) AD can be diagnosed with high accuracy, because non-AD dementias would not benefit from an AD-specific treatment; (2) AD can be diagnosed in very early stages when any intervention would be most effective; and (3) treatment efficacy can be reliably and meaningfully monitored. Although there currently is no ideal biomarker that would fulfill all these requirements, there is increasing evidence that a combination of currently existing neuroimaging and cerebrospinal fluid (CSF) and blood biomarkers can provide important complementary information and thus contribute to a more accurate and earlier diagnosis of AD. The Alzheimer's Disease Neuroimaging Initiative (ADNI) is exploring which combinations of these biomarkers are the most powerful for diagnosis of AD and monitoring of treatment effects.

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Prevalence, correlates and course of behavioural and psychological symptoms of dementia in the population.

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Behavioural and psychological symptoms of dementia (BPSD) are major contributors to the burden of dementia. To describe the prevalence, correlates and course of BPSD in the population of England and Wales. The prevalence of 12 symptoms was estimated in 587 participants with dementia and 2050 participants without dementia as part of a population-based longitudinal study of ageing. The effect of risk factors and the factor structure were estimated using 1782 interviews provided by participants with dementia throughout the study. Each symptom apart from sleeping problems was more common in the population with dementia. The co-occurrence of the symptoms was explained by a four-factor solution, corresponding to psychosis/apathy, depression/anxiety, irritability/persecution and wandering/sleep problems. Psychosis occurred more frequently with declining cognition. Anxiety and depression were more common in younger individuals and in those with poor self-reported health. Persistence varied between symptoms. Behavioural and psychological symptoms of dementia affect nearly all people with dementia. Symptoms co-occur, and the symptoms that affected individuals experience are related to their socio-demographic and clinical characteristics.

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Epidemiology of and risk factors for psychosis of Alzheimer's disease: a review of 55 studies published from 1990 to 2003.

Dilip V. Jeste, Susan A. Ropacki (2005)

The authors reviewed studies published between 1990 and 2003 that reported the prevalence, incidence, and persistence of, as well as the risk factors associated with, psychosis of Alzheimer's disease. PubMed and PsycINFO databases were searched by using the terms "psychosis and Alzheimer disease" and "psychosis and dementia." Empirical investigations presenting quantitative data on the epidemiology of and/or risk factors for psychotic symptoms in Alzheimer's disease were included in the review. A total of 55 studies, including a total of 9,749 subjects, met the inclusion criteria. Psychosis was reported in 41% of patients with Alzheimer's disease, including delusions in 36% and hallucinations in 18%. The incidence of psychosis increased progressively over the first 3 years of observation, after which the incidence seemed to plateau. Psychotic symptoms tended to last for several months but became less prominent after 1 year. African American or black ethnicity and more severe cognitive impairment were associated with a higher rate of psychosis. Psychosis was also associated with more rapid cognitive decline. Some studies found a significant association between psychosis and age, age at onset of Alzheimer's disease, and illness duration. Gender, education, and family history of dementia or psychiatric illness showed weak or inconsistent relationships with psychosis. Psychotic symptoms are common and persistent in patients with Alzheimer's disease. Improved methods have advanced the understanding of psychosis in Alzheimer's disease, although continued research, particularly longitudinal studies, may unveil biological and clinical associations that will inform treatments for these problematic psychological disturbances.

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Author and article information

Contributors

Byron Creese:

ORCID: http://orcid.org/0000-0001-6490-6037

+01392 724837 , b.creese@exeter.ac.uk

Journal

Journal ID (nlm-ta): Transl Psychiatry

Journal ID (iso-abbrev): Transl Psychiatry

Title: Translational Psychiatry

Publisher: Nature Publishing Group UK (London )

ISSN (Electronic): 2158-3188

Publication date (Electronic): 22 October 2019

Publication date PMC-release: 22 October 2019

Publication date Collection: 2019

Volume: 9

Electronic Location Identifier: 273

Affiliations

[1 ]ISNI 0000 0004 1936 8024, GRID grid.8391.3, University of Exeter Medical School, ; Exeter, UK

[2 ]Norwegian, Exeter and King’s College Consortium for Genetics of Neuropsychiatric Symptoms in Dementia, Exeter, UK

[3 ]ISNI 0000 0001 2322 6764, GRID grid.13097.3c, Social Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, , King’s College London, ; London, UK

[4 ]ISNI 0000 0004 0627 386X, GRID grid.412929.5, Research Centre of Age-Related Functional Decline and Disease, , Innlandet Hospital Trust, ; Pb 68, 2312 Ottestad, Norway

[5 ]ISNI 0000 0004 0627 3659, GRID grid.417292.b, Norwegian National Advisory Unit on Ageing and Health, , Vestfold Hospital Trust, ; Tønsberg, Norway

[6 ]ISNI 0000 0004 1936 8921, GRID grid.5510.1, NORMENT, Institute of Clinical Medicine, , University of Oslo, ; Oslo, Norway

[7 ]ISNI 0000 0004 0389 8485, GRID grid.55325.34, NORMENT, Division of Mental Health and Addiction, , Oslo University Hospital, ; Oslo, Norway

[8 ]ISNI 0000 0001 2322 6764, GRID grid.13097.3c, Department of Old Age Psychiatry, , Institute of Psychiatry, Psychology and Neuroscience, King’s College London, ; London, UK

[9 ]GRID grid.413782.b, Department of Research and Innovation, , Helse Fonna, ; Haugesund, Norway

[10 ]ISNI 0000 0004 1936 7443, GRID grid.7914.b, Department of Clinical Medicine, , University of Bergen, ; Bergen, Norway

[11 ]ISNI 0000 0004 0389 8485, GRID grid.55325.34, Department of Geriatric Medicine, , Oslo University Hospital, ; Oslo, Norway

[12 ]ISNI 0000000122595234, GRID grid.10919.30, Department of Community Medicine, , University of Tromsø, ; Tromsø, Norway

[13 ]ISNI 0000 0004 0389 8485, GRID grid.55325.34, Department of Neurology, , Oslo University Hospital, ; Oslo, Norway

[14 ]ISNI 0000 0004 1936 7443, GRID grid.7914.b, NORMENT, Department of Clinical Science, , University of Bergen, ; Bergen, Norway

[15 ]ISNI 0000 0004 0389 8485, GRID grid.55325.34, Department of Medical Genetics, , Oslo University Hospital, ; Oslo, Norway

[16 ]ISNI 0000 0004 1757 9135, GRID grid.413503.0, Complex Structure of Geriatrics, Department of Medical Sciences, , Fondazione IRCCS “Casa Sollievo della Sofferenza”, ; San Giovanni Rotondo, FG Italy

[17 ]ISNI 0000 0001 2322 6764, GRID grid.13097.3c, Department of Basic and Clinical Neuroscience, , Institute of Psychiatry, Psychology and Neuroscience, King’s College London, ; London, UK

[18 ]ISNI 0000 0004 0627 3560, GRID grid.52522.32, Geriatric Department, St. Olav Hospital, , University Hospital of Trondheim, ; Trondheim, Norway

[19 ]ISNI 0000 0001 1516 2393, GRID grid.5947.f, Department of Neuromedicine and Movement Science, , Norwegian University of Science and Technology, ; Trondheim, Norway

[20 ]ISNI 0000 0001 1516 2393, GRID grid.5947.f, Department of Mental Health, , Norwegian University of Science and Technology, ; Trondheim, Norway

[21 ]ISNI 0000 0004 0627 3042, GRID grid.461096.c, Department of Psychiatry, , Namsos Hospital, ; Namsos, Norway

[22 ]ISNI 0000 0000 9637 455X, GRID grid.411279.8, Department of Neurology, , Akershus University Hospital, ; Lørenskog, Norway

[23 ]ISNI 0000 0004 1936 8921, GRID grid.5510.1, Institute of Clinical Medicine, Campus Ahus, , University of Oslo, ; Oslo, Norway

[24 ]ISNI 0000 0004 0627 2891, GRID grid.412835.9, Centre for Age-Related Medicine, , Stavanger University Hospital, ; Stavanger, Norway

[25 ]ISNI 0000 0004 1936 8921, GRID grid.5510.1, Faculty of Medicine, , University of Oslo, ; Oslo, Norway

Author information

Byron Creese http://orcid.org/0000-0001-6490-6037

Evangelos Vassos http://orcid.org/0000-0001-6363-0438

Francesco Bettella http://orcid.org/0000-0001-7968-8642

Srdjan Djurovic http://orcid.org/0000-0002-8140-8061

Petroula Proitsi http://orcid.org/0000-0002-2553-6974

Geir Selbaek http://orcid.org/0000-0001-6511-8219

Article

Publisher ID: 592

DOI: 10.1038/s41398-019-0592-5

PMC ID: 6805870

PubMed ID: 31641104

SO-VID: a73226c0-abaa-446f-80d6-221930abbdd2

License:

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