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This article discusses a study that aimed to investigate the relationship between functional brain connectivity (FC) and long-term mental health outcomes during the COVID-19 pandemic. The study involved 702 healthy, middle-aged individuals who underwent resting-state functional magnetic resonance imaging before the pandemic. The results showed that FC measures of specific brain networks were associated with different trajectories of mental health components. The study suggests that assessing brain network integration versus segregation can help predict individual resilience and vulnerability across mental health dimensions, allowing for early identification of at-risk individuals and the development of personalized preventive strategies. [Extracted from the article]

Background: Over 55 million people worldwide are currently diagnosed with Alzheimer's disease (AD) and live with debilitating episodic memory deficits (World Health Organization, 2022). Current pharmacological treatments have limited efficacy. Recently, transcranial alternating current stimulation (tACS) has shown memory improvement in AD by normalizing high‐frequency neuronal activity (Benussi et al., 2022). Our goal was to assess the safety, feasibility, and preliminary effects on episodic memory of a caregiver‐led home‐based tACS approach (HB‐tACS). Method: 8 participants diagnosed with AD (Table 1) underwent high‐definition HB‐tACS (40 Hz, 20‐minutes) targeting the left angular gyrus (AG), a key node of the memory network. The Acute Phase comprised 14‐weeks of HB‐tACS with at least five weekly sessions. Three participants underwent resting‐state electroencephalography (EEG) before and after. Subsequently, participants completed a 2–3‐month Hiatus Phase not receiving tACS. In the Taper Phase, participants received 2‐3 sessions per week over 3‐months. Primary outcomes were memory and global cognition, measured with the Memory Index Score (MIS) and Montreal Cognitive Assessment (MoCA), respectively, and EEG theta/gamma ratio. Results reported as mean±SD. Result: All participants completed the study with, on average, 97 HB‐tACS sessions; reporting mild side effects during 25% of sessions, moderate during 5%, and severe during 1%. Acute Phase adherence was 98±6.8% and Taper Phase was 125±22.3% (from minimum of 2/week). After the Acute Phase, all participants showed memory improvement, MIS of 7.25±3.77, sustained during Hiatus 7.00±4.90 and Taper 4.63±2.39 Phases (Table 2), and decreased theta/gamma ratio in AG (Figure 1A). Conversely, participants did not show improvement in the MoCA, 1.13±3.80 after the Acute Phase, and there was modest decrease during the Hiatus ‐0.64± 3.28 and Taper ‐2.56±5.03 phases. These results suggest the specificity of the intervention for memory functioning (Figure 1B) and relate improvement to decreased theta/gamma ratio. Conclusion: This pilot study shows the feasibility of a novel, remotely supervised, caregiver‐led HB‐tACS intervention for AD. Targeting the left AG, memory was noticeably improved while global cognition was relatively stable, indicating that future interventions might benefit from multifocal neuromodulation targeting multiple cognitive domains. These results are encouraging for the prospect of safe and feasible treatment within patients' homes. [ABSTRACT FROM AUTHOR]

Background: Positive and negative psychological factors represent pertinent moderators of relative risk and protection for cognitive decline and dementia. For example, repetitive negative thinking has been associated with accelerated cognitive decline and AD pathology1, whereas self‐reflection and purpose in life have been related to better cognition and cognitive resilience2,3. Existing studies predominately focus on individual factors, thus it is unknown whether psychological profiles, combining risk and protective features, are differentially associated with cognitive function. Method: Individuals without objective cognitive impairment were included from two European studies: the middle‐aged Barcelona Brain Health Initiative (N = 741)4 and the older‐adult Medit‐Ageing (N = 279)5,6 cohorts. Self‐report questionnaires to assess levels of psychological risk and protective factors were completed and global cognitive assessments obtained in both studies (Table 1). Latent Profile Analysis (LPA) was performed on psychological questionnaire data to identify statistically different groups of individuals in each cohort separately. ANCOVA (adjusting for age, sex, and education), were then conducted to compare different psychological profiles according to cognitive status. Result: LPA identified a three‐class solution in both cohorts (Table 1 and Figure 1): "low levels of psychological protective factors" (class‐1), "high levels of psychological risk factors" (class‐2), and "average levels of psychological risk and protective factors" (class‐3). In both cohorts, psychological profile membership was significantly associated with cognition. Specifically, individuals with low levels of psychological protective factors had worse global cognitive function compared with individuals with other profiles (BBHI: F:6.05, p<0.002; Medit‐Ageing: F:7.99, p<0.001; Figure 2). Conclusion: Individual psychological risk and protective factors aggregated into three identifiable psychological profiles that were evident across two independent cohorts. In both cohorts, having a psychological profile with low levels of protective factors rather than high levels of risk factors, was associated with worse global cognitive function. Such observations may have implications for future, more personalized, application of psychological therapies contributing to dementia prevention. [ABSTRACT FROM AUTHOR]

Background: Alzheimer's disease is characterized by cortical hyperexcitability in the early stages, which may be attributed to the intricate interplay between tau and amyloid β pathologies. To combat the propagation of tau pathology and cognitive decline, it may be beneficial to maintain a high degree of functional brain network segregation. Additionally, the use of non‐invasive brain stimulation techniques to alter cortical excitability could help alleviate cognitive deficits. However, it is unclear how these interventions are related to tau or amyloid biomarkers. Method: In this study, 530 participants aged 40 to 65 from the Barcelona Brain Health Initiative cohort were analyzed to investigate the connection between plasma concentration of tau phosphorylated at amino acid 181 (pTau181), cortical excitability, and segregation of functional brain networks. Participants had functional magnetic resonance imaging (fMRI), electroencephalography (EEG), and pTau181 available. A subset of 47 participants also underwent transcranial magnetic stimulation with concurrent EEG (TMS‐EEG). Cortical excitability was assessed using the one‐over‐f slope of the EEG power spectrum (1/f‐slope) and evoked response to a TMS perturbation (TEP) of the left prefrontal cortex (L‐PFC) between 160‐240ms post single‐pulse TMS. The degree of segregation between major functional networks was measured from fMRI data using the system segregation statistic. Result: A generalized linear model with a gamma distribution (Table 1) revealed that steeper 1/f‐slope correlated with higher pTau181 concentration, particularly in participants older than 53 years of age (Figure 1.A), or system segregation below 0.28 (Figure 1.B). A multiple linear regression within the TMS‐EEG subsample (Table 2) revealed that the TEP response correlated positively with pTau181 as age increased, and that this model, despite including a smaller sample size, better explained pTau181 concentrations. Conclusion: The study shows that cortical excitability is related to pTau181 based on age and system segregation. The TEP response is a more sensitive marker than unperturbed EEG metrics in explaining the relation between excitability and pTau181 concentrations. Combined TMS with EEG could potentially be an inexpensive and scalable approach for early identification and longitudinal tracking of middle‐aged adults at risk for cognitive decline and dementia. [ABSTRACT FROM AUTHOR]

Background: Repetitive Negative Thinking (RNT) includes negative thoughts about the future (worry) and past (ruminative brooding). RNT has been associated with Alzheimer's disease (AD) pathology (Marchant et al. Alzheimers Dement. 2020;16(7)) and different patterns of functional connectivity of the triple network of attention, namely, the default mode, executive control and anterior salience networks (Solé‐Padullés et al. Front Aging Neurosci. 2022;14). However, the association between RNT and white matter microstructure is unclear (Demnitz‐King et al. Psychiatry Res Neuroimaging. 2021;316) and no existing studies have examined this association longitudinally among non‐clinical adults. Method: Healthy adults (age range: 50‐70, 51.2% women) from the Barcelona Brain Health Initiative (Cattaneo et al. Front Aging Neurosci. 2018 11;10) completed the Perseverative Thinking Questionnaire (PTQ), Rumination Response Scale (RRS), and Penn‐State Worry Questionnaire (PSWQ) at baseline to measure RNT levels. Participants underwent a magnetic resonance imaging (MRI) with T1 and T2‐weighted acquisitions to assess volume of white matter hypointensities (WMH) at baseline (N = 588) and two years later (N = 425). Change in WMH was computed taking into account time interval between scans. Stepwise linear regression analyses were conducted to investigate associations between change in WMH and baseline age, sex, PTQ, PSWQ and RRS subscale scores (brooding, reflection and depression). Result: Baseline age (t = 3.71, p<0.0001) and brooding (t = 2.82, p = 0.005) were associated with increased WMH across scans (see partial regression plots, Fig 1A/B). No cross‐sectional associations were observed between volume of WMH and RNT‐related variables. Conclusion: Brooding was associated with increase of WMH in healthy adults. Brooding, a maladaptive form of emotion regulation, enhances repetitive focus on one's distress and is associated with altered connectivity of attentional networks and greater asymmetry of the Superior Longitudinal Fasciculus in depressed adults (Pisner et al. Neuroimage Clin. 2019;24). Our results are of importance considering that: WMH correlate with CSF‐amyloid in cognitively unimpaired older adults (Wei et al. Brain Behav. 2019;9(12)) and this is the first longitudinal study focusing on white matter change as related to psychological variables linked to cognitive decline and AD‐related pathology. The putative impact of psychological factors on brain integrity can be detected even at sub‐clinical levels and in earlier stages within the dementia continuum. [ABSTRACT FROM AUTHOR]

Background: Cognitive dispersion index (CDI), a measure of intraindividual variability across neuropsychological tests, is considered a sensitive marker of prodromic stages of Alzheimer's Disease (Halliday et al. J. Intell 2018;6(1):12). CDI has been negatively associated with cognitive reserve (CR), another factor that influences the risk of dementia (Stern et al. Alzh&Dement 2020;16(9):1305‐1311). Nevertheless, how these two elements interact with each other and are linked with cognition and brain state (e.g., functional connectivity), remains unclear. Our aim was to investigate whether CDI has a differential influence on cognitive performance (CP) and on resting‐state functional connectivity (rsFC) as a function of CR level, in a healthy middle‐aged sample. Method: Five hundred forty‐four healthy volunteers (aged 53.11±7.10 years; 269 female) from the Barcelona Brain Health Initiative cohort (BBHI, https://bbhi.cat/en), were stratified by CR (median = 14) into High CR (HCR, N = 230) and Low CR (LCR, N = 314) using the cognitive reserve questionnaire (CRQ; Rami et al. Rev Neurol 2011;52(4):195‐201). CDI was extracted by intraindividual standard deviation method (Costa et al. Clinic Neuropsychol 2019;33(2):369‐389) and CP was calculated as a global cognition composite score including episodic memory, speed of processing and executive function tests. Functional magnetic resonance imaging (fMRI) was acquired, and measures of rsFC within networks were computed through Shirer atlas (Shirer et al. Cerebral Cortex 2012;22(1):158‐165). Statistical analyses were based on univariate ANCOVA GLMs, and partial correlations adjusted by age and gender. Result: Though no significant group interaction was found, a negative correlation between CDI and CP was identified for the HCR group (r = ‐0.170,p = 0.010; Fig.1A). On fMRI there was a significant group difference (HCR vs. LCR) in the association between CDI and rsFC in anterior salience network (aSN: F = 5.005,p = 0.026), where only HCR participants showed a significant negative association between CDI and aSN rsFC values (r = ‐0.187,p = 0.010; Fig.1B&C). Conclusion: Our findings suggested that CDI has a clearly measurable effect on HCR participants, both in terms of its effect on CP and on rsFC. These results highlight the value of considering CDI measurements when performing neuropsychological assessments in middle‐aged individuals, particularly in those with high CR estimates. [ABSTRACT FROM AUTHOR]

Background: Repetitive Negative Thinking (RNT) includes negative thoughts about the future (worry) and past (rumination), and has been associated with AD physiopathology (Marchant et al. Alzh&Dement 2020;16:1054). Prefrontal and anterior cingulate cortices play a major role in RNT (Demnitz‐King et al., Psychiatry Res Neuroimaging. 2021;316:111353). Nonetheless, RNT involves several brain regions within large‐scale networks (Makovac et al., Psychiatry Res Neuroimaging. 2020;295:111020), the efficiency of which depends on their ability to remain segregated (Tononi et al., PNAS, 1994;91:11). We investigated associations between RNT and system segregation (SyS) of the Anterior Salience Network (ASN), Default Mode Network (DMN) and Executive Control Network (ECN) in middle‐aged adults. Method: 248 healthy controls (mean age: 59.17 (SD 4.79), 50.61% women) from the Barcelona Brain Health Initiative (Cattaneo et al. Front Aging Neurosci. 2018;10:321) underwent resting‐state functional magnetic resonance imaging to compute SyS using a node‐based approach with the Shirer atlas (Shirer et al., Cereb Cortex. 2012;22:1). RNT was estimated from questionnaires as previously (Schlosser et al., BMC Psychiatry, 2020;20:1), and a global RNT score was computed. Regression analyses investigated associations between RNT and SyS of ASN, DMN and ECN, including age, depression and stress ratings, emotional stability and cognitive complaints. Result: RNT was positively predicted by cognitive complaints (t = 3.18, p = 0.002) and depression (t = 6.55, p<0.0001), and negatively by emotional stability (t = ‐4.77, p<0.0001). Likewise, RNT was negatively associated with SyS_ASN (t = ‐2.57, p = 0.011; Fig1). Post‐hoc analyses revealed increased connectivity between ASN and ventral DMN (vDMN, t = 2.57, p = 0.01) and the reverse for ASN‐dorsal DMN (dDMN, t = ‐2.03, p = 0.04; Fig2). Conclusion: Higher levels of RNT amongst middle‐aged subjects were related to less segregation of the ASN. Results are of importance considering that declining brain segregation predicts dementia severity (Chan et al. Nat Aging 2021;1:1053). Specifically, the ASN presented higher coupling with the vDMN (medial temporal lobe and precuneus), linked to self‐processing and autobiographical processes (Bayley et al., J Neurosci. 2006;26:51), and lower coupling with the dDMN (medial prefrontal regions) associated with cognitive control (Piguet et al., Biol Psychol. 2014;103:195). This dissociative connectivity may partially explain poorer cognitive control and increased self‐referential processes characteristic of RNT (Piguet et al., Biol Psychol. 2014;103:195). [ABSTRACT FROM AUTHOR]

Beware of Optimism Bias in the Context of the COVID-19 Pandemic The coronavirus (severe acute respiratory syndrome-coronavirus 2 [SARS-CoV-2], coronavirus disease 2019 [COVID-19]) pandemic has caused over 88 million confirmed cases and nearly 2 million deaths worldwide as of December 2020.1 Months ago, governments launched unprecedented responses in an attempt to contain the staggering health and economic threats. On average, in the United States, people are about 15% more worried about the health impact of COVID-19 for others than for their own health, in Europe the average difference is 22%, whereas in the Far East countries it is only 9%. [Extracted from the article]

Background: Disease‐modifying agents to counteract cognitive impairment in aging remain elusive, and identifying modifiable factors promoting brain reserve is paramount. In AD, education, occupation, and physical activity represent typical reserve proxies (Stern et al. Alzheimers Dement.2020;16(9):1305‐1311), but psychological factors are increasingly being recognized, as their operating biological mechanisms are elucidated (i.e., Arenaza‐Urquijo et al. Neurology 2020;95:e1571). Purpose in life (PiL), one of the pillars of psychological well‐being, was found to reduce the deleterious effects of AD‐related pathological changes on cognition (Boyle et al., Arch Gen Psychiatry. 2012;69(5):499‐505). However, whether PiL operates as a cognitive resilience factor in middle‐aged individuals, as well as its associated neural mechanisms remains unknown. Method: Data was obtained from 573 middle‐aged adults (mean age 54.28±7.2; 275 women) from the Barcelona Brain Health Initiative cohort (Cattaneo et al. Front Aging Neurosci. 2018;10:321). Individuals with lower (LP; N = 131) and higher (HP; N = 94) PiL rates, according to the division of this variable into quintiles, were compared in terms of cognitive status; a measure reflecting brain burden (MRI‐derived white matter hyperintensities; WMHs); and resting‐state functional connectivity (rs‐FC), examining system segregation (SyS) using 14 brain circuits (Shirer et al. Cereb Cortex. 2012;22(1):158‐165). Results: Neuropsychological status and WMHs burden did not differ between PiL groups. However, only in the LP group, greater WMHs entailed a negative impact on speed of processing and logical reasoning (Fig.1A‐B). Subjects in the HP group showed lower SyS on the dorsal DMN (dDMN), indicating lesser segregation of this network from other brain circuits (t = 2.423, p = 0.016; Fig.1C). Specifically, HP individuals had greater inter‐network connectivity between dDMN nodes and the rest of the brain. Conversely, subjects in the LP group exhibited more connectivity across DMN‐like regions. Notably, in the HP group, greater functional connectivity was positively correlated with cognitive function previously related to WMHs, while the opposite pattern was observed in the LP group (Fig.1D‐F). Conclusion: Expanding previous findings on AD‐pathology and advanced age, present results suggest that higher rates of PiL may promote cognitive resilience already in middle age. Possible neurobiological mechanism by which PiL might operate could imply greater integration between the DMN and other brain areas. [ABSTRACT FROM AUTHOR]

Background: High concentrations of circulating C‐reactive protein (CRP) have been related to poorer cognition in adults (Lewis et al. Age Ageing. 2021;50:2199). Within the Lifebrain consortium (Walhovd et al. Eur Psychiatry. 2018;50:47), we recently reported overall lifespan associations between increased CRP and smaller hippocampal (HPC) volumes, albeit these could not be observed in one subsample of middle‐aged individuals (Wang et al. Brain Behav Immun. 2022;100:243). Here we hypothesized that functional brain integrity measures would be sensitive to predict CRP levels in this group. We focused on global system segregation (SyS) a graph theory‐based metric which quantifies the extent to which major functional networks are segregated from each other. Method: We included 336 volunteers (mean age 53.8; SD: 7.1; 47.9% women) from the Barcelona Brain Health Initiative (Cattaneo et al. Front Aging Neurosci. 2018;10:321). High‐sensitive CRP (hsCRP) concentrations were determined through dry blood samples and log10 transformed (Wang et al. Brain Behav Immun. 2022;100:243). Adjusted HPC volumes were estimated from T1‐wheigthed 3T MRI acquisitions (Raz et al. Cereb Cortex 2005;15:1676). SyS values were calculated (Ewers et al. Brain. 2021;144:2176) from 100 nodes defined by the Schaefer‐Yeo atlas (Fig 1a). Multiple linear regression investigated the associations between age, gender, cognitive function (MMSE and episodic memory), HPC volumes, APOE status and SyS as predictor variables and hs‐CRP as the dependent measure. Result: In the adjusted model only SyS (β= ‐0.56, p<0.05) and APOE (β= ‐0.21, p=0.003) predicted hsCRP concentrations. Global SyS was negatively related to hsCRP (Fig 1b). As in Wang et al (2022), APOE E4 carriers (N=71; mean:‐0.43; SD=0.62) exhibited lower CRP circulating levels than non‐E4 bearers (N=265; mean: ‐0.20; SD=0.51; t=3.23, p<0.001), however there were no differences in SyS according to APOE genotypes (t=0.95, p=0.34). Conclusion: hs‐CRP blood concentrations were predicted by global segregation of functional networks in absence of HPC volume or cognitive status effects. As such, blood derived hsCRP levels may represent an early indicator of middle‐age individual variations in a measure recently reported to predict future cognitive decline (Chan et al. Nat Aging 2021;1:1053) and represent a cognitive resilience mechanism in the face of AD pathology (Ewers et al. Brain. 2021;144:2176). [ABSTRACT FROM AUTHOR]

Background: Meaning in life (MiL) encompasses purpose in life (PiL), engagement with life (EwL), and sense of coherence (SoC) dimensions. MiL estimates have been associated with self‐reported cognitive status amongst middle‐aged individuals (Bartrés‐Faz et al., Alzheimers Res Ther. 2018;10(1):47). Later in life, MiL factors have been related to reduced cognitive decline and delayed onset of dementia in Alzheimer's disease (AD; Boyle et al., Arch Gen Psychiatry. 2010;67(3):304‐310). However, how MiL dimensions are associated with brain networks' expression and if these functional systems could mediate the influence of MiL on self‐perceived cognition remains unknown. Methods: Demographic, cognitive, and neuroimaging data was obtained from 585 middle‐aged adults (mean age 54.26 ± 7.1; 289 women) from the Barcelona Brain Health Initiative cohort (https://bbhi.cat/en/). Linear regression analyses were used to investigate the associations between MiL and its three dimensions [motivational (PiL), emotional (EwL), and cognitive (SoC)] and the strength of functional connectivity within the main brain resting‐state networks (RSNs; Shirer et al. Cereb Cortex. 2012;22(1):158‐165). Further analyses were computed to explore to which extent RSNs mediate the effect of MiL and its dimensions on self‐reported cognition, derived from the PROMIS® Cognitive Abilities and Concerns scale. Data was adjusted for age, personality, cognitive reserve, and affective status. Correction for multiple comparisons was applied. Results: MiL estimates and its SoC factor, but not EwL and PiL, were correlated with RSNs. Specifically, significant associations for SoC emerged for those RSNs linked to higher‐order cognitive processing, such as the default‐mode, the salience and the left and right executive‐control networks. However, associations with sensorimotor systems were not significant. The links between SoC and self‐perceived cognitive function were mediated by the salience and the left executive‐control circuits (Fig. 1). Conclusion: The observed associations between SoC and the functional systems subtending cognitive processing, but not sensorimotor functions, may be related to previous observations indicating that MiL‐related factors are associated to greater than expected cognitive function for a given level of AD pathological load (Boyle et al., Arch Gen Psychiatry. 2012;69(5):499‐505), therefore promoting brain resilience in advanced age. [ABSTRACT FROM AUTHOR]

Background: Social, economic and psychological hardships associated with the COVID‐19 pandemic are expected to result in a global burden on mental health outcomes. However, while some individuals suffer from increasing distress and reduced quality of life, others will show no negative effects. A better understanding of brain mechanisms subtending resilience would be helpful in informing future recommendations to individuals and societies facing the present pandemic and future similar events. Here, we compared neurophysiological brain markers between individuals who exhibited resilience or vulnerability to pandemic associated psychological stress. Method: 23 participants from the longitudinal study cohort of the Barcelona Brain Health Initiative (Cattaneo et al., Front. Aging Neurosci. 2018;10:321) who underwent concurrent transcranial magnetic stimulation with electroencephalography (TMS‐EEG), were classified as either resilient (n=16) or non‐resilient (n=7), based on their scoring in the PHQ‐4 questionnaire (Kroenke et al., Psychosomatics 2009;50(6):613–21) along four timepoints; one before COVID‐19 outbreak and three spanning 2.5 months during the pandemic. Individuals maintaining a score below 3 across all timepoints were deemed resilient, while those scoring below 3 before pandemic but higher than 2 at any pandemic timepoint were considered non‐resilient. TMS‐EEG data was collected by delivering 120 single TMS pulses to the dorsolateral prefrontal cortex (DLPFC) and inferior parietal lobule (IPL). TMS evoked global mean field amplitude and local response at the stimulation site were computed. Result: Figure 1 depicts time‐series for DLPFC and IPL responses for both groups of subjects. Overall, non‐resilient individuals exhibited a larger global response to TMS perturbation during DLPFC stimulation, as well as larger local current density estimates during IPL stimulation. Conclusion: These preliminary results revealed that non‐resilient individuals were more susceptible to TMS perturbation, shown by global DLPFC and local IPL reactivity. Notably, these targets are nodes of the default mode and cognitive control networks affected by stress (van Oort et al., Neurosci. Biobehav. Rev. 2017;83:281–97), and the left frontal cortex has been proposed as a cognitive resilience hub (Franzmeier et al., J. Alzheimer's Dis. 2017;59(4):1381–92.). Future studies should investigate and confirm the possibility that these nodes constitute a shared neurophysiological substrate for psychological and cognitive resilience. [ABSTRACT FROM AUTHOR]

Background: The reduction in social interactions often associated with old age frequently initiates or aggravates loneliness, increasing the risk of a number of diseases including depression and dementia (Mushtaq et al., JCDR. 2014;8(9):E01–WE4.). Loneliness has been related to particular patterns of brain resting‐state networks (RSNs; Spreng et al., Nat Commun. 2020;11(1):6393). However, the role of RSNs in a resilient response to reductions of social interactions remains unknown and the COVID‐19 pandemic provides a unprecedent opportunity to investigate it. Method: Repeated loneliness assessments were collected by the Barcelona Brain Health Initiative (BBHI; www.bbhi.cat/en/) using the short UCLA Loneliness Scale (Russell et al., J Pers Assess. 1978; 42(3):290–294). Two timepoints were measured over two years prior to COVID‐19 outbreak and four thereafter (March, April, June and October 2020). We used baseline resting‐state functional magnetic resonance imaging (rs‐fMRI), from 281 participants (mean age 53.91±7.35; 137 women), acquired within 1‐2 years prior to the pandemic to compute resting‐state functional connectivity (rs‐FC) for each pair of nodes defined by the Schaefer‐Yeo atlas. Then, we utilized partial least squares (PLS) analysis for the decomposition of two multivariate sets (i.e., rs‐FC and loneliness scores) into latent variables of maximal covariation. Result: We identified two latent trajectories significantly correlated with two latent connectivity patterns, each of them describing approximately opposite baseline rs‐FC and loneliness levels during the months with the most severe restrictions (i.e., March and April). The first latent trajectory showed greater baseline loneliness improving during the pandemic, associated with higher within‐network connectivity in the limbic and salience networks. The second trajectory captured individuals with baseline loneliness levels similar to the average population, improving in March, at the beginning of outbreak, and worsening in April, which was related to lower baseline within‐network connectivity in the DMN and higher in the dorsal attention and visual circuits. Conclusion: Present findings reveal specific associations between RSNs' functional connectivity and opposite changes in feelings of loneliness during an unanticipated period of severe social restrictions. Specifically, lower rs‐FC of limbic networks combined with high connectivity of salience system at baseline suggested greater resilience to the negative impact during the pandemic on loneliness. [ABSTRACT FROM AUTHOR]

Background: Three previous studies administrated the Spanish version of the Face Name Associative Memory Exam task (S‐FNAME) to Spanish participants. Sanabria and collaborators, (2018) in their investigation on subjective cognitive decline individuals, reported associations between task performance and amyloid‐β (Aβ) burden, in accordance with the original publication (Renz et al., 2011). Alegret and colleagues (2015) provided normative data and psychometric characteristics, albeit the study was limited to subjects attending a memory clinic and included a reduced number of participants (N=110) with gender inequality distribution. The purpose of this study was to provide normative data and psychometric characteristics of the S‐FNAME in a larger independent sample of cognitively healthy individuals. Method: S‐FNAME was administered, according to standardized procedure published by Alegret et al. (2015), to 513 cognitively volunteers (243 women, mean age= 52,67±7,04, age range 41‐65, years of education= 17,28±3,71) participating in a longitudinal prospective cohort study (Barcelona Brain Health Initiative; Cattaneo et al., 2018). Subjects with diagnosis of neurological or psychiatric disease, substance abuse or treatment with psychopharmacological drugs, MMSE < 27, and cognitive impairments were excluded. Result: Factor analysis supported construct validity revealing two underlying components: face‐name and face‐occupation and explaining 95,36% of the total variance. Correlations between S‐FNAME and Rey Auditory Verbal Learning Test (RAVLT) were significant (ρ=.392, p=.00) and confirm its concurrent criterion validity. We also found weak and no significant correlations with other non‐memory cognitive tests supporting divergent criterion validity. Women showed better scores and S‐FNAME scales were positively correlated with years of education and negatively with age. Finally, we generated normative data for Spanish population aged 40–65 years. Conclusion: S‐FNAME exhibits good psychometric properties, consistent with previous findings regarding factorial structure and correlation with other measures and socio‐demographics variables (Alegret et al., 2015; Amariglio et al., 2012), although we found association with education in contrast to previous publications. S‐FNAME could serve as useful tool to assess memory impairments in Spanish population both for research purposes and clinical practice, to examine healthy older adult population and capture subtle cognitive decline or memory dysfunction associated to abnormal brain aging. [ABSTRACT FROM AUTHOR]

Background: Neurodegenerative brain changes that lead to cognitive decline generally begin decades prior to the onset of symptoms. On the other hand, brain health relates to overall, and specifically cardio‐vascular health, and vice‐versa. The objective of this investigation was to assess the relationships between two important domains of cardiovascular health (cardiorespiratory fitness, CRF, and cardiovascular risk, CVR) and two important markers of brain health (cognitive performance and volumetric measures of brain structure) in late middle age. Method: In a relatively large sample (n=327) of middle‐aged adults in the Barcelona Brain Health Initiative (Cattaneo et al., 2018), we assessed the associations between CRF (measured by VO2 max), CVR (measured by Framingham risk score), domain‐specific cognitive performance (measured by performance in a neuropsychological test battery) and brain volumes (measured by high‐resolution brain MRI). All regression models were corrected for age and education. Result: We found differential associations between CRF and CVR and cognitive performance. CRF was significantly associated with visuo‐spatial abilities and frontal loading abstract problem solving (p=.003), whereas CVR was associated with visuo‐spatial abilities (p=.023), flexibility (p=.005), processing speed (p<.001) and memory (p<.001). Moreover we found that CRF was associated with frontal (p=.042), temporal (p=.016) and sensorimotor (p=.013) cortical volume, whereas CVR was significantly associated with all cortical volume measures (frontal, temporal, parietal, occipital and sensorimotor; ps<0.05). Conclusion: We found that two modifiable factors in mid‐life (CRF and CVR) are significantly associated with a number of metrics of brain health in a cross‐sectional analysis. Future longitudinal analyses of this cohort will show whether these associations have predictive value for the maintenance of brain health across the lifespan. Finally, our findings suggest that lifestyle habits that promote CRF and reduce CVR, e.g. sufficient physical activity and appropriate nutrition, might help sustain brain health across the lifespan and prevent cognitive decline. [ABSTRACT FROM AUTHOR]

Background: Aging has been associated with changes in the mechanisms of brain plasticity, specifically with the reduction of motor cortex excitability and decreased effectiveness of mechanisms of cortical inhibition (Pascual‐Leone et al., 2011; Lissemore et al., 2018). Emerging evidence suggests that regular practice of physical activity, which can increase cardiorespiratory fitness (Sobol et al., 2016), may prevent age‐related decline in the mechanisms of brain plasticity (Gomes‐Osman et al., 2017). We therefore hypothesized that those who engage in more physical activity would have greater corticospinal excitability and more efficient cortical inhibition. Methods: Seventy‐eight healthy adults (39 women), between 41 and 65 years old were included in the study. The amount of physical activity was assessed using a self‐reported 5‐point Likert scale where 1 equalled sedentary and 5 equalled engagement in aerobic physical activity >3 hours/week. The peak respiratory oxygen uptake (VO2 peak), aerobic threshold (VT1) and anaerobic threshold (VT2) were measured by cardiopulmonary exercise test with ventilatory gas analyses. Transcranial magnetic stimulation was used to assess resting motor threshold, motor evoked potential (MEP) amplitude and long‐interval intracortical inhibition (LICI), a measure of cortical inhibition. Results: Spearman's rank correlation revealed that greater engagement in regular physical activity was associated with higher VO2 peak (ρ=.470, p =.001), VT1 (ρ=.371, p =.001) and VT2 (ρ=.414, p =.001), and higher amplitude of resting MEP (ρ=.287, p =.018). Mann‐Whitney U tests revealed higher MEP amplitude (p =.003) and more efficient LICI (p =.018) in the group who exercised >3 hours/week compared to the sedentary group. Conclusions: Regular physical activity in middle‐aged adults is related with better cardiorespiratory fitness, greater corticospinal excitability and more efficient cortical inhibitory mechanisms. [ABSTRACT FROM AUTHOR]

Background: Thanks to technological advances the administration of cognitive assessments via computers, tablets or smartphones continues to increase, both in research and clinical practice. Several systems are commercially available and have been validated. However, there are limited tools that provide a baseline assessment and guide a personalized training program with the seamless integration of follow‐up evaluations. The "Guttmann Cognitest"® app has been specifically designed as a smartphone or tablet app to be eventually integrated as an assessment module of the "Guttmann, NeuroPersonalTrainer"® (Solana et al., 2014), a tele‐cognitive rehabilitation platform. Method: In the context of the Barcelona Brain Health Initiative (BBHI, Cattaneo et al., 2018) 57 healthy subjects (28 women, mean age= 56.1±7, age range 42‐65, years of education= 16.1±3.6) underwent an extensive paper‐and‐pencil classical neuropsychological assessment and a cognitive assessment via the mobile app. The two cognitive assessments were completed on different days and their order was counterbalanced across subjects. The "Guttmann Cognitest"® app includes 6 tests designed to assess main cognitive functions and be completed in about 17 minutes (range 9‐30). Results: Factorial analysis confirmed that the app measured the intended 6 different cognitive domains. Internal consistency was good (α=0.71) and convergent validity analysis demonstrated that performance in each of the 6 tests in the app correlated with the a priori defined correspondent gold standard paper and pencil test. We found no gender effects, and an expected correlation with age in 5 out of 7 tests. Conclusions: Cognitive assessment with a mobile phone is feasible and useful. Preliminary results reveal that the "Guttmann Cognitest"® app has good psychometric properties and is suitable to test cognitive performance in large samples. Once integrated within the "Guttmann NeuroPersonalTrainer"® platform, it will enable automatically screening and effectively monitoring patient's cognitive capacities over time while undergoing personalized cognitive training and allowing automatic adjustment of treatments in intensity and difficulty according to performance. [ABSTRACT FROM AUTHOR]