Remote testing in Abbiategrasso (RTA): results from a counterbalanced cross-over study on direct-to-home neuropsychology with older adults.

BACKGROUND: The SARS-CoV-2 pandemic forced to rethink teleneuropsychology, since neuropsychological assessments started to be performed by phone or videoconference, with personal devices and without direct assistance from the clinician, a practice called "Direct-To-Home NeuroPsychology" (DTH-NP). AIMS: The present study, employing a counterbalanced cross-over design, was aimed at evaluating (1) the feasibility and (2) the acceptability of DTH-NP in Italian older adults without previously diagnosed neurocognitive disorder, (3) the comparability between remote and face-to-face administration of selected neuropsychological tests. METHODS: Fifty-eight community-dwelling older adults (65-85 years) were randomly assigned to one of two groups performing a complete neuropsychological assessment remotely (via phone call and videoconference) and face-to-face, in a counterbalance order, 8 weeks apart. The study recruitment rate was calculated, and the number of uncompleted tests and acceptability questionnaire responses were compared between the two administration modalities. Comparability was defined as good reliability of DTH-NP (intraclass correlation coefficient) and agreement between remote and face-to-face scores (Bland-Altman plots). RESULTS: Recruitment rate was 81%, with a preference for telephonic contact (79%). The acceptability analysis did not reveal any issues related to the DTH-NP assessment, even if most participants would rather repeat it face-to-face. Tests assessing short-term memory, language, and reasoning showed good comparability. DISCUSSION AND CONCLUSION: Our results point out to a good recruitment rate in a DTH-NP study in an Italian population of older adults (mean age = 80), satisfying acceptability of DTH-NP and remote-face-to-face comparability of certain verbally mediated tests. Further studies including larger samples in videoconference modality, and outpatients, could better clarify its strengths and limits.

COVID-19 Pathology in the Lung, Kidney, Heart and Brain: The Different Roles of T-Cells, Macrophages, and Microthrombosis.

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.

The impact of ICT use on feelings of loneliness and isolation during the COVID-19 lockdown among older people

Background 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. Methods Data were extracted from the fourth follow-up (2018) of the InveCe.Ab, a multidimensional population-based study (NCT01345110) on 70-75 older people living in Abbiategrasso (Milan, Lombardy) at baseline (2009). Sixty-six of them were trained for SNS use in 2019, as a part of the ANS-SE study (NCT04242628). A telephone interview was administered during the lockdown period (March-May 2020), collecting information on self-perceived loneliness measured by the 3-item UCLA loneliness scale and ICT use [smartphones, computers, internet and Social Network Sites (SNSs)]. Participants in the pre-lockdown assessment reporting use of any ICT were defined as ICTusers. Cross-sectional differences between ICTusers and non-users were explored using Independent Sample t-test or Chi-square test. Analysis of covariance (ANCOVA) was applied to compare the long-term effect of being ICTusers and non-users on loneliness change (UCLA 3-item total and subscales) and ICT use change, including the pre-lockdown measures and being trained for SNSs use as covariates, followed by post-hoc comparisons. Results Pre-lockdown participants with ICT use data available were 623 (163 ICT users, 460 non-users). Table 1 shows that ICTusers were mostly men, more educated, showed fewer depressive symptoms (GDS) and higher global cognition (MMSE) than ICTnon-users. ICTusers felt less total loneliness, fewer feelings of a lack of companionship and isolation from others than ICTnon-users. Pre-lockdown ICT use was on average 2.11 (DS 1.05). Longitudinal significant difference emerged between the two groups on total loneliness, with ICTusers (n=130), showing a decrease (mean difference (SE): -0.382 (0.179);95% CI: -0.733, -0.030;p=0.033) compared to non-users (n=296). ICTusers (n=130), reported fewer feelings of isolation (mean difference (SE): -0.213 (0.068);95% CI: -0.348, -0.079;p=0.002) than non-users (n=300). Conclusions During the COVID-19 lockdown, former ICTusers were protected against feelings of loneliness and isolation. The ICT use did not change in both groups.

COVID-19 patients and Dementia: Frontal cortex transcriptomic data.

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.

COVID-19-related neuropathology and microglial activation in elderly with and without dementia.

The actual role of SARS-CoV-2 in brain damage remains controversial due to lack of matched controls. We aim to highlight to what extent is neuropathology determined by SARS-CoV-2 or by pre-existing conditions. Findings of 9 Coronavirus disease 2019 (COVID-19) cases and 6 matched non-COVID controls (mean age 79 y/o) were compared. Brains were analyzed through immunohistochemistry to detect SARS-CoV-2, lymphocytes, astrocytes, endothelium, and microglia. A semi-quantitative scoring was applied to grade microglial activation. Thal-Braak stages and the presence of small vessel disease were determined in all cases. COVID-19 cases had a relatively short clinical course (0-32 days; mean: 10 days), and did not undergo mechanical ventilation. Five patients with neurocognitive disorder had delirium. All COVID-19 cases showed non-SARS-CoV-2-specific changes including hypoxic-agonal alterations, and a variable degree of neurodegeneration and/or pre-existent SVD. The neuroinflammatory picture was dominated by ameboid CD68 positive microglia, while only scant lymphocytic presence and very few traces of SARS-CoV-2 were detected. Microglial activation in the brainstem was significantly greater in COVID-19 cases (p = 0.046). Instead, microglial hyperactivation in the frontal cortex and hippocampus was clearly associated to AD pathology (p = 0.001), regardless of the SARS-CoV-2 infection. In COVID-19 cases complicated by delirium (all with neurocognitive disorders), there was a significant enhancement of microglia in the hippocampus (p = 0.048). Although higher in cases with both Alzheimer's pathology and COVID-19, cortical neuroinflammation is not related to COVID-19 per se but mostly to pre-existing neurodegeneration. COVID-19 brains seem to manifest a boosting of innate immunity with microglial reinforcement, and adaptive immunity suppression with low number of brain lymphocytes probably related to systemic lymphopenia. Thus, no neuropathological evidence of SARS-CoV-2-specific encephalitis is detectable. The microglial hyperactivation in the brainstem, and in the hippocampus of COVID-19 patients with delirium, appears as a specific topographical phenomenon, and probably represents the neuropathological basis of the "COVID-19 encephalopathic syndrome" in the elderly.

Detection of SARS-CoV-2 genome and whole transcriptome sequencing in frontal cortex of COVID-19 patients.

SARS-Cov-2 infection is frequently associated with Nervous System manifestations. However, it is not clear how SARS-CoV-2 can cause neurological dysfunctions and which molecular processes are affected in the brain. In this work, we examined the frontal cortex tissue of patients who died of COVID-19 for the presence of SARS-CoV-2, comparing qRT-PCR with ddPCR. We also investigated the transcriptomic profile of frontal cortex from COVID-19 patients and matched controls by RNA-seq analysis to characterize the transcriptional signature. Our data showed that SARS-CoV-2 could be detected by ddPCR in 8 (88%) of 9 examined samples while by qRT-PCR in one case only (11%). Transcriptomic analysis revealed that 11 genes (10 mRNAs and 1 lncRNA) were differential expressed when frontal cortex of COVID-19 patients were compared to controls. These genes fall into categories including hypoxia, hemoglobin-stabilizing protein, hydrogen peroxide processes. This work demonstrated that the quantity of viral RNA in frontal cortex is minimal and it can be detected only with a very sensitive method (ddPCR). Thus, it is likely that SARS-CoV-2 does not actively infect and replicate in the brain; its topography within encephalic structures remains uncertain. Moreover, COVID-19 may have a role on brain gene expression, since we observed an important downregulation of genes associated to hypoxia inducting factor system (HIF) that may inhibit the capacity of defense system during infection and oxigen deprivation, showing that hypoxia, well known multi organ condition associated to COVID-19, also marked the brain.

Life during COVID-19 lockdown in Italy: the influence of cognitive state on psychosocial, behavioral and lifestyle profiles of older adults.

OBJECTIVE: Few studies have examined lockdown effects on the way of living and well-being of older adults stratified by cognitive state. Since cognitive deficits are common in this population, we investigated how cognition influenced their understanding of the pandemic, socio-behavioral responses and lifestyle adaptations during lockdown, and how these factors affected their mood or memory. METHOD: Telephone-based survey involving 204 older adults ≥65 y/o (median: 82) with previous assessments of cognitive state: 164 normal-old (NOLD), 24 mild-neurocognitive disorder (mild-NCD), 18 mild-moderate dementia. A structured questionnaire was developed to assess psychological and socio-behavioral variables. Logistic regression was used to ascertain their effects on mood and memory. RESULTS: With increasing cognitive deficits, understanding of the pandemic and the ability to follow lockdown policies, adapt to lifestyle changes, and maintain remote interactions decreased. Participants with dementia were more depressed; NOLDs remained physically and mentally active but were more bored and anxious. Sleeping and health problems independently increased the likelihood of depression (OR: 2.29; CI: 1.06-4.93; p = 0.034 and OR: 2.45; CI: 1.16-5.16; p = 0.018, respectively); Regular exercise was protective (OR: 0.30; CI: 0.12-0.72; p = 0.007). Worsening subjective memory complaints were associated with dementia (p = 0.006) and depression (p = 0.004); New-onset sleeping problems raised their odds (OR: 10.26; CI: 1.13-93.41; p = 0.039). Finally, >40% with health problems avoided healthcare mainly due to fear of contagion. DISCUSSION: NOLD and mild-NCD groups showed similar mood-behavioral profiles suggesting better tolerance of lockdown. Those with dementia were unable to adapt and suffered from depression and cognitive complaints. To counteract lockdown effects, physical and mental activities and digital literacy should be encouraged.

Loneliness and social engagement in older adults based in Lombardy during COVID-19 lockdown: The long-term effects of social networking sites training course

Abstract Background Older people are at greater risk of infection and mortality from COVID-19 and 52.3% of the deceased in Italy are Lombardy?s residents. Moreover, lockdown measurements may disproportionately affect elderly, since they are less familiar with communication technology used to overcome the lack of in person social contacts. The present study aimed at exploring how older adults residing in Lombardy are experiencing the lockdown period, in relation to loneliness, social isolation and use of communication technology. Method In the first two weeks of May (2020) a telephone interview was conducted with people aged between 81 and 85, residing in the community, who participated in a study aimed at evaluating the impact of Social Networking Sites (SNS) use and older people?s social relationship (clinicaltrials.gov: NCT04242628). We collected information on SNS use, self-perceived loneliness (UCLA scale 3-item), social engagement with family and friends (Lubben Social Network Scale 6-item). Among the eligible individuals (N=144), 1 deceased, 4 refused and 9 were unreachable, resulting in a sample of 130 interviewed. For the aim of the present investigation, participants were stratified as trained (N=60) and untrained (N=70) for SNS use, based on their attendance to group courses held last year as part of the main experimental study. Result Trained and untrained participants were comparable for age, sex, education, percentage of living alone, global cognition, depressive symptoms and comorbidity (Table 1). Participants trained for SNS use reported significantly higher usage of Facebook and WhatsApp and reduced feeling of being left out during the COVID-19 lockdown (Table 2). Moreover, a trend toward significance was found for an inverse relationship between WhatsApp usage frequency and feeling of lack of companionship (rs = -0.257, p = 0.051;Table 3). Conclusion Though SNS are unable to completely replace in person contact, these preliminary results support the utility to train older adults for SNS use in order to improve their social inclusion, even in extreme conditions of self-isolation and vulnerability due to COVID-19 pandemic.

Loneliness and Social Engagement in Older Adults Based in Lombardy during the COVID-19 Lockdown: The Long-Term Effects of a Course on Social Networking Sites Use.

Older adults are less familiar with communication technology, which became essential to maintain social contacts during the COVID-19 lockdown. The present study aimed at exploring how older adults, previously trained for Social Networking Sites (SNSs) use, experienced the lockdown period. In the first two weeks of May 2020, telephone surveys were conducted with individuals aged 81-85 years and resident in Abbiategrasso (Milan), who previously participated in a study aimed at evaluating the impact of SNSs use on loneliness in old age (ClinicalTrials.gov, NCT04242628). We collected information on SNSs use, self-perceived loneliness, and social engagement with family and friends. Interviewed participants were stratified as trained (N = 60) and untrained (N = 70) for SNSs use, based on their attendance to group courses held the previous year as part of the main experimental study. The groups were comparable for sociodemographics and clinical features. Participants trained for SNSs use reported significantly higher usage of SNSs and reduced feeling of being left out. Compared to pre-lockdown levels, individuals trained for SNSs use showed a lighter reduction in social contacts. These findings support the utility of training older adults for SNSs use in order to improve their social inclusion, even in extreme conditions of self-isolation and perceived vulnerability.

Prevalence and prognostic value of Delirium as the initial presentation of COVID-19 in the elderly with dementia: An Italian retrospective study.

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 (96⋅6%) tested positive (mean age: 82⋅8; women: 66⋅7%). Comorbidities were present in all participants, with 18/57 (31⋅6%) having three or more concomitant diseases. Delirium-Onset COVID-19 (DOC) was observed in 21/57 (36⋅8%) subjects who were chiefly older (mean age: 85⋅4 y/o) and with multiple comorbidities. Eleven/21 DOC patients (52⋅4%) had hypoactive delirium, while hyperactive delirium occurred in ten/21 (47⋅6%). Lymphopenia was present in almost all subjects (median: 1⋅3 × 109/L). Overall mortality rate was 24⋅6% (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<0⋅001). Also, DOC and male gender were independently associated with increased risk of mortality (OR: 17⋅0, 95% CI: 2⋅8-102⋅7, p = 0⋅002 and 13⋅6, 95% CI: 2⋅3-79⋅2, p = 0⋅001 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.