Subjective and Objective Cognitive Deficits in Patients with Post-COVID Syndrome A Challenge for Neuropsychologists

Cognitive impairment is a prominent symptom of the post-COVID syndrome (PCS). However, the correspondence between subjective cognitive complaints (SCC) and objective results is inconsistent. Here, we investigated this discrepancy. This longitudinal study included N = 42 individuals who reported SCC as PCS after mild infection at inclusion. Data collection comprised questionnaires and neuropsychological assessment at baseline and follow-up (FU). At FU - on average 15 months after acute COVID-19 - 88 % of patients reported persisting SCC. There was an approx. 40 % discrepancy between subjective report and test results at both visits. Patients with SCC and objective impairment indicated elevated fatigue and reduced quality of life compared to patients without SCC at FU. A growing number of patients is anticipated to request neuropsychological assessments even after mild infections.

Association of Anxiety and Depression with Objective and Subjective Cognitive Decline in Outpatient Healthcare Consumers with COVID-19: А Cross-Sectional Study

Background: In addition to the neurological complications affecting people infected with COVID-19, cognitive impairment symptoms and symptoms of anxiety and depression remain a frequent cause of complaints. The specificity of cognitive impairment in patients with COVID-19 is still poorly understood. AIM: An exploratory study of factors that may be associated with cognitive decline during the COVID-19 pandemic. MEtHODs: The cross-sectional multicentre observational study was conducted in a polyclinic unit in Saint Petersburg and in the regions of the North-Western Federal Region. During the study, socio-demographic parameters and information about the somatic condition of patients who applied for primary health care was collected. Emotional and cognitive state were investigated using the Hospital Anxiety and Depression Scale (HADS) and Montreal Cognitive Assessment (MoCA). Mathematical and statistical data processing was carried out using SPSS and RStudio statistical programs. rEsULts: The study included 515 participants, 60% (n=310) of which were women. The sample was divided into those who did (28.5%, n=147) and did not (71.4%, n=368) complain of cognitive decline. Patients with complaints of cognitive decline were significantly older, had lower levels of education and higher levels of depression and anxiety according to HADS (p <0.05). Patients with complaints of cognitive decline underwent the MoCA test (24.3%, n=125). The median MoCA test scores were within the normal range (Median=27, Q1=25, Q3=28), and cognitive decline (MoCA less than 26 points) was detected in 40% (n=50) of patients with complaints of cognitive decline. No significant correlations were found between the MoCA scores and the levels of anxiety and depression according to the HADS (p >0.05). Patients with mild severity of the COVID-19 course were more successful with MoCA subtests than patients with moderate and severe courses. CONCLUSION: We found no linear association between objective cognitive deficit and the affective state of respondents. Patients' subjective complaints about cognitive dysfunction were mostly caused by their emotional state than an objective decrease of their cognitive functions. Therefore, in case of subjective complaints on cognitive decline, it is necessary to assess not only the cognitive but also the affective state of the patient. The severity of the COVID-19 course affects the functions of the cognitive sphere, including attention, regulatory functions and speech fluency. Mild and moderate severity of the COVID-19 correlates with clinically determined depression. The absence of this relationship with the severe course of the disease is probably explained by the significant somatic decompensation of patients. © 2022, Eco-Vector LLC. All rights reserved.

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.

Associated factors of new subjective cognitive decline complaints after a 6-month period among community-dwelling older adults during the COVID-19 pandemic in Japan.

BACKGROUND: The aim of this study was to determine the number of new subjective cognitive decline (SCD) complaints and associated factors in community-dwelling older adults during the COVID-19 pandemic in Japan. METHOD: A prospective cohort study was conducted in two periods: May to June 2020, and November 2020 to January 2021. We mailed a questionnaire to 1953 older adults in the first survey, and received 700 responses in the second. We analysed 534 participants without SCD in the first survey. We collected data on sociodemographic characteristics and administered the Questionnaire for Medical Checkup of Old-Old (QMCOO) to assess respondents' health condition. SCD was operationally defined using the QMCOO as reports of (1) forgetfulness, and (2) difficulty in naming dates. The subjects were divided into two groups by their condition at the second survey: an SCD (new SCD complaints) and a no-SCD (no new SCD complaints) group. RESULTS: A total of 85 (15.9%) participants had new SCD complaints. The Mann-Whitney U-test and chi-squared test showed that the SCD group had significantly more risk factors of SCD: walking speed (P = 0.001), smoking (P = 0.001), and existence of person with whom the patient could consult when disordered (P = 0.002). Multiple logistic regression analysis revealed that walking speed (odds ratio (OR) = 2.115, 95% confidence interval (CI): 1.259-3.553) and the presence of person to consult (OR = 3.619, 95% CI: 1.553-8.433) were significant related factors of new SCD complaints. CONCLUSION: Maintenance of physical condition and social support were associated with new SCD complaints during the COVID-19 pandemic.

Subjective cognitive decline and anxious/depressive symptoms during the COVID-19 pandemic: what is the role of stress perception, stress resilience, and ß-amyloid?

BACKGROUND: The COVID-19 pandemic may worsen the mental health of people reporting subjective cognitive decline (SCD) and therefore their clinical prognosis. We aimed to investigate the association between the intensity of SCD and anxious/depressive symptoms during confinement and the underlying mechanisms. METHODS: Two hundred fifty cognitively unimpaired participants completed the Hospital Anxiety and Depression Scale (HADS) and SCD-Questionnaire (SCD-Q) and underwent amyloid-ß positron emission tomography imaging with [18F] flutemetamol (N = 205) on average 2.4 (± 0.8) years before the COVID-19 confinement. During the confinement, participants completed the HADS, Perceived Stress Scale (PSS), Brief Resilience Scale (BRS), and an ad hoc questionnaire on worries (access to primary products, self-protection materials, economic situation) and lifestyle changes (sleep duration, sleep quality, eating habits). We investigated stress-related measurements, worries, and lifestyle changes in relation to SCD. We then conducted an analysis of covariance to investigate the association of SCD-Q with HADS scores during the confinement while controlling for pre-confinement anxiety/depression scores and demographics. Furthermore, we introduced amyloid-ß positivity, PSS, and BRS in the models and performed mediation analyses to explore the mechanisms explaining the association between SCD and anxiety/depression. RESULTS: In the whole sample, the average SCD-Q score was 4.1 (± 4.4); 70 (28%) participants were classified as SCD, and 26 (12.7%) were amyloid-ß-positive. During the confinement, participants reporting SCD showed higher PSS (p = 0.035) but not BRS scores (p = 0.65) than those that did not report SCD. No differences in worries or lifestyle changes were observed. Higher SCD-Q scores showed an association with greater anxiety/depression scores irrespective of pre-confinement anxiety/depression levels (p = 0.002). This association was not significant after introducing amyloid-ß positivity and stress-related variables in the model (p = 0.069). Amyloid-ß positivity and PSS were associated with greater HADS irrespective of pre-confinement anxiety/depression scores (p = 0.023; p < 0.001). The association of SCD-Q with HADS was mediated by PSS (p = 0.01). CONCLUSIONS: Higher intensity of SCD, amyloid-ß positivity, and stress perception showed independent associations with anxious/depressive symptoms during the COVID-19 confinement irrespective of pre-confinement anxiety/depression levels. The association of SCD intensity with anxiety/depression was mediated by stress perception, suggesting stress regulation as a potential intervention to reduce affective symptomatology in the SCD population in the face of stressors.

Feasibility and preliminary efficacy of the LEAD trial: a cluster randomized controlled lifestyle intervention to improve hippocampal volume in older adults at-risk for dementia.

BACKGROUND: Healthy diet and exercise are associated with reduced risk of dementia in older adults. The impact of diet and exercise interventions on brain health is less consistent, especially with dietary interventions which rely on varying approaches. Our objective was to evaluate the feasibility and preliminary efficacy of a 6-month intervention combining exercise with a novel dietary counseling approach to improve hippocampal volume among older adults at-risk for dementia. METHODS: Participants with vascular risk factors and subjective cognitive decline or early mild cognitive impairment were cluster randomized in groups of 3-4 to the diet intervention (DIET) or control education (ED) group. All participants engaged in 1 h of supervised exercise per week and additional exercise at home. DIET involved 1 h per week of group-based dietary counseling comprising education, goal setting, and strategy training. ED involved 1 h per week of group-based brain health education classes. Our primary outcome was change in hippocampal volume from baseline to 6 months. Secondary outcomes included changes in cognitive function, blood biomarkers, diet, and fitness. Recruitment challenges and early discontinuation of the trial due to COVID-19 necessitated a revised focus on feasibility and preliminary efficacy. RESULTS: Of 190 older adults contacted, 14 (7%) were eligible and enrolled, constituting 21% of our recruitment target. All participants completed the intervention and attended 90% of exercise and DIET/ED sessions on average. All 6-month assessments prior to COVID-19 were completed but disruptions to in-person testing resulted in incomplete data collection. No serious adverse events occurred and all participants expressed positive feedback about the study. Preliminary findings did not identify any significant changes in hippocampal volume; however, substantial improvements in diet and HbA1c were observed with DIET compared to ED (d = 1.75 and 1.07, respectively). CONCLUSIONS: High adherence and retention rates were observed among participants and preliminary findings illustrate improvements in diet quality and HbA1c. These results indicate that a larger trial is feasible if difficulties surrounding recruitment can be mitigated. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03056508 .

Psychosocial Effects of COVID-19 Measures on (Pre-)Dementia Patients During Second Lockdown.

BACKGROUND: The COVID-19 pandemic poses enormous social challenges, especially during lockdown. People with cognitive decline and their caregivers are particularly at risk of lockdown consequences. OBJECTIVE: To investigate psychosocial effects in (pre-)dementia patients and caregivers during second lockdown and compare effects between first and second lockdown. METHODS: We included n = 511 (pre-)dementia patients and n = 826 caregivers from the Amsterdam Dementia Cohort and via Alzheimer Nederland. All respondents completed a self-designed survey on psychosocial effects of COVID-19. We examined relations between experienced support and psychosocial and behavioral symptoms using logistic regression. In a subset of patients and caregivers we compared responses between first and second lockdown using generalized estimating equation (GEE). RESULTS: The majority of patients (≥58%) and caregivers (≥60%) reported that family and friends, hobbies, and music helped them cope. Support from family and friends was strongly related to less negative feelings in patients (loneliness: OR = 0.3[0.1-0.6]) and caregivers (loneliness: OR = 0.2[0.1-0.3]; depression: OR = 0.4[0.2-0.5]; anxiety: OR = 0.4[0.3-0.6]; uncertainty: OR = 0.3[0.2-0.5]; fatigue: OR = 0.3[0.2-0.4]; stress: OR = 0.3[0.2-0.5]). In second lockdown, less psychosocial and behavioral symptoms were reported compared to first lockdown (patients; e.g., anxiety: 22% versus 13%, p = 0.007; apathy: 27% versus 8%, p < 0.001, caregivers; e.g., anxiety: 23% versus 16%, p = 0.033; patient's behavioral problems: 50% versus 35%, p < 0.001). Patients experienced more support (e.g., family and friends: 52% versus 93%, p < 0.001; neighbors: 28% versus 66%, p < 0.001). CONCLUSION: During second lockdown, patients and caregivers adapted to challenges posed by lockdown, as psychosocial and behavioral effects decreased, while patients experienced more social support compared to first lockdown. Support from family and friends is a major protective factor for negative outcomes in patients and caregivers.

Difference in Amyloid Load Between Single Memory Domain and Multidomain Subjective Cognitive Decline: A Study from the SILCODE.

BACKGROUND: Subjective cognitive decline (SCD), an at-risk condition of Alzheimer's disease (AD), can involve various cognitive domains, such as memory, language, planning, and attention. OBJECTIVE: We aim to explore the difference in amyloid load between the single memory domain SCD (sd-SCD) and the multidomain SCD (md-SCD) and assess the relationship of amyloid pathology with quantitative SCD scores and objective cognition. METHODS: A total of 63 SCD participants from the SILCODE study underwent the clinical evaluation, neuropsychological assessment, and 18F-florbetapir PET scan. Global amyloid standard uptake value ratio (SUVr) was calculated. Additionally, regional amyloid SUVr was quantified in 12 brain regions of interests. A nonparametric rank ANCOVA was used to compare the global and regional amyloid SUVr between the md-SCD (n = 34) and sd-SCD (n = 29) groups. A multiple linear regression analysis was conducted to test the relationship of amyloid SUVr with quantitative SCD scores and objective cognition. RESULTS: Compared with individuals with sd-SCD, individuals with md-SCD had increased global amyloid SUVr (F = 5.033, p = 0.029) and regional amyloid SUVr in the left middle temporal gyrus (F = 12.309, p = 0.001; Bonferroni corrected), after controlling for the effects of age, sex, and education. When pooling all SCD participants together, the increased global amyloid SUVr was related with higher SCD-plus sum scores and lower Auditory Verbal Learning Test-delayed recall scores. CONCLUSION: According to our findings, individuals with md-SCD showed higher amyloid accumulation than individuals with sd-SCD, suggesting that md-SCD may experience a more advanced stage of SCD. Additionally, increased global amyloid load was predictive of a poorer episodic memory function in SCD individuals.

Social connectedness and dementia prevention: Pilot of the APPLE-Tree video-call intervention during the Covid-19 pandemic.

BACKGROUND AND OBJECTIVES: The Covid-19 pandemic reduced access to social activities and routine health care that are central to dementia prevention. We developed a group-based, video-call, cognitive well-being intervention; and investigated its acceptability and feasibility; exploring through participants' accounts how the intervention was experienced and used in the pandemic context. RESEARCH DESIGN AND METHOD: We recruited adults aged 60+ years with memory concerns (without dementia). Participants completed baseline assessments and qualitative interviews/focus groups before and after the 10-week intervention. Qualitative interview data and facilitator notes were integrated in a thematic analysis. RESULTS: 12/17 participants approached completed baseline assessments, attended 100/120 (83.3%) intervention sessions and met 140/170 (82.4%) of goals set. Most had not used video calling before. In the thematic analysis, our overarching theme was social connectedness. Three sub-themes were as follows: Retaining independence and social connectedness: social connectedness could not be at the expense of independence; Adapting social connectedness in the pandemic: participants strived to compensate for previous social connectedness as the pandemic reduced support networks; Managing social connections within and through the intervention: although there were tensions, for example, between sharing of achievements feeling supportive and competitive, participants engaged with various lifestyle changes; social connections supported group attendance and implementation of lifestyle changes. DISCUSSION AND IMPLICATIONS: Our intervention was acceptable and feasible to deliver by group video-call. We argue that dementia prevention is both an individual and societal concern. For more vulnerable populations, messages that lifestyle change can help memory should be communicated alongside supportive, relational approaches to enabling lifestyle changes.

Effects of COVID-19 Home Confinement on Mental Health in Individuals with Increased Risk of Alzheimer's Disease.

We explored the impact of the Spanish COVID-19 strict home confinement on mental health and cognition in non-infected subjects (N = 16, 60-80 years) diagnosed with subjective cognitive decline and APOEɛ3/ɛ4 carriers. Mental health was monitored for 2 months on a daily, weekly, or monthly basis, and compared to pre-confinement values. Emotional distress, anxiety, and depression scores increased to pathological threshold values during and after confinement. Those with lower mood during confinement experienced a decline in their mood after confinement. Cognition did not change. These preliminary results suggest that mental health consequences of corona measures in preclinical stages of Alzheimer's disease should be further evaluated.

The Effects of COVID-19 and Quarantine Measures on the Lifestyles and Mental Health of People Over 60 at Increased Risk of Dementia.

Background: The lockdown strategies adopted to limit the spread of COVID-19 infection may lead to adopt unhealthy lifestyles which may impact on the mental well-being and future risk of dementia. Older adults with mild cognitive impairment (MCI) or subjective cognitive decline (SCD) may suffer important mental health consequences from measures of quarantine and confinement. Aims: The study aimed to explore the effects of COVID-19 and quarantine measures on lifestyles and mental health of elderly at increased risk of dementia. Methods: One hundred and twenty six community-dwelling seniors with MCI or SCD were phone-interviewed and assessed with questions regarding variables related to COVID-19 pandemic, lifestyle changes and scales validated for the assessment of depression, anxiety, and apathy. Results: The sample included 55.6% patients with MCI and 56 people with SCD. Over 1/3 of the sample reduced their physical activity and nearly 70% reported an increase in idle time. Adherence to the Mediterranean diet decreased in almost 1/3 of respondents and over 35% reported weight gain. Social activities were abolished and 1/6 of participants also decreased productive and mental-stimulating activities. 19.8% were depressed, 9.5% anxious, and 9.5% apathetic. A significant association existed between depression and living alone or having a poor relation with cohabitants and between anxiety and SCD, cold or flu symptoms, and reduction in productive leisure activities. Conclusions: Seniors with SCD and MCI underwent lifestyle changes that are potentially harmful to their future cognitive decline, even if, with the exception of leisure activities, they do not appear to be cross-sectionally associated with psychiatric symptoms.