INTRODUCTION: Loneliness has a rising public health impact, but research involving neuropathology and representative cohorts has been limited. METHODS: Inverse odds of selection weights were generalized from the autopsy sample of Rush Alzheimer's Disease Center cohorts (N = 680; 89 ± 9 years old; 25% dementia) to the US-representative Health and Retirement Study (N = 8469; 76 ± 7 years old; 5% dementia) to extend external validity. Regressions tested cross-sectional associations between loneliness and (1) Alzheimer's disease (AD) and cerebrovascular pathology; (2) five cognitive domains; and (3) relationships between pathology and cognition, adjusting for depression. RESULTS: In weighted models, greater loneliness was associated with microinfarcts, lower episodic and working memory in the absence of AD pathology, lower working memory in the absence of infarcts, a stronger association of infarcts with lower episodic memory, and a stronger association of microinfarcts with lower working and semantic memory. DISCUSSION: Loneliness may relate to AD through multiple pathways involving cerebrovascular pathology and cognitive reserve. HIGHLIGHTS: Loneliness was associated with worse cognition in five domains. Loneliness was associated with the presence of microinfarcts. Loneliness moderated cognition-neuropathology associations. Transportability methods can provide insight into selection bias.

• Klíčová slova
• Alzheimer's disease pathology, autopsy, cognition, cognitive reserve, infarcts, inverse odds of selection weights, loneliness, microinfarcts, transportability,
• MeSH
• Alzheimerova nemoc * psychologie   patologie   MeSH
• cerebrovaskulární poruchy * psychologie   patologie   MeSH
• kognice * fyziologie   MeSH
• lidé MeSH
• neuropsychologické testy statistika a číselné údaje   MeSH
• osamocení * psychologie   MeSH
• průřezové studie MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Magnetic resonance imaging (MRI) visual scales of brain atrophy are important for differential diagnosis of dementias in routine clinical practice. Atrophy patterns in early- and late-onset Alzheimer's disease (AD) can be different according to some studies. OBJECTIVE: Our goal was to assess brain atrophy patterns in early- and late-onset AD using our recently developed simple MRI visual scales and evaluate their reliability. METHODS: We used Hippocampo-horn percentage (Hip-hop) and Parietal Atrophy Score (PAS) to compare mediotemporal and parietal atrophy on brain MRI among 4 groups: 26 patients with early-onset AD, 21 younger cognitively normal persons, 32 patients with late-onset AD, and 36 older cognitively normal persons. Two raters scored all brain MRI to assess reliability of the Hip-hop and PAS. Brain MRIs were obtained from Alzheimer's Disease Neuroimaging Initiative (ADNI) database. RESULTS: The patients with early-onset AD had significantly more pronounced mediotemporal and also parietal atrophy bilaterally compared to the controls (both p < 0.01). The patients with late-onset AD had significantly more pronounced only mediotemporal atrophy bilaterally compared to the controls (p < 0.000001), but parietal lobes were the same. Intra-rater and inter-rater reliability of both visual scales Hip-hop and PAS were almost perfect in all cases (weighted-kappa value ranged from 0.90 to 0.99). CONCLUSION: While mediotemporal atrophy detected using Hip-hop is universal across the whole AD age spectrum, parietal atrophy detected using PAS is worth rating only in early-onset AD. Hip-hop and PAS are very reliable MRI visual scales.

• Klíčová slova
• Early-onset Alzheimer’s disease, hippocampo-horn percentage, late-onset Alzheimer’s disease, mediotemporal atrophy, parietal atrophy, parietal atrophy score, reliability,
• MeSH
• Alzheimerova nemoc patologie   MeSH
• atrofie patologie   MeSH
• hipokampus patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• magnetická rezonanční tomografie MeSH
• mozek patologie   MeSH
• reprodukovatelnost výsledků MeSH
• senioři nad 80 let MeSH
• temenní lalok patologie   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Research Support, U.S. Gov't, Non-P.H.S. MeSH

Brain white matter fiber bundles in patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD) have abnormalities not usually seen in unaffected subjects. Ideal algorithm of the localization-specific properties in white matter integrity might reveal the changes of tissue properties varying along each tract, while previous studies only detected the mean DTI parameters of each fiber. The aim of this study was to investigate whether these abnormalities of nerve fiber tracts are localized to specific regions of the tracts or spread throughout and to analyze which of the examined fiber tracts are involved in the early stages of Alzheimer's disease. In this study, we utilized VBA, TBSS as well as AFQ together to comprehensively investigate the white matter fiber impairment on 25 CE patients, 29 MCI patients and 34 normal control (NC) subjects. Two tract profiles, fractional anisotropy (FA) and mean diffusivity (MD), were extracted to evaluate the white matter integrity at 100 locations along each of 20 fiber tracts and then we validated the results with 27 CE patients, 21 MCI patients and 22 NC from the ADNI cohort. Also, we compare the AFQ with VBA and TBSS in our cohort. In comparison with NC, AD patients showed widespread FA reduction in 25% (5 /20) and MD increase in 65%(13/20) of the examined fiber tracts. The MCI patients showed a regional FA reduction in 5% (1/20) of the examined fiber tracts (right cingulum cingulate) and MD increase in 5%(1/20) of the examined fiber tracts (left arcuate fasciculus). Among these changed tracts, only the right cingulum cingulate showed widespread disruption of myelin or/and fiber axons in MCI and aggravated deterioration in AD, findings supported by FA/MD changes both by the mean and FA changes by point wise methods and TBSS. And the AFQ findings from ADNI cohort showed some similarity with our cohort, especially in the pointwise comparison of MD profiles between AD vs NC. Furthermore, the pattern of white matter abnormalities was different across neuronal fiber tracts; for example, the MCI and AD patients showed similar FA reduction in the middle part of the right cingulum cingulate, and the anterior part were not damaged. However, the left arcuate fasciculus showed MD elevation located at the temporal part of the fibers in the MCI patients and expanding to the temporal and middle part of the fibers in AD patients. So, the AFQ may be an alternative complementary method of VBA and TBSS, and may provide new insights into white matter degeneration in MCI and its association with AD.

• Klíčová slova
• Alzheimer's disease, Automated fiber quantification, Diffusion tensor imaging, Mild cognitive impairment, Pointwise comparison,
• MeSH
• Alzheimerova nemoc diagnostické zobrazování   patologie   MeSH
• bílá hmota diagnostické zobrazování   patologie   MeSH
• interpretace obrazu počítačem metody   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nervová vlákna patologie   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• zobrazování difuzních tenzorů metody   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH

Alzheimer's disease is a progressive, irreversible, incurable, neurodegenerative illness and the most common of the dementing disorders. It starts usually after 60 years of age and may span 8 to 12 years. The continuous and slow decline caused by this disease, is characterized by cognitive deterioration, loss of functional independence, changes in behaviour, and expanding needs for care. In the last three decades, the proteins predominating neuritic plaques and neurofibrillary tangles have been detected and researched: amyloid-beta protein in the plaques and hyperphosphorylated tau in the tangles. Alzheimer's disease is now considered a long-term process with a slow progress and with a prolonged development of pathological changes that precedes symptoms by years. AD is becoming one of the most problematic and expensive illness for the civilization, also known as "silent threat".

• Klíčová slova
• Alzheimer's disease, Beta amyloid, Clinical aspects, Dementia, Plaques, Tangles, Tau protein,
• MeSH
• Alzheimerova nemoc diagnóza   etiologie   MeSH
• behaviorální symptomy MeSH
• lidé MeSH
• rizikové faktory MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

The incidence of both diabetes and Alzheimer's disease (AD) is increasing and is becoming a social and economic threat worldwide. Recent research studies indicate that both diseases share some pathophysiological features and that specifically, Type 2 Diabetes Mellitus (T2DM) is a risk factor of Alzheimer's disease. The aim of this study is to explore the relationship between diabetes mellitus and AD, explore the efficacy of selected drugs on patients with diabetes and AD, and compare the relative risk of diabetes for Alzheimer's disease within different clinical studies. The method of literature search in several acknowledged databases such as Web of Science, Elsevier Science Direct, PubMed and Scopus in the period from 2000 to 2015 for the following keywords: "Alzheimer's AND disease AND diabetes AND mellitus" was used. The identified studies were divided into two basic groups, based on their focus: efficacy of the selected drugs on patients suffering from AD and diabetes, and a link between diabetes and AD; as diabetes is seen as a risk factor of AD. The findings of this study confirm that there is a close and direct link between diabetes and AD, which indicates that there is a need for early diagnosis of metabolic syndrome, insulin resistance, and T2DM. In fact, the reviewed clinical trials have proved an increase in the risk of AD. However, the values of this risk are relatively low. The results also illustrate that both pharmacological (e.g., the antidiabetic drugs together with insulin dosing) and nonpharmacological (e.g., being intensively engaged in physical activities) treatments can have a positive effect. The results of this study confirm that diabetes and AD are not independent disorders since they share some common pathophysiological mechanisms. In addition, more clinical randomized control trials are needed to explore the efficacy of both pharmacological and non-pharmacological approaches to the treatment of T2DM and AD.

• Klíčová slova
• Alzheimer's disease, chronic diseases, dementia, diabetes mellitus, risk factors, systematic review.,
• MeSH
• Alzheimerova nemoc * epidemiologie   patofyziologie   terapie   MeSH
• diabetes mellitus 2. typu * epidemiologie   patofyziologie   terapie   MeSH
• lidé MeSH
• rizikové faktory MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

The COVID-19 pandemic has disproportionately affected more vulnerable populations, including those living with dementia. Over 50 million individuals worldwide are living with Alzheimer's disease (AD) or other dementia, and it is crucial to continue the fight against the condition during the global pandemic. Since the start of mandated lockdowns in March 2020, charity and non-profit organizations that fund AD and related dementia research continue to respond to the needs of the AD research community, ensuring the momentum continues and accelerates. Members of the International Alzheimer's and Related Dementia Research Funder Consortium, a group of nearly 40 funding organizations that informally convene throughout the year to share updates and information, have taken a number of steps to ensure the continued support of the research community. Even during times of uncertainty, it is essential that the field moves forward to uncover preventions, diagnoses, and treatments for these diseases that affect many millions globally.

• Klíčová slova
• Alzheimer's disease, COVID-19, dementia, nonprofit, public health, research funding,
• MeSH
• Alzheimerova nemoc * diagnóza   MeSH
• COVID-19 * MeSH
• kontrola infekčních nemocí MeSH
• lidé MeSH
• pandemie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Alzheimer's disease (AD) is a neurodegenerative disease whose various pathophysiological aspects are still being investigated. Recently, it has been hypothesized that AD may be associated with a dysbiosis of microbes in the intestine. In fact, the intestinal flora is able to influence the activity of the brain and cause its dysfunctions.Given the growing interest in this topic, the purpose of this review is to analyze the role of antibiotics in relation to the gut microbiota and AD. In the first part of the review, we briefly review the role of gut microbiota in the brain and the various theories supporting the hypothesis that dysbiosis can be associated with AD pathophysiology. In the second part, we analyze the possible role of antibiotics in these events. Antibiotics are normally used to remove or prevent bacterial colonization in the human body, without targeting specific types of bacteria. As a result, broad-spectrum antibiotics can greatly affect the composition of the gut microbiota, reduce its biodiversity, and delay colonization for a long period after administration. Thus, the action of antibiotics in AD could be wide and even opposite, depending on the type of antibiotic and on the specific role of the microbiome in AD pathogenesis.Alteration of the gut microbiota can induce changes in brain activity, which raise the possibility of therapeutic manipulation of the microbiome in AD and other neurological disorders. This field of research is currently undergoing great development, but therapeutic applications are still far away. Whether a therapeutic manipulation of gut microbiota in AD could be achieved using antibiotics is still not known. The future of antibiotics in AD depends on the research progresses in the role of gut bacteria. We must first understand how and when gut bacteria act to promote AD. Once the role of gut microbiota in AD is well established, one can think to induce modifications of the gut microbiota with the use of pre-, pro-, or antibiotics to produce therapeutic effects.

• Klíčová slova
• Alzheimer’s disease, Antibiotics, Gut microbiota, Neuroinflammation,
• MeSH
• Alzheimerova nemoc chemicky indukované   farmakoterapie   mikrobiologie   MeSH
• antibakteriální látky aplikace a dávkování   škodlivé účinky   MeSH
• dysbióza chemicky indukované   mikrobiologie   MeSH
• lidé MeSH
• mozek účinky léků   fyziologie   MeSH
• probiotika aplikace a dávkování   škodlivé účinky   MeSH
• střevní mikroflóra účinky léků   fyziologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• antibakteriální látky MeSH

There is evidence indicating that a vegan diet could be beneficial in the prevention of neurodegenerative disorders, including Alzheimer's disease (AD). The purpose of this review is to summarize the current knowledge on the positive and negative aspects of a vegan diet regarding the risk of AD. Regarding AD prevention, a vegan diet includes low levels of saturated fats and cholesterol, contributing to a healthy blood lipid profile. Furthermore, it is rich in phytonutrients, such as vitamins, antioxidants, and dietary fiber, that may help prevent cognitive decline. Moreover, a vegan diet contributes to the assumption of quercetin, a natural inhibitor of monoamine oxidase (MAO), which can contribute to maintaining mental health and reducing AD risk. Nonetheless, the data available do not allow an assessment of whether strict veganism is beneficial for AD prevention compared with vegetarianism or other diets. A vegan diet lacks specific vitamins and micronutrients and may result in nutritional deficiencies. Vegans not supplementing micronutrients are more prone to vitamin B12, vitamin D, and DHA deficiencies, which have been linked to AD. Thus, an evaluation of the net effect of a vegan diet on AD prevention and/or progression should be ascertained by taking into account all the positive and negative effects described here.

• Klíčová slova
• Alzheimer’s disease, cognition, vegan diet,
• MeSH
• Alzheimerova nemoc * etiologie   prevence a kontrola   MeSH
• dieta veganská * MeSH
• dieta vegetariánská MeSH
• dieta MeSH
• lidé MeSH
• mikroživiny MeSH
• vegani MeSH
• vitaminy MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• mikroživiny MeSH
• vitaminy MeSH

Alzheimer's disease (AD) is a progressive, neurodegenerative disease characterized by an increasing incidence. One of the pathologic processes that underlie this disorder is impairment of brain microvasculature. Transcranial ultrasound is a non-invasive examination of cerebral blood flow that can be employed as a simple and useful screening tool for assessing the vascular status of brain circulation in preclinical and clinical stages of AD. The objective of this review is to explore the utility of using a transcranial ultrasound to diagnose AD. With transcranial ultrasound, the most frequently studied parameters are cerebral blood flow velocities and pulsatility indices, cerebrovascular reserve capacity, and cerebral microembolization. On the basis of current knowledge, we recommend using as a transcranial Doppler sonography screening method of choice the assessment of cerebrovascular reserve capacity with breath-holding test.

• Klíčová slova
• Alzheimer's disease, breath-holding test, cerebrovascular reserve capacity, minimal cognitive impairment, transcranial color coded duplex ultrasonography, transcranial doppler sonography,
• MeSH
• Alzheimerova nemoc diagnostické zobrazování   patofyziologie   MeSH
• kognitivní poruchy etiologie   MeSH
• lidé MeSH
• mozkový krevní oběh fyziologie   MeSH
• ultrasonografie dopplerovská transkraniální * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

The choroid plexus (ChP) produces and is bathed in the cerebrospinal fluid (CSF), which in aging and Alzheimer's disease (AD) shows extensive proteomic alterations including evidence of inflammation. Considering inflammation hampers functions of the involved tissues, the CSF abnormalities reported in these conditions are suggestive of ChP injury. Indeed, several studies document ChP damage in aging and AD, which nevertheless remains to be systematically characterized. We here report that the changes elicited in the CSF by AD are consistent with a perturbed aging process and accompanied by aberrant accumulation of inflammatory signals and metabolically active proteins in the ChP. Magnetic resonance imaging (MRI) imaging shows that these molecular aberrancies correspond to significant remodeling of ChP in AD, which correlates with aging and cognitive decline. Collectively, our preliminary post-mortem and in vivo findings reveal a repertoire of ChP pathologies indicative of its dysfunction and involvement in the pathogenesis of AD. HIGHLIGHTS: Cerebrospinal fluid changes associated with aging are perturbed in Alzheimer's disease Paradoxically, in Alzheimer's disease, the choroid plexus exhibits increased cytokine levels without evidence of inflammatory activation or infiltrates In Alzheimer's disease, increased choroid plexus volumes correlate with age and cognitive performance.

• Klíčová slova
• Alzheimer's disease, aging, cerebrospinal fluid, choroid plexus, pathology,
• MeSH
• Alzheimerova nemoc * patologie   MeSH
• lidé MeSH
• plexus chorioideus metabolismus   patologie   MeSH
• proteomika MeSH
• stárnutí MeSH
• zánět MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH