Search

Brain derived neutrophic factor (BDNF) is a protein and a member of the neurotrophin family of growth factors, supports the survival of existing neurons and encourages the growth and differentiation of new neurons and synapses. The BDNF gene Val66Met polymorphism (rs6265/G196A) is responsible for BDNF synthesis that impact BDNF function that includes memory and cognition. This study investigated whether the BDNF gene Val66Met polymorphism (rs6265/G196A) is associated with cognitive function changes in both Alzheimer disease (AD) patients and elderly participants. In addition the impact of SSRI use on cognition improvement will be assessed. Healthy young, middle ages (25-59 years old) and elderly (more than 60 years old) participants (140) as well as 40 AD patients of whom are both of Saudi Arabian origin were recruited. The genotyping for the association study was performed by real-time PCR using Taqman chemistry in the ABI Prism 7900HT Sequence Detection System. Both Mini-Mental Status Examination (MMSE) and Clinical Dementia Rating (CDR) were used to assess cognitive function of healthy and AD participants, respectively. The findings showed that the BDNF Val66Met genotype distributions and allele frequencies have significant association with cognitive performance in both elderly control group and AD patients. The main findings showed that carriers of GG homozygotes (Val/Val) have superior cognitive performance among AD patients and elderly control subjects. In addition the use of SSRIs in 13 AD patients and 17 elderly participants positively improved cognitive function in elderly (p>0.001) but not in AD patients (p=0.1).

Oxidative stress (OS) is a common toxic feature in various neurodegenerative diseases. Therefore, reducing OS could provide a potential approach to achieve neuroprotection. Prolyl oligopeptidase (PREP) is a serine protease that is linked to neurodegeneration, as endogenous PREP inhibits autophagy and induces the accumulation of detrimental protein aggregates. As such, inhibition of PREP by a small-molecular inhibitor has provided neuroprotection in preclinical models of neurodegenerative diseases. In addition, PREP inhibition has been shown to reduce production of reactive oxygen species (ROS) and the absence of PREP blocks stress-induced ROS production. However, the mechanism behind PREP-related ROS regulation is not known. As we recently discovered PREP's physiological role as a protein phosphatase 2A (PP2A) regulator, we wanted to characterize PREP inhibition as an approach to reduce OS. We studied the impact of a PREP inhibitor, KYP-2047, on hydrogen peroxide and ferrous chloride induced ROS production and on cellular antioxidant response in HEK-293 and SHSY5Y cells. In addition, we used HEK-293 and SH-SY5Y PREP knock-out cells to validate the role of PREP on stress-induced ROS production. We were able to show that absence of PREP almost entirely blocks the stressinduced ROS production in both cell lines. Reduced ROS production and smaller antioxidant response was also seen in both cell lines after PREP inhibition by 10 mu M KYP-2047. Our results also revealed that the OS reducing mechanism of PREP inhibition is related to reduced activation of ROS producing NADPH oxidase through enhanced PP2A activation. In conclusion, our results suggest that PREP inhibition could also provide neuroprotection by reducing OS, thus broadening the scope of its beneficial effects on neurodegeneration.

Despite the fact that the diagnosis of dementia is mainly based on clinical criteria, the role of neuroimaging is still expanding. Among other imaging techniques, magnetic resonance imaging (MRI) plays a core role in assisting with the differentiation between various dementia syndromes and excluding other underlying pathologies that cause dementia, such as brain tumors and subdural hemorrhages. This article gives an overview of the standard MRI protocol and of structural radiological reporting systems in patients who suffer from dementia. Moreover, it presents characteristic MRI features of the most common dementia subtypes.Trotz der Tatsache, dass Demenzdiagnostik vor allem auf klinischen Kriterien basiert, erhält die Bildgebung einen immer höheren Stellenwert. Neben diversen weitern bildgebenden Verfahren spielt die Magnetresonanztomographie (MRT) eine zentrale Rolle bei der Differenzierung zwischen den unterschiedlichen Demenzsyndromen bzw. zum Ausschluss etwaiger anderer zugrunde liegender Pathologien, die eine Demenz verursachen können, wie Hirntumoren und subdurale Blutungen. Dieser Artikel gibt einerseits einen Überblick über standardisierte MRT-Protokolle sowie andererseits über eine strukturierte radiologische Befundung im Rahmen einer bildgebenden Demenzabklärung. Darüber hinaus werden charakteristische MRT-Merkmale der häufigsten Demenz-Subtypen vorgestellt.

Introduction The association between cerebral amyloid‐β accumulation and downstream CSF biomarkers is not fully understood, particularly in asymptomatic stages. Methods In 318 cognitively unimpaired participants, we assessed the association between amyloid‐β PET (Centiloid), and cerebrospinal fluid (CSF) biomarkers of several pathophysiological pathways. Interactions by Alzheimer's disease risk factors (age, sex and APOE‐ε4), and the mediation effect of tau and neurodegeneration were also investigated. Results Centiloids were positively associated with CSF biomarkers of tau pathology (p‐tau), neurodegeneration (t‐tau, NfL), synaptic dysfunction (neurogranin) and neuroinflammation (YKL‐40, GFAP, sTREM2), presenting interactions with age (p‐tau, t‐tau, neurogranin) and sex (sTREM2, NfL). Most of these associations were mediated by p‐tau, except for NfL. The interaction between sex and amyloid‐β on sTREM2 and NfL was also tau‐independent. Discussion Early amyloid‐β accumulation has a tau‐independent effect on neurodegeneration and a tau‐dependent effect on neuroinflammation. Besides, sex has a modifier effect on these associations independent of tau.

Mitochondrial injury plays a key role in the aetiopathology of multifactorial diseases exhibiting a “vicious circle” characteristic for pathomechanisms of the mitochondrial and multi-organ damage frequently developed in a reciprocal manner. Although the origin of the damage is common (uncontrolled ROS release, diminished energy production and extensive oxidative stress to life-important biomolecules such as mtDNA and chrDNA), individual outcomes differ significantly representing a spectrum of associated pathologies including but not restricted to neurodegeneration, cardiovascular diseases and cancers. Contextually, the role of predictive, preventive and personalised (PPPM/3P) medicine is to introduce predictive analytical approaches which allow for distinguishing between individual outcomes under circumstance of mitochondrial impairments followed by cost-effective targeted prevention and personalisation of medical services. Current article considers innovative concepts and analytical instruments to advance management of mitochondriopathies and associated pathologies.

Recent political processes have rendered people with dementia an increasingly surveilled population. Surveillance is a contentious issue within dementia research, spanning technological monitoring, biomarker research and epidemiological data gathering. This paper explores surveillance in the relationships of people affected by dementia, how older relatives both with and without diagnoses are surveilled in everyday interactions, and the importance of expectations in guiding surveillance. This paper presents data from 41 in-depth interviews with people affected by dementia living in the community in the United Kingdom. Agedness was a key contributor to expectations that a person may have dementia, based on previous experiences, media accounts and wider awareness. Expectations provoked surveillance in interactions, with participants looking for signs of dementia when interacting with older relatives. Older people also enacted self-surveillance, monitoring their own behaviour. Various actions could be attributed to dementia because interpretation is malleable, partly vindicating expectations while leaving some uncertainties. Expectant surveillance transformed people’s experiences because they organised their own actions, and interpreted those of others, in line with pre-existing meanings. The ability to interpret behaviours to fit expectations can bring coherence to uncertainties of ageing, cognition and dementia, but risks ascribing dementia to many older people who straddle those uncertainties.

Accumulation of misfolded host proteins is central to neuropathogenesis of numerous human brain diseases including prion and prion-like diseases. Neurons of retina are also affected by these diseases. Previously, our group and others found that prion-induced retinal damage to photoreceptor cells in mice and humans resembled pathology of human retinitis pigmentosa caused by mutations in retinal proteins. Here, using confocal, epifluorescent and electron microscopy we followed deposition of disease-associated prion protein (PrPSc) and its association with damage to critical retinal structures following intracerebral prion inoculation. The earliest time and place of retinal PrPSc deposition was 67 days post-inoculation (dpi) on the inner segment (IS) of cone photoreceptors. At 104 and 118 dpi, PrPSc was associated with the base of cilia and swollen cone inner segments, suggesting ciliopathy as a pathogenic mechanism. By 118 dpi, PrPSc was deposited in both rods and cones which showed rootlet damage in the IS, and photoreceptor cell death was indicated by thinning of the outer nuclear layer. In the outer plexiform layer (OPL) in uninfected mice, normal host PrP (PrPC) was mainly associated with cone bipolar cell processes, but in infected mice, at 118 dpi, PrPSc was detected on cone and rod bipolar cell dendrites extending into ribbon synapses. Loss of ribbon synapses in cone pedicles and rod spherules in the OPL was observed to precede destruction of most rods and cones over the next 2–3 weeks. However, bipolar cells and horizontal cells were less damaged, indicating high selectivity among neurons for injury by prions. PrPSc deposition in cone and rod inner segments and on the bipolar cell processes participating in ribbon synapses appear to be critical early events leading to damage and death of photoreceptors after prion infection. These mechanisms may also occur in human retinitis pigmentosa and prion-like diseases, such as AD.

© Neural Regeneration Research. This is an open access journal, and articles are distributed under the terms of the Creative Commons AttributionNonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms., Alzheimer’s disease (AD) is a neurodegenerative disorder that affects millions worldwide. Due to population ageing, the incidence of AD is increasing. AD patients develop cognitive decline and dementia, features for which is known, requiring permanent care. This poses a major socio-economic burden on healthcare systems as AD patients’ relatives and healthcare workers are forced to cope with rising numbers of affected people. Despite recent advances, AD pathological mechanisms are not fully understood. Nevertheless, it is clear that the amyloid beta (Aβ) peptide, which forms amyloid plaques in AD patients’ brains, plays a key role. Type 2 diabetes, the most common form of diabetes, affects hundreds of million people globally. Islet amyloid polypeptide (IAPP) is a hormone coproduced and secreted with insulin in pancreatic β-cells, with a key role in diabetes, as it helps regulate glucose levels and control adiposity and satiation. Similarly to Aβ, IAPP is very amyloidogenic, generating intracellular amyloid deposits that cause β-cell dysfunction and death. It is now clear that IAPP can also have a pathological role in AD, decreasing cognitive function. IAPP harms the blood-brain barrier, directly interacts and co-deposits with Aβ, promoting diabetes-associated dementia. IAPP can cause a metabolic dysfunction in the brain, leading to other diabetes-related forms of AD. Thus, here we discuss IAPP association with diabetes, Aβ and dementia, in the context of what we designate a “diabetes brain phenotype” AD hypothesis. Such approach helps to set a conceptual framework for future IAPP-based drugs against AD., This work was supported by iNOVA4Health – UID/Multi/04462/2019, a program financially supported by Fundação para a Ciência e Tecnologia/ Ministério da Educação e Ciência, through national funds and co-funded by FEDER under the PT2020 Partnership Agreement, Funding from INTERFACE Programme, through the Innovation, Technology and Circular Economy Fund (FITEC), FCT via PTDC/BIA-MOL/31104/2017 and UID/Multi/04462/2019-SubProj iNOVA4Health C44 (to RM), PD/BD/135504/2018 (to AFR), Sociedade Portuguesa de Diabetologia for the Nuno Castelo-Branco Prize – 2016 (to RM), and ICM acknowledges FCT-MCTES Program “Concurso de Estímulo ao Emprego Científico” (CEECIND/01670/2017)

Alzheimer’s disease (AD) is the most common type of dementia. The exact cause and treatment of the disease are still unknown. Different neuroimaging modalities, such as magnetic resonance imaging (MRI), positron emission tomography, and single-photon emission computed tomography, have played a significant role in the study of AD. However, the effective diagnosis of AD, as well as mild cognitive impairment (MCI), has recently drawn large attention. Various technological advancements, such as robots, global positioning system technology, sensors, and machine learning (ML) algorithms, have helped improve the diagnostic process of AD. This study aimed to determine the influence of implementing different ML classifiers in MRI and analyze the use of support vector machines with various multimodal scans for classifying patients with AD/MCI and healthy controls. Conclusions have been drawn in terms of employing different classifier techniques and presenting the optimal multimodal paradigm for the classification of AD.

Memantine, a non-competitive NMDA receptor antagonist possessing neuroprotective properties, belongs to the small group of drugs which have been approved for the treatment of Alzheimer’s disease (AD). While several preclinical studies employing different transgenic AD mouse models have described beneficial effects with regard to rescued behavioral deficits or reduced amyloid plaque pathology, it is largely unknown whether memantine might have beneficial effects on neurodegeneration. In the current study, we assessed whether memantine treatment has an impact on hippocampal neuron loss and associated behavioral deficits in the Tg4-42 mouse model of AD. We demonstrate that a chronic oral memantine treatment for 4 months diminishes hippocampal CA1 neuron loss and rescues learning and memory performance in different behavioral paradigms, such as Morris water maze or a novel object recognition task. Cognitive benefits of chronic memantine treatment were accompanied by an amelioration of impaired adult hippocampal neurogenesis. Taken together, our results demonstrate that memantine successfully counteracts pathological alterations in a preclinical mouse model of AD. Electronic supplementary material The online version of this article (10.1007/s12035-020-02120-z) contains supplementary material, which is available to authorized users.

Objectives: Cognitive stimulation therapy (CST) is a brief, non-pharmacological intervention for people with dementia, with an established evidence base for improving cognition and quality of life. It is widely implemented in National Health Service (NHS) settings, but little is known about its naturalistic use. The aim of this survey was to identify and explore inclusion criteria, dose and quality of CST across services in Great Britain (England, Scotland and Wales).\ud \ud Methods: All NHS memory clinics and services for people with dementia were contacted and asked to complete a mixed methods online survey on CST delivery in their service. Questions were centred on who provided CST, who received CST, the dose of CST and any outcomes that were routinely measured.\ud \ud Results: A total of 57/186 services responded, giving a response rate of 30.7%. While the majority reported offering CST (87.7%), there was variability in how this was delivered. Differing inclusion criteria included the use of varying cognitive and behavioural outcome measures, and CST was reported as being offered once and twice weekly. Services also differed in how they evaluated the quality of CST and how this evidence was incorporated for future sessions.\ud \ud Conclusion: While there was a low response rate, this survey indicates that there is significant variability in how CST is used in clinical practice, with many trusts not adhering to the evidence base. To ensure that people with dementia are consistently offered evidence-based, high-quality CST across NHS settings, further standardisation of inclusion criteria, dose and outcomes is needed.

BACKGROUND The relation of retinal thickness to neuropsychological indexes of cognitive impairment in patients with Alzheimer disease (AD) remains an area of investigation. The scope of this investigation was to compare volume and thickness changes of neuronal retinal layers in subjects with AD with those of age-matched healthy controls and to estimate the relation between cognitive functioning evaluated by neuropsychological assessment and thickness changes of the retina. METHODS This was a prospective single-site study where we evaluated 25 subjects with probable AD matched for age, sex, and education to 17 healthy control subjects (HC). All participants underwent a full medical evaluation, neuropsychological assessment, and optical coherence tomography (OCT) to evaluate the peripapillary retinal nerve fiber layer (pRNFL) thickness, ganglion cell complex (GCC) thickness, and macular volume. RESULTS The pRNFL thickness of AD patients showed a significant overall reduction compared with healthy controls (P =

Background: India is undergoing a rapid epidemiological transition, from underweight to overweight/obese population. Obesity is a major risk factor in type 2 diabetes and cardiovascular diseases, and is also implicated as a factor in neurological diseases such as Alzheimer’s disease. A robust, pan-Indian estimate of obesity is not yet available. Purpose: This study estimates the pan-Indian prevalence of obesity, stratified across nonmodifiable (age and gender) and modifiable (education and physical activity levels) factors, and across zones and urban/rural. Methodology: Data for 1,00,531 adults from a nationwide randomized cluster sample survey ( Niyantrita Madhumeha Bharata 2017, phase 1) were analyzed. Obesity was determined using body mass index, and cross-tabulations were calculated across zones, age, gender, education, physical activity, and area. To determine statistical significance, t-tests were used. The odds of obesity within each category of the various factors were calculated using binary logistic regression. Results: Prevalence of obesity in India is 40.3%. Zonal variations were seen as follows: south highest at 46.51% and east lowest at 32.96%. Obesity was higher among women than men (41.88% vs. 38.67%), urban than rural (44.17% vs. 36.08%), and over 40 than under 40 (45.81% vs. 34.58%). More education implied a higher obesity (44.6% college vs. 38% uneducated), as did lowered physical activity (43.71% inactive vs. 32.56% vigorously active). The odds ratio for physical activity was 3.83, stronger than age (1.58), education (1.4), urban (1.3), and gender (1.2). Conclusion: Obesity levels in India are very high, across all zones. The odds of being obese increases with age, and is higher among women and among urban dwellers. Obesity is the highest among aging urban men and women who are college educated and are sedentary. Physical activity and aging are the strongest determinants of obesity. Given the high cost of obesity in terms of type 2 diabetes, cardiovascular diseases, and Alzheimer’s disease, urgent public health measures are necessary to reduce its impact.

La demencia es un síndrome adquirido, de naturaleza orgánica caracterizado por un deterioro permanente de la memoria y de otras funciones intelectuales, y frecuentemente acompañado de otros trastornos psiquiátricos, que ocurren sin alteración del nivel de conciencia, afectando al funcionamiento social. Las pruebas diagnósticas disponibles en la actualidad se basan fundamentalmente en criterios clínicos, apoyadas por pruebas neuropsicológicas, analíticas y de imagen. En la actualidad no se conoce el complejo proceso neurodegenerativo de esta enfermedad, pero si tenemos datos sobre la intervención de los síntomas de esta. El diseño experimental utilizado en este trabajo es de tipo “cuasiexperimental” con evaluación antes y después del programa de estimulación (taller de memoria y automatismos; lectura y lenguaje; ejercicio físico y psicomotricidad; musicoterapia y reconocimiento corporal). La muestra está formada por 21 sujetos de ambos sexos, diagnosticados de Demencia Tipo Alzheimer (DTA) probable, tratados en los centros de día y residencia durante 6 meses. La media de edad de los sujetos es de 80,71 años (Sx= 4,85). Los resultados muestran una disminución en puntuación del MEC (máximo 35 puntos) de -1,67 (Sx 3.88; p0.05); cuando el/la cuidadora principal acude a apoyo psicológico, la puntuación del MEC aumenta de media en 0.8 (Sx 2.9), si no acude la puntuación disminuye en 3.91 (Sx 3.3) con un p valor de 0.03. Las conclusiones extraídas son que el tratamiento de estimulación es igual de eficaz para el mantenimiento del rendimiento cognitivo general y capacidad funcional en pacientes con deterioro cognitivo leve, moderado y grave; Cuando el trabajo se extiende al binomio familia-enfermo, mediante la aplicación de un tratamiento paralelo no farmacológico a los familiares los resultados son significativamente mejores.

Background: Awareness of the diagnosis or related changes in functioning varies in people with dementia (PwD), with implications for the well-being of PwD and their carers. Measuring awareness in a clinical setting could facilitate tailored support and optimize involvement in personal health and care decisions. This scoping review aimed to identify validated methods of assessing awareness in dementia and appraise their clinical utility. Method: A systematic search was conducted of English-language publications that measured awareness in PwD, in 6 electronic databases. Search terms included dement*, Alzheimer*, Pick disease, and awareness, unawareness, anosognosia, insight, denial, metacognit*, or discrepanc*. Results: We screened 30,634 articles, finding 345 articles that met our inclusion criteria. We identified 76 measures, most commonly using a discrepancy questionnaire comparing evaluations of function by PwD and an informant. There were 30 awareness measures developed and validated for use in dementia populations but few designed for general clinical use. Conclusions: Although we found a range of clinical indications for measuring awareness, there were few studies investigating clinical applications and few tools designed for clinical purposes. Further investigation and development of a person-centered tool could facilitate health and care choices in mild-to-moderate dementia.

Beta amyloid (A beta) accumulation is the earliest pathological marker of Alzheimer's disease (AD), but early AD pathology also affects white matter (WM) integrity. We performed a cross-sectional study including 44 subjects (23 healthy controls and 21 mild cognitive impairment or early AD patients) who underwent simultaneous PET-MR using 18F-Florbetapir, and were categorized into 3 groups based on Ab burden: A beta- [mean mSUVr = 1.17]. Intergroup comparisons of diffusion MRI metrics revealed significant differences across multiple WM tracts. A beta i group displayed more restricted diffusion (higher fractional anisotropy, radial kurtosis, axonal water fraction, and lower radial diffusivity) than both A beta- and A beta+ groups. This nonmonotonic trend was confirmed by significant continuous correlations between mSUVr and diffusion metrics going in opposite direction for 2 cohorts: pooled A beta-/A beta i and pooled A beta i/A beta+. The transient period of increased diffusion restriction may be due to inflammation that accompanies rising A beta burden. In the later stages of A beta accumulation, neurodegeneration is the predominant factor affecting diffusion. (C) 2020 Elsevier Inc. All rights reserved.

In a neuropsychological assessment, each test aims at measuring a single cognitive function. However, test performance depends on an interconnected system of cognitive functions and individual characteristics. For a better understanding of cognitive deficits, it is fundamental to recognize this complexity and study the relationships between test performances. This study aims to evaluate complexity in neuropsychological assessment through network analysis (NA) in 165 healthy older adults, 191 patients with Alzheimer's disease (AD), and 129 patients with vascular encephalopathy (VaE). NA is a flexible method to explore different domains where many variables are correlated with each other, and the relationships are key for understanding the domains. We included general aspects of individual differences (i.e., age, sex, years of education) and the raw scores of a clinically used neuropsychological battery in the network. Healthy subjects showed a segregated pattern, suggesting a good specificity of each test in measuring a specific cognitive function. Moreover, the scores were related to age and education. In the patient groups, the identified patterns changed in a consistent manner, showing less specificity and new relationships between the various tests, thereby reducing the impact of age and education on the performance. In particular, AD patients showed worse performance on the tests but also a different balance between different tasks, suggesting a reorganization of the cognitive system and not a mere decline. These results provide a new perspective in looking at the complexity of cognitive function assessment.

Neurodegenerative disorders such as Alzheimer's disease (AD) represent a mounting public health challenge. As these diseases are difficult to diagnose clinically, biomarkers of underlying pathophysiology are playing an ever‐increasing role in research, clinical trials, and in the clinical work‐up of patients. Though cerebrospinal fluid (CSF) and positron emission tomography (PET)‐based measures are available, their use is not widespread due to limitations, including high costs and perceived invasiveness. As a result of rapid advances in the development of ultra‐sensitive assays, the levels of pathological brain‐ and AD‐related proteins can now be measured in blood, with recent work showing promising results. Plasma P‐tau appears to be the best candidate marker during symptomatic AD (i.e., prodromal AD and AD dementia) and preclinical AD when combined with Aβ42/Aβ40. Though not AD‐specific, blood NfL appears promising for the detection of neurodegeneration and could potentially be used to detect the effects of disease‐modifying therapies. This review provides an overview of the progress achieved thus far using AD blood‐based biomarkers, highlighting key areas of application and unmet challenges., This Review discusses recent advances in blood‐based biomarkers for Alzheimer's disease, highlighting the key areas of application and unmet challenges.

Introduction Large-scale worldwide COVID-19 vaccination programs are being rapidly deployed, and high-risk patients with comorbidity are now receiving the first doses of the vaccine. Physicians should be, therefore, aware of new pitfalls associated with the current pandemic vaccination program, also in the case of [18F]Florbetaben PET/CT. Case Presentation We described the first image of [18F]Florbetaben PET/CT in the evaluation of a 70-year-old male with suspicious Alzheimer disease and unclear history of heart disease. We detailed the diagnostic imaging PET/CT workup with different findings. Conclusion In this case, [18F]Florbetaben PET/CT can demonstrate potential beta-amyloid immune-reactivity and deposition associated with the current COVID-19 pandemic vaccination programs.

Alexithymia is widely recognized as the inability to identify and express emotions. It is a construct which consists of four cognitive traits such as difficulty in identifying feelings, describing feelings to others, externally oriented thinking, and limited imaginative capacity. Several studies have linked alexithymia to cognitive functioning, observing greater alexithymia scores associated with poorer cognitive abilities. Despite Alzheimer&rsquo, s disease (AD) being a neurodegenerative pathology characterized by cognitive troubles from the early stages, associated to behavioral and emotional disturbances, very few investigations have studied the alexithymia in AD. These studies have shown that alexithymia scores&mdash, assessed with Toronto Alexithymia Scale (TAS)&mdash, were greater in AD patients than healthy participants. The objective of the study was to investigate if the alexithymia was present in patients with mild AD. We hypothesized that the AD group would show more alexithymia features than the control group. We evaluated 54 subjects, including 27 patients diagnosed with mild AD and 27 normal healthy controls, using the Shalling Sifneos Psychosomatic Scale (SSPS-R) and a neuropsychological test battery. Using non-parametric statistical analyses&mdash, Wilcoxon and Mann&ndash, Whitney U tests&mdash, we observed that the SSPS-R scores were similar in the AD and control groups. All participants showed SSPS-R scores below to 10 points, which means no-alexithymia. We did not find significant correlations between SSPS-R scores and cognitive variables in both groups (p &gt, 0.22), but we observed a negative association between name abilities and alexithymia, but it does not reach to significance (p = 0.07). However, a significant correlation between SSPS-R score and mood state, assessed using Zerssen Rating Scale, was found in both groups (p = 0.01). Because we did not find a significant difference in the alexithymia assessment between both subject groups, pot hoc analyses were computed for each item of the SSPS-R. We made comparisons of alexithymic responses percentages in each SSPS-R item between AD and control groups, using Fisher&rsquo, s test. We observed that AD patients produced more alexithymic responses in some items of SSPS-R test than the control group, particularly about difficulties to find the words to describe feelings, as well as difficulties of imagination capacity and externally oriented thinking. The present results do not confirm our hypothesis and they do not support the results of previous studies revealing great alexithymia in AD.

Background The mechanism of synaptic loss in Alzheimer’s disease is poorly understood and may be associated with tau pathology. In this combined positron emission tomography (PET) and magnetoencephalography (MEG) study, we aimed to investigate spatial associations between regional tau pathology ([18F]flortaucipir PET), synaptic density (synaptic vesicle 2A [11C]UCB-J PET) and synaptic function (MEG) in Alzheimer’s disease. Methods Seven amyloid-positive Alzheimer’s disease subjects from the Amsterdam Dementia Cohort underwent dynamic 130-min [18F]flortaucipir PET, dynamic 60-min [11C]UCB-J PET with arterial sampling and 2 × 5-min resting-state MEG measurement. [18F]flortaucipir- and [11C]UCB-J-specific binding (binding potential, BPND) and MEG spectral measures (relative delta, theta and alpha power; broadband power; and peak frequency) were assessed in cortical brain regions of interest. Associations between regional [18F]flortaucipir BPND, [11C]UCB-J BPND and MEG spectral measures were assessed using Spearman correlations and generalized estimating equation models. Results Across subjects, higher regional [18F]flortaucipir uptake was associated with lower [11C]UCB-J uptake. Within subjects, the association between [11C]UCB-J and [18F]flortaucipir depended on within-subject neocortical tau load; negative associations were observed when neocortical tau load was high, gradually changing into opposite patterns with decreasing neocortical tau burden. Both higher [18F]flortaucipir and lower [11C]UCB-J uptake were associated with altered synaptic function, indicative of slowing of oscillatory activity, most pronounced in the occipital lobe. Conclusions These results indicate that in Alzheimer’s disease, tau pathology is closely associated with reduced synaptic density and synaptic dysfunction.

Background To meet the needs of aging and dementia patients in Taiwan, this study designed a nursing system that includes communication, location tracking, and fall detection, and early warning services. The main purpose of this research is to provide timely services to the elderly and patients and hope to reduce the burden when the number of nursing staff decreases. This article is a remote disease care service platform with the Internet of Things (IoT) devices to monitor the location of the elderly and whether they have dropped warning alerts. Results The device is connected to the patient's waist and chest, monitors the patient's movement and behavior, and transmits messages to the back-end system, and informs caregivers through mobile phone applications when unexpected or shocking events occur. The system can identify whether the patient has fallen, accidentally, or long-term inactivity. The device is equipped with sensors that enable it to monitor the patient's location and behavior data through Bluetooth and GPS technology. Finally, we proposed a basic model and an integrated model that will industrialize the system and is expected to play a role in a larger patient population. Conclusions The system developed in this research has passed the Activities of Daily Living (ADL) test and verification, and is expected to provide appropriate safety care services for nursing homes and elderly residences.

A significant positive correlation was previously reported (Fox et al.Evol Med Public Health 2013; 2013:173–86) between hygiene and the global prevalence of Alzheimer's disease (AD) based on World Health Organization (2004) data. These data have now been updated by the Global Burden of Disease (GBD; 2016) dataset that takes into account under-registration and other potential confounds. We therefore addressed whether the association between hygiene and AD is maintained in light of these more recent data. We report a significant positive correlation between GBD AD prevalence rates and parasite burden, and a negative association with hygiene. These newer data argue that hygiene is not a risk factor for AD, and instead suggest that parasite burden may increase AD risk. Lay summary: It was previously hypothesized that hygeine might be a risk factor for the development of Alzheimer disease (AD), based on a global gradient of dementia. Newer data that correct global AD rates for under-reporting now demonstrate that parasite burden is positively correlated with AD.

The decline in cognitive function is generally the result of the complex interaction of several factors. First of all, age, but also demographic, educational, genetic, socio-economic, and environmental determinants, including nutrition. Cognitive decline and dementia prevalence are increasing, and they are projected to continue increasing in the next decades due to the aging of the world population. Currently, there are no effective pharmacological treatments for these devastating and disabling conditions, which emphasize the key role of preventive strategies. There is compelling evidence of the role of diet and lifestyle on cognitive function. Therefore, dietary/ nutritional approaches that contribute to prevent, or slow cognitive decline may have a remarkable public health impact. Numerous studies have explored the role of dietary components and patterns on age-associated cognitive decline, with accruing evidence that combinations of foods and nutrients can have synergistic effects beyond those attributable to individual foods or nutrients. Dietary patterns show the strongest evidence for slowing the development of cognitive decline, Alzheimer’s disease and other dementias including the Mediterranean diet, the Dietary Approaches to Stop Hypertension diet, and their combination (the MedDiet-DASH Intervention for Neurodegenerative Delay - MIND), among others with few positive results. There are also dietary patterns with no evidence of such effects. This review examines the evidence for the effects of some dietary patterns as neuroprotective with a potential to delay cognitive decline and the onset of dementia.

Recent literature agrees that neurodegenerative processes involve both the retina and the central nervous system, which are two strictly related anatomical structures. However, the causal mechanisms of this dual involvement are still uncertain. To date, anterograde transsynaptic neurodegeneration, triggered by retinal ganglion cells’ death, and retrograde transsynaptic neurodegeneration, induced by neurodegenerative processes of the central nervous system, has been considered the major possible causal mechanisms. The development of novel neuroimaging techniques has recently supported both the study of the central stations of the visual pathway as well as the study of the retina which is possibly an open window to the central nervous system.

Background: Alzheimer's disease (AD) prevalence is increasing, but its etiology remains elusive. Gut microbes can contribute to AD pathology and may help identifying novel markers and therapies against AD. Methods: A randomized crossover pilot study of modified Mediterranean-ketogenic diet (MMKD) and American Heart Association Diet (AHAD) intervention is performed on 17 subjects (age: 63.4±3.7yr), of which 11 have mild cognitive impairment (MCI), while 6 are cognitively normal (CN). Subjects undergo MMKD and AHAD intervention for 6-weeks separated by 6-weeks washout periods. Gut microbiome, fecal short-chain fatty acids (SCFAs), and markers of AD in cerebrospinal fluid (CSF) including amyloid β (Aβ)-40 and As-42, total tau, and phosphorylated tau-181 (tau-p181) are measured at before and after diet interventions. Findings: At baseline, MCI and CN subjects show no notable difference in microbiome diversity but several unique microbial signatures are detected in MCI subjects. Proteobacteria correlate positively with Aβ-42: Aβ-40 while fecal propionate and butyrate correlates negatively with Aβ-42 in MCI subjects. Several bacteria are differently affected by the two diets with distinct patterns between CN and MCI subjects. Notably, the abundance of Enterobacteriaceae, Akkermansia, Slackia, Christensenellaceae and Erysipelotriaceae increases while that of Bifidobacterium and Lachnobacterium reduces on MMKD, while AHAD increases Mollicutes. MMKD slightly reduces fecal lactate and acetate while increasing propionate and butyrate. Conversely, AHAD increases acetate and propionate while reducing butyrate. Interpretation: The data suggest that specific gut microbial signatures may predict the MCI and that the MMKD can modulate the gut microbiome and metabolites in association with improved AD biomarkers. Funding Statement: The work was supported by National Institutes of Health grant P30AG049638; R01AG055122 (SC), the Department of Defense funding W81XWH-18-1-0118 (HY), as well as the funds and services provided from Center for Diabetes, Obesity and Metabolism, Wake Forest Baptist Medical Center and National Center for Advancing Translational Sciences (NCATS), National Institutes of Health funded Wake Forest Clinical and Translational Science Institute (WF CTSI) through Grant Award Number UL1TR001420. Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: The study was approved by the Institutional Review Boards of the Wake Forest School of Medicine and was conducted in the Wake Forest Clinical Research Units. All protocols related to the cohorts involved in the study have been reviewed and approved by the Institutional Review Board of the Wake Forest School of Medicine. All experiments and samplings were carried out in accordance with ethical and biosafety protocols approved by the Institutional guidelines.

Background: Little is known on investigating how healthcare teams in dementia wards act for promoting personhood in persons with Alzheimer’s disease (PWA). Objective: The current research aimed to identify the social networks of dementia health carers promoting the personhood of PWA in acute or long-term dementia wards in public and private psychiatric hospitals. Methods: We used a mixed-method research approach. Ethnographic observations and two-mode Social Network Analysis (SNA) captured the role and social networks of healthcare professionals promoting PWA personhood, using SocNetv version 2.4. The social network graphs illustrated how professionals participated in PWA care by computing the degree of centrality (%DC) for each professional; higher values indicated more statistical significance of a professional role compared to others in the provision of personhood care. The categories of personhood were biological, individual, and sociologic. Nurses, doctors, ward managers, hospital managers, clinical psychologists, occupational therapists, care coordinators, physiotherapists, healthcare assistants, and family members were observed if they were promoting PWA personhood. Method: We used a mixed-method research approach. Ethnographic observations and two-mode Social Network Analysis (SNA) captured the role and social networks of healthcare professionals promoting PWA personhood, using SocNetv version 2.4. The social network graphs illustrated how professionals participated in PWA care by computing the degree of centrality (%DC) for each professional; higher values indicated more statistical significance of a professional role compared to others in the provision of personhood care. The categories of personhood were biological, individual, and sociologic. Nurses, doctors, ward managers, hospital managers, clinical psychologists, occupational therapists, care coordinators, physiotherapists, healthcare assistants, and family members were observed if they were promoting PWA personhood. Results: The highest %DC in SNA in biological personhood was held by the ward nurses (36%), followed by the ward doctors (20%) and ward managers (20%). All professional roles were involved in 16% of cases in the promotion of individual personhood, while the hospital managers had the highest %DC (33%) followed by the ward managers and nurses (27%) in the sociologic personhood. Conclusion: All professional roles were deemed to promote PWA personhood in dementia wards, although some limitation exists according to the context of the assessment.

Background Alzheimer’s disease (AD) is a progressive neurodegenerative disease, and due to various physiological and psychological factors the patients are at risk of nutritional insufficiencies. The purpose of this study was to assess the dietary fatty acid intake and its effect on plasma fatty acids in elderly Saudi women and to compare the differences in their food and plasma fatty acid profile on the basis of their residence. Methods A total of 76 elderly women (50–100 years) were recruited through a random sampling method. A structured proforma was designed to gather information related to their age, income, dietary habits, and presence of any disease and awareness of AD. A 24-h dietary recall method for 3 days and food frequency questionnaire, concentrating on fish consumption and consumption of foods rich in ω-3 fatty acids, which was planned by dietitians, was used for dietary assessment. The gathered data were then analyzed using food processor software. The blood samples were collected to determine plasma fatty acids. Results The mean age of women diagnosed with AD was more than 75 years, and the prevalence of illiteracy was higher among AD subjects. As compared to the AD group, the concentration of LA and total ω-6 was significantly (p ≤ 0.05) higher in the control group from both recruitment sites [National Guard Health Affairs, King Abdulaziz Medical City, Riyadh (NGH) and Social Welfare Homes for the Elderly (SWH)]. Similarly, the concentrations of EPA, DHA, and ω-3 were also slightly higher in the control group at both sites, but the difference between the control and AD subjects was only significant (p ≤ 0.05) in subjects from NGH. We found no significant difference in the ω-6/ ω-3 ratio between groups. Also, no significant difference was found in the mean level of the plasma fatty acid when comparing the control and AD groups. The concentration of DHA in controls only and AA, EPA and ω-6 in both control and AD were significant (although weakly) correlated with their respective dietary intakes. No correlations were found between the intake of 18 C precursors (LA and ALA) and plasma levels of their long chain derivatives (AA, EPA, and DHA). Education, income, overall health status and the concentration of various fatty acids from food was higher and better in subjects from SWH than NGH. The lower plasma level indicates lower impaired systemic availability of several nutrients. Conclusion We found that dietary intervention might play a role in the prevention of AD.

Since the 1970s, when ATP was identified as a co-transmitter in sympathetic and parasympathetic nerves, it and its active metabolite adenosine have been considered relevant signaling molecules in biological and pathological processes in the central nervous system (CNS). Meanwhile, inosine, a naturally occurring purine nucleoside formed by adenosine breakdown, was considered an inert adenosine metabolite and remained a neglected actor on the purinergic signaling scene in the CNS. However, this scenario began to change in the 1980s. In the last four decades, an extensive group of shreds of evidence has supported the importance of mediated effects by inosine in the CNS. Also, inosine was identified as a natural trigger of adenosine receptors. This evidence has shed light on the therapeutic potential of inosine on disease processes involved in neurological and psychiatric disorders. Here, we highlight the clinical and preclinical studies investigating the involvement of inosine in chronic pain, schizophrenia, epilepsy, depression, anxiety, and in neural regeneration and neurodegenerative diseases, such as Parkinson and Alzheimer. Thus, we hope that this review will strengthen the knowledge and stimulate more studies about the effects promoted by inosine in neurological and psychiatric disorders.

Objective: Purpose in life tends to decline in older adulthood and it is thought that intact cognitive functioning is required for purposeful living. Thus, it is likely that individuals may perceive older adults who are experiencing cognitive declines associated with dementia as having a reduced sense of purpose. Biases such as these may influence how individuals, especially care partners, interact with those with dementia.Method: This study examined how sense of purpose changed following a dementia diagnostic appointment for both the person receiving a diagnosis and their care partner. This study also explored how each individual perceived the other member of the dyad’s sense of purpose. Older adults (47 care recipients and 75 care partners, 57% female; Mage = 68.5 years, SDage = 12.0 years) provided self- and other-report ratings of sense of purpose before and after their appointment at a specialized memory clinic.Results: Overall, both care recipients and care partners’ sense of purpose declined following a dementia diagnostic appointment [t(85) = 7.01, p < 0.001]. However, when comparing self-reports and other-reports of purpose, care partners reported that care recipients experienced a lower sense of purpose in life than the care recipients reported about themselves.Conclusions: Care recipients and partners reported less purpose in life following their dementia diagnostic appointment. Care partners may hold certain biases regarding sense of purpose toward care recipients. These findings can inform future work regarding how care recipients and care partners can plan purposeful lives following a dementia diagnosis.

We compared the prognosis of inpatients with a known diagnosis of Alzheimer's or Parkinson's disease who have COVID-19 infection with other hospitalized patients with COVID-19. Our cohort study started in October 2020 and ended in May 2021 and included inpatients with COVID-19 infection who were admitted to hospitals. From a total of 67,871 patients with a confirmed diagnosis of COVID-19, a sample of 3732 individuals were selected of which 363 had Alzheimer's, and 259 had Parkinson's disease. All patients had both positive RT-PCR test and positive chest CT for COVID-19. The outcome was dead within 28 days of admission and the predictors were a large number of demographic and clinical features, and comorbidities recorded at patients’ bedside. Mortality were 37.5%, 35.1%, and 29.5% in patients with Alzheimer's disease, Parkinson's disease; and in other patients, respectively. The hazard ratio for Alzheimer's disease was 1.27 (95% CI, 1.06–1.53, p = 0.010) and for Parkinson's disease was 1.17 (95% CI, 0.94–1.46, p = 0.171). Age was a predictor of mortality, hazard ratio = 1.04 (95% CI, 1.03–1.05, p

Alzheimer's disease (AD) is a disorder which is today treated and approached at the crossroad of two medical specialties - psychiatry and neurology. The insidious onset which can often mimic depressive disorders or other type of psychiatric disorders, the behavioral changes, the paranoid thoughts usually send people to the psychiatrist, while the brain changes observed on magnetic resonance imaging (MRI) scans and other imaging techniques may indicate the need for neurological monitoring also. The complex symptomatology and progression of this dementia requires a multidisciplinary approach and recent studies focused on adding a third perspective: a metabolic one. The common findings regarding type 2 diabetes and AD made some researchers to informally name it "the third type diabetes". This mini review aims to highlight the mechanisms through which brain insulin resistance can lead to cognitive impairment and to make a short overview of the current findings which demonstrate why insulin may be a promising adjunctive treatment of Alzheimer's dementia, for certain patients.

Metabolic dysfunction and protein aggregation are common characteristics that occur in age‐related neurodegenerative disease. However, the mechanisms underlying these abnormalities remain poorly understood. We have found that mutations in the gene encoding presenilin in Caenorhabditis elegans, sel‐12, results in elevated mitochondrial activity that drives oxidative stress and neuronal dysfunction. Mutations in the human presenilin genes are the primary cause of familial Alzheimer's disease. Here, we demonstrate that loss of SEL‐12/presenilin results in the hyperactivation of the mTORC1 pathway. This hyperactivation is caused by elevated mitochondrial calcium influx and, likely, the associated increase in mitochondrial activity. Reducing mTORC1 activity improves proteostasis defects and neurodegenerative phenotypes associated with loss of SEL‐12 function. Consistent with high mTORC1 activity, we find that SEL‐12 loss reduces autophagosome formation, and this reduction is prevented by limiting mitochondrial calcium uptake. Moreover, the improvements of proteostasis and neuronal defects in sel‐12 mutants due to mTORC1 inhibition require the induction of autophagy. These results indicate that mTORC1 hyperactivation exacerbates the defects in proteostasis and neuronal function in sel‐12 mutants and demonstrate a critical role of presenilin in promoting neuronal health., Proteostasis decline is a common feature in age‐related disease. Loss of SEL‐12/presenilin function leads to increased calcium transfer from the endoplasmic reticulum to the mitochondria resulting in mitochondrial hyperactivity. The mitochondrial hyperactivity promotes mTORC1 signaling that deregulates proteostasis by inhibiting autophagy, which ultimately impairs neuronal fitness.

CD47 is a receptor belonging to the immunoglobulin (Ig) superfamily and broadly expressed on cell membranes. Through interactions with ligands such as SIRPα, TSP-1, integrins, and SH2-domain bearing protein tyrosine phosphatase substrate-1 (SHPS-1), CD47 regulates numerous functions like cell adhesion, proliferation, apoptosis, migration, homeostasis, and the immune system. In this aspect, previous research has shown that CD47 modulates phagocytosis via macrophages, the transmigration of neutrophils, and the activation of T-cells, dendritic cells, and B-cells. Moreover, several studies have reported the increased expression of the CD47 receptor in a variety of diseases, including acute lymphoblastic leukemia (ALL), chronic myeloid leukemia, non-Hodgkin’s lymphoma (NHL), multiple myeloma (MM), bladder cancer, acute myeloid leukemia (AML), Gaucher disease, Multiple Sclerosis and stroke among others. The ubiquitous expression of the CD47 cell receptor on most resident cells of the CNS has previously been established through different methodologies. However, there is little information concerning its precise functions in the development of different neurodegenerative pathologies in the CNS. Consequently, further research pertaining to the specific functions and roles of CD47 and SIRP is required prior to its exploitation as a druggable approach for the targeting of various neurodegenerative diseases that affect the human population. The present review attempts to summarize the role of both CD47 and SIRP and their therapeutic potential in neurodegenerative disorders.

Toxoplasma gondii (T. gondii) is one of the most pervasive neurotropic pathogens causing different lesions in a wide variety of mammals as intermediate hosts, including humans. It is estimated that one-third of the world population is infected with T. gondii; however, for a long time, there has been much interest in the examination of the possible role of this parasite in the development of mental disorders, such as Alzheimer's disease (AD). T. gondii may play a role in the progression of AD using mechanisms, such as the induction of the host's immune responses, inflammation of the central nervous system (CNS), alteration in the levels of neurotransmitters, and activation of indoleamine-2,3-dyoxigenase. This paper presents an appraisal of the literature, reports, and studies that seek to the possible role of T. gondii in the development of AD. For achieving the purpose of the current study, a search of six English databases (PubMed, ScienceDirect, Web of Science, Scopus, ProQuest, and Google Scholar) was performed. The results support the involvement of T. gondii in the induction and development of AD. Indeed, T. gondii can be considered a risk factor for the development of AD and requires the special attention of specialists and patients. Furthermore, the results of this study may contribute to prevent or delay the progress of AD worldwide. Therefore, it is required to carry out further studies in order to better perceive the parasitic mechanisms in the progression of AD., Alzheimer, toxoplasmosis, risk factors, neurotransmitter, cytokine

Genetic and sporadic forms of tauopathies, the most prevalent of which is Alzheimer’s Disease, are a scourge of the aging society, and in case of genetic forms, can also affect children and young adults. All tauopathies share ectopic expression, mislocalization, or aggregation of the microtubule associated protein TAU, encoded by the MAPT gene. As TAU is a neuronal protein widely expressed in the CNS, the overwhelming majority of tauopathies are neurological disorders. They are characterized by cognitive dysfunction often leading to dementia, and are frequently accompanied by movement abnormalities such as parkinsonism. Tauopathies can lead to severe neurological deficits and premature death. For some tauopathies there is a clear genetic cause and/ or an epigenetic contribution. However, for several others the disease etiology is unclear, with few tauopathies being environmentally triggered. Here we review current knowledge of tauopathies listing known genetic and important sporadic forms of this disease. Further, we discuss how DNA methylation as a major epigenetic mechanism emerges to be involved in the disease pathophysiology of Alzheimer’s, and related genetic and non-genetic tauopathies. Finally, we debate the application of epigenetic signatures in peripheral blood samples as diagnostic tool and usage of epigenetic therapy strategies for these diseases.

Light therapy for older persons with dementia is often administered with light boxes, even though indoor ambient light may more comfortably support the diverse lighting needs of this population. Our objective is to investigate the influence of indoor daylight and lighting on the health of older adults with dementia living in long-term care facilities. A systematic literature search was performed within PubMed, CINAHL, PsycINFO, Web of Science and Scopus databases. The included articles (n=37) were published from 1991 to 2020. These articles researched the influence of existing and changed indoor light conditions on health and resulted in seven categories of health outcomes. Although no conclusive evidence was found to support the ability of indoor light to decrease challenging behaviors or improve circadian rhythms, findings of two studies indicate that exposure to (very) cool light of moderate intensity diminished agitation. Promising effects of indoor light were to reduce depressive symptoms and facilitate spatial orientation. Furthermore, there were indications that indoor light improved one’s quality of life. Despite interventions with dynamic lighting having yielded little evidence of its efficacy, its potential has been insufficiently researched among this study population. This review provides a clear and comprehensive description of the impact of diverse indoor light conditions on the health of older adults with dementia living in long-term care facilities. Variation was seen in terms of research methods, (the description of) light conditions, and participants’ characteristics (types and severity of dementia), thus confounding the reliability of the findings. The authors recommend further research to corroborate the beneficial effects of indoor light on depression and to clarify its role in supporting everyday activities of this population. An implication for practice in long-term care facilities is raising the awareness of the increased lighting needs of aged residents. Original article at: https://doi.org/10.2147/CIA.S297865

International audience; Purinergic signaling regulates neuronal and glial cell functions in the healthy CNS. In neurodegenerative diseases, purinergic signaling becomes dysregulated and can affect disease-associated phenotypes of glial cells. In this review, we discuss how cell-specific expression patterns of purinergic signaling components change in neurodegeneration and how dysregulated glial purinergic signaling and crosstalk may contribute to disease pathophysiology, thus bearing promising potential for the development of new therapeutical options for neurodegenerative diseases.

Simple Summary Epidemiological studies have identified a link between neurodegenerative disorders and a reduced risk of overall cancer. Increases and decreases in the risk of site-specific cancers have also been reported. However, it is still unknown whether these associations arise due to shared genetic and molecular factors or are explained by other phenomena (e.g., biases in epidemiological studies or the use of medication). In this study, we aimed to investigate the potential molecular, genetic, and pharmacological links between Alzheimer’s and Parkinson’s diseases and a large panel of 22 cancer types. To examine the overlapping involvement of genes and pathways, we obtained differential gene expression profiles through meta-analyses of post-mortem brain tissues from Alzheimer’s and Parkinson’s disease patients, primary tumors, and tissue-matched controls, and compared them. Genetic similarities were assessed through network-based methods and the computation of genetic correlations. Finally, the potential impact of drugs indicated for each disorder in the identified associations was evaluated using transcriptomic methods. Our research extends previous work in the field by identifying new significant patterns of transcriptomic associations (direct and inverse) between Alzheimer’s disease, Parkinson’s disease, and different site-specific cancers. The results reveal significant genetic correlations between Parkinson’s disease, prostate cancer, and melanoma. In addition, to our knowledge, this is the first time that the role of drugs indicated for the treatment of both sets of disorders has been investigated in the context of their comorbid associations using transcriptomic methods. Abstract Alzheimer’s (AD) and Parkinson’s diseases (PD) are the two most prevalent neurodegenerative disorders in human populations. Epidemiological studies have shown that patients suffering from either condition present a reduced overall risk of cancer than controls (i.e., inverse comorbidity), suggesting that neurodegeneration provides a protective effect against cancer. Reduced risks of several site-specific tumors, including colorectal, lung, and prostate cancers, have also been observed in AD and PD. By contrast, an increased risk of melanoma has been described in PD patients (i.e., direct comorbidity). Therefore, a fundamental question to address is whether these associations are due to shared genetic and molecular factors or are explained by other phenomena, such as flaws in epidemiological studies, exposure to shared risk factors, or the effect of medications. To this end, we first evaluated the transcriptomes of AD and PD post-mortem brain tissues derived from the hippocampus and the substantia nigra and analyzed their similarities to those of a large panel of 22 site-specific cancers, which were obtained through differential gene expression meta-analyses of array-based studies available in public repositories. Genes and pathways that were deregulated in both disorders in each analyzed pair were examined. Second, we assessed potential genetic links between AD, PD, and the selected cancers by establishing interactome-based overlaps of genes previously linked to each disorder. Then, their genetic correlations were computed using cross-trait LD score regression and GWAS summary statistics data. Finally, the potential role of medications in the reported comorbidities was assessed by comparing disease-specific differential gene expression profiles to an extensive collection of differential gene expression signatures generated by exposing cell lines to drugs indicated for AD, PD, and cancer treatment (LINCS L1000). We identified significant inverse associations of transcriptomic deregulation between AD hippocampal tissues and breast, lung, liver, and prostate cancers, and between PD substantia nigra tissues and breast, lung, and prostate cancers. Moreover, significant direct (same direction) associations of deregulation were observed between AD and PD and brain and thyroid cancers, as well as between PD and kidney cancer. Several biological processes, including the immune system, oxidative phosphorylation, PI3K/AKT/mTOR signaling, and the cell cycle, were found to be deregulated in both cancer and neurodegenerative disorders. Significant genetic correlations were found between PD and melanoma and prostate cancers. Several drugs indicated for the treatment of neurodegenerative disorders and cancer, such as galantamine, selegiline, exemestane, and estradiol, were identified as potential modulators of the comorbidities observed between neurodegeneration and cancer.

There is increasing evidence that several mitochondrial abnormalities are present in the brains of patients with Alzheimer’s disease (AD). Decreased alpha-ketoglutarate dehydrogenase complex (αKGDHc) activity was identified in some patients with AD. The αKGDHc is a key enzyme in the Krebs cycle. This enzyme is very sensitive to the harmful effect of reactive oxygen species, which gives them a critical role in the Alzheimer and mitochondrial disease research area. Previously, several genetic risk factors were described in association with AD. Our aim was to analyze the associations of rare damaging variants in the genes encoding αKGDHc subunits and AD. The three genes (OGDH, DLST, DLD) encoding αKGDHc subunits were sequenced from different brain regions of 11 patients with histologically confirmed AD and the blood of further 35 AD patients. As a control group, we screened 134 persons with whole-exome sequencing. In all subunits, a one–one rare variant was identified with unknown significance based on American College of Medical Genetics and Genomics (ACMG) classification. Based on the literature research and our experience, R263H mutation in the DLD gene seems likely to be pathogenic. In the different cerebral areas, the αKGDHc mutational profile was the same, indicating the presence of germline variants. We hypothesize that the heterozygous missense R263H in the DLD gene may have a role in AD as a mild genetic risk factor.

The risk of dementia and Alzheimer's disease in Latin America and the Caribbean (LAC) rises with increasing age and polluted air. Currently, at least 172 million people breathe unhealthy levels of air pollution in LAC countries. Several cohort studies have indicated that air pollution increases the risk of developing dementia and neurodegenerative diseases, but the mechanisms underlying the association are still not clear. Air pollution causes and aggravates five established risk factors for dementia (obesity, hypertension, stroke, diabetes mellitus, and heart diseases) and is linked to three other risk factors (physical inactivity, cognitive inactivity, and depression). Some of these risk factors could be mediating the association between air pollution and dementia. Reducing the risks for dementia is crucial and urgently needed in LAC countries. There is room for improving air quality in many urban areas in the LAC region and other low- and middle-income countries (LMICs), a routealready explored by many urban areas in developing regions. Moreover, reducing air pollution has proved to improve health outcomes before. In this article, we propose that despite the ongoing and valid scientific discussion, if air pollution can or cannot directly affect the brain and cause or aggravate dementia, we are ready to consider air pollution as a potentially modifiable risk factor for dementia in LAC and possibly in other LMICs. We suggest that controlling and reducing current air pollution levels in LAC and other LMIC regions now could strongly contribute.

Flavonoids, a class of polyphenols, consumed daily in our diet, are associated with a reduced risk for oxidative stress (OS)-related chronic diseases, such as cardiovascular disease, neurodegenerative diseases, cancer, and inflammation. The involvement of flavonoids with OS-related chronic diseases have been traditionally attributed to their antioxidant activity. However, evidence from recent studies indicate that flavonoids’ beneficial impact may be assigned to their interaction with cellular macromolecules, rather than exerting a direct antioxidant effect. This review provides an overview of the recent evolving research on interactions between the flavonoids and lipoproteins, proteins, chromatin, DNA, and cell-signaling molecules that are involved in the OS-related chronic diseases; it focuses on the mechanisms by which flavonoids attenuate the development of the aforementioned chronic diseases via direct and indirect effects on gene expression and cellular functions. The current review summarizes data from the literature and from our recent research and then compares specific flavonoids’ interactions with their targets, focusing on flavonoid structure–activity relationships. In addition, the various methods of evaluating flavonoid–protein and flavonoid–DNA interactions are presented. Our aim is to shed light on flavonoids action in the body, beyond their well-established, direct antioxidant activity, and to provide insights into the mechanisms by which these small molecules, consumed daily, influence cellular functions.

Alzheimer’s disease (AD) is the most prevalent form of dementia, and the numbers of AD patients are expected to increase as human life expectancy improves. Deposition of β-amyloid protein (Aβ) in the extracellular matrix and intracellular neurofibrillary tangles are molecular hallmarks of the disease. Since the precise pathophysiology of AD has not been elucidated yet, effective treatment is not available. Thus, understanding the disease pathology, as well as identification and development of valid biomarkers, is imperative for early diagnosis as well as for monitoring disease progression and therapeutic responses. Keeping this goal in mind several studies using quantitative proteomics platform have been carried out on both clinical specimens including the brain, cerebrospinal fluid (CSF), plasma and on animal models of AD. In this review, we summarize the mass spectrometry (MS)-based proteomics studies on AD and discuss the discovery as well as validation stages in brief to identify candidate biomarkers.

Simple Summary Constant exposure to endogenous and environmental factors induces oxidative stress and DNA damage. Rare brain disorders caused by defects in DNA repair and DNA damage response (DDR) signaling establish that failure to process DNA damage may lead to neurodegeneration. In this review, we present mechanisms that link DDR with neurodegeneration in these disorders and discuss their relevance for common age-related neurodegenerative diseases (NDDs). Moreover, we highlight recent insight into the crosstalk between the DDR and other cellular processes known to be disturbed during NDDs. Abstract Genomic integrity is maintained by DNA repair and the DNA damage response (DDR). Defects in certain DNA repair genes give rise to many rare progressive neurodegenerative diseases (NDDs), such as ocular motor ataxia, Huntington disease (HD), and spinocerebellar ataxias (SCA). Dysregulation or dysfunction of DDR is also proposed to contribute to more common NDDs, such as Parkinson’s disease (PD), Alzheimer’s disease (AD), and Amyotrophic Lateral Sclerosis (ALS). Here, we present mechanisms that link DDR with neurodegeneration in rare NDDs caused by defects in the DDR and discuss the relevance for more common age-related neurodegenerative diseases. Moreover, we highlight recent insight into the crosstalk between the DDR and other cellular processes known to be disturbed during NDDs. We compare the strengths and limitations of established model systems to model human NDDs, ranging from C. elegans and mouse models towards advanced stem cell-based 3D models.

Transitions into informal care roles are associated with various characteristics, for example gender and geographic proximity, but such associations are insufficient to explain role delegation, overlooking the interpersonal structure–agency nexuses that constitute role trajectories. This paper explores unequal role delegation within 7 families affected by dementia, presenting data from interviews with 7 people with dementia and 26 carers living in the community in the United Kingdom. Two key care roles are identified: the relatively un-involved role of peripheral actors and the lynchpin role of main carers who take on most of the care tasks. These roles emerge from negotiations around a range of extraneous factors that collectively comprise cumulative baggage, including historic conflicts and childcare commitments. The unequal distribution of care reflects widely noted demographic associations with role delegation, but is enacted and justified through the interpersonal negotiation of personalised meanings regarding individual circumstances and suitability. Though deeply personal when taken at face value, these meanings imbibe sociocultural norms and political economies of care to structurally position family members in relation to each other and signpost appropriate candidates for caring roles, even before such care is required.

Multiple factors combined are currently recognized as contributors to cognitive decline. The main independent risk factor for cognitive impairment and dementia is advanced age followed by other determinants such as genetic, socioeconomic, and environmental factors, including nutrition and physical activity. In the next decades, a rise in dementia cases is expected due largely to the aging of the world population. There are no hitherto effective pharmaceutical therapies to treat age-associated cognitive impairment and dementia, which underscores the crucial role of prevention. A relationship among diet, physical activity, and other lifestyle factors with cognitive function has been intensively studied with mounting evidence supporting the role of these determinants in the development of cognitive decline and dementia, which is a chief cause of disability globally. Several dietary patterns, foods, and nutrients have been investigated in this regard, with some encouraging and other disappointing results. This review presents the current evidence for the effects of dietary patterns, dietary components, some supplements, physical activity, sleep patterns, and social engagement on the prevention or delay of the onset of age-related cognitive decline and dementia. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Caring for a person with dementia burdens family caregivers, and there is a close negative relationship between this burden and their quality of life (QoL). Research suggests that caregivers’ main needs are information and training about the disease and support from others experiencing the same situation, and Internet interventions hold considerable promise for meeting these needs. Virtual communities of practice (VCoPs) are Internet frameworks to share knowledge where members collaborate and achieve a sense of trust in the community. This paper seeks to evaluate the impact of participating in a VCoP (developed through an App) on the QoL of caregivers to people with Alzheimer’s. Results show QoL before and after the intervention changed significantly. The impact of VCoP on caregivers’ overall QoL is moderated by age and relation with the person with Alzheimer’s, specifically those over 65, and spouses. VCoPs allow interaction and knowledge sharing among caregivers which provide them mainly with information and support from peers helping them to meet their needs. Furthermore, caregivers’ QoL did not decrease when their relative deteriorated functionally, which could be due to the participation in VCoP. Although we found significant pre- and post differences in caregivers’ health literacy, we must report the ambiguous result that this variable only impacts on QoL’s physical domain. Participants also reported that they had a positive experience because the App was perceived to be a useful tool, because they could manage their own participation and they met peers and felt less lonely. Results suggest that participation in a VCoP impacts positively on caregivers’ QoL.

Neurodegenerative diseases are a major public health problem worldwide with a wide spectrum of symptoms and physiological effects. It has been long reported that the dysregulation of the cholinergic system and the adrenergic system are linked to the etiology of Alzheimer’s disease. Cholinergic neurons are widely distributed in brain regions that play a role in cognitive functions and normal cholinergic signaling related to learning and memory is dependent on acetylcholine. The Locus Coeruleus norepinephrine (LC-NE) is the main noradrenergic nucleus that projects and supplies norepinephrine to different brain regions. Norepinephrine has been shown to be neuroprotective against neurodegeneration and plays a role in behavior and cognition. Cholinergic and adrenergic signaling are dysregulated in Alzheimer’s disease. The degeneration of cholinergic neurons in nucleus basalis of Meynert in the basal forebrain and the degeneration of LC-NE neurons were reported in Alzheimer’s disease. The aim of this review is to describe current literature on the role of the cholinergic system and the adrenergic system (LC-NE) in the pathology of Alzheimer’s disease and potential therapeutic implications.

Small guanosine triphosphatases (GTPases) of the Rab and Arf families are key regulators of vesicle formation and membrane trafficking. Membrane transport plays an important role in the central nervous system. In this regard, neurons require a constant flow of membranes for the correct distribution of receptors, for the precise composition of proteins and organelles in dendrites and axons, for the continuous exocytosis/endocytosis of synaptic vesicles and for the elimination of dysfunctional proteins. Thus, it is not surprising that Rab and Arf GTPases have been associated with neurodegenerative diseases such as Alzheimer’s and Parkinson’s. Both pathologies share characteristics such as the presence of protein aggregates and/or the fragmentation of the Golgi apparatus, hallmarks that have been related to both Rab and Arf GTPases functions. Despite their relationship with neurodegenerative disorders, very few studies have focused on the role of these GTPases in the pathogenesis of neurodegeneration. In this review, we summarize their importance in the onset and progression of Alzheimer’s and Parkinson’s diseases, as well as their emergence as potential therapeutical targets for neurodegeneration. A.A.S. is a recipient of a predoctoral fellowship (PRE_2017_1_0016) from the Basque Government. M.L.M. is a recipient of a fellowship from Foundation “Jesús de Gangoiti y Barrera”. J.L.Z. was supported by the Instituto de Salud Carlos III (PI18/00207) and the University of Basque Country Grant (US19/04).