Home alone: A population neuroscience investigation of brain morphology substrates.

As a social species, ready exchange with peers is a pivotal asset - our "social capital". Yet, single-person households have come to pervade metropolitan cities worldwide, with unknown consequences in the long run. Here, we systematically explore the morphological manifestations associated with singular living in ∼40,000 UK Biobank participants. The uncovered population-level signature spotlights the highly associative default mode network, in addition to findings such as in the amygdala central, cortical and corticoamygdaloid nuclei groups, as well as the hippocampal fimbria and dentate gyrus. Both positive effects, equating to greater gray matter volume associated with living alone, and negative effects, which can be interpreted as greater gray matter associations with not living alone, were found across the cortex and subcortical structures Sex-stratified analyses revealed male-specific neural substrates, including somatomotor, saliency and visual systems, while female-specific neural substrates centered on the dorsomedial prefrontal cortex. In line with our demographic profiling results, the discovered neural pattern of living alone is potentially linked to alcohol and tobacco consumption, anxiety, sleep quality as well as daily TV watching. The persistent trend for solitary living will require new answers from public-health decision makers. SIGNIFICANCE STATEMENT: Living alone has profound consequences for mental and physical health. Despite this, there has been a rapid increase in single-person households worldwide, with the long-term consequences yet unknown. In the largest study of its kind, we investigate how the objective lack of everyday social interaction, through living alone, manifests in the brain. Our population neuroscience approach uncovered a gray matter signature that converged on the 'default network', alongside targeted subcortical, sex and demographic profiling analyses. The human urge for social relationships is highlighted by the evolving COVID-19 pandemic. Better understanding of how social isolation relates to the brain will influence health and social policy decision-making of pandemic planning, as well as social interventions in light of global shifts in houseful structures.

Social isolation and the brain in the pandemic era.

Intense sociality has been a catalyst for human culture and civilization, and our social relationships at a personal level play a pivotal role in our health and well-being. These relationships are, however, sensitive to the time we invest in them. To understand how and why this should be, we first outline the evolutionary background in primate sociality from which our human social world has emerged. We then review defining features of that human sociality, putting forward a framework within which one can understand the consequences of mass social isolation during the COVID-19 pandemic, including mental health deterioration, stress, sleep disturbance and substance misuse. We outline recent research on the neural basis of prolonged social isolation, highlighting especially higher-order neural circuits such as the default mode network. Our survey of studies covers the negative effects of prolonged social deprivation and the multifaceted drivers of day-to-day pandemic experiences.

Multivariate, Transgenerational Associations of the COVID-19 Pandemic Across Minoritized and Marginalized Communities.

IMPORTANCE: The experienced consequences of the COVID-19 pandemic have diverged across individuals, families, and communities, resulting in inequity within a host of factors. There is a gap of quantitative evidence about the transgenerational impacts of these experiences and factors. OBJECTIVE: To identify baseline predictors of COVID-19 experiences, as defined by child and parent report, using a multivariate pattern-learning framework from the Adolescent Brain and Cognitive Development (ABCD) cohort. DESIGN, SETTING, AND PARTICIPANTS: ABCD is an ongoing prospective longitudinal study of child and adolescent development in the United States including 11 875 youths, enrolled at age 9 to 10 years. Using nationally collected longitudinal profiling data from 9267 families, a multivariate pattern-learning strategy was developed to identify factor combinations associated with transgenerational costs of the ongoing COVID-19 pandemic. ABCD data (release 3.0) collected from 2016 to 2020 and released between 2019 and 2021 were analyzed in combination with ABCD COVID-19 rapid response data from the first 3 collection points (May-August 2020). EXPOSURES: Social distancing and other response measures imposed by COVID-19, including school closures and shutdown of many childhood recreational activities. MAIN OUTCOMES AND MEASURES: Mid-COVID-19 experiences as defined by the ABCD's parent and child COVID-19 assessments. RESULTS: Deep profiles from 9267 youth (5681 female [47.8%]; mean [SD] age, 119.0 [7.5] months) and their caregivers were quantitatively examined. Enabled by a pattern-learning analysis, social determinants of inequity, including family structure, socioeconomic status, and the experience of racism, were found to be primarily associated with transgenerational impacts of COVID-19, above and beyond other candidate predictors such as preexisting medical or psychiatric conditions. Pooling information across more than 17 000 baseline pre-COVID-19 family indicators and more than 280 measures of day-to-day COVID-19 experiences, non-White (ie, families who reported being Asian, Black, Hispanic, other, or a combination of those choices) and/or Spanish-speaking families were found to have decreased resources (mode 1, canonical vector weight [CVW] = 0.19; rank 5 of 281), escalated likelihoods of financial worry (mode 1, CVW = -0.20; rank 4), and food insecurity (mode 1, CVW = 0.21; rank 2), yet were more likely to have parent-child discussions regarding COVID-19-associated health and prevention issues, such as handwashing (mode 1, CVW = 0.14; rank 9), conserving food or other items (mode 1, CVW = 0.21; rank 1), protecting elderly individuals (mode 1, CVW = 0.11; rank 21), and isolating from others (mode 1, CVW = 0.11; rank 23). In contrast, White families (mode 1, CVW = -0.07; rank 3), those with higher pre-COVID-19 income (mode 1, CVW = -0.07; rank 5), and presence of a parent with a postgraduate degree (mode 1, CVW = -0.06; rank 14) experienced reduced COVID-19-associated impact. In turn, children from families experiencing reduced COVID-19 impacts reported longer nighttime sleep durations (mode 1, CVW = 0.13; rank 14), less difficulties with remote learning (mode 2, CVW = 0.14; rank 7), and decreased worry about the impact of COVID-19 on their family's financial stability (mode 1, CVW = 0.134; rank 13). CONCLUSIONS AND RELEVANCE: The findings of this study indicate that community-level, transgenerational intervention strategies may be needed to combat the disproportionate burden of pandemics on minoritized and marginalized racial and ethnic populations.

Tau-load in the lingual gyrus impacts anxiety levels during the COVID-19 pandemic in participants of longitudinal observational studies in aging

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.

Tau-PET is associated with knowledge of COVID-19, COVID-19-related distress, and change in sleep quality during the pandemic

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.

Cognitive health mediates the effect of hippocampal volume on COVID-19‒related knowledge or anxiety change during the COVID-19 pandemic

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.

Adapting to the COVID-19 pandemic in cohort studies: Validation of online assessments of cognition and neuropsychiatric symptoms in an aging population

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.

Loneliness and Neurocognitive Aging.

Loneliness imposes significant risks to physical, mental and brain health in older adulthood. With the social distancing regimes implemented during the COVID-19 pandemic, there is even greater urgency to understand the human health costs of social isolation. In this viewpoint we describe how the experience of loneliness may alter the structure and function of the human brain, and how these discoveries may guide public health policy to reduce the burden of loneliness in later life.

The Neurobiology of Social Distance.

Never before have we experienced social isolation on such a massive scale as we have in response to coronavirus disease 2019 (COVID-19). However, we know that the social environment has a dramatic impact on our sense of life satisfaction and well-being. In times of distress, crisis, or disaster, human resilience depends on the richness and strength of social connections, as well as on active engagement in groups and communities. Over recent years, evidence emerging from various disciplines has made it abundantly clear: perceived social isolation (i.e., loneliness) may be the most potent threat to survival and longevity. We highlight the benefits of social bonds, the choreographies of bond creation and maintenance, as well as the neurocognitive basis of social isolation and its deep consequences for mental and physical health.