TY - JOUR A1 - Haberstumpf, Sophia A1 - Forster, André A1 - Leinweber, Jonas A1 - Rauskolb, Stefanie A1 - Hewig, Johannes A1 - Sendtner, Michael A1 - Lauer, Martin A1 - Polak, Thomas A1 - Deckert, Jürgen A1 - Herrmann, Martin J. T1 - Measurement invariance testing of longitudinal neuropsychiatric test scores distinguishes pathological from normative cognitive decline and highlights its potential in early detection research JF - Journal of Neuropsychology N2 - Objective Alzheimer’s disease (AD) is a growing challenge worldwide, which is why the search for early-onset predictors must be focused as soon as possible. Longitudinal studies that investigate courses of neuropsychological and other variables screen for such predictors correlated to mild cognitive impairment (MCI). However, one often neglected issue in analyses of such studies is measurement invariance (MI), which is often assumed but not tested for. This study uses the absence of MI (non-MI) and latent factor scores instead of composite variables to assess properties of cognitive domains, compensation mechanisms, and their predictability to establish a method for a more comprehensive understanding of pathological cognitive decline. Methods An exploratory factor analysis (EFA) and a set of increasingly restricted confirmatory factor analyses (CFAs) were conducted to find latent factors, compared them with the composite approach, and to test for longitudinal (partial-)MI in a neuropsychiatric test battery, consisting of 14 test variables. A total of 330 elderly (mean age: 73.78 ± 1.52 years at baseline) were analyzed two times (3 years apart). Results EFA revealed a four-factor model representing declarative memory, attention, working memory, and visual–spatial processing. Based on CFA, an accurate model was estimated across both measurement timepoints. Partial non-MI was found for parameters such as loadings, test- and latent factor intercepts as well as latent factor variances. The latent factor approach was preferable to the composite approach. Conclusion The overall assessment of non-MI latent factors may pose a possible target for this field of research. Hence, the non-MI of variances indicated variables that are especially suited for the prediction of pathological cognitive decline, while non-MI of intercepts indicated general aging-related decline. As a result, the sole assessment of MI may help distinguish pathological from normative aging processes and additionally may reveal compensatory neuropsychological mechanisms. KW - Alzheimer’s disease KW - early-onset predictors KW - mild cognitive impairment Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-318932 VL - 16 IS - 2 SP - 324 EP - 352 ER - TY - JOUR A1 - Riederer, Peter A1 - ter Meulen, Volker T1 - Coronaviruses: a challenge of today and a call for extended human postmortem brain analyses JF - Journal of Neural Transmission N2 - While there is abounding literature on virus-induced pathology in general and coronavirus in particular, recent evidence accumulates showing distinct and deleterious brain affection. As the respiratory tract connects to the brain without protection of the blood–brain barrier, SARS-CoV-2 might in the early invasive phase attack the cardiorespiratory centres located in the medulla/pons areas, giving rise to disturbances of respiration and cardiac problems. Furthermore, brainstem regions are at risk to lose their functional integrity. Therefore, long-term neurological as well as psychiatric symptomatology and eventual respective disorders cannot be excluded as evidenced from influenza-A triggered post-encephalitic Parkinsonism and HIV-1 triggered AIDS–dementia complex. From the available evidences for coronavirus-induced brain pathology, this review concludes a number of unmet needs for further research strategies like human postmortem brain analyses. SARS-CoV-2 mirroring experimental animal brain studies, characterization of time-dependent and region-dependent spreading behaviours of coronaviruses, enlightening of pathological mechanisms after coronavirus infection using long-term animal models and clinical observations of patients having had COVID-19 infection are calling to develop both protective strategies and drug discoveries to avoid early and late coronavirus-induced functional brain disturbances, symptoms and eventually disorders. To fight SARS-CoV-2, it is an urgent need to enforce clinical, molecular biological, neurochemical and genetic research including brain-related studies on a worldwide harmonized basis. KW - coronavirus KW - COVID-19 KW - SARS-CoV-2 brain disorders KW - cardiorespiratory centre KW - brain pathology KW - neurological symptoms/disorders KW - brain stem KW - Parkinson’s disease KW - Parkinsonism KW - Alzheimer’s disease KW - multiple sclerosis KW - movement disorders KW - neuroinvasion KW - therapy KW - neuroprotection KW - depression KW - cognitive dysfunction KW - brain bank KW - postmortem studies Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-314637 SN - 0300-9564 SN - 1435-1463 VL - 127 IS - 9 ER - TY - JOUR A1 - Sun, Ping A1 - Ortega, Gabriela A1 - Tan, Yan A1 - Hua, Qian A1 - Riederer, Peter F. A1 - Deckert, Jürgen A1 - Schmitt-Böhrer, Angelika G. T1 - Streptozotocin impairs proliferation and differentiation of adult hippocampal neural stem cells in vitro-correlation with alterations in the expression of proteins associated with the insulin system JF - Frontiers in Aging Neuroscience N2 - Rats intracerebroventricularily (icv) treated with streptozotocin (STZ), shown to generate an insulin resistant brain state, were used as an animal model for the sporadic form of Alzheimer's disease (sAD). Previously, we showed in an in vivo study that 3 months after STZ icv treatment hippocampal adult neurogenesis (AN) is impaired. In the present study, we examined the effects of STZ on isolated adult hippocampal neural stem cells (NSCs) using an in vitro approach. We revealed that 2.5 mM STZ inhibits the proliferation of NSCs as indicated by reduced number and size of neurospheres as well as by less BrdU-immunoreactive NSCs. Double immunofluorescence stainings of NSCs already being triggered to start with their differentiation showed that STZ primarily impairs the generation of new neurons, but not of astrocytes. For revealing mechanisms possibly involved in mediating STZ effects we analyzed expression levels of insulin/glucose system-related molecules such as the glucose transporter (GLUT) 1 and 3, the insulin receptor (IR) and the insulin-like growth factor (IGF) 1 receptor. Applying quantitative Real time-PCR (qRT-PCR) and immunofluorescence stainings we showed that STZ exerts its strongest effects on GLUT3 expression, as GLUT3 mRNA levels were found to be reduced in NSCs, and less GLUT3-immunoreactive NSCs as well as differentiating cells were detected after STZ treatment. These findings suggest that cultured NSCs are a good model for developing new strategies to treat nerve cell loss in AD and other degenerative disorders. KW - Alzheimer’s disease KW - streptozotocin KW - proliferation KW - neural stem cells KW - insulin-like growth factor 1 receptor KW - insulin receptor KW - glucose transporter KW - differentiation Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-176741 VL - 10 IS - 145 ER - TY - JOUR A1 - Hibar, Derrek P. A1 - Adams, Hieab H.H. A1 - Jahanshad, Neda A1 - Chauhan, Ganesh A1 - Stein, Jason L A1 - Hofer, Edith A1 - Renteria, Miguel E. A1 - Bis, Joshua C. A1 - Arias-Vasquez, Alejandro A1 - Ikram, M. Kamran A1 - Desrivières, Sylvane A1 - Vernooij, Meike W. A1 - Abramovic, Lucija A1 - Alhusaini, Saud A1 - Amin, Najaf A1 - Andersson, Micael A1 - Arfanakis, Konstantinos A1 - Aribisala, Benjamin S. A1 - Armstrong, Nicola J. A1 - Athanasiu, Lavinia A1 - Axelsson, Tomas A1 - Beecham, Ashley H. A1 - Beiser, Alexa A1 - Bernard, Manon A1 - Blanton, Susan H. A1 - Bohlken, Marc M. A1 - Boks, Marco P. A1 - Bralten, Janita A1 - Brickman, Adam M. A1 - Carmichael, Owen T1 - Novel genetic loci associated with hippocampal volume JF - Nature Communications N2 - The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer’s disease (r\(_g\)=−0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness. KW - brain KW - hippocampal formation KW - neuropsychiatric disorders KW - Alzheimer’s disease KW - genetic loci KW - hippocampal volume Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-182115 VL - 8 ER -