Patient-reported outcome and cognitive measures to be used in vascular and brain tumor surgery: proposal for a minimum set.

BACKGROUND: The standardization of outcome measures is needed for comparing studies and using common measures in clinical practice. We aimed to identify cognitive and patient-reported outcomes and timing of assessment for glioma, meningioma, and vascular surgery. METHOD: A consensus study was conducted. Participants selected cognitive and patient-reported measures among a list of instruments identified through a literature search. RESULTS: Seventeen cognitive tests for the glioma and meningioma's evaluation, 8 for the vascular diseases, and one questionnaire on quality of life and one on emotional distress were identified. The timing of outcome assessment selected was before surgery, at discharge, and after 3 and 12 months for glioma; before surgery and after 3 months for meningioma; before surgery, at discharge, and after 6 months for vascular diseases. CONCLUSION: The identification of common outcome measures is the first step toward a shared data collection improving the quality and comparability of future studies.

The rehabilitation of object agnosia and prosopagnosia: A systematic review.

BACKGROUND: Agnosia for objects is often overlooked in neuropsychology, especially with respect to rehabilitation. Prosopagnosia has been studied more extensively, yet there have been few attempts at training it. The lack of training protocols may partially be accounted for by their relatively low incidence and specificity to sensory modality. However, finding effective rehabilitations for such deficits may help to reduce their impact on the social and psychological functioning of individuals. OBJECTIVE: Our aim in this study was to provide clinicians and researchers with useful information with which to conduct new studies on the rehabilitation of object agnosia and prosopagnosia. To accomplish this, we performed a systematic and comprehensive review of the effect of neuropsychological rehabilitation on visual object and prosopagnosia. METHODS: The Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines were followed. In addition, the Single-Case Experimental Design (SCED) and the Critical Appraisal Skills Programme (CASP) scales were used to assess the quality of reporting. RESULTS: Seven articles regarding object agnosia, eight articles describing treatments for prosopagnosia, and two articles describing treatments for both deficits were included. CONCLUSIONS: In the light of the studies reviewed, treatments based on analysis of parts seem effective for object agnosia, while prosopagnosia appears to benefit most from treatments relying on holistic/configural processing. However, more attempts at rehabilitation of face and object agnosia are needed to clarify the mechanisms of these processes and possible rehabilitations. Moreover, a publication bias could mask a broader attempt to find effective treatments for visual agnosia and leaving out studies that are potentially more informative.

Comparison of Oxford Cognitive Screen and Montreal Cognitive Assessment feasibility in the stroke unit setting. A pilot study.

Background: : Cognitive status evaluation is not routine in the acute stroke setting and there is no consensus on which neuropsychological tool is more feasible and informative. The aim of this pilot study was to compare the feasibility and acceptability of two brief cognitive tests, the Montreal Cognitive Assessment (MoCA) and the Oxford Cognitive Screen (OCS), in acute stroke, with a focus on patients' experience, administration time, and the cognitive data obtained. Methods: : Patients with a diagnosis of ischemic or hemorrhagic stroke or of transient ischemic attack admitted to two stroke units were included. The sample consisted of 34 participants (mean age ±SD 71.1 ± 16.1 years, 25 males). Within five days of onset, patients were evaluated by means of the MoCA and OCS by a trained neuropsychologist. Results: Both tests were feasible in the stroke unit setting and had a high level of acceptability by patients. MoCA test was fully completed by 25 patients, OCS by 21 patients. The OCS administration time was longer than that of the MoCA. However, OCS was perceived less demanding than MoCA by patients. Twenty patients completed both the MoCA and the OCS entirely, and only 2 of them did not show any impairment in both tests. Seventeen patients showed at least an impaired domain on the OCS and 15 patients presented with a MoCA global score below cut-off for cognitive impairment. Conclusions: Our preliminary study did not show a superiority of the OCS over the widely used MoCA, and suggests the need for further validation in larger samples of stroke patients, exploring tests accuracy in detecting cognitive post-stroke impairment.

Altered neural oscillations and connectivity in the beta band underlie detail-oriented visual processing in autism.

Sensory and perceptual anomalies may have a major impact on basic cognitive and social skills in humans. Autism Spectrum Disorder (ASD) represents a special perspective to explore this relationship, being characterized by both these features. The present study employed electroencephalography (EEG) to test whether detail-oriented visual perception, a recognized hallmark of ASD, is associated with altered neural oscillations and functional connectivity in the beta frequency band, considering its role in feedback and top-down reentrant signalling in the typical population. Using a visual crowding task, where participants had to discriminate a peripheral target letter surrounded by flankers at different distances, we found that detail-oriented processing in children with ASD, as compared to typically developing peers, could be attributed to anomalous oscillatory activity in the beta band (15-30 Hz), while no differences emerged in the alpha band (8-12 Hz). Altered beta oscillatory response reflected in turn atypical functional connectivity between occipital areas, where the initial stimulus analysis is accomplished, and infero-temporal regions, where objects identity is extracted. Such atypical beta connectivity predicted both ASD symptomatology and their detail-oriented processing. Overall, these results might be explained by an altered feedback connectivity within the visual system, with potential cascade effects in visual scene parsing and higher order functions.

Centenarians' offspring as a model of healthy aging: a reappraisal of the data on Italian subjects and a comprehensive overview.

Within the scenario of an increasing life expectancy worldwide it is mandatory to identify determinants of healthy aging. Centenarian offspring (CO) is one of the most informative model to identify trajectories of healthy aging and their determinants (genetic and environmental), being representative of elderly in their 70th whose lifestyle can be still modified to attain a better health. This study is the first comprehensive investigation of the health status of 267 CO (mean age: 70.2 years) and adopts the innovative approach of comparing CO with 107 age-matched offspring of non-long-lived parents (hereafter indicated as NCO controls), recruited according to strict inclusion demographic criteria of Italian population. We adopted a multidimensional approach which integrates functional and cognitive assessment together with epidemiological and clinical data, including pro- and anti-inflammatory cytokines and adipokines, lipid profile, and insulin resistance. CO have a lower prevalence of stroke, cerebral thrombosis-hemorrhage, hypertension, hypercholesterolemia, and other minor diseases, lower BMI and waist circumference, a better functional and cognitive status and lower plasma level of FT4 compared to NCO controls. We conclude that a multidimensional approach is a reliable strategy to identify the health status of elderly at an age when interventions to modify their health trajectory are feasible.

Inflammaging and cancer: a challenge for the Mediterranean diet.

Aging is considered the major risk factor for cancer, one of the most important mortality causes in the western world. Inflammaging, a state of chronic, low-level systemic inflammation, is a pervasive feature of human aging. Chronic inflammation increases cancer risk and affects all cancer stages, triggering the initial genetic mutation or epigenetic mechanism, promoting cancer initiation, progression and metastatic diffusion. Thus, inflammaging is a strong candidate to connect age and cancer. A corollary of this hypothesis is that interventions aiming to decrease inflammaging should protect against cancer, as well as most/all age-related diseases. Epidemiological data are concordant in suggesting that the Mediterranean Diet (MD) decreases the risk of a variety of cancers but the underpinning mechanism(s) is (are) still unclear. Here we review data indicating that the MD (as a whole diet or single bioactive nutrients typical of the MD) modulates multiple interconnected processes involved in carcinogenesis and inflammatory response such as free radical production, NF-κB activation and expression of inflammatory mediators, and the eicosanoids pathway. Particular attention is devoted to the capability of MD to affect the balance between pro- and anti-inflammaging as well as to emerging topics such as maintenance of gut microbiota (GM) homeostasis and epigenetic modulation of oncogenesis through specific microRNAs.

Combating inflammaging through a Mediterranean whole diet approach: the NU-AGE project's conceptual framework and design.

The development of a chronic, low grade, inflammatory status named "inflammaging" is a major characteristic of ageing, which plays a critical role in the pathogenesis of age-related diseases. Inflammaging is both local and systemic, and a variety of organs and systems contribute inflammatory stimuli that accumulate lifelong. The NU-AGE rationale is that a one year Mediterranean whole diet (considered by UNESCO a heritage of humanity), newly designed to meet the nutritional needs of the elderly, will reduce inflammaging in fully characterized subjects aged 65-79 years of age, and will have systemic beneficial effects on health status (physical and cognitive). Before and after the dietary intervention a comprehensive set of analyses, including omics (transcriptomics, epigenetics, metabolomics and metagenomics) will be performed to identify the underpinning molecular mechanisms. NU-AGE will set up a comprehensive database as a tool for a systems biology approach to inflammaging and nutrition. NU-AGE is highly interdisciplinary, includes leading research centres in Europe on nutrition and ageing, and is complemented by EU multinational food industries and SMEs, interested in the production of functional and enriched/advanced traditional food tailored for the elderly market, and European Federations targeting policy makers and major stakeholders, from consumers to EU Food & Drink Industries.

Reprint of: A parallel randomized trial on the effect of a healthful diet on inflammageing and its consequences in European elderly people: design of the NU-AGE dietary intervention study.

BACKGROUND: The proportion of European elderly is expected to increase to 30% in 2060. Combining dietary components may modulate many processes involved in ageing. So, it is likely that a healthful diet approach might have greater favourable impact on age-related decline than individual dietary components. This paper describes the design of a healthful diet intervention on inflammageing and its consequences in the elderly. METHODS: The NU-AGE study is a parallel randomized one-year trial in 1250 apparently healthy, independently living European participants aged 65-80 years. Participants are randomised into either the diet group or control group. Participants in the diet group received dietary advice aimed at meeting the nutritional requirements of the ageing population. Special attention was paid to nutrients that may be inadequate or limiting in diets of elderly, such as vitamin D, vitamin B12, and calcium. C-reactive protein is measured as primary outcome. DISCUSSION: The NU-AGE study is the first dietary intervention investigating the effect of a healthful diet providing targeted nutritional recommendations for optimal health and quality of life in apparently healthy European elderly. Results of this intervention will provide evidence on the effect of a healthful diet on the prevention of age related decline.

A parallel randomized trial on the effect of a healthful diet on inflammageing and its consequences in European elderly people: design of the NU-AGE dietary intervention study.

BACKGROUND: The proportion of European elderly is expected to increase to 30% in 2060. Combining dietary components may modulate many processes involved in ageing. So, it is likely that a healthful diet approach might have greater favourable impact on age-related decline than individual dietary components. This paper describes the design of a healthful diet intervention on inflammageing and its consequences in the elderly. METHODS: The NU-AGE study is a parallel randomized one-year trial in 1250 apparently healthy, independently living European participants aged 65-80 years. Participants are randomised into either the diet group or control group. Participants in the diet group received dietary advice aimed at meeting the nutritional requirements of the ageing population. Special attention was paid to nutrients that may be inadequate or limiting in diets of elderly, such as vitamin D, vitamin B12, and calcium. C-reactive protein is measured as primary outcome. DISCUSSION: The NU-AGE study is the first dietary intervention investigating the effect of a healthful diet providing targeted nutritional recommendations for optimal health and quality of life in apparently healthy European elderly. Results of this intervention will provide evidence on the effect of a healthful diet on the prevention of age related decline.

Immune system, cell senescence, aging and longevity--inflamm-aging reappraised.

Inflamm-aging, that is the age-associated inflammatory status, is considered one of the most striking consequences of immunosenescence, as it is believed to be linked to the majority of age-associated diseases sharing an inflammatory basis. Nevertheless, evidence is emerging that inflamm-aging is at least in part independent from immunological stimuli. Moreover, centenarians who avoided or delayed major inflammatory diseases display markers of inflammation. In this paper we proposed a reappraisal of the concept of inflamm-aging, suggesting that its pathological effects can be independent from the total amount of pro-inflammatory mediators, but they would be rather associated with the anatomical district and type of cells where they are produced and where they primarily act.

Space/population and time/age in DNA methylation variability in humans: a study on IGF2/H19 locus in different Italian populations and in mono- and di-zygotic twins of different age.

Little is known about the impact of space (geography/ancestry) and time (age of the individuals) on DNA methylation variability in humans. We investigated DNA methylation of the imprinted IGF2/H19 locus in: i) a cohort of individuals homogeneous for age and gender (males with restricted age range: 30-50 years) belonging to four Italian districts representative of the major genetic clines, informative for the geographical dimension; ii) a cohort of monozygotic (MZ) and dizygotic (DZ) twins of different ages (age-range: 22-97 years), informative for the temporal dimension. DNA methylation of the analyzed regions displayed high levels of inter-individual variability that could not be ascribed to any geographical cline. In MZ twins we identified two IGF2/H19 regions where the intra-couple variations significantly increased after the age of 60 years. The analysis of twins' individual life histories suggests that the within twin pairs difference is likely the result of the aging process itself, as sharing a common environment for long periods had no effect on DNA methylation divergence. On the whole, the data here reported suggest that: i) aging more than population genetics is responsible for the inter-individual variability in DNA methylation patterns in humans; ii) DNA methylation variability appears to be highly region-specific.

Through ageing, and beyond: gut microbiota and inflammatory status in seniors and centenarians.

BACKGROUND: Age-related physiological changes in the gastrointestinal tract, as well as modifications in lifestyle, nutritional behaviour, and functionality of the host immune system, inevitably affect the gut microbiota, resulting in a greater susceptibility to infections. METHODOLOGY/PRINCIPAL FINDINGS: By using the Human Intestinal Tract Chip (HITChip) and quantitative PCR of 16S rRNA genes of Bacteria and Archaea, we explored the age-related differences in the gut microbiota composition among young adults, elderly, and centenarians, i.e subjects who reached the extreme limits of the human lifespan, living for over 100 years. We observed that the microbial composition and diversity of the gut ecosystem of young adults and seventy-years old people is highly similar but differs significantly from that of the centenarians. After 100 years of symbiotic association with the human host, the microbiota is characterized by a rearrangement in the Firmicutes population and an enrichment in facultative anaerobes, notably pathobionts. The presence of such a compromised microbiota in the centenarians is associated with an increased inflammatory status, also known as inflammageing, as determined by a range of peripheral blood inflammatory markers. This may be explained by a remodelling of the centenarians' microbiota, with a marked decrease in Faecalibacterium prauznitzii and relatives, symbiotic species with reported anti-inflammatory properties. As signature bacteria of the long life we identified specifically Eubacterium limosum and relatives that were more than ten-fold increased in the centenarians. CONCLUSIONS/SIGNIFICANCE: We provide evidence for the fact that the ageing process deeply affects the structure of the human gut microbiota, as well as its homeostasis with the host's immune system. Because of its crucial role in the host physiology and health status, age-related differences in the gut microbiota composition may be related to the progression of diseases and frailty in the elderly population.