Adipose tissue, systematic inflammation, and neurodegenerative diseases

Obesity is associated with several diseases, including mental health. Adipose tissue is distributed around the internal organs, acting in the regulation of metabolism by storing and releasing fatty acids and adipokine in the tissues. Excessive nutritional intake results in hypertrophy and proliferation of adipocytes, leading to local hypoxia in adipose tissue and changes in these adipokine releases. This leads to the recruitment of immune cells to adipose tissue and the release of pro-inflammatory cytokines. The presence of high levels of free fatty acids and inflammatory molecules interfere with intracellular insulin signaling, which can generate a neuroinflammatory process. In this review, we provide an up-to-date discussion of how excessive obesity can lead to possible cognitive dysfunction. We also address the idea that obesity-associated systemic inflammation leads to neuroinflammation in the brain, particularly the hypothalamus and hippocampus, and that this is partially responsible for these negative cognitive outcomes. In addition, we discuss some clinical models and animal studies for obesity and clarify the mechanism of action of anti-obesity drugs in the central nervous system.Copyright © 2023 Wolters Kluwer Medknow Publications. All rights reserved.

The Role of Monoclonal Antibodies in Contrasting Cases of Norse

1. A 42-year-old female developed status ten days following admission for alcohol-related liver disease. MRI brain showed symmetrical medial temporal high signal. No cause was identified. Though the convulsive seizures settled, focal seizures persisted. A second MRI showed extensive multi-lobar signal change, presumed inflammatory in nature. Pulsed methylprednisolone and plasma exchange were ineffective. Tocilizumab was administered ten weeks following onset of seizures. Sequential MRIs showed resolution of inflammatory changes. The patient was discharged to rehabilitation-Modified Rankin Score 3. 2. A 79-year-old female presented with convulsive NORSE, 24hours after first dose of Pfizer COVID vaccine. She had a background of vascular dementia. The patient never recovered her GCS. Convulsive seizures were replaced by epilepsy partialis continua. Sequential MRIs showed diffuse left parietal cortical high signal. An inflammatory aetiology was presumed, pulsed methylprednisolone and the ketogenic diet (3 months) were ineffective. Anakinra was administered on week twelve. Subsequent MRIs showed progression of confluent white matter disease, now bi-hemispheric. She remains symptomatic, a year post presentation. We hypothesise that both patients had NORSE arising from an unidentified inflammatory aetiology. Age and premorbid function are known to influence recovery. Early use of monoclonal antibodies may be beneficial, including in those with systemic disease.

The impact of the UK COVID-19 pandemic on patients following stroke: insights from the R4VaD study of post-stroke cognition and mood

Introduction: There are few reports of the effect of the COVID-19 pandemic, and subsequent lockdown, on the everyday lives of people affected by stroke. Method(s): We present a narrative of experiences of people participating in the Rates, Risks and Routes to Reduce Vascular Dementia (R4VaD) stroke study, an ongoing UK-wide, observational study of cognitive, physical and neuropsychiatric complications after stroke. Participants were recruited up to a year prior to or during the outbreak, and were in follow-up during introduction of the UK social distancing measures. During participants' 1- year follow-up we performed standardized assessments, including free text responses regarding experiences of the pandemic, encompassing many aspects of healthcare including cognition, mood and anxiety. Result(s): In our study of over 2000 stroke survivors from across the UK, we found that the COVID-19 pandemic has had an adverse effect on health, including poorer mental health and wellbeing, feelings of loneliness, poorer health related behaviours and disengagement with, or lack of access to, health services, including rehabilitation. This was most evident between March and May 2020, during which time 1 in 3 patients spontaneously reported negative effects of the pandemic during telephone followups. After the national roll out of the vaccine, participants reported barriers to resuming community activities and hesitancy and anxiety regarding the transition from self-isolation to "normal life". Conclusion(s): The pandemic has caused significant challenges for stroke survivors and their families, which, unless addressed, are likely to have substantial physical and mental health consequences, which will impact significantly on stroke survivors' recovery.

RATES, RISKS AND ROUTES TO REDUCE VASCULAR DEMENTIA (R4VAD)

Background and aims: R4VAD is a multi-site longitudinal, inclusive observational study of patients presenting with stroke to UK stroke centres aiming to determine rates of, and risk factors for, cognitive and related impairments after stroke, assess mechanisms and improve prediction models. Methods: R4VaD is recruiting patients within six weeks of stroke and collecting clinical, socioeconomic, lifestyle, cognitive, mood and informant data using clinical trial methods. Detailed assessments are obtained at 6+/-2 weeks post baseline assessment, with annual follow-up by phone and post to at least 2 years plus data linkage for 10 years. Diagnostic neuroimaging is assessed in all, and inflammatory blood markers and genetic analysis in as many patients as possible. Recruitment opened in September 2018, paused briefly in March 2020 and reopened in April 2020 with a COVID-19 substudy. Results: To date, we have recruited 2371 participants (initial target 2000) in 53 centres across the UK (mean age=68.3 years, SD=13.6;40.1% female). So far, 85% of participants have ischaemic stroke;8% ICH;6%;mean NIHSS=2.9 (SD=3.4);6% lack capacity;29% have an informant. Prevalent vascular risk factors include: hypertension (63%);hyperlipidaemia (46%);current/ex-smoker (59%);previous stroke/TIA (28%). At baseline, mean scores were: MOCA=23.2/30, SD=4.2;Zung depression= 46.0/80, SD=13.3 (≥50 suggests depression) and anxiety (GAD- 7)=3.9/21, SD=4.8 (≥5 suggests anxiety). Conclusions: R4VAD will provide reliable data on cognitive and neuropsychiatric consequences long-term after stroke;improve understanding of clinical, demographic, laboratory, neuroimaging and social predictors of post-stroke cognitive impairment and dementia and provide objective data on the impacts of COVID-19 on stroke.

COVID-19 case fatality and Alzheimer's disease

Objective: Our objective was to determine whether AD increases COVID-19 case fatality rate (CFR). Background: Previous studies have identified dementia as a risk factor for death from coronavirus disease 2019 (COVID-19). However, it is unclear whether Alzheimer's disease (AD) is an independent risk factor for COVID-19 mortality. Design/Methods: In a retrospective cohort study, we identified 387,841 COVID-19 patientes through TriNetX, and performed a multivariable logistic regression to determine the odds ratio of dying from COVID-19 between patients with and without AD. We accounted for differences between cohorts in three ways. First, we included age, gender, race, ethnicity, and 30 comorbidities from the Elixhauser comorbidity index in our regression. Second, we matched each AD COVID-19 case to control COVID-19 cases with the same age, gender, race, and Elixhauser Comorbidity Index, and then performed conditional logistic regression to account for residual confounding. Third, we performed propensity score matching followed by conditional logistic regression. We extended this analysis to vascular dementia, dementia with Lewy bodies (DLB) and frontotemporal dementia (FTD). Results: We found that AD patients had higher odds of dying from COVID-19 compared to patients without AD (Odds Ratio(OR): 1.20, 95% confidence interval(CI): 1.09-1.32, p<0.001). This result is corroborated by conditional logistic regression analyses with exact-matching and propensity score matching. Interestingly, we did not observe increased mortality from COVID-19 among patients with vascular dementia (OR: 0.99, 95% CI: 0.88-1.10, p=0.83), DLB or FTD. Conclusions: AD increases CFR associated with COVID-19, though vascular dementia does not. These data are relevant to the evolving global COVID-19 pandemic and future pandemics.