Cardiometabolic multimorbidity (CMM) and depression are often co-occurring in older adults and associated with neurodegenerative outcomes. The present study aimed to estimate the independent and joint associations of CMM and depression on cognitive function in multi-regional cohorts, and to validate the generalizability of the findings in additional settings, including clinical. Data harmonization was performed across 14 longitudinal cohort studies within the Cohort Studies of Memory in an International Consortium (COSMIC) group, spanning North America, South America, Europe, Africa, Asia, and Australia. Three external validation studies with distinct settings were employed for generalization. Participants were eligible for inclusion if they had data for CMM and were free of dementia at baseline. Baseline CMM was defined as: 1) CMM 5, ≥2 among hypertension, hyperlipidemia, diabetes, stroke, and heart disease and 2) CMM 3 (aligned with previous studies), ≥2 among diabetes, stroke, and heart disease. Baseline depression was primarily characterized by binary classification of depressive symptom measurements, employing the Geriatric Depression Scale and the Center for Epidemiological Studies-Depression scale. Global cognition was standardized as z-scores through harmonizing multiple cognitive measures. Longitudinal cognition was calculated as changes in global cognitive z-scores. A pooled individual participant data (IPD) analysis was utilized to estimate the independent and joint associations of CMM and depression on cognitive outcomes in COSMIC studies, both cross-sectionally and longitudinally. Repeated analyses were performed in three external validation studies. Of the 32,931 older adults in the 14 COSMIC cohorts, we included 30,382 participants with complete data on baseline CMM, depression, and cognitive assessments for cross-sectional analyses. Among them, 22,599 who had at least 1 follow-up cognitive assessment were included in the longitudinal analyses. The three external studies for validation had 1964 participants from 3 multi-ethnic Asian older adult cohorts in different settings (community-based, memory clinic, and post-stroke study). In COSMIC studies, each of CMM and depression was independently associated with cross-sectional and longitudinal cognitive function, without significant interactions between them (Ps > 0.05). Participants with both CMM and depression had lower cross-sectional cognitive performance (e.g. β = −0.207, 95% CI = (−0.255, −0.159) for CMM5 (+)/depression (+)) and a faster rate of cognitive decline (e.g. β = −0.040, 95% CI = (−0.047, −0.034) for CMM5 (+)/depression (+)), compared with those without either condition. These associations remained consistent after additional adjustment for APOE genotype and were robust in two-step random-effects IPD analyses. The findings regarding the joint association of CMM and depression on cognitive function were reproduced in the three external validation studies. Our findings highlighted the importance of investigating age-related co-morbidities in a multi-dimensional perspective. Targeting both cardiometabolic and psychological conditions to prevent cognitive decline could enhance effectiveness. 10.13039/501100001809 Natural Science Foundation of China and 10.13039/100000049 National Institute on Aging / 10.13039/100000002 National Institutes of Health .

Here, we aim to describe COVID-19 pathology across different tissues to clarify the disease’s pathophysiology. Lungs, kidneys, hearts, and brains from nine COVID-19 autopsies were compared by using antibodies against SARS-CoV-2, macrophages-microglia, T-lymphocytes, B-lymphocytes, and activated platelets. Alzheimer’s Disease pathology was also assessed. PCR techniques were used to verify the presence of viral RNA. COVID-19 cases had a short clinical course (0–32 days) and their mean age was 77.4 y/o. Hypoxic changes and inflammatory infiltrates were present across all tissues. The lymphocytic component in the lungs and kidneys was predominant over that of other tissues (p < 0.001), with a significantly greater presence of T-lymphocytes in the lungs (p = 0.020), which showed the greatest presence of viral antigens. The heart showed scant SARS-CoV-2 traces in the endothelium–endocardium, foci of activated macrophages, and rare lymphocytes. The brain showed scarce SARS-CoV-2 traces, prominent microglial activation, and rare lymphocytes. The pons exhibited the highest microglial activation (p = 0.017). Microthrombosis was significantly higher in COVID-19 lungs (p = 0.023) compared with controls. The most characteristic pathological features of COVID-19 were an abundance of T-lymphocytes and microthrombosis in the lung and relevant microglial hyperactivation in the brainstem. This study suggests that the long-term sequelae of COVID-19 derive from persistent inflammation, rather than persistent viral replication.

Alzheimer’s disease (AD) is a neurodegenerative disorder that progressively involves brain regions with an often-predictable pattern. Damage to the brain appears to spread and worsen with time, but the molecular mechanisms underlying the region-specific distribution of AD pathology at different stages of the disease are still under-investigated. In this study, a whole-transcriptome analysis was carried out on brain samples from the hippocampus (HI), temporal and parietal cortices (TC and PC, respectively), cingulate cortex (CG), and substantia nigra (SN) of six subjects with a definite AD diagnosis and three healthy age-matched controls in duplicate. The transcriptomic results showed a greater number of differentially expressed genes (DEGs) in the TC (1571) and CG (1210) and a smaller number of DEGs in the HI (206), PC (109), and SN (60). Furthermore, the GSEA showed a difference between the group of brain areas affected early (HI and TC) and the group of areas that were subsequently involved (PC, CG, and SN). Notably, in the HI and TC, there was a significant downregulation of shared DEGs primarily involved in synaptic transmission, while in the PC, CG, and SN, there was a significant downregulation of genes primarily involved in protein folding and trafficking. The course of AD could follow a definite time- and severity-related pattern that arises from protein misfolding, as observed in the PC, CG, and SN, and leads to synaptic impairment, as observed in the HI and TC. Therefore, a map of the molecular and biological processes involved in AD pathogenesis may be traced. This could aid in the discovery of novel biological targets in order to develop effective and well-timed therapeutic approaches.

Background: During the COVID-19 pandemic, information and communication technology (ICT) became crucial for staying connected with loved ones and accessing health services. In this scenario, disparities in ICT use may have exacerbated other forms of inequality, especially among older adults who were less familiar with technology and more vulnerable to severe COVID-19 health consequences. Objective: This study investigated changes in ICT use, psychological and physical health, and social capital before and after the pandemic among the oldest old population (aged 80 years or older after the pandemic) and explored how internet use influenced these changes. Methods: We leveraged data from the InveCe.Ab study, a population-based longitudinal cohort of people born between 1935 and 1939 and living in Abbiategrasso, a municipality on the outskirts of Milan, Italy. Participants underwent multidimensional assessment at baseline (2010) and after 2, 4, 8, and 12 years. We restricted our analysis to cohort members who participated in the last wave (ie, 2022) and who did not have a diagnosis of dementia (n=391). We used linear mixed models to assess the impact of COVID-19 and time on changes in social capital, physical and psychological health, and ICT use in a discontinuity regression design while controlling for age, sex, education, and income satisfaction. Then, we assessed the influence of internet use and its interaction with COVID-19 on these changes. Results: COVID-19 had a significant impact on social relationships (β=–4.35, 95% CI 6.38 to –2.32; P<.001), cultural activities (β=–.55, 95% CI –0.75 to –0.35; P<.001), cognitive functioning (β=–1.00, 95% CI –1.28 to –0.72; P<.001), depressive symptoms (β=.42, 95% CI 0.10-0.74; P=.009), physical health (β=.07, 95% CI 0.04-0.10; P<.001), and ICT use (β=–.11, 95% CI –0.18 to –0.03; P=.008). Internet use predicts reduced depressive symptoms (β=–.56, 95% CI –1.07 to –0.06; P=.03) over time. The interaction between internet use and COVID-19 was significant for cultural activities (β=–.73, 95% CI –1.22 to –0.24; P=.003) and cognitive functioning (β=1.36, 95% CI 0.67-2.05; P<.001). Conclusions: The pandemic had adverse effects on older adults’ health and social capital. Contrary to expectations, even ICT use dropped significantly after the pandemic. Internet users maintained higher psychological health regardless of time and COVID-19 status. However, COVID-19 was associated with a steeper decline in cognitive functioning among internet nonusers. Policy makers may develop initiatives to encourage ICT adoption among older adults or strengthen their digital skills. Trial Registration: ClinicalTrials.gov NCT01345110; https://clinicaltrials.gov/study/NCT01345110

Pressure ulcers are an important public health issue, impacting quality of life and causing health deterioration. Blue light photobiomodulation has been shown promoting wound healing in vascular, diabetic, rheumatologic ulcers and lesions in spinal cord injury patients. Based on these preliminary results, this study was developed to assess the effectiveness of blue light therapy in second and third stage pressure ulcers. This study was a randomized controlled trial enrolling hospitalized patients with poor mobility. The intervention group included blue light treatment in addition to standard care, three times a week, for 4 consecutive weeks. The primary objective is the difference in the healing process by measuring the average difference of the lesion's PUSH score between the first and the last visit. The analysis shows that the mean PUSH reduction and the probability of belonging to responder patients were higher in the treatment group. A latent profile analysis that identifies two trajectory classes based on treatment response, shows an association in the probability of following best trajectory for the treatment group (30 % vs 2 %). The result shows that blue light photobiomodulation promotes recovery of tissue repair in pressure ulcers, and in stabilizing wounds that would otherwise worsen despite standard of care treatment. This therapy may be a valuable contribution to the daily management of pressure lesions since it has an excellent safety profile and the addition of this therapy to a treatment program may speed healing, improving the quality of life. (Clinicaltrials.gov Ref. numb.: NCT05130814).

Alzheimer’s disease (AD), the leading cause of dementia, is expected to markedly increase in prevalence in the coming decades. Beyond amyloid and tau pathologies, accumulating evidence suggests that mitochondrial dysfunction and impaired protein homeostasis play crucial roles in AD onset and progression. Building on our previous identification of molecular signatures associated with disease progression, this study investigated whether epigenetic alterations of mitochondrial DNA (mtDNA) contribute to cognitive decline. Specifically, we analyzed the methylation status of the mtDNA regulatory D-loop region and mtDNA copy number in blood-derived DNA samples from 75 participants who we followed longitudinally over eight years. Subjects were classified into four groups according to clinical progression from healthy cognition to mild cognitive impairment (MCI) and AD. Using a linear mixed-effects model, we observed significant differences in methylation dynamics and mtDNA copy number across groups and time points. Healthy controls showed a progressive increase in D-loop methylation, whereas individuals converting to AD exhibited a marked decrease in its level. An opposite trend was evidenced for mtDNA copy number. These findings suggest that reduced D-loop methylation and increased mtDNA are associated with mitochondrial dysfunction and disease progression, whereas increased methylation may represent a possible protective mechanism.