Clinicopathological investigation of the background of cognitive decline in elderly schizophrenia

2020 ◽  
pp. 1-7
Author(s):  
Ayako Miwa ◽  
Mitsuaki Hirano ◽  
Youta Torii ◽  
Hirotaka Sekiguchi ◽  
Chikako Habuchi ◽  
...  
Keyword(s):  
Cognitive Decline ◽  
Clinical Symptoms ◽  
Dementia Syndrome ◽  
Increased Risk ◽  
Neuropathological Diagnosis ◽  
Schizophrenic Patients ◽  
Β Amyloid ◽  
The Brain ◽  
Normal Controls

Abstract Objective: We have often observed dementia symptoms or severe neurocognitive decline in the long-term course of schizophrenia. While there are epidemiological reports that patients with schizophrenia are at an increased risk of developing dementia, there are also neuropathological reports that the prevalence of Alzheimer’s disease (AD) in schizophrenia is similar to that in normal controls. It is difficult to distinguish, based solely on the clinical symptoms, whether the remarkable dementia symptoms and cognitive decline seen in elderly schizophrenia are due to the course of the disease itself or a concomitant neurocognitive disease. Neuropathological observation is needed for discrimination. Methods: We conducted a neuropathological search on three cases of schizophrenia that developed cognitive decline or dementia symptoms after a long illness course of schizophrenia. The clinical symptoms of total disease course were confirmed retrospectively in the medical record. We have evaluated neuropathological diagnosis based on not only Hematoxylin–Eosin and Klüver–Barrera staining specimens but also immunohistochemical stained specimens including tau, β-amyloid, pTDP-43 and α-synuclein protein throughout clinicopathological conference with multiple neuropathologists and psychiatrists. Results: The three cases showed no significant pathological findings or preclinical degenerative findings, and poor findings consistent with symptoms of dementia were noted. Conclusion: Although the biological background of dementia symptoms in elderly schizophrenic patients is still unclear, regarding the brain capacity/cognitive reserve ability, preclinical neurodegeneration changes in combination with certain brain vulnerabilities due to schizophrenia itself are thought to induce dementia syndrome and severe cognitive decline.

scholarly journals White matter hyperintensities are common in midlife and already associated with cognitive decline

2019 ◽  
Vol 1 (1) ◽  
Author(s):  
Tracy d’Arbeloff ◽  
Maxwell L Elliott ◽  
Annchen R Knodt ◽  
Tracy R Melzer ◽  
Ross Keenan ◽  
...  
Keyword(s):  
White Matter ◽  
Cognitive Decline ◽  
White Matter Hyperintensities ◽  
Clinical Symptoms ◽  
White Matter Hyperintensity ◽  
Dementia Prevention ◽  
Increased Risk ◽  
Weighted Magnetic Resonance Imaging ◽  
Intervention Trials ◽  
The Brain

Abstract White matter hyperintensities proliferate as the brain ages and are associated with increased risk for cognitive decline as well as Alzheimer’s disease and related dementias. As such, white matter hyperintensities have been targeted as a surrogate biomarker in intervention trials with older adults. However, it is unclear at what stage of aging white matter hyperintensities begin to relate to cognition and if they may be a viable target for early prevention. In the Dunedin Study, a population-representative cohort followed since birth, we measured white matter hyperintensities in 843 45-year-old participants using T2-weighted magnetic resonance imaging and we assessed cognitive decline from childhood to midlife. We found that white matter hyperintensities were common at age 45 and that white matter hyperintensity volume was modestly associated with both lower childhood (ß = −0.08, P = 0.013) and adult IQ (ß=−0.15, P < 0.001). Moreover, white matter hyperintensity volume was associated with greater cognitive decline from childhood to midlife (ß=−0.09, P < 0.001). Our results demonstrate that a link between white matter hyperintensities and early signs of cognitive decline is detectable decades before clinical symptoms of dementia emerge. Thus, white matter hyperintensities may be a useful surrogate biomarker for identifying individuals in midlife at risk for future accelerated cognitive decline and selecting participants for dementia prevention trials.

scholarly journals White matter hyperintensities are common in midlife and already associated with cognitive decline

2019 ◽  
Author(s):  
Tracy d’Arbeloff ◽  
Maxwell L. Elliott ◽  
Annchen R. Knodt ◽  
Tracy R. Melzer ◽  
Ross Keenan ◽  
...  
Keyword(s):  
White Matter ◽  
Cognitive Decline ◽  
White Matter Hyperintensities ◽  
Clinical Symptoms ◽  
Early Prevention ◽  
Dementia Prevention ◽  
Increased Risk ◽  
Prevention Trials ◽  
Intervention Trials ◽  
The Brain

AbstractWhite matter hyperintensities (WMHs) proliferate as the brain ages and are associated with increased risk for cognitive decline as well as Alzheimer’s disease and related dementias. As such, WMHs have been targeted as a surrogate biomarker in intervention trials with older adults. However, it is unclear at what stage of aging WMHs begin to relate to cognition and if they may be a viable target for early prevention. In a population-representative birth cohort of 843 45-year-olds we measured WMHs using T2-weighted MRI, and we assessed cognitive decline from childhood to midlife. We found that WMHs were common at age 45 and that WMH volume was modestly associated with both lower childhood (ß=-0.08, p=0.013) and adult IQ (ß=-0.15, p<0.001). Moreover, WMH volume was associated with greater cognitive decline from childhood to midlife (ß=-0.09, p<0.001). Our results demonstrate that a link between WMHs and early signs of cognitive decline is detectable decades before clinical symptoms of dementia emerge. Thus, WMHs may be a useful surrogate biomarker for identifying individuals in midlife at risk for future accelerated cognitive decline and selecting participants for dementia prevention trials.

scholarly journals Can Anti–β-amyloid Monoclonal Antibodies Work in Autosomal Dominant Alzheimer Disease?

2020 ◽  
Vol 7 (1) ◽  
pp. e535
Author(s):  
Bruno P. Imbimbo ◽  
Ugo Lucca ◽  
Mark Watling
Keyword(s):  
Alzheimer Disease ◽  
Cognitive Decline ◽  
Autosomal Dominant ◽  
Amyloid Β ◽  
Functional Deficits ◽  
Β Amyloid ◽  
Set Up ◽  
The Brain ◽  
Dominant Theory

The dominant theory of Alzheimer disease (AD) has been that amyloid-β (Aβ) accumulation in the brain is the initial cause of the degeneration leading to cognitive and functional deficits. Autosomal dominant Alzheimer disease (ADAD), in which pathologic mutations of the amyloid precursor protein (APP) or presenilins (PSENs) genes are known to cause abnormalities of Aβ metabolism, should thus offer perhaps the best opportunity to test anti-Aβ drugs. Two long-term preventive studies (Dominantly Inherited Alzheimer Network Trials Unit Adaptive Prevention Trial [DIAN-TU-APT] and Alzheimer Preventive Initiative–ADAD) were set up to evaluate the efficacy of monoclonal anti-Aβ antibodies (solanezumab, gantenerumab, and crenezumab) in carriers of ADAD, but the results of the DIAN-TU-APT study have shown that neither solanezumab nor gantenerumab slowed cognitive decline in 144 subjects with ADAD followed for 4 years, despite one of the drugs (gantenerumab) significantly affected biomarkers relevant to their intended mechanism of action. Surprisingly, solanezumab significantly accelerated cognitive decline of both asymptomatic and symptomatic subjects. These failures further undermine the Aβ hypothesis and could support the suggestion that ADAD is triggered by accumulation of other APP metabolites, rather than Aβ.

Epidemiological Evidence that Maternal Influenza Contributes to the Aetiology of Schizophrenia

1993 ◽  
Vol 163 (4) ◽  
pp. 522-534 ◽  
Author(s):  
W. Adams ◽  
R. E. Kendell ◽  
E. H. Hare ◽  
P. Munk-Jørgensen
Keyword(s):  
Data Sets ◽  
Time Lags ◽  
Epidemiological Evidence ◽  
Intrauterine Development ◽  
Increased Risk ◽  
Schizophrenic Patients ◽  
The Relationship ◽  
Monthly Incidence ◽  
Maternal Influenza

The epidemiological evidence that the offspring of women exposed to influenza in pregnancy are at increased risk of schizophrenia is conflicting. In an attempt to clarify the issue we explored the relationship between the monthly incidence of influenza (and measles) in the general population and the distribution of birth dates of three large series of schizophrenic patients - 16 960 Scottish patients born in 1932–60; 22 021 English patients born in 1921–60; and 18 723 Danish patients born in 1911–65. Exposure to the 1957 epidemic of A2 influenza in midpregnancy was associated with an increased incidence of schizophrenia, at least in females, in all three data sets. We also confirmed the previous report of a statistically significant long-term relationship between patients' birth dates and outbreaks of influenza in the English series, with time lags of - 2 and - 3 months (the sixth and seventh months of pregnancy). Despite several other negative studies by ourselves and others we conclude that these relationships are probably both genuine and causal; and that maternal influenza during the middle third of intrauterine development, or something closely associated with it, is implicated in the aetiology of some cases of schizophrenia.

scholarly journals Brain β-Amyloid and Atrophy in Individuals at Increased Risk of Cognitive Decline

2018 ◽  
Vol 40 (1) ◽  
pp. 80-85 ◽  
Author(s):  
I.K. Martikainen ◽  
N. Kemppainen ◽  
J. Johansson ◽  
J. Teuho ◽  
S. Helin ◽  
...  
Keyword(s):  
Cognitive Decline ◽  
Increased Risk ◽  
Β Amyloid

scholarly journals The Causes and Long-Term Consequences of Viral Encephalitis

2021 ◽  
Vol 15 ◽  
Author(s):  
Karen Bohmwald ◽  
Catalina A. Andrade ◽  
Nicolás M. S. Gálvez ◽  
Valentina P. Mora ◽  
José T. Muñoz ◽  
...  
Keyword(s):  
Viral Encephalitis ◽  
Viral Infections ◽  
Immune Cell ◽  
Clinical Symptoms ◽  
Brain Inflammation ◽  
High Morbidity ◽  
Stiff Neck ◽  
The Impact ◽  
The Brain

Reports regarding brain inflammation, known as encephalitis, have shown an increasing frequency during the past years. Encephalitis is a relevant concern to public health due to its high morbidity and mortality. Infectious or autoimmune diseases are the most common cause of encephalitis. The clinical symptoms of this pathology can vary depending on the brain zone affected, with mild ones such as fever, headache, confusion, and stiff neck, or severe ones, such as seizures, weakness, hallucinations, and coma, among others. Encephalitis can affect individuals of all ages, but it is frequently observed in pediatric and elderly populations, and the most common causes are viral infections. Several viral agents have been described to induce encephalitis, such as arboviruses, rhabdoviruses, enteroviruses, herpesviruses, retroviruses, orthomyxoviruses, orthopneumovirus, and coronaviruses, among others. Once a neurotropic virus reaches the brain parenchyma, the resident cells such as neurons, astrocytes, and microglia, can be infected, promoting the secretion of pro-inflammatory molecules and the subsequent immune cell infiltration that leads to brain damage. After resolving the viral infection, the local immune response can remain active, contributing to long-term neuropsychiatric disorders, neurocognitive impairment, and degenerative diseases. In this article, we will discuss how viruses can reach the brain, the impact of viral encephalitis on brain function, and we will focus especially on the neurocognitive sequelae reported even after viral clearance.

scholarly journals Expert consensus and evidence-based recommendations for the assessment of flow-mediated dilation in humans

2019 ◽  
Vol 40 (30) ◽  
pp. 2534-2547 ◽  
Author(s):  
Dick H J Thijssen ◽  
Rosa Maria Bruno ◽  
Anke C C M van Mil ◽  
Sophie M Holder ◽  
Francesco Faita ◽  
...  
Keyword(s):  
Endothelial Function ◽  
Clinical Symptoms ◽  
Clinical Manifestations ◽  
Arterial Disease ◽  
Expert Consensus ◽  
Flow Mediated Dilation ◽  
Pharmacological Interventions ◽  
Increased Risk ◽  
Long Term Impact

Abstract Endothelial dysfunction is involved in the development of atherosclerosis, which precedes asymptomatic structural vascular alterations as well as clinical manifestations of cardiovascular disease (CVD). Endothelial function can be assessed non-invasively using the flow-mediated dilation (FMD) technique. Flow-mediated dilation represents an endothelium-dependent, largely nitric oxide (NO)-mediated dilatation of conduit arteries in response to an imposed increase in blood flow and shear stress. Flow-mediated dilation is affected by cardiovascular (CV) risk factors, relates to coronary artery endothelial function, and independently predicts CVD outcome. Accordingly, FMD is a tool for examining the pathophysiology of CVD and possibly identifying subjects at increased risk for future CV events. Moreover, it has merit in examining the acute and long-term impact of physiological and pharmacological interventions in humans. Despite concerns about its reproducibility, the available evidence shows that highly reliable FMD measurements can be achieved when specialized laboratories follow standardized protocols. For this purpose, updated expert consensus guidelines for the performance of FMD are presented, which are based on critical appraisal of novel technical approaches, development of analysis software, and studies exploring the physiological principles underlying the technique. Uniformity in FMD performance will (i) improve comparability between studies, (ii) contribute to construction of reference values, and (iii) offer an easy accessible and early marker of atherosclerosis that could complement clinical symptoms of structural arterial disease and facilitate early diagnosis and prediction of CVD outcomes.

Cognitive decline in schizophrenic patients and normal control followed long term

1995 ◽  
Vol 15 (1-2) ◽  
pp. 130-131
Author(s):  
M.N. Nilsson ◽  
W.E. Bunney ◽  
S.G. Potkin ◽  
C. Sandman
Keyword(s):  
Cognitive Decline ◽  
Normal Control ◽  
Schizophrenic Patients

Is benzodiazepine use a risk factor for cognitive decline and dementia? A literature review of epidemiological studies

2004 ◽  
Vol 35 (3) ◽  
pp. 307-315 ◽  
Author(s):  
HELENE VERDOUX ◽  
RAJAA LAGNAOUI ◽  
BERNARD BEGAUD
Keyword(s):  
General Population ◽  
Cognitive Decline ◽  
Epidemiological Studies ◽  
Cognitive Outcome ◽  
Public Health Issue ◽  
Hand Search ◽  
Increased Risk ◽  
Benzodiazepine Use

Background. A major public health issue is to determine whether long-term benzodiazepine use may induce cognitive deficits persisting after withdrawal. The aim of the present review was to examine findings from prospective studies carried out in general population samples exploring whether exposure to benzodiazepines is associated with an increased risk of incident cognitive decline.Method. Using a MEDLINE search and a hand-search of related references in selected papers, we retrieved original studies published in peer-reviewed journals that explored in general population samples the association between benzodiazepine exposure and change in cognitive performance between baseline and follow-up assessment.Results. Six papers met the inclusion criteria. Two studies reported a lower risk of cognitive decline in former or ever users, two found no association whatever the category of user, and three found an increased risk of cognitive decline in benzodiazepine users.Conclusions. The discrepant findings obtained by studies examining the link between benzodiazepine exposure and risk of cognitive decline may be due to methodological differences, especially regarding the definitions of exposure and cognitive outcome. As a large proportion of subjects are exposed to benzodiazepines, a small increase in the risk of cognitive decline may have marked deleterious consequences for the health of the general population. This issue needs to be explored further by pharmaco-epidemiological studies.

scholarly journals Chronic administration of a positive allosteric modulator at the α5-GABAA receptor reverses age-related dendritic shrinkage

2020 ◽  
Author(s):  
Thomas D. Prevot ◽  
Akiko Sumitomo ◽  
Toshifumi Tomoda ◽  
Daniel E. Knutson ◽  
Guanguan Li ◽  
...  
Keyword(s):  
Life Expectancy ◽  
Cognitive Decline ◽  
Neuronal Morphology ◽  
Aging Brain ◽  
Primary Neuronal Culture ◽  
Efficient Treatment ◽  
Gaba A ◽  
Age Related ◽  
Β Amyloid ◽  
The Brain

ABSTRACTOver the last 15 years, worldwide life expectancy increased by 5 years jumping from 66 years to 71 years. With progress in science, medicine, and care we tend to live longer. Such extended life expectancy is still associated with age-related changes, including in the brain. The aging brain goes through various changes that can be called morphomolecular senescence. Overall, the brain volume changes, neuronal activity is modified and plasticity of the cells diminishes, sometimes leading to neuronal atrophy and death. Altogether, these changes contribute to the emergence of cognitive decline that still does not have an efficient treatment available. Many studies in the context of cognitive decline focused on pathological aging, targeting β-amyloid in Alzheimer’s disease, for example. However, β-amyloid plaques are also present in healthy adults and treatments targeting plaques have failed to improve cognitive functions. In order to improve the quality of life of aging population, it is crucial to focus on the development of novel therapies targeting different systems altered during aging, such as the GABAergic system. In previous studies, it has been shown that positive allosteric modulators (PAM) acting at the α5-containing GABA-A receptors improve cognitive performances, and that these α5-GABA-A receptors are implicated in dendritic growth of pyramidal neurons. Here, we hypothesized that targeting the α5-GABA-A receptors could contribute to the reduction of cognitive decline, directly through activity of the receptors, and indirectly by increasing neuronal morphology. Using primary neuronal culture and chronic treatment in mice, we demonstrated that an α5-PAM increased dendritic length, spine count and spine density in brain regions involved in cognitive processes (prefrontal cortex and hippocampus). We also confirmed the procognitive efficacy of the α5-PAM and showed that the washout period diminishes the precognitive effects without altering the effect on neuronal morphology. Future studies will be needed to investigate what downstream mechanisms responsible for the neurotrophic effect of the α5-PAM.

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