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2.
J Neurochem ; 161(2): 146-157, 2022 04.
Article in English | MEDLINE | ID: covidwho-1673193

ABSTRACT

SARS-CoV-2 infection can damage the nervous system with multiple neurological manifestations described. However, there is limited understanding of the mechanisms underlying COVID-19 neurological injury. This is a cross-sectional exploratory prospective biomarker cohort study of 21 patients with COVID-19 neurological syndromes (Guillain-Barre Syndrome [GBS], encephalitis, encephalopathy, acute disseminated encephalomyelitis [ADEM], intracranial hypertension, and central pain syndrome) and 23 healthy COVID-19 negative controls. We measured cerebrospinal fluid (CSF) and serum biomarkers of amyloid processing, neuronal injury (neurofilament light), astrocyte activation (GFAp), and neuroinflammation (tissue necrosis factor [TNF] ɑ, interleukin [IL]-6, IL-1ß, IL-8). Patients with COVID-19 neurological syndromes had significantly reduced CSF soluble amyloid precursor protein (sAPP)-ɑ (p = 0.004) and sAPPß (p = 0.03) as well as amyloid ß (Aß) 40 (p = 5.2 × 10-8 ), Aß42 (p = 3.5 × 10-7 ), and Aß42/Aß40 ratio (p = 0.005) compared to controls. Patients with COVID-19 neurological syndromes showed significantly increased neurofilament light (NfL, p = 0.001) and this negatively correlated with sAPPɑ and sAPPß. Conversely, GFAp was significantly reduced in COVID-19 neurological syndromes (p = 0.0001) and this positively correlated with sAPPɑ and sAPPß. COVID-19 neurological patients also displayed significantly increased CSF proinflammatory cytokines and these negatively correlated with sAPPɑ and sAPPß. A sensitivity analysis of COVID-19-associated GBS revealed a non-significant trend toward greater impairment of amyloid processing in COVID-19 central than peripheral neurological syndromes. This pilot study raises the possibility that patients with COVID-19-associated neurological syndromes exhibit impaired amyloid processing. Altered amyloid processing was linked to neuronal injury and neuroinflammation but reduced astrocyte activation.


Subject(s)
Alzheimer Disease , Amyloidosis , COVID-19 , Alzheimer Disease/cerebrospinal fluid , Amyloid beta-Peptides/metabolism , Amyloid beta-Protein Precursor/cerebrospinal fluid , Biomarkers/cerebrospinal fluid , COVID-19/complications , Cohort Studies , Cross-Sectional Studies , Humans , Pilot Projects , Prospective Studies , SARS-CoV-2
3.
Alzheimer's & Dementia ; 17(S1):e053980, 2021.
Article in English | Wiley | ID: covidwho-1589237

ABSTRACT

Background By obtaining a better grasp on the impact of the COVID-19 pandemic on individuals with cognitive impairment, this knowledge could be used to improve the delivery of information to this particular group. We aimed to assess the relationship between tau deposition and the change in anxiety levels, before and during the pandemic. We hypothesized that since the pandemic, higher tau loads would lower the change in anxiety. Furthermore, we expected these anxiety levels not to be associated with COVID-19 related stress in participants with cognitive decline. Methods 63 participants of the Translational Biomarker of Aging and Dementia (TRIAD) cohort (cognitively healthy, N=38;cognitively impaired, N=25, of which 7 had dementia due to Alzheimer?s disease), were assessed to evaluate their individual change in anxiety levels (GAD-7). This was done at three different timepoints, of which the latest fell during the COVID-19 lockdown period. Two rates of change, one before and one during the pandemic, were determined using the following definition: (next timepoint ? current timepoint)/time difference. In addition, at the latest timepoint, subjective stress due to COVID-19 was measured using the Montreal Assessment of Stress related to COVID-19 (MASC). To assess the levels of tau, standard uptake value ratios (SUVR) from previously obtained [18F]MK-6240 PET-scans were used. Results [18F]MK-6240 tracer binding in the lingual gyrus was negatively associated with the rate of change in GAD-7 scores after correcting for age, sex, years of education and the presence of APOE ε4, but only in cognitively impaired individuals during the pandemic (fig 1A). In addition, the GAD-7 score at the latest timepoint was associated with stress related to COVID-19, but only in cognitively healthy individuals (fig 1B and 1C). Conclusions The presence of tau in the lingual gyrus negatively affected the rate of change in GAD-7 scores during the COVID-19 pandemic in individuals with cognitive impairment. This could indicate that information pertaining to the pandemic does not reach these individuals in an efficient manner. The missing association between COVID-19 induced stress and the latest GAD-7 scores in these individuals is a further indication of this.

4.
Alzheimer's & Dementia ; 17(S6):e054133, 2021.
Article in English | Wiley | ID: covidwho-1589235

ABSTRACT

Background While the global COVID-19 pandemic has hindered many human research operations, it has allowed for the investigation of novel scientific questions. Particularly, the effects of the pandemic and its resulting social isolation on elderly individuals and their association with Alzheimer?s disease biomarkers remains a broad and open question. Here, we sought to investigate whether knowledge of COVID-19, pandemic-related distress, and changes in sleep quality were associated with in vivo tau deposition in an AD-enriched cohort. Methods COVID-19 telephone assessments were conducted in N=292 individuals (29 young/174 CN/52 MCI/19 AD/18 other) of the TRIAD cohort in April-July 2020. Assessment consisted of clinical and neuropsychiatric, instruments, including scales assessing the individual?s experience of the pandemic. Structural MRI and [18F]MK6240 tau-PET were acquired before the pandemic. [18F]MK6240 standardized uptake value ratio (SUVR) were calculated 90-110 minutes post-injection using cerebellar grey matter as the reference region. Voxel-based regression analyses were conducted to examine the associations between baseline [18F]MK6240 SUVR and knowledge of COVID-19, distress related to COVID-19, and change in sleep quality since the pandemic. Results Higher tau-PET SUVR was associated with less knowledge of COVID-19 in N=210 individuals in the cuneus, cingulate and superior temporal regions. Tau-PET was similarly associated with lower levels of COVID-19-related distress in the isthmus and rostral anterior cingulate (N=201 individuals). Furthermore, tau-PET tracer uptake was significantly associated with increases in sleep quality as assessed by rate of change in Pittsburgh Sleep Quality Index before and during the pandemic (N=176 individuals). All results survived correction for multiple comparisons using random field theory with a cluster threshold of p < 0.001. Conclusion Our results suggest that those with increased tau deposition may have a weaker understanding of symptoms and prevention of COVID-19 and lower levels of distress related to the pandemic than individuals with less brain tau. Individuals with higher tau may also experience improved sleep quality during the pandemic. While these observations appear to be favourable effects of tau, the first may suggest that public health information about COVID-19 is less accessible to the aging population. The interactions and mediation of these effects remain to be properly elucidated.

5.
Alzheimer's & Dementia ; 17(S1):e054773, 2021.
Article in English | Wiley | ID: covidwho-1589233

ABSTRACT

Background Individuals with cognitive/memory impairments may be more vulnerable to COVID19 due to having poor knowledge of COVID19 and how to protect themselves under current policies. Here, we aimed to show cognitive/memory impairment is associated with less knowledge or less anxiety change related to COVID19. We hypothesized that the effect of hippocampal volume on COVID19-related knowledge or anxiety change during the pandemic is mediated by cognitive health. Method A total of 247 participants (162 cognitively normal (CN) and 85 cognitively impaired (CI)) from the Montreal TRIAD cohort underwent a structural MRI and cognition and anxiety assessments using CDRSOB and GAD score, respectively before the COVID19 pandemic. During the first wave of COVID19, the participants were assessed for anxiety using GAD score and knowledge related to COVID19. Hippocampal volume was measured using Freesurfer, and the anxiety was evaluated as the rate of change in the GAD score: (follow-up ? baseline)/time difference. Then, the effect of hippocampal volume on the rate of change in the anxiety or knowledge on COVID19 was evaluated based on a mediation analysis with CDRSOB as a mediator, 2000 bootstrapping, and age, sex, education, and APOEe4 as covariates. Result The CI group showed significantly less knowledge of COVID19, or less anxiety change compared to the CN group, while hippocampal volume showed a significant association with knowledge of COVID19 or the rate of change in anxiety. Upon further examination, we revealed that the effect of hippocampal volume on COVID19 knowledge or the rate of change in anxiety was significantly mediated by cognitive health, indicated by CDRSOB (Figure 1). Conclusion Our finding highlights the poorer knowledge of COVID19 and related risks in individuals with cognitive/memory impairments;the CDRSOB, indicative of cognitive health, significantly mediated the effect of hippocampal volume on the rate of change in anxiety or knowledge on COVID19 in our cohort. This study urges for a more effective strategy and policy about informing and educating the individual with cognitive/memory impairment on COVID19 and related risks.

6.
Alzheimer's & Dementia ; 17(S1):e056573, 2021.
Article in English | Wiley | ID: covidwho-1589204

ABSTRACT

Background Following the rapid spread of the COVID-19 virus throughout Quebec, the TRIAD cohort, a longitudinal observational study, evaluated the effects of COVID-19 on it?s aging and vulnerable population and their caregivers. This study aims at investigating the behavioural and psychological effects of COVID-19 and social isolation on the aging population. The TRIAD Assessment of Social Isolation and Cognition (TASIC) was developed to assess these effects on participants of observational trials. Method Pre-pandemic data including, demographical information, Clinical Dementia Rating (CDR), Mini-Mental State Examination (MMSE), Geriatric Depression Scale (GDS), Montreal Cognitive Assessment (MoCA) and a Social Support Questionnaire, were collected during in-person visits and take-home questionnaires. Following the onset of COVID-19, TASIC was created to include additional COVID-19 specific scales developed by Dr. Rosa-Neto and Dr. King that include Knowledge of COVID-19 scale, the Montreal Assessment of Stress related to COVID-19 (MASC), as well as the Impact of Events Scale (IESR), the Peritraumatic Distress Inventory (PDI), the Peritraumatic Dissociative Experiences Questionnaire (PDEQ) for COVID-19. Assessments were conducted via telephone interviews with TRIAD participants (n=292) and their informants (n=243) by eight trained research assistants from April through June 2020. All participants enrolled in previous TRIAD studies, deemed eligible through detailed screening criteria were contacted. Result As a result of this study, and previous work done by the cohort, a culmination of information is available, with 90% of TRIAD participants having completed the COVID-19 study also having plasma collected. 80% of participants from the COVID-19 study have PET imaging using [18F]AZD4694 and [18F]MK6240 and MRI sequencing. Conclusion The COVID-19 study conducted by TRIAD provides a unique opportunity to understand the effects of a global pandemic on our aging population as well as caregiver burden. This data, in conjunction with other measures available in the cohort, can make important strides in finding ways to help, and better understand those most impacted by the crisis.

7.
Alzheimer's & Dementia ; 17(S6):e056606, 2021.
Article in English | Wiley | ID: covidwho-1589203

ABSTRACT

Background The occurrence of the COVID-19 pandemic has had a significant impact on cohort studies, particularly those whose subjects are at higher risk of developing complications from the virus. As such, assessment methods must be adapted to minimize COVID-19 exposure risk. The TRIAD (Translational Biomarkers of Aging and Dementia) cohort assessed N=292 individuals during initial COVID-19 lockdown measures by telephone interview to rate cognition, neuropsychiatric symptoms, and impact of the pandemic. To increase speed and efficiency of data collection, we aim to follow these individuals by means of online survey. Here, we present a validation of our online assessment tools by comparing data obtained through both methods (phone interview and online survey) in the same subjects. Methods 10 subjects (4 elderly CN/3 MCI/3 AD) and their informants participated in this study. Subjects were varied for assessment language (English/French) and first assessment method (phone/online). 18 instruments were administered (listed in Table 1). Instrument scores were first compared by computing individual differences (phone-online), then by pooling all scores by assessment type and calculating an effect size. Pearson correlation coefficient between phone and online scores was also computed. Results Mean interval between assessments was 8.8±4.8 days. Mean length of online assessment (63.7±20.7mins) was comparable to mean phone interview length (72.6±32.4mins). Instrument scores from phone interviews had a total mean of 102.60, while scores from online surveys had a total mean of 103.93, with a pooled SD of 716.09. Effect size was -0.00186. Correlation of phone and online scores yielded a Pearson?s R of 0.85 (p<0.05). Pearson?s R was also computed by applying bootstrapping using 1000 resamples without replacement with a sample size of 50. The Pearson R coefficient after bootstrapping was 0.91 (95% CI: [0.7699-0.998]). Conclusion Our results suggest that instrument scores from phone and online assessments are comparable, and not significantly different from each other. The observed variance in scores between phone and online assessments may be due in part to the normal test-retest variability associated with re-administering instruments. This validation of online assessment tools in an aging population is of significant importance to human studies in the context of COVID-19.

9.
Brain Commun ; 3(3): fcab099, 2021.
Article in English | MEDLINE | ID: covidwho-1358433

ABSTRACT

Preliminary pathological and biomarker data suggest that SARS-CoV-2 infection can damage the nervous system. To understand what, where and how damage occurs, we collected serum and CSF from patients with COVID-19 and characterized neurological syndromes involving the PNS and CNS (n = 34). We measured biomarkers of neuronal damage and neuroinflammation, and compared these with non-neurological control groups, which included patients with (n = 94) and without (n = 24) COVID-19. We detected increased concentrations of neurofilament light, a dynamic biomarker of neuronal damage, in the CSF of those with CNS inflammation (encephalitis and acute disseminated encephalomyelitis) [14 800 pg/ml (400, 32 400)], compared to those with encephalopathy [1410 pg/ml (756, 1446)], peripheral syndromes (Guillain-Barré syndrome) [740 pg/ml (507, 881)] and controls [872 pg/ml (654, 1200)]. Serum neurofilament light levels were elevated across patients hospitalized with COVID-19, irrespective of neurological manifestations. There was not the usual close correlation between CSF and serum neurofilament light, suggesting serum neurofilament light elevation in the non-neurological patients may reflect peripheral nerve damage in response to severe illness. We did not find significantly elevated levels of serum neurofilament light in community cases of COVID-19 arguing against significant neurological damage. Glial fibrillary acidic protein, a marker of astrocytic activation, was not elevated in the CSF or serum of any group, suggesting astrocytic activation is not a major mediator of neuronal damage in COVID-19.

10.
Alzheimers Dement (N Y) ; 6(1): e12085, 2020.
Article in English | MEDLINE | ID: covidwho-1030708

ABSTRACT

The COVID-19 pandemic has caused tremendous suffering for patients with dementia and their caregivers. We conducted a survey to study the impact of the pandemic on patients with mild frontotemporal dementia (FTD). Our preliminary findings demonstrate that patients with FTD have significant worsening in behavior and social cognition, as well as suffer greater negative consequences from disruption to health-care services compared to patients with AD. The reduced ability to cope with sudden changes to social environments places patients with FTD at increased vulnerability to COVID-19 infection as well as to poorer clinical and social outcomes. Caregivers of FTD patients also demonstrate high burden during crisis situations. A proportion of patients with FTD benefitted from use of web-based interactive platforms. In this article, we outline the priority areas for research as well as a roadmap for future collaborative research to ensure greatest benefit for patients with FTD and their caregivers.

11.
Can Geriatr J ; 23(3): 216-218, 2020 Sep.
Article in English | MEDLINE | ID: covidwho-971352

ABSTRACT

Hospitals and intensive care units are straining to provide care for a large surge of patients with coronavirus disease 19 (Covid-19). Contingency plans are being made for the possibility that resources for lifesaving care, including mechanical ventilators, will be in short supply. Covid-19 is more severe and more likely to be fatal in older persons. Dementia is one of the commonest severe comorbidities of aging. Persons with dementia are vulnerable and often need the support of others to make their voices heard. This commentary, created by a task force commissioned by the Alzheimer Society of Canada, provides guidance for triaging persons with dementia to scarce medical resources during the Covid-19 pandemic.

12.
Alzheimers Dement (Amst) ; 12(1): e12111, 2020.
Article in English | MEDLINE | ID: covidwho-808863

ABSTRACT

INTRODUCTION: Despite the urgent need for remote neurobehavioral assessment of individuals with cognitive impairment, guidance is lacking. Our goal is to provide a multi-dimensional framework for remotely assessing cognitive, functional, behavioral, and physical aspects of people with cognitive impairment, along with ethical and technical considerations. METHODS: Literature review on remote cognitive assessment and multidisciplinary expert opinion from behavioral neurologists, neuropsychiatrists, neuropsychologists, and geriatricians was integrated under the auspices of the Alzheimer Society of Canada Task Force on Dementia Care Best Practices for COVID-19. Telephone and video approaches to assessments were considered. RESULTS: Remote assessment is shown to be acceptable to patients and caregivers. Informed consent, informant history, and attention to privacy and autonomy are paramount. A range of screening and domain-specific instruments are available for telephone or video assessment of cognition, function, and behavior. Some neuropsychological tests administered by videoconferencing show good agreement with in-person assessment but still lack validation and norms. Aspects of the remote dementia-focused neurological examination can be performed reliably. DISCUSSION: Despite challenges, current literature and practice support implementation of telemedicine assessments for patients with cognitive impairment. Convergence of data across the clinical interview, reliable and brief remote cognitive tests, and remote neurological exam increase confidence in clinical interpretation and diagnosis.

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