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Author(s): M L C Leite [sup.1] , F Prinelli [sup.1] Author Affiliations: (1) National Research Council, Institute of Biomedical Technologies, Milan, Italy Introduction When studying the relationship between nutrition and [...]

This abstract was awarded the prize for best poster presentation. Undernutrition is common among older adults and, if untreated, can lead to weight loss, adverse cognitive and functional health outcomes and poorer quality of life. The Mediterranean diet (MedDiet) has been associated with reduced nutrient deficiency1 and better cognitive health in older adults2, while adequate protein intake combined with exercise is crucial for maintaining muscle health during ageing3. Early intervention with MedDiet to meet energy and increased protein (1.2g/kg/day)4 and micronutrient needs of older adults in combination with exercise could help to prevent undernutrition during ageing but has not yet been tested. The PROMED-EX trial is a 6-month randomised controlled trial evaluating a PROtein-enriched MED Diet, with and without Exercise on nutritional status and cognitive performance, in older adults at increased risk of undernutrition and cognitive decline.5 The current objective is to evaluate the 3month change in nutritional status and diet quality measured using repeated Mini Nutritional Assessment (MNA), 4-day food diaries and PROMED diet score (0-14). Food diaries were analysed for energy and nutrients using Nutritics at each time-point. Data was analysed on the intention-totreat principle using multiple linear regression to compare outcomes at 3 months after adjusting for baseline values. Dunnett's procedure was used to control for multiple comparisons when comparing the two intervention groups with the control group. One hundred and five eligible participants (69% female; mean age 67.7years [60-87 years]; BMI: 23.8 ± 3.4 kg/m2) were recruited and randomised into one of three groups: PROMED-EX (diet + exercise; n = 34), PROMED (diet only; n = 35) and Standard Care (control; n = 36). After 3-months, the MNA score improved in both PROMED-EX and PROMED intervention groups compared with the control group by on average 2.6 points (95% CI 1.1, 4.1; P<0.01) and 2.2 points (95% CI 0.8, 3.7; P<0.01) respectively; after adjusting for baseline MNA. Similarly, the mean 3-month increase in diet quality score was +4.0 (95% CI 3.1, 5.0); +4.6 (95% CI 3.7, 5.4) points in PROMEDEX and PROMED respectively; P<0.001, versus Control. No between group changes in energy intake were detected, however protein and selected micronutrient intakes improved in the intervention groups. Compared to the control group, the between-group difference in mean protein intake was +21.4g/day (95% CI 9.8, 32.9) in PROMED (P<0.001) and +9.0g/day (95% CI -3.1, 21.0) in PROMED-EX (P>0.05). There was significantly greater improvement in dietary fibre, selenium, iron and vitamin D intakes in both interventions relative to Control (all P<0.001). This 3-month analysis demonstrates the positive effects of the PROMED-EX and PROMED interventions on nutritional status and diet quality, as well as improvement in selected nutrients in older adults vulnerable to both undernutrition and cognitive decline. [ABSTRACT FROM AUTHOR]

Objectives: The PROtein-enriched MEDiterranean diet to combat undernutrition and promote healthy neuroCOGnitive ageing in older adults (PROMED-COG) is a European project that investigates the role of nutritional status on neurocognitive ageing. This methodological paper describes the harmonization process of dietary data from four Italian observational studies (Pro.V.A., ILSA, BEST-FU, and NutBrain). Methods: Portion sizes and food frequency consumption within different food frequency questionnaires were retrospectively harmonized across the datasets on daily food frequency, initially analyzing raw data using the original codebook and establishing a uniform food categorization system. Individual foods were then aggregated into 27 common food groups. Results: The pooled cohort consisted of 9326 individuals (40-101 years, 52.4% female). BEST-FU recruited younger participants who were more often smokers and less physically active than those of the other studies. Dietary instruments varied across the studies differing in the number of items and time intervals assessed, but all collected dietary intake through face-to-face interviews with a common subset of items. The average daily intakes of the 27 food groups across studies varied, with BEST-FU participants generally consuming more fruits, vegetables, red meat, and fish than the other studies. Conclusions: Harmonization of dietary data presents challenges but allows for the integration of information from diverse studies, leading to a more robust and statistically powerful dataset. The study highlights the feasibility and benefits of data harmonization, despite inherent limitations, and sets the stage for future research into the effects of diet on cognitive health and aging.

Introduction: Human induced pluripotent stem cells (hiPSCs), derived from reprogrammed adult somatic cells, hold significant promise for disease modelling, personalized medicine, drug discovery, and regenerative therapies. Public awareness and understanding of hiPSCs are crucial for advancing research in this field. However, limited data exists on the general population's knowledge and attitudes toward their use., Methods: This study aimed to assess the awareness and perceptions of hiPSCs among Italian adults through a web-based survey conducted via the EUSurvey platform, using a snowball sampling approach. The survey included demographic information and mandatory questions on knowledge, awareness, and concerns regarding hiPSC technology, with responses collected on a 3-point scale. Statistical analysis was performed using chi-squared tests, with significance set at p  ≤ 0.05., Results: Out of 1874 respondents, the majority were aged 18-35 years (40.5%), female (63.4%), and university-educated (67.2%). Among those familiar with hiPSCs (54.1%, n  = 1,201), 95.3% expressed willingness to donate blood samples for hiPSC generation to treat individuals with incurable diseases. Concerns about current research and therapeutic applications were low (less than 20%), but nearly half of the respondents were hesitant or opposed to the use of hiPSCs in animal experiments and their commercialization by pharmaceutical companies. Increased skepticism was observed in older, less educated, religious individuals, and those who were not blood donors. Overall, the Italian public shows strong support for hiPSC-based therapies, though reservations exist around specific ethical and economic issues., Discussion: These findings underscore the importance of addressing public concerns through targeted educational campaigns, not only in Italy but globally, to foster a more informed and supportive environment for advancing stem cell research and its clinical applications worldwide. Similar studies have been conducted in Japan, the United States, and Sweden, but there remains a need for all countries to engage with their citizens to better understand how stem cell research is perceived locally. Such engagement is crucial for guiding international strategies in personalized medicine and regenerative therapies, ensuring that emerging technologies are met with both ethical integrity and public trust., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Elia, Prinelli, Peli, Conti, Barilani, Mei, Castaldi and Lazzari.)

Background & Aims: Undernutrition may negatively impact cognitive function, but evidence of this relationship is not yet consolidated. Under the "PROtein enriched MEDiterranean diet to combat undernutrition and promote healthy neuroCOGnitive ageing" (PROMED-COG) project, we evaluated the association between undernutrition, and cognitive decline and incident dementia in older adults., Methods: Retrospective data harmonization was performed on three Italian population-based studies: the Italian Longitudinal Study of Ageing (ILSA), the Progetto Veneto Anziani (Pro.V.A.), and the Bollate Eye Study-Follow-Up (BEST-FU). The associations between undernutrition, operationalized using the Global Leadership Initiative on Malnutrition (GLIM) criteria, and decline on the Mini-Mental State Examination (MMSE) or dementia incidence follow-up were evaluated with Cox proportional hazard regression models., Results: The pooled cohort comprised 9071 individuals (52% females) aged between 42 and 101 years. The prevalence of undernutrition at the baseline was 14.3%, significantly higher among females (15.4% vs 13%) and in older age, ranging from 3.5% in those aged <60 years to 28.8% in those 85+ years. Undernutrition was associated with both cognitive decline over a median 8.3-year follow-up (Hazard Ratio (HR) 1.20, 95% Confidence Interval (CI) 1.02-1.41, p = 0.028) and incidence of dementia over a median 8.6-year follow-up (HR = 1.57, 95%CI 1.01-2.43, p = 0.046). For cognitive decline, the association with undernutrition was more marked in males than females (HR = 1.36, 95%CI 1.05-1.77, p = 0.019 vs HR = 1.10, 95% CI 0.89-1.36, p = 0.375)., Conclusion: Undernutrition is prevalent among older people and is associated with an increased risk of experiencing cognitive decline and dementia. The prevention and early identification of undernutrition could be an important nonpharmacologic strategy to counteract neurodegeneration., Competing Interests: Conflict of interest None., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

The COVID-19 pandemic has induced significant impairments, including sleep disturbances. The present study aimed to explore the impact of fear in relation to stress on sleep disorders among Italian adults and older participants in the second phase of the EPICOVID19 web-based survey (January-February 2021). Sleep disturbances during the pandemic were evaluated using the Jenkins Sleep Scale, perceived stress through the 10-item Perceived Stress Scale and fear of contagion and about economic and job situation with four ad hoc items. The strength of the pathways between stress, sleep disturbances and fear was explored using structural equation modelling, hypothesising that stress was related to sleep disturbances and that fear was associated with both stress and sleep problems. Out of 41,473 participants (74.7% women; mean age 49.7 ± 13.1 years), 8.1% reported sleep disturbances and were more frequently women, employed in a work category at risk of infection or unemployed, and showed higher deprivation scores. Considering an a priori hypotheses model defining sleep and stress scores as endogenous variables and fear as an exogenous variable, we found that fear was associated with sleep problems and stress, and stress was associated with sleep problems; almost half of the total impact of fear on sleep quality was mediated by stress. The impact of stress on sleep quality was more evident in the younger age group, among individuals with a lower socioeconomic status and healthcare workers. Fear related to COVID-19 seem to be associated with sleep disturbances directly and indirectly through stress., (© 2024 John Wiley & Sons Ltd.)

Data on the association of the Mediterranean diet (MD) with depressive symptoms in older people at high risk of depression are scarce. This study aimed to investigate the cross-sectional association of the adherence to the MD and its components with depressive symptoms in an Italian cohort of older men and women. A total of 325 men and 473 women aged 65–97 years (2019–2023) answered a 102-item semi-quantitative FFQ, which was used to calculate the Mediterranean diet score (MDS). Depressive symptoms were assessed using the Centre for Epidemiological Studies Depression Scale; subjects with a score of 16 or more were considered to have depression. Multivariable logistic regression was used for statistical analysis. The occurrence of depressive symptoms was 19·8 % (8·0 % men, 27·9 % women). High adherence to MDS (highest tertile) significantly reduced the odds of having depressive symptoms by 54·6 % (OR 0·454, 95 % CI 0·266, 0·776). In sex-stratified analysis, the reduction was evident in women (OR 0·385, 95 % CI 0·206, 0·719) but not in men (OR 0·828, 95 % CI 0·254, 2·705). Looking at the association of MDS components with depressive symptoms, we found an inverse significant association with fish consumption and the MUFA:SFA ratio above the median only in women (OR 0·444, 95 % CI 0·283, 0·697 and OR 0·579, 95 % CI 0·345, 0·971, respectively). High adherence to the MDS, and a high fish intake and MUFA:SFA ratio were associated with lower depressive symptoms in women only. Future longitudinal studies are needed to confirm these findings and to explore the underlying biological mechanisms.

Background: The COVID-19 lockdown had a profound effect on everyday life, including sleep health. This systematic review and meta-analysis evaluated changes in quantitative sleep parameters during the first lockdown compared with pre-lockdown in the general population., Methods: A search in scientific databases was performed to identify eligible observational studies from inception to 8 February 2023. We performed a random effects meta-analysis of those studies reporting (a) means of sleep duration, time in bed (TIB), and sleep timing (bedtime and wake-up time); (b) the percentages of atypical sleep duration before and during the lockdown; (c) the percentages of change in sleep duration and sleep timing., Results: A total of 154 studies were included. A small increase in sleep duration (0.25 standardized mean difference, 95% CI 0.180-0.315) was found, with 55.0% of the individuals reporting changes, predominantly an increase (35.2%). The pooled relative risk for sleeping more than 8/9 h per night was 3.31 (95% IC 2.60-4.21). There was a moderately significant delay in sleep timing and a surge in napping., Conclusion: An increase in sleep duration and napping, and delayed sleep timing were observed. High-quality studies should evaluate whether these parameters have now become chronic or have returned to pre-lockdown values.

Polypharmacy (PP) use is very common in older people and may lead to drug-drug interactions (DDIs) and anticholinergic burden (ACB) that may affect cognitive function. We aimed to determine the occurrence of PP, potential DDIs and ACB and their role in cognitive outcomes in an older population. Cross-sectional data from 636 community-dwelling adults (73.2 ± 6.0 SD, 58.6% women) participating in the NutBrain study (2019-2023) were analyzed. Participants were asked about their medication use, and data on potential DDIs and ACB were extracted. The associations of PP (≥ 5 drugs/day), potential DDIs, and ACB with mild cognitive impairment (MCI) and specific cognitive domains were assessed using logistic regression adjusted for confounders. Sex-stratified analysis was performed. Overall, 27.2% of the participants were exposed to PP, 42.3% to potential DDIs and 19% to cumulative ACB. Women were less exposed to PP and more exposed to ACB than men. In multivariate analysis, the odds of having MCI (24%) were three times higher in those with severe ACB (≥ 3) (OR 3.34, 95%CI 1.35-8.25). ACB was positively associated with poor executive function (OR 4.45, 95%CI 1.72-11.49) and specifically with the Frontal Assessment Battery and neuropsychological tests of phonological and semantic fluency. In sex-stratified analysis, ACB was statistically significantly associated with MCI and executive function in women and with memory in men. PP, potential DDIs and anticholinergics use are very common in community-dwelling older people. ACB exposure is associated with MCI, particularly with poor executive function. Clinicians are encouraged to be vigilant when prescribing anticholinergics.Trial registration: Trial registration number NCT04461951, date of registration July 7, 2020 (retrospectively registered, ClinicalTrials.gov)., (© 2024. The Author(s).)

Objectives: Despite extensive research, a clear understanding of the role of the interaction between lifestyle and socioeconomic status (SES) on cognitive health is still lacking. We investigated the joint association of socioeconomic factors in early to midlife and lifestyle in later life and Mild Cognitive Impairment (MCI)., Design: Observational cross-sectional study., Setting: NutBrain study in northern Italy., Participants: 773 community-dwelling adults aged 65 years and older (73.2 ± 6.0 SD, 58.6% females) participating in the NutBrain study (2019-2023)., Measurements: Three SES indicators (home ownership, educational level, occupation) and five lifestyle factors (adherence to Mediterranean diet, physical activity, smoking habits, social network, leisure activities) were selected. Each factor was scored and summed to calculate SES and healthy lifestyle scores; their joint effect was also examined. The association with MCI was assessed by logistic regression controlling for potential confounders. Sex-stratified analysis was performed., Results: In total, 24% of the subjects had MCI. The multivariable logistic model showed that a high SES and a high lifestyle score were associated with 81.8% (OR0.182; 95%CI 0.095-0.351), and 44.1% (OR0.559; 95%CI 0.323-0.968) lower odds of having MCI, respectively. When examining the joint effect of SES and lifestyle factors, the cognitive benefits of a healthy lifestyle were most pronounced in participants with low SES. A healthier lifestyle score was found to be significantly associated with lower odds of MCI, only in females., Conclusions: According to our findings, SES was positively associated with preserved cognitive function, highlighting the importance of active lifestyles in reducing socioeconomic health inequalities, particularly among those with a relatively low SES., Trial Registration: Trial registration number NCT04461951, date of registration July 7, 2020 (retrospectively registered, ClinicalTrials.gov)., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

From the initial COVID-19 outbreak, Italy was the first Western country to be seriously affected by the pandemic. Understanding vaccine hesitancy can help efforts to achieve broad vaccination coverage. The objectives of this research were to determine the extent of vaccine hesitancy in Italy and to understand the characteristics of those segments of the population with some hesitancy. Between January and February 2021, 41,473 subjects answered the second questionnaire delivered in phase II of the web-based EPICOVID19 survey. Among the included adult volunteers living in Italy, 4653 (11.2%) reported having previously received at least one dose of the COVID-19 vaccine. In the sample of 36,820 respondents, all not vaccinated (age 51.1 ± 13.5; 59.7% female; 63.6% high level of education), the comparison between hesitant and inclined participants was accompanied by percentages and odds ratios. A total of 2449 individuals were hesitant (6.7% of the unvaccinated ones). Hesitancy was higher among women (OR = 1.48; 95%CI: 1.36-1.62); it was highest in the 50-59 and 40-49 age groups and among those with a lower educational level. A higher level of education was associated with a lower proportion of hesitancy (5.54%) compared with 9.44% among respondents with a low level of education (OR = 0.56; 95%CI: 0.46-0.68). Hesitancy was most common in subjects who did not report fear of infection (12.4%, OR = 4.0; 95%CI: 3.46-4.61). The results can guide the design of tailored information and communication campaigns through considering objective and subjective characteristics.

Introduction: Undernutrition leading to unplanned weight loss is common in older age and has been linked to increased dementia risk in later life. Weight loss can precede dementia by a decade or more, providing a unique opportunity for early intervention to correct undernutrition and potentially prevent or delay cognitive impairment. The combined effects of diet and exercise on undernutrition have not yet been evaluated. The objective of this trial is to determine the effect of a protein-enriched Mediterranean diet, with and without exercise, on nutritional status and cognitive performance in older adults at risk of undernutrition and cognitive decline., Methods: One hundred and five participants aged 60 years and over at risk of undernutrition and with subjective cognitive decline will be recruited to participate in a 6-month, single-blind, parallel-group randomised controlled trial. Participants will be block randomised into one of three groups: group 1-PROMED-EX (diet+exercise), group 2-PROMED (diet only) and group 3-standard care (control). The primary outcome is nutritional status measured using the Mini Nutritional Assessment. Secondary outcomes include cognitive function, nutritional intake, body composition, physical function and quality of life. Mechanistic pathways for potential diet and exercise-induced change in nutritional status and cognition will be explored by measuring inflammatory, metabolic, nutritional and metabolomic biomarkers., Ethics and Dissemination: The study is approved by the UK Office for Research Ethics Committee (ref: 21/NW/0215). Written informed consent will be obtained from participants prior to recruitment. Research results will be disseminated to the public via meetings and media and the scientific community through conference presentations and publication in academic journals., Trial Registration Number: ClinicalTrials.gov Registry (NCT05166564)., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

Dementia prevalence is a global public health concern. Adherence towards a healthy dietary pattern (DP) may reduce the risk of cognitive decline and dementia. This narrative systematic review aimed to synthesise prospective and intervention study data to evaluate the impact of a -posteriori and a -priori derived DPs on cognitive ageing, from cognitive decline to incident dementia. Ninety-three studies were included: 83 prospective studies and 10 randomised controlled trials (RCT). Most prospective studies (77%) examined a -priori DPs, with the Mediterranean diet examined most frequently. A total of 52% of prospective and 50% of RCTs reported a protective relationship between 'healthy' DPs and global cognitive decline. Overall, 59% of prospective studies reported positive associations between healthy DPs and risk of cognitive disorder. Incident cognitive disorder was examined by only one intervention study (subgroup analysis) which reported a beneficial effect of a low-fat diet on risk of probable dementia in women. Unhealthy DPs were examined less frequently ( n = 17; 21%), with 41% of these studies reporting associations between adherence and poorer cognitive outcomes. Overall, there were mixed results for healthy and unhealthy DPs on cognition, likely due to between-study heterogeneity. Standardisation of diet exposure and cognitive outcome measurement would help to reduce this. Future research would benefit from investigating effects of culturally appropriate DPs on individual cognitive domains and incident cognitive disorders in diverse and high-risk populations.

Background: COVID-19 has caused a parallel epidemic of fear, anxiety, depression, stress, and frustration, particularly among the most fragile and vulnerable individuals, such as older people and those with previous mental health disorders. The present study aims to investigate the association between pre-existing mental health disorders, particularly depressive symptoms and Mild Cognitive Impairment (MCI), and the fear of COVID-19 and to explore which cognitive domains were involved in coping with fear in older people., Materials and Methods: In April 2020, we conducted a phone-interview questionnaire on community-dwelling older adults living in Lombardy Region (Italy) who participated in the NutBrain study. At baseline, socio-demographic characteristics along with lifestyles, and medical history were recorded. Participants underwent a neuropsychological battery exploring the global cognitive function and specific cognitive domains, to detect cases of MCI. The Center for Epidemiologic Studies Depression scale (CES-D) was used for screening depressive symptoms. During the phone survey, respondents were assessed using a structured questionnaire querying about fear of the COVID-19 pandemic. We performed multivariate logistic regression models to study the association between MCI and depressive symptomatology and fear. We also explored which cognitive domains were associated with fear. Odds Ratios (OR) with Confidence Intervals (95%CI) were estimated adjusting for potential confounders., Results: Out of the 351 respondents (mean age 73.5 ± 6.1 years, 59.8% women, 49.1% high education), at baseline, 22.9% had MCI and 18.8% had depressive symptoms. In the multivariate analyses gender, age, and body mass index were significantly associated with the fear score. Considering different domains of fear, MCI was associated with fear of being infected themselves (OR 2.55, 95%CI 1.39-4.70) while depressive symptoms were associated with fear of contagion for family members (OR 2.38, 95%CI 1.25-4.52). Impaired executive cognitive function was positively associated with the highest tertile of the fear score (OR 3.28, 95%CI 1.37-7.74) and with fear of contagion for themselves (OR 3.39, 95%CI 1.61-7.17)., Conclusion: Older adults experienced different fear reactions, particularly when suffering from neurocognitive disorders and depressive symptoms; executive dysfunction was associated with increased fear. These results highlighted the need to pay attention to the psychological effects of the outbreak of COVID-19 to target intervention, especially among vulnerable subgroups of individuals., Clinical Trial Registration: [ClinicalTrials.gov], identifier [NCT04461951]., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Perdixi, Bernini, Conti, Jesuthasan, Cotta Ramusino, Costa and Prinelli.)

Dementia is a major public health challenge owing to its increasing prevalence and recognised impact on disability among older adults. Observational data indicate that weight loss is associated with increased dementia risk of 30%-40% and precedes a diagnosis of cognitive impairment or dementia by at least one decade. Although relatively little is known about the mechanisms of unintentional weight loss in dementia, this provides a window of opportunity to intervene with strategies to counteract undernutrition and delay, or prevent, the onset of dementia. This article provides an overview of the PROMED-COG project and associated work packages. The project aimes to (1) strengthen the epidemiologic evidence to better understand the potential benefits of combating undernutrition for healthy neurocognitive ageing; (2) increase scientific knowledge on the balance between a protein enriched Mediterranean diet (PROMED) and physical exercise to prevent undernutrition and promote healthy neurocognitive ageing, and generate data on mechanistic pathways; (3) stimulate collaboration and capacity building for nutrition and neurocognitive ageing research in Europe; and (4) develop public and practice recommendations to combat undernutrition and promote healthy neurocognitive ageing in older adults. Findings will provide new and critical insights into the role of undernutrition in neurocognitive ageing, how this role can differ by sex, genetic risk and timing of undernutrition exposure, and how modifications of dietary and physical activity behaviour can reduce the burden of undernutrition and neurodegeneration. The research outcomes will be useful to inform policy and practice about the dietary guidelines of older people and provide insight to industry for the development of food-based solutions to prevent undernutrition., (© 2022 The Authors. Nutrition Bulletin published by John Wiley & Sons Ltd on behalf of British Nutrition Foundation.)

Dementia is a complex, growing challenge for population health worldwide. Dietary patterns (DPs) may offer an opportunity to beneficially influence cognitive ageing and potentially reduce an individuals' risk of dementia through diet-related mechanisms. However, previous studies within this area have shown mixed results, which may be partly explained by the lack of sensitivity and accuracy within cognitive testing methods. Novel neuroimaging techniques provide a sensitive method to analyse brain changes preceding cognitive impairment which may have previously remained undetected. The purpose of this systematic review was to elucidate the role of DPs in relation to brain ageing processes, by summarising current prospective and intervention studies. Nine prospective studies met the inclusion criteria for the review, seven evaluated the Mediterranean diet (MeDi), one evaluated the Alternative Healthy Eating Index-2010, and one evaluated a posteriori derived DPs. No intervention studies were eligible for inclusion in this review. There was some evidence of an association between healthy DPs and neuroimaging markers including changes within these markers over time. Consequently, it is plausible that better adherence to such DPs may positively influence brain ageing and neurodegeneration. Future studies may benefit from the use of multi-modal neuroimaging techniques, to further investigate how adherence to a DP influences brain health. The review also highlights the crucial need for further intervention studies within this research area., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Townsend, Woodside, Prinelli, O’Neill and McEvoy.)

Objective To investigate sex- and gender-based differences linked to SARS-COV-2 infection and to explore the role of hormonal therapy (HT) in females. Study design Data from the self-administered, cross-sectional, web-based EPICOVID19 survey of 198,822 adults living in Italy who completed an online questionnaire during the first wave of the epidemic in Italy (April-May 2020) were analyzed. Main outcomes measures Multivariate binary logistic and multinomial regression models were respectively used to estimate the odds ratios (ORs) with 95% confidence intervals (CIs) for positive nasopharyngeal swab (NPS) test results and severe SARS-CoV-2 infection. Results The data from 6,873 participants (mean age 47.9 ± 14.1 years, 65.8% females) who had a known result from an NPS test were analyzed. According to the multivariate analysis, females had lower odds of a positive result from the NPS test (aOR 0.75, 95%CI 0.66-0.85) and of having a severe infection (aOR 0.46, 95%CI 0.37-0.57) than did their male counterparts. These differences were greater with decreasing age in both sexes. In addition, females aged ≥60 years receiving HT (N = 2,153, 47.6%) had a 46% lower probability of having a positive NPS test (aOR 0.54, 95%CI 0.36-0.80) than their same-aged peers who had never used HT; there were no differences in the younger age groups with respect to HT status. Conclusion Female sex was associated with an age-dependent lower risk of having a severe SARS-CoV-2 infection than their male counterparts. Age seemed to modify the relationship between HT status and infection: while the two were not related among younger participants, it was negative in the older ones. Future prospective studies are needed to elucidate the potential protective role sex hormones may play. Trial registration ClinicalTrials.gov NCT04471701., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Obesity amongst children and adolescents is becoming a major health problem globally and mobile food records can play a crucial role in promoting healthy dietary habits., Objective: To describe the methodology for the implementation of the e-Diary mobile food record, to assess its capability in promoting healthy eating habits, to evaluate the factors associated with its usage and engagement., Methods: This is a descriptive study that compared the characteristics of participants engaged in the e-Diary, which was part of the PEGASO project in which an app to provide proactive health promotion was given to 365 students at 4 European sites enrolled during October to December 2016: England (UK), Scotland (UK), Lombardy (Italy), and Catalonia (Spain). The e-Diary tracked the users' dietary habits in terms of food groups, dietary indexes, and 6 dietary target behaviors relating to consumption of: fruit; vegetable; breakfast; sugar-sweetened beverages; fast-food; and snacks. The e-Diary provided also personalized suggestions for the next meal and gamification., Results: The e-Diary was used for 6 months by 357 adolescents (53.8% females). The study showed that females used the e-Diary much more than males (aOR 3.8, 95% CI 1.6-8.8). Participants aged 14 years were more engaged in the e-Diary than older age groups (aOR 5.1, 95% CI 1.4-18.8) as were those with a very good/excellent self-perceived health status compared to their peers with fair/poor health perception (aOR 4.2, 95% CI 1.3-13.3). Compared to the intervention sites, those living in Catalonia (aOR 13.2 95% CI 2.5-68.8) were more engaged. In terms of behavior change, a significant positive correlation between fruit ( p < 0.0001) and vegetables ( p = 0.0087) intake was observed in association with increased engagement in the e-Diary. Similarly, adolescents who used the app for more than 2 weeks had significantly higher odds of not skipping breakfast over the study period (aOR 2.5, 95% CI 1.0-6.3)., Conclusions: The users highly engaged with the e-Diary were associated with improved dietary behaviors: increased consumption of fruit and vegetables and reduced skipping of breakfast. Although the overall usage of the e-Diary was high during the first weeks, it declined thereafter. Future applications should foster user engagement, particularly targeting adolescents at high risk., Clinical Trial Registration: https://www.clinicaltrials.gov/, identifier: NCT02930148., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Caon, Prinelli, Angelini, Carrino, Mugellini, Orte, Serrano, Atkinson, Martin and Adorni.)

To assess influenza vaccine uptake during the 2020/2021 flu season and compare it with that of the 2019/2020 flu season among respondents to the second phase of the web-based EPICOVID-19 survey, we performed an observational web-based nationwide online survey (January-February 2021) in which respondents to the first survey (April-June 2020) were contacted and asked to complete a second questionnaire. Factors associated with vaccine uptake in the 2020/2021 flu season were assessed by applying a multivariable multinomial logistic regression model. Out of the 198,822 respondents to the first survey, 41,473 (20.9%) agreed to fill out the follow-up questionnaire; of these, 8339 (20.1%) were vaccinated only during the 2020/2021 season, 8828 (21.3%) were vaccinated during both seasons and 22,710 (54.8%) were vaccinated in neither season. Educational level (medium (aOR 1.33 95%CI 1.13-1.56) and high (aOR 1.69 95%CI 1.44-1.97) vs. low) and socio-economic deprivation according to SES scoring (1 point aOR 0.83 (95%CI 0.78-0.89), 2 aOR 0.68 (95%CI 0.60-0.77) points or ≥3 points aOR 0.42 (95%CI 0.28-0.45) vs. 0 points) were found to be associated with flu vaccine uptake. Our study shows that social determinants seemed to affect flu vaccination uptake and identifies specific categories of the population to target during future influenza vaccination campaigns.

Digital technologies have been extensively employed in response to the SARS-CoV-2 pandemic worldwide. This study describes the methodology of the two-phase internet-based EPICOVID19 survey, and the characteristics of the adult volunteer respondents who lived in Italy during the first (April-May 2020) and the second wave (January-February 2021) of the epidemic. Validated scales and ad hoc questionnaires were used to collect socio-demographic, medical and behavioural characteristics, as well as information on COVID-19. Among those who provided email addresses during phase I (105,355), 41,473 participated in phase II (mean age 50.7 years ± 13.5 SD, 60.6% females). After a median follow-up of ten months, 52.8% had undergone nasopharyngeal swab (NPS) testing and 13.2% had a positive result. More than 40% had undergone serological test (ST) and 11.9% were positive. Out of the 2073 participants with at least one positive ST, 72.8% had only negative results from NPS or never performed it. These results indicate that a large fraction of individuals remained undiagnosed, possibly contributing to the spread of the virus in the community. Participatory online surveys offer a unique opportunity to collect relevant data at individual level from large samples during confinement.

Although COVID-19 affects older people more severely, health policies during the first wave of the pandemic often prioritized younger individuals. We investigated whether age had influenced the access to a diagnostic test for SARS-CoV-2 infection and whether clinical complexity and healthcare resources availability could have impacted such differences. This work included 126,741 Italian participants in the EPICOVID19 web-based survey, who reported having had contacts with known/suspected COVID-19 cases (epidemiological criterion) and/or COVID-19-like signs/symptoms (clinical criterion) from February to June 2020. Data on sociodemographic, medical history and access to SARS-CoV-2 nasopharyngeal swab (NPS) were collected. Logistic regressions estimated the probability of accessing NPS as a function of age and the possible modifying effect of chronic diseases' number and residential areas in such association. A total of 6136 (4.8%) participants had undergone an NPS. Older participants had lower NPS frequencies than the younger ones when reporting epidemiological (14.9% vs. 8.8%) or both epidemiological and clinical criteria (17.5% vs. 13.7%). After adjustment for potential confounders, including epidemiological and clinical criteria, the chance of NPS access decreased by 29% (OR=0.71, 95%CI:0.63-0.79) in older vs. younger individuals. Such disparity was accentuated in areas with greater healthcare resources. In conclusion, in the first wave of the pandemic, age may have affected the access to COVID-19 diagnostic testing, disadvantaging older people., Competing Interests: Declaration of Competing Interest None., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Introduction: Decline in physical function varies substantially across older individuals due to several extrinsic modifiable factors such as dietary patterns, physical activity and social support. We aimed to determine the association of these factors and their interaction with mobility and muscle strength decline., Methods: We analyzed data from 1686 functionally healthy individuals aged 60 + from the population-based Swedish National study on Aging and Care in Kungsholmen (SNAC-K). The Mediterranean Diet Score (MDS) was calculated based on a validated food frequency questionnaire. Self-reported physical activity was categorized based on current recommendations, and social support was measured according to participants' perceived material and psychological support from relatives and friends. Participants' physical function was assessed over 12 years through changes in walking speed (m/s) and chair stand time (s). Linear mixed models adjusted for socio-demographic and clinical factors were used. In order to explore the combined effect of the different exposures, two indicator variables were created by cross-classifying individuals' levels of Mediterranean diet adherence and social support or physical activity., Results: Participants with a high adherence to Mediterranean diet were primarily < 78 years (82.3%), women (56.1%), married (61.1%), with university education (52.8%), high levels of social support (39.3%) and health-enhancing levels of physical activity (51.5%). A one-point increase in MDS (score range 0-9) was associated with less annual deterioration in walking speed (β*time[year] = 0.001; p = 0.024) and chair-stand time (β*time[year] = -0.014; p = 0.008). The potential protective effect of Mediterranean diet was highest among participants reporting high social support (β*time[year] = -0.065, p = 0.026 for chair stands) and high physical activity (β*time[year] = 0.010, p = 0.001 for walking speed), beyond the effect of each exposure individually., Conclusion: A higher adherence to Mediterranean diet, especially in combination with recommended levels of physical activity and high social support, may contribute to delay the decline in physical function observed with aging., (© 2021. The Author(s).)

Background: Several studies have reported a low prevalence of current smoking among hospitalized COVID-19 cases; however, no definitive conclusions can be drawn., Objective: We investigated the association of tobacco smoke exposure with nasopharyngeal swab (NPS) test results for SARS-CoV-2 infection and disease severity accounting for possible confounders., Methods: The nationwide, self-administered, cross-sectional web-based Italian National Epidemiological Survey on COVID-19 (EPICOVID19) was administered to an Italian population of 198,822 adult volunteers who filled in an online questionnaire between April 13 and June 2, 2020. For this study, we analyzed 6857 individuals with known NPS test results. The associations of smoking status and the dose-response relationship with a positive NPS test result and infection severity were calculated as odds ratios (ORs) with 95% CIs by means of logistic and multinomial regression models adjusting for sociodemographic, clinical, and behavioral characteristics., Results: Out of the 6857 individuals (mean age 47.9 years, SD 14.1; 4516/6857, 65.9% female), 63.2% (4334/6857) had never smoked, 21.3% (1463/6857) were former smokers, and 15.5% (1060/6857) were current smokers. Compared to nonsmokers, current smokers were younger, were more educated, were less affected by chronic diseases, reported COVID-19-like symptoms less frequently, were less frequently hospitalized, and less frequently tested positive for COVID-19. In multivariate analysis, current smokers had almost half the odds of a positive NPS test result (OR 0.54, 95% CI 0.45-0.65) compared to nonsmokers. We also found a dose-dependent relationship with tobacco smoke: mild smokers (adjusted OR [aOR] 0.76, 95% CI 0.55-1.05), moderate smokers (aOR 0.56, 95% CI 0.42-0.73), and heavy smokers (aOR 0.38, 95% CI 0.27-0.53). This inverse association also persisted when considering the severity of the infection. Current smokers had a statistically significantly lower probability of having asymptomatic (aOR 0.50, 95% CI 0.27-0.92), mild (aOR 0.65, 95% CI 0.53-0.81), and severe infections (aOR 0.27, 95% CI 0.17-0.42) compared to those who never smoked., Conclusions: Current smoking was negatively associated with SARS-CoV-2 infection with a dose-dependent relationship. Ad hoc experimental studies are needed to elucidate the mechanisms underlying this association., Trial Registration: ClinicalTrials.gov NCT04471701; https://clinicaltrials.gov/ct2/show/NCT04471701., (©Federica Prinelli, Fabrizio Bianchi, Gaspare Drago, Silvia Ruggieri, Aleksandra Sojic, Nithiya Jesuthasan, Sabrina Molinaro, Luca Bastiani, Stefania Maggi, Marianna Noale, Massimo Galli, Andrea Giacomelli, Raffaele Antonelli Incalzi, Fulvio Adorni, Fabio Cibella, EPICOVID19 Working Group. Originally published in JMIR Public Health and Surveillance (https://publichealth.jmir.org), 28.04.2021.)

Background: The influence of aging and multimorbidity on Covid-19 clinical presentation is still unclear., Objectives: We investigated whether the association between symptoms (or cluster of symptoms) and positive SARS-CoV-2 nasopharyngeal swab (NPS) was different according to patients' age and presence of multimorbidity., Methods: The study included 6680 participants in the EPICOVID19 web-based survey, who reported information about symptoms from February to June 2020 and who underwent at least one NPS. Symptom clusters were identified through hierarchical cluster analysis. The associations between symptoms (and clusters of symptoms) and positive NPS were investigated through multivariable binary logistic regression in the sample stratified by age (<65 vs ≥65 years) and number of chronic diseases (0 vs 1 vs ≥2)., Results: The direct association between taste/smell disorders and positive NPS was weaker in older and multimorbid patients than in their younger and healthier counterparts. Having reported no symptoms reduced the chance of positive NPS by 86% in younger (95%CI: 0.11-0.18), and by 46% in older participants (95%CI: 0.37-0.79). Of the four symptom clusters identified (asymptomatic, generic, flu-like, and combined generic and flu-like symptoms), those associated with a higher probability of SARS-CoV-2 infection were the flu-like for older people, and the combined generic and flu-like for the younger ones., Conclusions: Older age and pre-existing chronic diseases may influence the clinical presentation of Covid-19. Symptoms at disease onset tend to aggregate differently by age. New diagnostic algorithms considering age and chronic conditions may ease Covid-19 diagnosis and optimize health resources allocation., Trial Registration: NCT04471701 (ClinicalTrials.gov)., (Copyright © 2021. Published by Elsevier B.V.)

The study analyzed the association of the fear of contagion for oneself and for family members (FMs) during the first wave of the COVID-19 pandemic, with demographic and socioeconomic status (SES) and health factors. The study was performed within the EPICOVID19 web-based Italian survey, involving adults from April-June 2020. Out of 207,341 respondents, 95.9% completed the questionnaire (60% women with an average age of 47.3 vs. 48.9 years among men). The association between fear and demographic and SES characteristics, contacts with COVID-19 cases, nasopharyngeal swab, self-perceived health, flu vaccination, chronic diseases and specific symptoms was analyzed by logistic regression model; odds ratios adjusted for sex, age, education and occupation were calculated (aORs). Fear for FMs prevailed over fear for oneself and was higher among women than men. Fear for oneself decreased with higher levels of education and in those who perceived good health. Among those vaccinated for the flu, 40.8% responded they had feelings of fear for themselves vs. 34.2% of the not vaccinated. Fear increased when diseases were declared and it was higher when associated with symptoms such as chest pain, olfactory/taste disorders, heart palpitations (aORs > 1.5), lung or kidney diseases, hypertension, depression and/or anxiety. Trends in fear by region showed the highest percentage of positive responses in the southern regions. The knowledge gained from these results should be used to produce tailored messages and shared public health decisions.

Background: Confirmed COVID-19 cases have been registered in more than 200 countries, and as of July 28, 2020, over 16 million cases have been reported to the World Health Organization. This study was conducted during the epidemic peak of COVID-19 in Italy. The early identification of individuals with suspected COVID-19 is critical in immediately quarantining such individuals. Although surveys are widely used for identifying COVID-19 cases, outcomes, and associated risks, no validated epidemiological tool exists for surveying SARS-CoV-2 infection in the general population., Objective: We evaluated the capability of self-reported symptoms in discriminating COVID-19 to identify individuals who need to undergo instrumental measurements. We defined and validated a method for identifying a cutoff score., Methods: Our study is phase II of the EPICOVID19 Italian national survey, which launched in April 2020 and included a convenience sample of 201,121 adults who completed the EPICOVID19 questionnaire. The Phase II questionnaire, which focused on the results of nasopharyngeal swab (NPS) and serological tests, was mailed to all subjects who previously underwent NPS tests., Results: Of 2703 subjects who completed the Phase II questionnaire, 694 (25.7%) were NPS positive. Of the 472 subjects who underwent the immunoglobulin G (IgG) test and 421 who underwent the immunoglobulin M test, 22.9% (108/472) and 11.6% (49/421) tested positive, respectively. Compared to NPS-negative subjects, NPS-positive subjects had a higher incidence of fever (421/694, 60.7% vs 391/2009, 19.5%; P<.001), loss of taste and smell (365/694, 52.6% vs 239/2009, 11.9%; P<.001), and cough (352/694, 50.7% vs 580/2009, 28.9%; P<.001). With regard to subjects who underwent serological tests, IgG-positive subjects had a higher incidence of fever (65/108, 60.2% vs 43/364, 11.8%; P<.001) and pain in muscles/bones/joints (73/108, 67.6% vs 71/364, 19.5%; P<.001) than IgG-negative subjects. An analysis of self-reported COVID-19 symptom items revealed a 1-factor solution, the EPICOVID19 diagnostic scale. The following optimal scores were identified: 1.03 for respiratory problems, 1.07 for chest pain, 0.97 for loss of taste and smell 0.97, and 1.05 for tachycardia (ie, heart palpitations). These were the most important symptoms. For adults aged 18-84 years, the cutoff score was 2.56 (sensitivity: 76.56%; specificity: 68.24%) for NPS-positive subjects and 2.59 (sensitivity: 80.37%; specificity: 80.17%) for IgG-positive subjects. For subjects aged ≥60 years, the cutoff score was 1.28, and accuracy based on the presence of IgG antibodies improved (sensitivity: 88.00%; specificity: 89.58%)., Conclusions: We developed a short diagnostic scale to detect subjects with symptoms that were potentially associated with COVID-19 from a wide population. Our results support the potential of self-reported symptoms in identifying individuals who require immediate clinical evaluations. Although these results come from the Italian pandemic period, this short diagnostic scale could be optimized and tested as a screening tool for future similar pandemics., (©Luca Bastiani, Loredana Fortunato, Stefania Pieroni, Fabrizio Bianchi, Fulvio Adorni, Federica Prinelli, Andrea Giacomelli, Gabriele Pagani, Stefania Maggi, Caterina Trevisan, Marianna Noale, Nithiya Jesuthasan, Aleksandra Sojic, Carla Pettenati, Massimo Andreoni, Raffaele Antonelli Incalzi, Massimo Galli, Sabrina Molinaro. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 06.01.2021.)

Background: Understanding the occurrence of symptoms resembling those of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a large nonhospitalized population at the peak of the epidemic in Italy is of paramount importance; however, data are currently scarce., Objective: The aims of this study were to evaluate the association of self-reported symptoms with SARS-CoV-2 nasopharyngeal swab (NPS) test results in nonhospitalized individuals and to estimate the occurrence of symptoms associated with coronavirus disease (COVID-19) in a larger nontested population., Methods: EPICOVID19 is a self-administered cross-sectional voluntary web-based survey of adults throughout Italy who completed an anonymous questionnaire in the period of April 13 to 21, 2020. The associations between symptoms potentially related to SARS-CoV-2 infection and NPS results were calculated as adjusted odds ratios (aORs) with 95% CIs by multiple logistic regression analysis controlling for age, sex, education, smoking habits, and number of comorbidities. Thereafter, for each symptom and for combinations of the symptoms, we calculated the sensitivity, specificity, accuracy, and areas under the curve (AUCs) in a receiver operating characteristic (ROC) analysis to estimate the occurrence of COVID-19-like infection in the nontested population., Results: A total of 171,310 people responded to the survey, of whom 102,543 (59.9%) were women; mean age 47.4 years. Out of the 4785 respondents with known NPS test results, 4392 were not hospitalized. Among the 4392 nonhospitalized respondents, those with positive NPS tests (856, 19.5%) most frequently reported myalgia (527, 61.6%), olfactory and taste disorders (507, 59.2%), cough (466, 54.4%), and fever (444, 51.9%), whereas 7.7% were asymptomatic. Multiple regression analysis showed that olfactory and taste disorders (aOR 10.3, 95% CI 8.4-12.7), fever (aOR 2.5, 95% CI 2.0-3.1), myalgia (aOR 1.5, 95% CI 1.2-1.8), and cough (aOR 1.3, 95% CI 1.0-1.6) were associated with NPS positivity. Having two to four of these symptoms increased the aOR from 7.4 (95% CI 5.6-9.7) to 35.5 (95% CI 24.6-52.2). The combination of the four symptoms showed an AUC of 0.810 (95% CI 0.795-0.825) in classifying positive NPS test results and then was applied to the nonhospitalized and nontested sample (n=165,782). We found that 7739 to 20,103 of these 165,782 respondents (4.4% to 12.1%) had experienced symptoms suggestive of COVID-19 infection., Conclusions: Our results suggest that self-reported symptoms are reliable indicators of SARS-CoV-2 infection in a pandemic context. A nonnegligible number of symptomatic respondents (up to 12.1%) were undiagnosed and potentially contributed to the spread of the infection., Trial Registration: ClinicalTrials.gov NCT04471701; https://clinicaltrials.gov/ct2/show/NCT04471701., (©Fulvio Adorni, Federica Prinelli, Fabrizio Bianchi, Andrea Giacomelli, Gabriele Pagani, Dario Bernacchia, Stefano Rusconi, Stefania Maggi, Caterina Trevisan, Marianna Noale, Sabrina Molinaro, Luca Bastiani, Loredana Fortunato, Nithiya Jesuthasan, Aleksandra Sojic, Carla Pettenati, Marcello Tavio, Massimo Andreoni, Claudio Mastroianni, Raffaele Antonelli Incalzi, Massimo Galli. Originally published in JMIR Public Health and Surveillance (http://publichealth.jmir.org), 18.09.2020.)

The present study aims to evaluate whether influenza and pneumococcal vaccinations are associated with positive nasopharyngeal swab (NPS) testing to detect SARS-CoV-2. Data from the Italian cross-sectional web-based survey (EPICOVID19), based on a self-selection sample of individuals aged ≥18, were considered. The probability of a positive SARS-CoV-2 NPS test result as a function of influenza or anti-pneumococcal vaccination was evaluated using multivariable logistic regression, stratifying analysis by age (<65 years, ≥65 years). From April 2020, 170,731 individuals aged <65 years and 28,097 ≥65 years filled out the EPICOVID19 questionnaire. Influenza and anti-pneumococcal vaccinations were received, respectively, by 16% and 2% of those <65 years, and by 53% and 13% of those ≥65 years. SARS-CoV-2 NPS testing was reported by 6680 participants. Anti-pneumococcal and influenza vaccinations were associated with a decreased probability of a SARS-CoV-2 NPS positive test in the younger participants (OR = 0.61, 95% CI 0.41-0.91; OR = 0.85, 95%CI 0.74-0.98; respectively). A significantly lower probability of a positive test result was detected in the individuals ≥65 years who received anti-pneumococcal vaccination (OR = 0.56, 95%CI 0.33-0.95). These results need to be confirmed by further investigations, but they are relevant given the probable coexistence of influenza, bacterial infections, and COVID-19 over the coming autumn-winter season.

Background: Epidemiological evidence suggests that healthy diet is associated with a slowdown of cognitive decline leading to dementia, but the underlying mechanisms are still partially unexplored. Diet is the main determinant of gut microbiota composition, which in turn impacts on brain structures and functions, however to date no studies on this topic are available. The goal of the present paper is to describe the design and methodology of the NutBrain Study aimed at investigating the association of dietary habits with cognitive function and their role in modulating the gut microbiota composition, and brain measures as well., Methods/design: This is a population-based cohort study of community-dwelling adults aged 65 years or more living in Northern Milan, Italy. At the point of presentation people are screened for cognitive functions. Socio-demographic characteristics along with lifestyles and dietary habits, medical history, drugs, functional status, and anthropometric measurements are also recorded. Individuals suspected to have cognitive impairment at the screening phase undergo a clinical evaluation including a neurological examination and a Magnetic Resonance Imaging (MRI) scanning (both structural and functional). Stool and blood samples for the gut microbiota analysis and for the evaluation of putative biological markers are also collected. For each subject with a confirmed diagnosis of Mild Cognitive Impairment (MCI), two cognitively intact controls of the same sex and age are visited. We intend to enrol at least 683 individuals for the screening phase and 240 persons for the clinical assessment., Discussion: The NutBrain is an innovative study that incorporates modern and advanced technologies (i.e. microbiome and neuroimaging) into traditional epidemiologic design. The study represents a unique opportunity to address key questions about the role of modifiable risk factors on cognitive impairment, with a particular focus on dietary habits and their association with gut microbiota and markers of the brain-aging process. These findings will help to encourage and plan lifestyle interventions, for both prevention and treatment, aiming at promoting healthy cognitive ageing., Trial Registration: Trial registration number NCT04461951 , date of registration July 7, 2020 (retrospectively registered, ClinicalTrials.gov ).

Background: Promotion of physical activity, healthy eating, adequate sleep, and reduced sedentary behavior in adolescents is a major priority globally given the current increase in population health challenges of noncommunicable diseases and risk factors such as obesity. Adolescents are highly engaged with mobile technology, but the challenge is to engage them with mobile health (mHealth) technology. Recent innovations in mobile technology provide opportunities to promote a healthy lifestyle in adolescents. An increasingly utilized approach to facilitate increased engagement with mHealth technology is to involve potential users in the creation of the technology., Objective: This study aimed to describe the process of and findings from co-designing and prototyping components of the PEGASO Fit for Future (F4F) mHealth intervention for adolescents from different cultural backgrounds., Methods: A total of 74 adolescents aged 13 to 16 years from Spain, Italy, and the United Kingdom participated in the co-design of the PEGASO F4F technology. In 3 iterative cycles over 12 months, participants were involved in the co-design, refinement, and feasibility testing of a system consisting of diverse mobile apps with a variety of functions and facilities to encourage healthy weight-promoting behaviors. In the first iteration, participants attended a single workshop session and were presented with mock-ups or early-version prototypes of different apps for user requirements assessment and review. During the second iteration, prototypes of all apps were tested by participants for 1 week at home or school. In the third iteration, further developed prototypes were tested for 2 weeks. Participants' user experience feedback and development ideas were collected through focus groups and completion of questionnaires., Results: For the PEGASO F4F technology to be motivating and engaging, participants suggested that it should (1) allow personalization of the interface, (2) have age-appropriate and easy-to-understand language (of icons, labels, instructions, and notifications), (3) provide easily accessible tutorials on how to use the app or navigate through a game, (4) present a clear purpose and end goal, (5) have an appealing and self-explanatory reward system, (6) offer variation in gamified activities within apps and the serious game, and (7) allow to seek peer support and connect with peers for competitive activities within the technology., Conclusions: Incorporating adolescents' preferences, the PEGASO F4F technology combines the functions of a self-monitoring, entertainment, advisory, and social support tool. This was the first study demonstrating that it is possible to develop a complex mobile phone-based technological system applying the principles of co-design to mHealth technology with adolescents across 3 countries. The findings from this study informed the development of an mHealth system for healthy weight promotion to be tested in a controlled multinational pilot trial., (©Anne Martin, Maurizio Caon, Fulvio Adorni, Giuseppe Andreoni, Antonio Ascolese, Sarah Atkinson, Kim Bul, Carme Carrion, Conxa Castell, Valentina Ciociola, Laura Condon, Mireia Espallargues, Janet Hanley, Nithiya Jesuthasan, Claudio L Lafortuna, Alexandra Lang, Federica Prinelli, Elisa Puidomenech Puig, Sarah A Tabozzi, Brian McKinstry. Originally published in JMIR mHealth and uHealth (http://mhealth.jmir.org), 02.03.2020.)

Background: Behaviour change interventions targeting physical activity, diet, sleep and sedentary behaviour of teenagers show promise when delivered through smartphones. However, to date there is no evidence of effectiveness of multicomponent smartphone-based interventions. Utilising a user-centred design approach, we developed a theory-based, multi-dimensional system, PEGASO Fit For Future (PEGASO F4F), which exploits sophisticated game mechanics involving smartphone applications, a smartphone game and activity sensors to motivate teenagers to take an active role in adopting and maintaining a healthy lifestyle. This paper describes the study protocol to assess the feasibility, usability and effectiveness (knowledge/awareness and behavioural change in lifestyle) of the PEGASO system., Methods: We are conducting a quasi-experimental controlled cluster trial in 4 sites in Spain, Italy, and UK (England, Scotland) over 6 months. We plan to recruit 525, in a 2:1 basis, teenagers aged 13-16 years from secondary schools. The intervention group is provided with the PEGASO system whereas the comparison group continues their usual educational routine. Outcomes include feasibility, acceptance, and usability of the PEGASO system as well as between and within group changes in motivation, self-reported diet, physical activity, sedentary and sleeping behaviour, anthropometric measures and knowledge about a healthy lifestyle., Discussion: PEGASO F4F will provide evidence into the cross-cultural similarities and differences in the feasibility, acceptability and usability of a multi-dimensional smartphone based behaviour change intervention for teenagers. The study will explore facilitating factors, challenges and barriers of engaging teenagers to adapt and maintain a healthy lifestyle when using smartphone technology. Positive results from this ICT based multi component intervention may have significant implications both at clinical level, improving teenagers health and at public health level since it can present an influential tool against the development of chronic disease during adulthood., Trial Registration: https://clinicaltrials.gov Registration number: NCT02930148, registered 4 October 2016.

The application of the isometric log-ratio (ilr) transformation to dietary data leads to the definition of nutrient balances that represent new variables which can be included in regression models as covariates. However, their effects on the response variable are not easy to quantify. We then propose borrowing the concept of elasticity from econometrics as an appealing means of improving the interpretability of the ilr-related coefficients. Using data from an Italian population-based study, a multiple linear regression model of the serum total-/HDL-cholesterol ratio on nutrient balances was fitted and the estimated coefficients were used to derive elasticities. The elasticities measure the relative changes in the cholesterol ratio in response to the relative changes in specific nutrient ratios, while keeping unchanged the proportional relationships between the other dietary elements. In a comprehensive overview of the diet, this alternative approach to dietary data analysis allows isocaloric analysis and may provide interesting new insights.

Background & Aims: The impact of nutrient patterns on cognitive decline is complex and findings are still inconclusive. We aimed to identify major nutrient patterns and to explore their association with cognitive decline over time among older adults., Methods: In a population-based cohort, 2250 cognitively healthy people aged ≥60 years were identified at baseline (2001-2004), and followed-up to 9 years. Global cognitive function was tested with the Mini-Mental State Examination (MMSE) at baseline and follow-ups. Nutrients intake was assessed on the basis of food intake using a 98-semi-quantitative food frequency questionnaire at baseline, and nutrient-based patterns were identified by principal components analysis based on 30 nutrients. Mixed-effects linear regression models were used to determine their association with change in cognitive function taking into account potential confounders., Results: Four major patterns (the plant-, animal-, dairy-derived nutrients and animal/plants-derived fats) were identified. Over the follow-up time, each one unit increment in plant- (β = 0.081, P = 0.002) and animal-derived nutrients pattern scores (β = 0.098, P < 0.001) was associated with slower decline in MMSE score. On the other hand, one-unit higher in dairy-derived nutrients pattern was related to a faster decline in global cognitive function (β = -0.064, P = 0.014). No significant association between animal/plants fats pattern and cognitive decline was observed. In stratified analyses, the association of high scores of plants- and animal-derived nutrient pattern with slower cognitive decline was stronger in APOE ε4 carriers than in ε4 non-carriers., Conclusions: Plant- and animal -derived nutrients are associated with preserved cognitive function, especially among the APOE ε4 carriers, whereas nutrients derived from dairy products may accelerate cognitive decline in older adults., (Copyright © 2018 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Optimal nutrition may play a beneficial role in maintaining a healthy brain. However, the relationship between nutrient intake and brain integrity is largely unknown. We investigated the association of specific nutrient dietary patterns with structural characteristics of the brain. Within the population-based Swedish National study on Aging and Care-Kungsholmen (SNAC-K), a cross-sectional study of 417 dementia-free participants aged ≥60 years who underwent structural magnetic resonance imaging (MRI) scans during 2001-2003, was carried-out. Data on dietary intake were collected using a food frequency questionnaire, from which intake of 21 nutrients was estimated. By principal component analysis, five nutrient patterns were extracted: (1) NP1 was characterized by fiber, vitamin C, E, β-carotene, and folate [Fiber&Antioxidants], (2) NP2 by eicosapentaenoic (EPA, 20:5 ω-3) and docosahexaenoic (DHA, 22:6 ω-3) polyunsaturated fatty acids (PUFAs), proteins, cholesterol, vitamin B3, B12, and D [long chain (LC) ω-3PUFAs&Proteins], (3) NP3 by α-linoleic (18:2 ω-6) and α-linolenic (18:3 ω-3) PUFAs, monounsaturated fatty acids (MUFAs), and vitamin E [MUFAs&ω-3,6PUFAs], (4) NP4 by saturated fatty acids (SFAs), trans fats, MUFAs, and cholesterol [SFAs&Trans fats], (5) NP5 by B-vitamins, retinol, and proteins [B-Vitamins&Retinol]. Nutrient patterns scores were tertiled with the lowest tertile as reference, and were related to total brain volume (TBV) and white matter hyperintensities volume (WMHV) using linear regression models adjusting for potential confounders. In the multi-adjusted model, compared to the lowest intake for each pattern, the highest intake of NP1 (β = 11.11, P = 0.009), NP2 (β = 7.47, P = 0.052), and NP3 (β = 10.54, P = 0.005) was associated with larger TBV whereas NP5 was related to smaller TBV (β = -12.82, P = 0.001). The highest intake of NP1 was associated with lower WMHV (β = -0.32, P = 0.049), whereas NP4 was associated with greater WMHV (β = 0.31, P = 0.036). In sum, our results suggest that the identified brain-health specific nutrient combinations characterized by higher intake of fruit, vegetables, legumes, olive and seed oils, fish, lean red meat, poultry and low in milk and dairy products, cream, butter, processed meat and offal, were strongly associated with greater brain integrity among older adults., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background & Aims: Accurate predictive equations of resting energy expenditure (REE) are crucial in devising nutritional strategies to manage overweight/obesity, especially in countries where these are highly prevalent. REE is the most common measurement used to estimate energy requirements in the nutritional context; the most accurate method of measuring REE is indirect calorimetry (IC). However, this method is costly and often rarely feasible in many clinical settings. The objective of the present study was to develop and validate a new equation for predicting REE in adults with overweight and obesity., Methods: This was a cross-sectional study including 410 men and women with overweight and obesity (20-60 y). Participants were randomly assigned; the development group included 200 subjects and the validation group 210 subjects. The new predictive equation was derived using stepwise multiple linear regression analysis. The accuracy of the new equation was compared to several existing predictive equations (PEs). The accuracy rate was calculated as the percentage of subjects whose REE-PE was within ±10% of the REE-IC. REE was measured by IC and anthropometric measurements., Results: One predictive equation was developed (NEQ) in which weight was the strongest predictor of REE. Compared with others predicted equations already using, the new designed equation showed the less mean bias (Kj/day): NEQ: 25.7, Valencia:129, WHO/FAO/United Nations University: 270, Mifflin-St Jeor: 308, Owen: -808, Carrasco: -1097, Korth: -36.4, Johnstone: -375, Livingstone: -315, De Lorenzo: -28.3, Lazzer: -123, Muller: -145, Huang: -399 and Bernstein: -1335., Conclusions: The present equation had the highest predictive accuracy in subjects with overweight or obesity compared with the previous equations derived from different populations. Thus, these new equation can be used to assist the nutritional management of these subjects., (Copyright © 2017 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

The joint effect of diet and leisure activity on cognitive function remains unknown. We aimed to verify the hypothesis that an active lifestyle reinforces the effect of the Nordic Prudent Dietary Pattern (NPDP) on cognitive function. A total of 2223 dementia-free Swedish adults aged ≥60 with Mini-Mental State Examination (MMSE) scores ≥27 were followed for an average of 6 years. MMSE was tested during follow-ups. Diet was assessed by food frequency questionnaire. The NPDP index was calculated and tertiled (low, moderate, and high adherence). Participation in physical, mental and social activities was trichotomised (low, moderate, and intense). An active lifestyle was defined based on the participation in each activity. Data were analyzed using mixed-effects models. Moderate-to-high adherence to NPDP was associated with a reduced decline in the MMSE score (β: 0.19, 95% Confidence Interval (CI): 0.14⁻0.24). This association became stronger when combined with moderate-to-intense physical (β: 0.34, 95% CI: 0.2⁻0.45), mental (β: 0.29, 95% CI: 0.21⁻0.37), or social (β: 0.27, 95% CI: 0.19⁻0.34) activities. An active lifestyle strengthened the effect of NPDP on cognitive function by two times, and further lowered risk of MMSE decline by 30%. Thus, an active lifestyle reinforces the effect of a healthy diet on preserved cognitive function, and further decreases the risk of cognitive decline.

Several studies reported that cancer is less frequent in persons with Alzheimer's and Parkinson's Diseases (AD/PD) and vice-versa. We evaluated whether a different distribution of known nongenetic risk factors for cancer and AD/PD, might explain their inverse relationship of occurrence. We nested 2 case-control studies in a subsample of a large cohort of 1,000,000 resident in Lombardy Region in Italy (n=1515), followed-up for cancer and AD/PD occurrence since 1991 until 2012. Conditional logistic regression was performed to determine the odds ratios (OR) and 95% confidence intervals (CI) of AD/PD in subjects with and without cancer and the risk of cancer in those with and without AD/PD. A total of 54 incident cases of AD/PD and 347 cancer cases were matched with 216 and 667 controls, respectively. After controlling for low education, obesity, history of hypertension, diabetes, dyslipidemia, physical activity, smoking habit, alcohol consumption, and dietary habit, cancer was found inversely associated with the risk of AD/PD (OR, 0.66; 95% CI, 0.32-1.38), and the risk of cancer in AD/PD was similarly reduced (OR, 0.42; 95% CI, 0.20-0.91). Different exposures to nongenetic risk factors of both diseases do not explain their competitive relationship of occurrence.