Background: The role of diet as a modifiable factor that may affect the incidence of dementia is ... more Background: The role of diet as a modifiable factor that may affect the incidence of dementia is currently under investigation. The diet effect could be mediated by blood level of Folic Acid and Cobalamin, whose low levels are recognized as risk factors for dementia. The aim of this work is to evaluate the effects of habitual fruit intake, Cobalamin and Folic Acid on the cumulative incidence of dementia over a period of 4 years in elderly people free of basal dementia. Method: The subjects were 1321 people born between 1935-39, enrolled in 2010 by the "InveCe.Ab" study (ClinicalTrials.gov ID: NCT01345110). The cohort was reevaluated in 2014 and the onset of dementia was ascertained. The association between fruit consumption and metabolic parameters with dementia at baseline was analyzed with t-test for quantitative variables and with Pearson chi-square for qualitative variables. The risk/protection effect of habitual fruit consumption and metabolic mediators on the onset of dementia after 4 years was evaluated by multiple logistic regression. Result: 988 subjects were included in the analysis, The new cases of dementia between 2010 and 2014 were 50. The high habitual fruit consumption was inversely associated with dementia incidence (p = 0.007) and also directly associated with higher levels of Folic Acid (p < 0.005). Women had higher levels of Folic Acid and Cobalamin (p < 0.001) and a tendency towards higher fruit consumption (p = 0.06). The logistic model using Folic Acid, Cobalamin, and sex as covariates, shows that the usual consumption of fruit reduces the 4-year risk of developing dementia, (OR: 0.421; 95% CI: 0.213-0.831) with a significant interaction between fruit consumption and Folate (OR: 0.771; 95% CI. 0.607-0.980). Furthermore a higher level of Cobalamin results protective versus dementia. Conclusion: Our data show that in a population of 70-75 years the cumulative incidence of dementia is significantly reduced by habitual fruit consumption independently of the plasma levels of Cobalamin. Folate could be the metabolic mediator of this protection.
Additional file 1. Proportional sub-distribution hazards assessment for diagnosis of dementia. De... more Additional file 1. Proportional sub-distribution hazards assessment for diagnosis of dementia. Description of data: assumption of proportionality of hazards for both univariable and multivariable models.
Background Depression is common in the elderly. The role of genetic and environmental factors in ... more Background Depression is common in the elderly. The role of genetic and environmental factors in mod-ulating depressive symptoms is not clear. Methods We evaluated the influence of serotonin transporter gene polymorphisms and recent adverse life events on depressive symptoms in an elderly Italian population. We used data from “InveCe.Ab”, a population-based study of 1321 subjects aged 70–74 years. We used the 15-item Geriatric Depression Scale (GDS) to assess depressive symptoms–a GDS score5 points (GDS5) indicated the presence of clinically relevant symptoms–and per-formed 5-HTTLPR and rs25531 genotyping to obtain the triallelic polymorphism of the sero-tonin transporter. We used the Geriatric Adverse Life Events Scale to measure adverse life events, and logistic regression models to evaluate the role of genotype and recent adverse life events in depressive symptoms, controlling for potential confounders and independent predictors.
Older adults are at risk of psychological consequences along home segregation during COVID‐19 pan... more Older adults are at risk of psychological consequences along home segregation during COVID‐19 pandemic. Information Communication Technologies (ICTs) are crucial in such context even among older people. Aim: to explore the impact of being ICTusers on loneliness and ICTs use among older adults from pre to lockdown period.
Research on brain tissue is essential to understand the biological mechanisms underlying neurodeg... more Research on brain tissue is essential to understand the biological mechanisms underlying neurodegenerative diseases and brain aging processes.Brain donation for research is influenced by many factors both in clinical and non‐clinical samples. The aim of the present study is to explore the features associated with the decision to join the brain donation program of the Abbiategrasso Brain Bank (ABB) in the context of a population‐based study on brain aging.
Background: Education and occupational complexity are main sources of mental engagement during ea... more Background: Education and occupational complexity are main sources of mental engagement during early life and adulthood respectively, but research findings are not conclusive regarding protective effects of these factors against late-life dementia. Objective: This project aimed to examine the unique contributions of education and occupational complexity to incident dementia, and to assess the mediating effects of occupational complexity on the association between education and dementia across diverse cohorts. Method: We used data from 10,195 participants (median baseline age = 74.1, range = 58∼103), representing 9 international datasets from 6 countries over 4 continents. Using a coordinated analysis approach, the accelerated failure time model was applied to each dataset, followed by meta-analysis. In addition, causal mediation analyses were performed. Result: The meta-analytic results indicated that both education and occupational complexity were independently associated with incr...
The multitasking nature of lncRNAs allows them to play a central role in both physiological and p... more The multitasking nature of lncRNAs allows them to play a central role in both physiological and pathological conditions. Often the same lncRNA can participate in different diseases. Specifically, the MYC-induced Long non-Coding RNA MINCR is upregulated in various cancer types, while downregulated in Amyotrophic Lateral Sclerosis patients. Therefore, this work aims to investigate MINCR potential mechanisms of action and its implications in cancer and neurodegeneration in relation to its expression levels in SH-SY5Y cells through RNA-sequencing approach. Our results show that MINCR overexpression causes massive alterations in cancer-related genes, leading to disruption in many fundamental processes, such as cell cycle and growth factor signaling. On the contrary, MINCR downregulation influences a small number of genes involved in different neurodegenerative disorders, mostly concerning RNA metabolism and inflammation. Thus, understanding the cause and functional consequences of MINCR deregulation gives important insights on potential pathogenetic mechanisms both in cancer and in neurodegeneration.
Since the association of SARS-Cov-2 infection with Nervous System (NS) manifestations, we perform... more Since the association of SARS-Cov-2 infection with Nervous System (NS) manifestations, we performed RNA-sequencing analysis in Frontal Cortex of COVID-19 positive or negative individuals and affected or not by Dementia individuals. We examined gene expression differences in individuals with COVID-19 and Dementia compared to Dementia only patients by collecting transcript counts in each sample and performing Differential Expression analysis. We found eleven genes satisfying our significance criteria, all of them being protein coding genes. These data are suitable for integration with supplemental samples and for analysis according to different individuals’ classification. Also, differential expression evaluation may be implemented with other scientific purposes, such as research of unannotated genes, mRNA splicing and genes isoforms. The analysis of Differential Expressed genes in COVID-19 positive patients compared to non-COVID-19 patients is published in: S. Gagliardi, E.T. Poloni, C. Pandini, M. Garofalo, F. Dragoni, V. Medici, A. Davin, S.D. Visonà, M. Moretti, D. Sproviero, O. Pansarasa, A. Guaita, M. Ceroni, L. Tronconi, C. Cereda, Detection of SARS-CoV-2 genome and whole transcriptome sequencing in frontal cortex of COVID-19 patients., Brain. Behav. Immun. (2021). https://doi.org/10.1016/j.bbi.2021.05.012.
AIMS Perilipins are conserved proteins that decorate intracellular lipid droplets and are essenti... more AIMS Perilipins are conserved proteins that decorate intracellular lipid droplets and are essential for lipid metabolism. To date, there is limited knowledge on their expression in human brain, or their involvement in brain aging and neurodegeneration. The aim of this study was to characterise the expression levels of perilipins (Plin1-5) in different cerebral areas from subjects of different age, with or without signs of neurodegeneration. METHODS We performed real time RT-PCR, western blotting, immunohistochemistry and confocal microscopy analyses in autoptic brain samples of frontal and temporal cortex, cerebellum and hippocampus from subjects ranging from 33 to 104 years of age, with or without histological signs of neurodegeneration. To test the possible relationship between Plins and inflammation, correlation analysis with IL-6 expression was also performed. RESULTS Plin2, Plin3 and Plin5, but not Plin1 and Plin4, are expressed in the considered brain areas with different intensities. Plin2 appears to be expressed more in grey matter, particularly in neurons in all the areas analysed, while Plin3 and Plin5 appear to be expressed more in white matter. Plin3 seems to be expressed more in astrocytes. Only Plin2 expression is higher in old subjects and patients with Early Tauopathy or Alzheimer's Disease, and is associated with IL-6 expression. CONCLUSIONS Perilipins are expressed in human brain but only Plin2 appears to be modulated with age and neurodegeneration, and linked to an inflammatory state. We propose that the accumulation of lipid droplets decorated with Plin2 occurs during brain aging, and that this accumulation may be an early marker and initial step of inflammation and neurodegeneration.
Frailty syndrome is an age-related condition involving a loss of resilience, susceptibility to ad... more Frailty syndrome is an age-related condition involving a loss of resilience, susceptibility to adverse health outcomes, and poor quality of life. This study was conducted in the framework of InveCe.Ab, an ongoing longitudinal population-based study. Plasma from 130 older individuals (older adults aged 76–78 years) was analyzed and validated (on 303 participants) using mass spectrometry-based metabolomics approaches. Equivalence tests showed that metabolites from the central cellular metabolic pathways were equivalent in frail and fit participants. Hippuric acid was the only cometabolite that distinguished fit from frail older adults. Logistic regression analysis indicated that high hippuric acid levels are significantly associated with a reduction of the risk of frailty after 4 years. Mediation analysis using a Frailty Index, hippuric acid, and fruit–vegetable intake supported the role of fruit–vegetable consumption in the hippuric acid relationship with the Frailty Index. These dat...
This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Background: Delirium may be one of the presenting symptoms of COVID-19, complicating diagnosis an... more Background: Delirium may be one of the presenting symptoms of COVID-19, complicating diagnosis and care of elderly patients with dementia. We aim to identify the prevalence and prognostic significance of delirium as the sole onset manifestation of COVID-19. Methods: This is a retrospective single-centre study based on review of medical charts, conducted during the outbreak peak (March 27-April 18, 2020) in a Lombard dementia facility, including 59 elderly subjects with dementia and laboratory-confirmed COVID-19. Findings: Of the 59 residents, 57 (96Á6%) tested positive (mean age: 82Á8; women: 66Á7%). Comorbidities were present in all participants, with 18/57 (31Á6%) having three or more concomitant diseases. Delirium-Onset COVID-19 (DOC) was observed in 21/57 (36Á8%) subjects who were chiefly older (mean age: 85Á4 y/o) and with multiple comorbidities. Eleven/21 DOC patients (52Á4%) had hypoactive delirium, while hyperactive delirium occurred in ten/21 (47Á6%). Lymphopenia was present in almost all subjects (median: 1Á3 £ 10 9 /L). Overall mortality rate was 24Á6% (14/57) and dementia severity per se had no impact on short-term mortality due to COVID-19. DOC was strongly associated with higher mortality (p<0Á001). Also, DOC and male gender were independently associated with increased risk of mortality (OR: 17Á0, 95% CI: 2Á8À102Á7, p = 0Á002 and 13Á6, 95% CI: 2Á3À79Á2, p = 0Á001 respectively). Interpretation: Delirium occurrence in the elderly with dementia may represent a prodromal phase of COVID-19, and thus deserves special attention, especially in the presence of lymphopenia. Hypoxia and a severe inflammatory state may develop subsequently. DOC cases have higher short-term mortality rate. Funding: None.
Background Preventing dementia onset is one of the global public health priorities: around 35% of... more Background Preventing dementia onset is one of the global public health priorities: around 35% of dementia cases could be attributable to modifiable risk factors. These estimates relied on secondary data and did not consider the concurrent effect of non-modifiable factors and death. Here, we aimed to estimate the potential reduction of dementia incidence due to modifiable risk factors elimination, controlling for non-modifiable risk factors and for the competing risk of death. Methods Participants from the InveCe.Ab population-based prospective cohort (Abbiategrasso, Italy) without a baseline dementia diagnosis and attending at least one follow-up visit were included (N = 1100). Participants underwent multidimensional assessment at baseline and after 2, 4, and 8 years, from November 2009 to January 2019. Modifiable risk factors were low education, obesity, hypertension, diabetes, depression, smoking, physical inactivity, hearing loss, loneliness, heart disease, stroke, head injury, ...
INTRODUCTION: Depression commonly accompanies Alzheimer's disease, but the nature of this associa... more INTRODUCTION: Depression commonly accompanies Alzheimer's disease, but the nature of this association remains uncertain. METHODS: Longitudinal data from the COSMIC consortium were harmonized for 8 population-based cohorts from 4 continents. Incident dementia was diagnosed in 646 participants, with a median followup time of 5.6 years to diagnosis. The association between years to dementia diagnosis and successive depressive states was assessed using a mixed effect logistic regression model. A generic inverse variance method was used to group study results, construct forest plots, and generate heterogeneity statistics. RESULTS: A common trajectory was observed showing an increase in the incidence of depression as the time to dementia diagnosis decreased despite cross-national variability in depression rates. DISCUSSION: The results support the hypothesis that depression occurring in the pre-clinical phases of dementia is more likely to be attributable to dementia-related brain changes than environment or reverse causality.
This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
All patients who appear on the video have provided written informed consent; authorization for th... more All patients who appear on the video have provided written informed consent; authorization for the videotaping and the publication of the videotape was obtained.
Subjective cognitive decline (SCD) is recognized as a risk stage for Alzheimer`s disease (AD) and... more Subjective cognitive decline (SCD) is recognized as a risk stage for Alzheimer`s disease (AD) and other dementias, but its prevalence is not well known. We aimed to use uniform criteria to better estimate SCD prevalence across international cohorts. Therefore, we combined individual participant data for 16 cohorts from 15 countries (members of the COSMIC consortium) and used qualitative and quantitative (Item Response Theory/IRT) harmonization techniques to estimate SCD prevalence. The sample comprised 39,387 cognitively unimpaired individuals above age 60. The prevalence of SCD across studies was around one quarter with both qualitative harmonization/QH (23.8%, 95%CI=23.3%-24.4%) and IRT (25.6%, 95%CI=25.1%-26.1%); however, prevalence estimates varied largely between studies (QH: 6.1%, 95%CI=5.1%-7.0%, to 52.7%, 95%CI=47.4%-58.0%; IRT: 7.8%, 95%%CI=6.8%-8.9%, to 52.7%, 95%CI = 47.4%-58.0%). Across studies, SCD prevalence was higher in men than women, in lower levels of education, i...
We aimed to examine the relationship between Apolipoprotein E ε4 (APOE*4) carriage on cognitive d... more We aimed to examine the relationship between Apolipoprotein E ε4 (APOE*4) carriage on cognitive decline, and whether these associations were moderated by sex, baseline age, ethnicity, and vascular risk factors. Participants were 19,225 individuals aged 54–103 years from 15 longitudinal cohort studies with a mean follow-up duration ranging between 1.2 and 10.7 years. Two-step individual participant data meta-analysis was used to pool results of study-wise analyses predicting memory and general cognitive decline from carriage of one or two APOE*4 alleles, and moderation of these associations by age, sex, vascular risk factors, and ethnicity. Separate pooled estimates were calculated in both men and women who were younger (ie, 62 years) and older (ie, 80 years) at baseline. Results showed that APOE*4 carriage was related to faster general cognitive decline in women, and faster memory decline in men. A stronger dose-dependent effect was observed in older men, with faster general cogniti...
Background: The role of diet as a modifiable factor that may affect the incidence of dementia is ... more Background: The role of diet as a modifiable factor that may affect the incidence of dementia is currently under investigation. The diet effect could be mediated by blood level of Folic Acid and Cobalamin, whose low levels are recognized as risk factors for dementia. The aim of this work is to evaluate the effects of habitual fruit intake, Cobalamin and Folic Acid on the cumulative incidence of dementia over a period of 4 years in elderly people free of basal dementia. Method: The subjects were 1321 people born between 1935-39, enrolled in 2010 by the "InveCe.Ab" study (ClinicalTrials.gov ID: NCT01345110). The cohort was reevaluated in 2014 and the onset of dementia was ascertained. The association between fruit consumption and metabolic parameters with dementia at baseline was analyzed with t-test for quantitative variables and with Pearson chi-square for qualitative variables. The risk/protection effect of habitual fruit consumption and metabolic mediators on the onset of dementia after 4 years was evaluated by multiple logistic regression. Result: 988 subjects were included in the analysis, The new cases of dementia between 2010 and 2014 were 50. The high habitual fruit consumption was inversely associated with dementia incidence (p = 0.007) and also directly associated with higher levels of Folic Acid (p < 0.005). Women had higher levels of Folic Acid and Cobalamin (p < 0.001) and a tendency towards higher fruit consumption (p = 0.06). The logistic model using Folic Acid, Cobalamin, and sex as covariates, shows that the usual consumption of fruit reduces the 4-year risk of developing dementia, (OR: 0.421; 95% CI: 0.213-0.831) with a significant interaction between fruit consumption and Folate (OR: 0.771; 95% CI. 0.607-0.980). Furthermore a higher level of Cobalamin results protective versus dementia. Conclusion: Our data show that in a population of 70-75 years the cumulative incidence of dementia is significantly reduced by habitual fruit consumption independently of the plasma levels of Cobalamin. Folate could be the metabolic mediator of this protection.
Additional file 1. Proportional sub-distribution hazards assessment for diagnosis of dementia. De... more Additional file 1. Proportional sub-distribution hazards assessment for diagnosis of dementia. Description of data: assumption of proportionality of hazards for both univariable and multivariable models.
Background Depression is common in the elderly. The role of genetic and environmental factors in ... more Background Depression is common in the elderly. The role of genetic and environmental factors in mod-ulating depressive symptoms is not clear. Methods We evaluated the influence of serotonin transporter gene polymorphisms and recent adverse life events on depressive symptoms in an elderly Italian population. We used data from “InveCe.Ab”, a population-based study of 1321 subjects aged 70–74 years. We used the 15-item Geriatric Depression Scale (GDS) to assess depressive symptoms–a GDS score5 points (GDS5) indicated the presence of clinically relevant symptoms–and per-formed 5-HTTLPR and rs25531 genotyping to obtain the triallelic polymorphism of the sero-tonin transporter. We used the Geriatric Adverse Life Events Scale to measure adverse life events, and logistic regression models to evaluate the role of genotype and recent adverse life events in depressive symptoms, controlling for potential confounders and independent predictors.
Older adults are at risk of psychological consequences along home segregation during COVID‐19 pan... more Older adults are at risk of psychological consequences along home segregation during COVID‐19 pandemic. Information Communication Technologies (ICTs) are crucial in such context even among older people. Aim: to explore the impact of being ICTusers on loneliness and ICTs use among older adults from pre to lockdown period.
Research on brain tissue is essential to understand the biological mechanisms underlying neurodeg... more Research on brain tissue is essential to understand the biological mechanisms underlying neurodegenerative diseases and brain aging processes.Brain donation for research is influenced by many factors both in clinical and non‐clinical samples. The aim of the present study is to explore the features associated with the decision to join the brain donation program of the Abbiategrasso Brain Bank (ABB) in the context of a population‐based study on brain aging.
Background: Education and occupational complexity are main sources of mental engagement during ea... more Background: Education and occupational complexity are main sources of mental engagement during early life and adulthood respectively, but research findings are not conclusive regarding protective effects of these factors against late-life dementia. Objective: This project aimed to examine the unique contributions of education and occupational complexity to incident dementia, and to assess the mediating effects of occupational complexity on the association between education and dementia across diverse cohorts. Method: We used data from 10,195 participants (median baseline age = 74.1, range = 58∼103), representing 9 international datasets from 6 countries over 4 continents. Using a coordinated analysis approach, the accelerated failure time model was applied to each dataset, followed by meta-analysis. In addition, causal mediation analyses were performed. Result: The meta-analytic results indicated that both education and occupational complexity were independently associated with incr...
The multitasking nature of lncRNAs allows them to play a central role in both physiological and p... more The multitasking nature of lncRNAs allows them to play a central role in both physiological and pathological conditions. Often the same lncRNA can participate in different diseases. Specifically, the MYC-induced Long non-Coding RNA MINCR is upregulated in various cancer types, while downregulated in Amyotrophic Lateral Sclerosis patients. Therefore, this work aims to investigate MINCR potential mechanisms of action and its implications in cancer and neurodegeneration in relation to its expression levels in SH-SY5Y cells through RNA-sequencing approach. Our results show that MINCR overexpression causes massive alterations in cancer-related genes, leading to disruption in many fundamental processes, such as cell cycle and growth factor signaling. On the contrary, MINCR downregulation influences a small number of genes involved in different neurodegenerative disorders, mostly concerning RNA metabolism and inflammation. Thus, understanding the cause and functional consequences of MINCR deregulation gives important insights on potential pathogenetic mechanisms both in cancer and in neurodegeneration.
Since the association of SARS-Cov-2 infection with Nervous System (NS) manifestations, we perform... more Since the association of SARS-Cov-2 infection with Nervous System (NS) manifestations, we performed RNA-sequencing analysis in Frontal Cortex of COVID-19 positive or negative individuals and affected or not by Dementia individuals. We examined gene expression differences in individuals with COVID-19 and Dementia compared to Dementia only patients by collecting transcript counts in each sample and performing Differential Expression analysis. We found eleven genes satisfying our significance criteria, all of them being protein coding genes. These data are suitable for integration with supplemental samples and for analysis according to different individuals’ classification. Also, differential expression evaluation may be implemented with other scientific purposes, such as research of unannotated genes, mRNA splicing and genes isoforms. The analysis of Differential Expressed genes in COVID-19 positive patients compared to non-COVID-19 patients is published in: S. Gagliardi, E.T. Poloni, C. Pandini, M. Garofalo, F. Dragoni, V. Medici, A. Davin, S.D. Visonà, M. Moretti, D. Sproviero, O. Pansarasa, A. Guaita, M. Ceroni, L. Tronconi, C. Cereda, Detection of SARS-CoV-2 genome and whole transcriptome sequencing in frontal cortex of COVID-19 patients., Brain. Behav. Immun. (2021). https://doi.org/10.1016/j.bbi.2021.05.012.
AIMS Perilipins are conserved proteins that decorate intracellular lipid droplets and are essenti... more AIMS Perilipins are conserved proteins that decorate intracellular lipid droplets and are essential for lipid metabolism. To date, there is limited knowledge on their expression in human brain, or their involvement in brain aging and neurodegeneration. The aim of this study was to characterise the expression levels of perilipins (Plin1-5) in different cerebral areas from subjects of different age, with or without signs of neurodegeneration. METHODS We performed real time RT-PCR, western blotting, immunohistochemistry and confocal microscopy analyses in autoptic brain samples of frontal and temporal cortex, cerebellum and hippocampus from subjects ranging from 33 to 104 years of age, with or without histological signs of neurodegeneration. To test the possible relationship between Plins and inflammation, correlation analysis with IL-6 expression was also performed. RESULTS Plin2, Plin3 and Plin5, but not Plin1 and Plin4, are expressed in the considered brain areas with different intensities. Plin2 appears to be expressed more in grey matter, particularly in neurons in all the areas analysed, while Plin3 and Plin5 appear to be expressed more in white matter. Plin3 seems to be expressed more in astrocytes. Only Plin2 expression is higher in old subjects and patients with Early Tauopathy or Alzheimer's Disease, and is associated with IL-6 expression. CONCLUSIONS Perilipins are expressed in human brain but only Plin2 appears to be modulated with age and neurodegeneration, and linked to an inflammatory state. We propose that the accumulation of lipid droplets decorated with Plin2 occurs during brain aging, and that this accumulation may be an early marker and initial step of inflammation and neurodegeneration.
Frailty syndrome is an age-related condition involving a loss of resilience, susceptibility to ad... more Frailty syndrome is an age-related condition involving a loss of resilience, susceptibility to adverse health outcomes, and poor quality of life. This study was conducted in the framework of InveCe.Ab, an ongoing longitudinal population-based study. Plasma from 130 older individuals (older adults aged 76–78 years) was analyzed and validated (on 303 participants) using mass spectrometry-based metabolomics approaches. Equivalence tests showed that metabolites from the central cellular metabolic pathways were equivalent in frail and fit participants. Hippuric acid was the only cometabolite that distinguished fit from frail older adults. Logistic regression analysis indicated that high hippuric acid levels are significantly associated with a reduction of the risk of frailty after 4 years. Mediation analysis using a Frailty Index, hippuric acid, and fruit–vegetable intake supported the role of fruit–vegetable consumption in the hippuric acid relationship with the Frailty Index. These dat...
This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Background: Delirium may be one of the presenting symptoms of COVID-19, complicating diagnosis an... more Background: Delirium may be one of the presenting symptoms of COVID-19, complicating diagnosis and care of elderly patients with dementia. We aim to identify the prevalence and prognostic significance of delirium as the sole onset manifestation of COVID-19. Methods: This is a retrospective single-centre study based on review of medical charts, conducted during the outbreak peak (March 27-April 18, 2020) in a Lombard dementia facility, including 59 elderly subjects with dementia and laboratory-confirmed COVID-19. Findings: Of the 59 residents, 57 (96Á6%) tested positive (mean age: 82Á8; women: 66Á7%). Comorbidities were present in all participants, with 18/57 (31Á6%) having three or more concomitant diseases. Delirium-Onset COVID-19 (DOC) was observed in 21/57 (36Á8%) subjects who were chiefly older (mean age: 85Á4 y/o) and with multiple comorbidities. Eleven/21 DOC patients (52Á4%) had hypoactive delirium, while hyperactive delirium occurred in ten/21 (47Á6%). Lymphopenia was present in almost all subjects (median: 1Á3 £ 10 9 /L). Overall mortality rate was 24Á6% (14/57) and dementia severity per se had no impact on short-term mortality due to COVID-19. DOC was strongly associated with higher mortality (p<0Á001). Also, DOC and male gender were independently associated with increased risk of mortality (OR: 17Á0, 95% CI: 2Á8À102Á7, p = 0Á002 and 13Á6, 95% CI: 2Á3À79Á2, p = 0Á001 respectively). Interpretation: Delirium occurrence in the elderly with dementia may represent a prodromal phase of COVID-19, and thus deserves special attention, especially in the presence of lymphopenia. Hypoxia and a severe inflammatory state may develop subsequently. DOC cases have higher short-term mortality rate. Funding: None.
Background Preventing dementia onset is one of the global public health priorities: around 35% of... more Background Preventing dementia onset is one of the global public health priorities: around 35% of dementia cases could be attributable to modifiable risk factors. These estimates relied on secondary data and did not consider the concurrent effect of non-modifiable factors and death. Here, we aimed to estimate the potential reduction of dementia incidence due to modifiable risk factors elimination, controlling for non-modifiable risk factors and for the competing risk of death. Methods Participants from the InveCe.Ab population-based prospective cohort (Abbiategrasso, Italy) without a baseline dementia diagnosis and attending at least one follow-up visit were included (N = 1100). Participants underwent multidimensional assessment at baseline and after 2, 4, and 8 years, from November 2009 to January 2019. Modifiable risk factors were low education, obesity, hypertension, diabetes, depression, smoking, physical inactivity, hearing loss, loneliness, heart disease, stroke, head injury, ...
INTRODUCTION: Depression commonly accompanies Alzheimer's disease, but the nature of this associa... more INTRODUCTION: Depression commonly accompanies Alzheimer's disease, but the nature of this association remains uncertain. METHODS: Longitudinal data from the COSMIC consortium were harmonized for 8 population-based cohorts from 4 continents. Incident dementia was diagnosed in 646 participants, with a median followup time of 5.6 years to diagnosis. The association between years to dementia diagnosis and successive depressive states was assessed using a mixed effect logistic regression model. A generic inverse variance method was used to group study results, construct forest plots, and generate heterogeneity statistics. RESULTS: A common trajectory was observed showing an increase in the incidence of depression as the time to dementia diagnosis decreased despite cross-national variability in depression rates. DISCUSSION: The results support the hypothesis that depression occurring in the pre-clinical phases of dementia is more likely to be attributable to dementia-related brain changes than environment or reverse causality.
This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
All patients who appear on the video have provided written informed consent; authorization for th... more All patients who appear on the video have provided written informed consent; authorization for the videotaping and the publication of the videotape was obtained.
Subjective cognitive decline (SCD) is recognized as a risk stage for Alzheimer`s disease (AD) and... more Subjective cognitive decline (SCD) is recognized as a risk stage for Alzheimer`s disease (AD) and other dementias, but its prevalence is not well known. We aimed to use uniform criteria to better estimate SCD prevalence across international cohorts. Therefore, we combined individual participant data for 16 cohorts from 15 countries (members of the COSMIC consortium) and used qualitative and quantitative (Item Response Theory/IRT) harmonization techniques to estimate SCD prevalence. The sample comprised 39,387 cognitively unimpaired individuals above age 60. The prevalence of SCD across studies was around one quarter with both qualitative harmonization/QH (23.8%, 95%CI=23.3%-24.4%) and IRT (25.6%, 95%CI=25.1%-26.1%); however, prevalence estimates varied largely between studies (QH: 6.1%, 95%CI=5.1%-7.0%, to 52.7%, 95%CI=47.4%-58.0%; IRT: 7.8%, 95%%CI=6.8%-8.9%, to 52.7%, 95%CI = 47.4%-58.0%). Across studies, SCD prevalence was higher in men than women, in lower levels of education, i...
We aimed to examine the relationship between Apolipoprotein E ε4 (APOE*4) carriage on cognitive d... more We aimed to examine the relationship between Apolipoprotein E ε4 (APOE*4) carriage on cognitive decline, and whether these associations were moderated by sex, baseline age, ethnicity, and vascular risk factors. Participants were 19,225 individuals aged 54–103 years from 15 longitudinal cohort studies with a mean follow-up duration ranging between 1.2 and 10.7 years. Two-step individual participant data meta-analysis was used to pool results of study-wise analyses predicting memory and general cognitive decline from carriage of one or two APOE*4 alleles, and moderation of these associations by age, sex, vascular risk factors, and ethnicity. Separate pooled estimates were calculated in both men and women who were younger (ie, 62 years) and older (ie, 80 years) at baseline. Results showed that APOE*4 carriage was related to faster general cognitive decline in women, and faster memory decline in men. A stronger dose-dependent effect was observed in older men, with faster general cogniti...
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