Neurodegenerative disorders including Parkinson’s disease (PD), Huntington’s disease (HD) and the most frequent, Alzheimer’s disease (AD), represent one of the most urgent medical needs worldwide. Despite a significantly developed understanding of disease development and pathology, treatments that stop AD progression are not yet available. The recent approval of sodium oligomannate (GV-971) for AD treatment in China emphasized the potential value of natural products for the treatment of neurodegenerative disorders. Many current clinical studies include the administration of a natural compound as a single and combination treatment. The most prominent mechanisms of action are anti-inflammatory and anti-oxidative activities, thus preserving cellular survival. Here, we review current natural products that are either approved or are in testing for a treatment of neurodegeneration in AD. In addition to the most important compounds of plant origin, we also put special emphasis on compounds from algae, given their neuroprotective activity and their underlying mechanisms of neuroprotection.

Background Corticobasal syndrome is associated with cerebral protein aggregates composed of 4-repeat (~50% of cases) or mixed 3-repeat/4-repeat tau isoforms (~25% of cases) or nontauopathies (~25% of cases). Objectives The aim of this single-center study was to investigate the diagnostic value of the tau PET-ligand [18F]PI-2620 in patients with corticobasal syndrome. Methods Forty-five patients (71.5 ± 7.6 years) with corticobasal syndrome and 14 age-matched healthy controls underwent [18F]PI-2620-PET. Beta-amyloid status was determined by cerebral β-amyloid PET and/or CSF analysis. Subcortical and cortical [18F]PI-2620 binding was quantitatively and visually compared between β-amyloid-positive and -negative patients and controls. Regional [18F]PI-2620 binding was correlated with clinical and demographic data. Results Twenty-four percent (11 of 45) were β-amyloid-positive. Significantly elevated [18F]PI-2620 distribution volume ratios were observed in both β-amyloid-positive and β-amyloid-negative patients versus controls in the dorsolateral prefrontal cortex and basal ganglia. Cortical [18F]PI-2620 PET positivity was distinctly higher in β-amyloid-positive compared with β-amyloid-negative patients with pronounced involvement of the dorsolateral prefrontal cortex. Semiquantitative analysis of [18F]PI-2620 PET revealed a sensitivity of 91% for β-amyloid-positive and of 65% for β-amyloid-negative cases, which is in excellent agreement with prior clinicopathological data. Regardless of β-amyloid status, hemispheric lateralization of [18F]PI-2620 signal reflected contralateral predominance of clinical disease severity. Conclusions Our data indicate a value of [18F]PI-2620 for evaluating corticobasal syndrome, providing quantitatively and regionally distinct signals in β-amyloid-positive as well as β-amyloid-negative corticobasal syndrome. In corticobasal syndrome, [18F]PI-2620 may potentially serve for a differential diagnosis and for monitoring disease progression. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society

It is estimated that there are currently fifty million people living with dementia worldwide. An accurate and early diagnosis of dementia is important in order to initiate appropriate treatment programs as soon as possible. Common methods of neuropsychological assessment can be sensitive to external factors which may compromise accuracy. The aim of this thesis was to investigate techniques that have the potential for the detection of dementia that avoid some of the external influences. The thesis looked at measurements of (i) postural stability (ii) facial analysis and (iii) fully-immersive virtual reality in cognitively-healthy individuals. These techniques were chosen as postural stability and facial analysis change in dementia and whilst virtual reality has previously been used in dementia research, fully-immersive virtual reality measures have not been established. To see if the measurements were associated with cognitive function, participants completed a series of cognitive tests. Results indicate that all techniques explored shared a relationship with memory performance, with lower anteroposterior postural sway (F(1,22) = 17.76, p < 0.01), number of activities participated in that involve a posture element (F(2, 39) = 3.77, p < .05; Wilk's Λ = 0.84, partial η2 = 0.16), the greater the frequency of negative facial expressions (F(2, 18) = 4.49, p < .05; Wilk's Λ = 0.67, partial η2 = 0.33.), and low blink rate (t(11.02) = 2.62 p < .05) all showing better scores on memory tests. Moreover, better scores on the fullyimmersive virtual reality task predicted better scores on with short-term memory (F(1,22) = 20.20 p < 0.01), LTM (F(1,22) = 09.10 p < .01), associative learning (F(1,22) = 08.75 p < .01), and a dual–task test (F(1,22) = 04.64 p < .05). The novel findings that elements such as postural stability, participation in sports, facial expressions of emotion, blink rates, and spatial memory as assessed in fully-immersive virtual reality highlight that non-invasive techniques can provide measurements that correspond to cognitive ability. This may hold implications for dementia diagnoses. Future research should assess whether these relationships can also be found in an older adult population. If this relationship is found in older adults, it could justify further research into how these techniques could be applied in a clinical context.

Syftet med studien var att undersöka sambandet mellan Alzheimers sjukdom (AS) och parodontit. Metoden som användes var en kvantitativ allmän litteraturstudie där sökningen av vetenskapliga artiklar gjordes i två medicinska databaser PubMed och Cinahl. Litteraturstudiens resultat sammanställdes utifrån sju vetenskapliga artiklar. Resultatet visade att i sex av sju sammanställda artiklar fanns det ett signifikant samband mellan AS och parodontit. Slutsatsen är att litteraturstudien visade ett klart samband mellan Alzheimers sjukdom (AS) och parodontit trotts olika definitioner på AS och parodontit. / The purpose of the study was to investigate the association between Alzheimer's disease (AS) and periodontitis. The method used was a quantitative general literature study where the search for scientific articles was done in two medical databases PubMed and Cinahl. The results of the literature study were compiled on the basis of seven scientific articles. The results showed that in six of the seven compiled articles, there was a significant association between AS and periodontitis. The conclusion is that the literature study showed a clear association between Alzheimer's disease (AS) and periodontitis despite different definitions of AS and periodontitis.

No / A neurological disorder is any disorder or abnormality in the nervous system. Among different neurological disorders, Alzheimer’s disease (AD) is recognized as the sixth leading cause of death globally. Considerable research has been conducted to find pioneer treatments for this devastating disorder among which cell therapy has attracted remarkable attentions over the last decade. Up to now, targeted differentiation into specific desirable cell types has remained a major obstacle to clinical application of cell therapy. Also, potential risks including uncontrolled growth of stem cells could be disastrous. In our novel protocol, we used basal forebrain cholinergic progenitor cells (BFCN) derived from human chorion-derived mesenchymal stem cells (hC-MSCs) which made it possible to obtain high-quality population of cholinergic neurons and in vivo in much shorter time period than previous established methods. Remarkably, the transplanted progenitors fully differentiated to cholinergic neurons which in turn integrated in higher cortical networks of host brains, resulting in significant improvement in cognitive assessments. This method may have profound implications in cell therapies for any other neurodegenerative disorders. / This work was carried outwithin the framework of a collaborative project (Project Grant No. 94-02-30-25922) by the School of Medicine, Iran University of Medical Sciences, (Project Grant No. REP209) council for stem cell sciences and technologies (Presidency of the Islamic Republic of Iran, vice-presidency for science and technology), and Iran National Science Foundation (INSF).

Yes / Group I metabotropic glutamate receptor (mGluR) dependent long-term depression (LTD) is a major form of synaptic plasticity underlying learning and memory. The molecular mechanisms involved in mGluR-LTD have been investigated intensively for the last two decades. In this 60th anniversary special issue article, we review the recent advances in determining the mechanisms that regulate the induction, transduction and expression of mGluR-LTD in the hippocampus, with a focus on the mitogen-activated protein kinase (MAPK) pathways. In particular we discuss the requirement of p38 MAPK and extracellular signal-regulated kinase 1/2 (ERK 1/2) activation. The recent advances in understanding the signaling cascades regulating mGluR-LTD are then related to the cognitive impairments observed in neurological disorders, such as fragile X syndrome and Alzheimer's disease.

Resting state (rs)fMRI allows measurement of brain functional connectivity and has identified default mode (DMN) and task positive (TPN) network disruptions as promising biomarkers for Alzheimer’s disease (AD). Quasi-periodic patterns (QPPs) of neural activity describe recurring spatiotemporal patterns that display DMN with TPN anti-correlation. We reasoned that QPPs could provide new insights into AD network dysfunction and improve disease diagnosis. We therefore used rsfMRI to investigate QPPs in old TG2576 mice, a model of amyloidosis, and age-matched controls. Multiple QPPs were determined and compared across groups. Using linear regression, we removed their contribution from the functional scans and assessed how they reflected functional connectivity. Lastly, we used elastic net regression to determine if QPPs improved disease classification. We present three prominent findings: (1) Compared to controls, TG2576 mice were marked by opposing neural dynamics in which DMN areas were anti-correlated and displayed diminished anti-correlation with the TPN. (2) QPPs reflected lowered DMN functional connectivity in TG2576 mice and revealed significantly decreased DMN-TPN anti-correlations. (3) QPP-derived measures significantly improved classification compared to conventional functional connectivity measures. Altogether, our findings provide insight into the neural dynamics of aberrant network connectivity in AD and indicate that QPPs might serve as a translational diagnostic tool.

Introduction: One characteristic of Alzheimer’s disease is the formation of amyloid-b plaques, which are typically linked to neuroinflammation and surrounded by inflammatory cells such as microglia and infiltrating immune cells. Methods: Here, we describe nonneurogenic doublecortin (DCX) positive cells, DCX being generally used as a marker for young immature neurons, at sites of amyloid-b plaques in various transgenic amyloid mouse models and in human brains with plaque pathology. Results: The plaque-associated DCX1 cells were not of neurogenic identity, instead most of them showed coexpression with markers for microglia (ionized calcium-binding adapter molecule 1) and for phagocytosis (CD68 and TREM2). Another subpopulation of plaque-associated DCX1 cells was negative for ionized calcium-binding adapter molecule 1 but was highly positive for the panleukocyte marker CD45. These hematopoietic cells were identified as CD3-and CD8-positive and CD4-negative T-cells. Discussion: Peculiarly, the DCX1/ionized calcium-binding adapter molecule 11 microglia and DCX1/CD81 T-cells were closely attached, suggesting that these two cell types are tightly interacting and that this interaction might shape plaque pathology.

Alzheimer’s sjukdom är en neurodegenerativ sjukdom som leder till demens. Den kan börja tyst i de tidiga stadierna och fortsätta under åren till en allvarlig och obotlig fas. Språkstörningar uppstår ofta som ett av de tidiga symptomen och kan till slut leda till fullständig mutism i de avancerade stadierna av sjukdomen. Därför är tal- och språkbaserad analys en lovande och icke-invasiv metod för att upptäcka Alzheimer’s sjukdom i dess tidiga stadier. Vårt mål är att använda maskininlärning för att jämföra informationmängden hos språkliga representationer i stora språkmodeller och förtränade akustiska representationer. Såvitt vi vet är detta första gången som GPT-3 och wav2vec2.0 har använts tillsammans för klassificering av Alzheimer’s sjukdom. Dessutom utnyttjade vi för första gången en kombination av två stora språkmodeller, GPT-3 och BERT, för denna specifika uppgift. Genom att utvärdera vår metod på två datamängder på engelska och svenska kan vi också belysa språkskillnaderna mellan dessa två språk. / Alzheimer’s disease is a neurodegenerative disease that leads to dementia. It can begin silently in the early stages and progresses over the years to a severe and incurable stage. Language impairment often emerges as one of the early symptoms and can eventually progress to complete mutism in advanced stages of the disease. As a result, speech processing is a promising and non-invasive approach for detecting Alzheimer’s disease in its early stages. Our objective is to compare the informativeness levels of linguistic embedding derived from large language models and pre-trained acoustic embedding extracted using wav2vec2.0, in a machine learning-based approach. To the best of our knowledge, this is the first time that fusing GPT-3 text embedding and wav2vec2.0 acoustic embedding has been explored for Alzheimer’s disease classification. In addition, we utilized a combination of two large language models, GPT-3 and BERT, for the first time on this specific task. By evaluating our method on two datasets in English and Swedish, we can also highlight the language differences between these two languages.

Inspection of the published research shows that sex differences in cognition in the general population have been widely cited with the direction of the advantage depending on the domain being examined. The most prevalent claims are that men are better than women at visuospatial and mathematical tasks whereas women have superior verbal skills and perform better than men on tasks assessing episodic memory. There is also some evidence that women are more accurate than men at identifying facial expressions of emotion. A more in-depth examination of the literature, however, reveals that evidence of such differences is not as conclusive as would at first appear. Not only is the direction and magnitude of sex differences dependent on the cognitive domain but also on the individual tasks. Some visuospatial tasks show no difference (e.g. figure copying) whist men have been shown to be better than women at confrontation naming (a verbal task). Alzheimer’s disease is a heterogeneous illness that affects the elderly. It manifests with deficits in cognitive abilities and behavioural difficulties. It has been suggested that some of the behavioural issues may arise from difficulties with recognising facial emotion expressions. There have been claims that AD affects men and women differently: women have been reported as being more likely to develop AD and showing a greater dementia severity than men with equivalent neuropathology. Despite this, research into sex differences in cognition in AD is scarce, and conflicting. This research was concerned with the effect of sex on the cognitive abilities of AD patients. The relative performance of men and women with AD was compared to that of elderly controls. The study focused on the verbal, visuospatial and facial emotion recognition domains. Data was collected and analysed from 70 AD patients (33 male, 37 female), 62 elderly controls (31 male, 31 female) and 80 young adults (40 male, 40 female). Results showed those with AD demonstrate cognitive deficits compared to elderly controls in verbal and visuospatial tasks but not in the recognition of facial emotions. There were no significant sex differences in either the young adults or the healthy elderly controls but sex differences favouring men emerged in the AD group for figure copying and recall and for confrontation naming. Given that elderly men and women perform equivalently for these tasks, this represents a deterioration in women’s cognitive abilities, relative to men’s. Further evidence of such an adverse effect of AD was apparent in other tasks, too: for most verbal and visuospatial tasks, either an effect favouring women in the elderly is reversed or a male advantage increases in magnitude. There is no evidence of sex differences in facial emotion recognition for any group. This suggests that the lack of published findings reporting on sex differences in this domain is due to the difficulty in getting null findings accepted for publication. The scarcity of research examining sex differences in other domains is also likely to be due to this bias.