Steeper memory decline after COVID-19 lockdown measures.

BACKGROUND: During COVID-19 lockdown measures, memory clinic patients reported worries for faster cognitive decline, due to loss of structure and feelings of loneliness and depression. We aimed to investigate the impact of the COVID-19 lockdown on rate of cognitive decline in a mixed memory clinic population, compared to matched historical controls. METHODS: We included patients who visited Alzheimer Center Amsterdam 6 months to 1 week before the first Dutch COVID-19 lockdown, and had a second visit 1 year later, after this lockdown period (n = 113; 66 ± 7 years old; 30% female; n = 55 dementia, n = 31 mild cognitive impairment (MCI), n = 18 subjective cognitive decline (SCD), n = 9 postponed diagnosis). Historical controls (visit in 2016/2017 and second visit 1 year later (n = 640)) were matched 1:1 to lockdown patients by optimal Mahalanobis distance matching (both groups n = 113). Groups were well matched. Differences between lockdown patients and historical controls over time in Mini-Mental State Examination, Trail Making Test part A and B, Rey-Auditory Verbal Learning Test (RAVLT) immediate and delayed recall, and category fluency scores were analyzed using linear mixed effect models with random intercepts. We examined differences in rate of cognitive decline between whole groups, and after stratification in SCD, MCI, and dementia separately. RESULTS: Lockdown patients had a faster rate of memory decline compared to controls on both RAVLT immediate [B(SE) = - 2.62 (1.07), p = 0.015] and delayed recall [B(SE) = - 1.07 (0.34), p = 0.002]. Stratification by syndrome diagnosis showed that this effect was largely attributable to non-demented participants, as we observed faster memory decline during lockdown in SCD and MCI (RAVLT immediate [SCD: B(SE) = - 6.85 (2.97), p = 0.027; MCI: B(SE) = - 6.14 (1.78), p = 0.001] and delayed recall [SCD: B(SE) = - 2.45 (1.11), p = 0.035; MCI: B(SE) = - 1.50 (0.51), p = 0.005]), but not in dementia. CONCLUSION: Memory clinic patients, specifically in pre-dementia stages, showed faster memory decline during COVID-19 lockdown, providing evidence that lockdown regulations had a deleterious effect on brain health. In individuals that may have been able to deal with accumulating, subclinical neuropathology under normal and structured circumstances, the additional stress of lockdown regulations may have acted as a "second hit," resulting in less beneficial disease trajectory.

Immunization with 674-685 fragment of SARS-Cov-2 spike protein induces neuroinflammation and impairs episodic memory of mice.

COVID-19 is accompanied by strong inflammatory reaction and is often followed by long-term cognitive disorders. The fragment 674-685 of SARS-Cov-2 spike protein was shown to interact with α7 nicotinic acetylcholine receptor involved in regulating both inflammatory reactions and cognitive functions. Here we show that mice immunized with the peptide corresponding to 674-685 fragment of SARS-Cov-2 spike protein conjugated to hemocyanin (KLH-674-685) demonstrate decreased level of α7 nicotinic acetylcholine receptors, increased levels of IL-1ß and TNFα in the brain and impairment of episodic memory. Choline injections prevented α7 nicotinic receptor decline and memory loss. Mice injected with immunoglobulins obtained from the blood of (KLH-674-685)-immunized mice also demonstrated episodic memory decline. These data allow suggesting that post-COVID memory impairment in humans is related to SARS-Cov-2 spike protein-specific immune reaction. The mechanisms of such effect are being discussed.

Longitudinal evaluation of neurologic-post acute sequelae SARS-CoV-2 infection symptoms.

OBJECTIVE: To assess the initial features and evolution of neurologic Postacute Sequelae of SARS-CoV-2 infection (neuro-PASC) in patients with and without prior neurologic disease. METHODS: Participants with neurologic symptoms following acute SARS-CoV-2 infection were recruited from October 9, 2020 to October 11, 2021. Clinical data included a SARS-CoV-2 infection history, neurologic review of systems, neurologic exam, Montreal cognitive assessment (MoCA), and symptom-based self-reported surveys at baseline (conducted after acute infection) and 6-month follow-up assessments. RESULTS: Fifty-six participants (69% female, mean age 50 years, 29% with prior neurologic disease such as multiple sclerosis) were enrolled, of which 27 had completed the 6-month follow-up visit in this ongoing study. SARS-CoV-2 infection severity was largely described as mild (39.3%) or moderate (42.9%). At baseline, following acute infection, the most common neurologic symptoms were fatigue (89.3%) and headaches (80.4%). At the 6-month follow-up, memory impairment (68.8%) and decreased concentration (61.5%) were the most prevalent, though on average all symptoms showed a reduction in reported severity score at the follow-up. Complete symptom resolution was reported in 33.3% of participants by 6 months. From baseline to 6 months, average MoCA scores improved overall though 26.3% of participants' scores decreased. A syndrome consisting of tremor, ataxia, and cognitive dysfunction (PASC-TAC) was observed in 7.1% of patients. INTERPRETATION: Early in the neuro-PASC syndrome, fatigue and headache are the most commonly reported symptoms. At 6 months, memory impairment and decreased concentration were most prominent. Only one-third of participants had completed resolution of neuro-PASC at 6 months, although persistent symptoms trended toward improvement at follow-up.

Effects of long-term social isolation on central, behavioural and metabolic parameters in middle-aged mice.

Social isolation gained discussion momentum due to the COVID-19 pandemic. Whereas many studies address the effects of long-term social isolation in post-weaning and adolescence and for periods ranging from 4 to 12 weeks, little is known about the repercussions of adult long-term social isolation in middle age. Thus, our aim was to investigate how long-term social isolation can influence metabolic, behavioural, and central nervous system-related areas in middle-aged mice. Adult male C57Bl/6 mice (4 months-old) were randomly divided into Social (2 cages, n = 5/cage) and Isolated (10 cages, n = 1/cage) housing groups, totalizing 30 weeks of social isolation, which ended concomitantly with the onset of middle age of mice. At the end of the trial, metabolic parameters, short-term memory, anxiety-like behaviour, and physical activity were assessed. Immunohistochemistry in the hippocampus (ΔFosB, BDNF, and 8OHDG) and hypothalamus (ΔFosB) was also performed. The Isolated group showed impaired memory along with a decrease in hippocampal ΔFosB at dentate gyrus and in BDNF at CA3. Food intake was also affected, but the direction depended on how it was measured in the Social group (individually or in the group) with no alteration in ΔFosB at the hypothalamus. Physical activity parameters increased with chronic isolation, but in the light cycle (inactive phase), with some evidence of anxiety-like behaviour. Future studies should better explore the timepoint at which the alterations found begin. In conclusion, long-term social isolation in adult mice contributes to alterations in feeding, physical activity pattern, and anxiety-like behaviour. Moreover, short-term memory deficit was associated with lower levels of hippocampal ΔFosB and BDNF in middle age.

Association of Coronary Artery Bypass Grafting vs Percutaneous Coronary Intervention With Memory Decline in Older Adults Undergoing Coronary Revascularization.

Importance: It is uncertain whether coronary artery bypass grafting (CABG) is associated with cognitive decline in older adults compared with a nonsurgical method of coronary revascularization (percutaneous coronary intervention [PCI]). Objective: To compare the change in the rate of memory decline after CABG vs PCI. Design, Setting, and Participants: Retrospective cohort study of community-dwelling participants in the Health and Retirement Study, who underwent CABG or PCI between 1998 and 2015 at age 65 years or older. Data were modeled for up to 5 years preceding and 10 years following revascularization or until death, drop out, or the 2016-2017 interview wave. The date of final follow-up was November 2017. Exposures: CABG (including on and off pump) or PCI, ascertained from Medicare fee-for-service billing records. Main Outcomes and Measures: The primary outcome was a summary measure of cognitive test scores and proxy cognition reports that were performed biennially in the Health and Retirement Study, referred to as memory score, normalized as a z score (ie, mean of 0, SD of 1 in a reference population of adults aged ≥72 years). Memory score was analyzed using multivariable linear mixed-effects models, with a prespecified subgroup analysis of on-pump and off-pump CABG. The minimum clinically important difference was a change of 1 SD of the population-level rate of memory decline (0.048 memory units/y). Results: Of 1680 participants (mean age at procedure, 75 years; 41% female), 665 underwent CABG (168 off pump) and 1015 underwent PCI. In the PCI group, the mean rate of memory decline was 0.064 memory units/y (95% CI, 0.052 to 0.078) before the procedure and 0.060 memory units/y (95% CI, 0.048 to 0.071) after the procedure (within-group change, 0.004 memory units/y [95% CI, -0.010 to 0.018]). In the CABG group, the mean rate of memory decline was 0.049 memory units/y (95% CI, 0.033 to 0.065) before the procedure and 0.059 memory units/y (95% CI, 0.047 to 0.072) after the procedure (within-group change, -0.011 memory units/y [95% CI, -0.029 to 0.008]). The between-group difference-in-differences estimate for memory decline for PCI vs CABG was 0.015 memory units/y (95% CI, -0.008 to 0.038; P = .21). There was statistically significant increase in the rate of memory decline after off-pump CABG compared with after PCI (difference-in-differences: mean increase in the rate of decline of 0.046 memory units/y [95% CI, 0.008 to 0.084] after off-pump CABG), but not after on-pump CABG compared with PCI (difference-in-differences: mean slowing of decline of 0.003 memory units/y [95% CI, -0.024 to 0.031] after on-pump CABG). Conclusions and Relevance: Among older adults undergoing coronary revascularization with CABG or PCI, the type of revascularization procedure was not significantly associated with differences in the change of rate of memory decline.

Half-year follow-up of patients recovering from severe COVID-19: Analysis of symptoms and their risk factors.

OBJECTIVES: To understand the sequelae of COVID-19. METHODS: We followed up 1174 patients with severe coronavirus disease 2019 (COVID-19)who were recovered and discharged for 6 months. RESULTS: There were 175 cases with clear IgG results 6 months after discharge, of which 82 (46.9%) were IgG (+) and 16 (9.1%) were IgG (dim+). Four hundred and forty-one participants (55.4%) had some kind of sequelae. The most common symptoms were fatigue (25.3%), sleep disorder (23.2%) and shortness of breath (20.4%). In those who had sequelae, 262 (59.4%) had more than one symptom. Critical cases were more likely to have cough (20.5% vs 11.6%, p = 0.023) and hypomnesis (15.1% vs 8.0%, p = 0.041) than severe cases. Furthermore, univariate and multivariate logistic regression analyses revealed that women are more likely to have multiple symptoms (p = 0.002), fatigue (p = 0.009) and sleep disorder (p = 0.008), whereas critical illness was found as independent risk factor for hypomnesis (p = 0.045). CONCLUSION: Our study demonstrated the duration of antibody and sequelae of COVID-19 and compared the differences amongst different populations.

Short-term neuropsychiatric outcomes and quality of life in COVID-19 survivors.

BACKGROUND: The general medical impacts of coronavirus (COVID-19) are increasingly appreciated. However, its impact on neurocognitive, psychiatric health and quality of life (QoL) in survivors after the acute phase is poorly understood. We aimed to evaluate neurocognitive function, psychiatric symptoms and QoL in COVID-19 survivors shortly after hospital discharge. METHODS: This was a cross-sectional analysis of a prospective study of hospitalized COVID-19 survivors followed up for 2 months after discharge. A battery of standardized instruments evaluating neurocognitive function, psychiatric morbidity and QoL (mental and physical components) was administered by telephone. RESULTS: Of the 229 screened patients, 179 were included in the final analysis. Amongst survivors, the prevalence of moderately impaired immediate verbal memory and learning was 38%, delayed verbal memory (11.8%), verbal fluency (34.6%) and working memory (executive function) (6.1%), respectively. Moreover, 58.7% of patients had neurocognitive impairment in at least one function. Rates of positive screening for anxiety, depression and post-traumatic stress disorder were 29.6%, 26.8% and 25.1%, respectively. In addition, 39.1% of the patients had psychiatric morbidity. Low QoL for physical and mental components was detected in 44.1% and 39.1% of patients respectively. Delirium and psychiatric morbidity were associated with neurocognitive impairment, and female gender was related with psychiatric morbidity. CONCLUSION: Hospitalized COVID-19 survivors showed a considerable prevalence of neurocognitive impairment, psychiatric morbidity and poor QoL in the short term. It is uncertain if these impacts persist over the long term.

Association between physical activity and subjective memory decline triggered by the COVID-19 pandemic: Findings from the PAMPA cohort.

Implementation of social distancing reduced the incidence of coronavirus disease (COVID-19) cases. Nevertheless, this strategy has other undesirable effects such as physical inactivity and psychological distress, which are associated with cognitive impairment. We aimed to examine whether physical activity during social distancing restrictions could reduce the risk of subjective memory decline in adults. Participants (n=2321) completed the baseline assessment of PAMPA cohort (Prospective Study About Mental and Physical Health), a ambispective cohort study conducted in southern Brazil. An online-based, self-administered questionnaire assessed physical activity and self-rated memory in two different periods: before and during social distancing. Data collection was executed from June 22nd to July 23rd 2020. Adjusted Poisson regression models were performed and values reported in prevalence ratio (PR) with 95% confidence interval (CI). Participants presented with a mean age of 38.2 (95%CI: 37.5, 38.9) years. Most were women (76.6%), had at least a university degree (66.7%), and were overweight or obese (53.3%). Subjective memory decline was reported by 30.0% (95%CI: 27.7%, 32.4%) of respondents. Most individuals with subjective memory decline reported being physically inactive during the pandemic of COVID-19. Participants were less likely to experience subjective memory decline if they either became (PR: 0.56; 95%CI: 0.36, 0.89) or remained (PR: 0.68; 95%CI: 0.49, 0.93) physically active compared to inactive respondents. Physical activity participation during social distancing reduced the likelihood of subjective memory decline in adults. Physical activity should be highlighted as a potential alternative to reduce the burden of the COVID-19 pandemic on cognitive function and mental health.

Online pharmacy navigation skills are associated with prospective memory in HIV disease.

OBJECTIVE: The increased use of online pharmacy services in the midst of the COVID-19 pandemic provides an important backdrop against which to examine the role of neurocognitive functions in health-related Internet navigation skills among persons with chronic medical conditions, such as HIV disease. Prospective memory (PM) is reliably impaired in HIV disease and is related to laboratory-based measures of medication management capacity in other populations. This study examined whether PM shows veridicality in relationship to online pharmacy navigation skills in persons with HIV disease. METHOD: Participants included 98 persons with HIV disease age 50 and older who completed the Cambridge Prospective Memory Test (CAMPROMPT) and the Medication-Management Test-Revised (MMT-R) as part of a neuropsychological study. Participants also completed the Test of Online Pharmacy Skills (TOPS), which required them to navigate a simulated, experimenter-controlled online pharmacy to perform several naturalistic tasks (e.g., refill an existing prescription). RESULTS: Lower PM had medium associations with poorer MMT-R and TOPS accuracy scores that were not better explained by other neurocognitive functions. The association between PM and TOPS accuracy was driven by errors of omission and did not vary meaningfully based on whether the intention was cued by time or an event. CONCLUSIONS: These data suggest that PM cue detection processes show veridicality with online pharmacy navigation skills. Future studies might examine the benefits of PM-based strategies (e.g., salient prompts) in supporting online health navigation skills in populations that experience clinically impactful PM failures.