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Patients with post-coronavirus disease 2019 (COVID-19) conditions typically experience cognitive problems. Some studies have linked COVID-19 severity with long-term cognitive damage, while others did not observe such associations. This discrepancy can be attributed to methodological and sample variations. We aimed to clarify the relationship between COVID-19 severity and long-term cognitive outcomes and determine whether the initial symptomatology can predict long-term cognitive problems. Cognitive evaluations were performed on 109 healthy controls and 319 post-COVID individuals categorized into three groups according to the WHO clinical progression scale: severe-critical ( n  = 77), moderate-hospitalized ( n  = 73), and outpatients ( n  = 169). Principal component analysis was used to identify factors associated with symptoms in the acute-phase and cognitive domains. Analyses of variance and regression linear models were used to study intergroup differences and the relationship between initial symptomatology and long-term cognitive problems. The severe-critical group performed significantly worse than the control group in general cognition (Montreal Cognitive Assessment), executive function (Digit symbol, Trail Making Test B, phonetic fluency), and social cognition (Reading the Mind in the Eyes test). Five components of symptoms emerged from the principal component analysis: the “Neurologic/Pain/Dermatologic” “Digestive/Headache”, “Respiratory/Fever/Fatigue/Psychiatric” and “Smell/ Taste” components were predictors of Montreal Cognitive Assessment scores; the “Neurologic/Pain/Dermatologic” component predicted attention and working memory; the “Neurologic/Pain/Dermatologic” and “Respiratory/Fever/Fatigue/Psychiatric” components predicted verbal memory, and the “Respiratory/Fever/Fatigue/Psychiatric,” “Neurologic/Pain/Dermatologic,” and “Digestive/Headache” components predicted executive function. Patients with severe COVID-19 exhibited persistent deficits in executive function. Several initial symptoms were predictors of long-term sequelae, indicating the role of systemic inflammation and neuroinflammation in the acute-phase symptoms of COVID-19.” Study Registration : www.ClinicalTrials.gov , identifier NCT05307549 and NCT05307575.

IntroductionThis is a 12-weeks randomized controlled trial examining the effects of aerobic exercise (AE), computerized cognitive training (CCT) and their combination (COMB). We aim to investigate their impact on cardiovascular health and white matter (WM) integrity and how they contribute to the cognitive benefits.Methods109 participants were recruited and 82 (62% female; age = 58.38 ± 5.47) finished the intervention with > 80% adherence. We report changes in cardiovascular risk factors and WM integrity (fractional anisotropy (FA); mean diffusivity (MD)), how they might be related to changes in physical activity, age and sex, and their potential role as mediators in cognitive improvements.ResultsA decrease in BMI (SMD = − 0.32, p = 0.039), waist circumference (SMD = − 0.42, p = 0.003) and diastolic blood pressure (DBP) (SMD = − 0.42, p = 0.006) in the AE group and a decrease in BMI (SMD = − 0.34, p = 0.031) and DBP (SMD = − 0.32, p = 0.034) in the COMB group compared to the waitlist control group was observed. We also found decreased global MD in the CCT group (SMD = − 0.34; p = 0.032) and significant intervention-related changes in FA and MD in the frontal and temporal lobes in the COMB group.ConclusionsWe found changes in anthropometric measures that suggest initial benefits on cardiovascular health after only 12 weeks of AE and changes in WM microstructure in the CCT and COMB groups. These results add evidence of the clinical relevance of lifestyle interventions and the potential benefits when combining them.Clinical Trial RegistrationClinicalTrials.gov NCT031123900.

Cognitive aging trajectories differ widely across individuals, and genetic factors such as APOE and BDNF polymorphisms may contribute to this variability. While APOE ε4 has been widely studied, the influence of APOE ε2, particularly in interaction with sex, remains underexplored. This study aims to examine the longitudinal trajectory of APOE ε2 individuals on cognitive performance, and their interactions with sex, age, and BDNF Val66Met polymorphism, in a population-based cohort of older adults with vascular risk. We analyzed data from 386 participants (mean age: 71.8) from the Barcelona-AsIA Neuropsychology Study, followed over a 7-year period. Verbal memory, verbal fluency, and visuospatial domains were assessed. Linear regression models tested associations between cognitive change and genotypes, controlling for age, sex, education, depression, and vascular risk. Interaction terms and permutation testing were applied. Regression to the mean (RTM) effects were assessed. BDNF showed no significant associations with cognitive performance. RTM effects were evident across subgroups, particularly among ε2 carriers, suggesting this phenomenon partly explains the divergent results over time. APOE ε2 does not confer a consistent protective effect on cognition over time. Our results highlight that APOE ε2 may be detrimental to verbal memory in aging males.

The original counterclockwise study carried out in the late 1970s provided an extreme example of \"reminiscence therapy,\" reporting improvements in older adults' cognitive and physical functioning after they had lived for 5 days in a house set up as if decades earlier (the 1950s). We tested a virtual reality (VR) analog of this approach, enhanced by embodying participants in a virtual body that looked like themselves at the corresponding younger age. This study aimed to examine whether brief VR exposures combining (1) embodiment in a virtual body as one's younger self and (2) immersion in an iconic past event improve age-related subjective and performance outcomes compared with a current-self VR control condition. We carried out a between-groups study with 23 healthy older adults (aged 65-85 years; mean age 71.2, SD 4.03 years). Participants were randomly allocated to either a Young Self condition (n=11; mean 72.3, SD 4.17), where they were embodied in a virtual body that looked like themselves from the 1960s, or in a Current Self control condition (n=12; mean 70.1, SD 3.75), where participants were embodied in their current body. There were 5 sessions. In Session 1, participants completed a baseline assessment. There were then 2 VR exposures, approximately 1 week apart (Sessions 2-3), and follow-ups at 1 week (Session 4) and approximately 2 weeks (Session 5) after the final VR exposure. Outcomes included subjective age, awareness of age-related change, World Health Organization-Five Well-Being Index, Trail Making Test performance, and physical functioning (eg, grip strength). A hierarchical Bayesian analysis revealed that 1 week after the final VR exposure, those in the Young Self condition demonstrated lower subjective age than those in the Current Self condition (prob=.95). They had higher awareness of positive age-related change (prob=.89) and a higher score on the World Health Organization-Five Well-Being Index (prob=.84). Moreover, with respect to performance variables, they took less time to trace a trail (prob≥.99), made fewer mistakes in doing so (prob=.89), had greater right-hand (prob=.85) and left-hand (prob≥.99) grip strength. However, 2 weeks after their final VR exposure, these differences diminished apart from positive awareness of age-related change (prob=.82), trail-making mistakes (prob=.83), and left-hand grip strength (prob≥.99). Here, \"prob\" refers to posterior probability. The results demonstrate that even 2 short VR exposures, where people were embodied in their younger body and immersed in an iconic event from more than 50 years earlier, resulted in improvement in some age-related responses. This is encouraging for further research with more extensive VR experiences over a longer time period.

Accumulating evidence suggests that physical activity improves explicit memory and executive cognitive functioning at the extreme ends of the lifespan (i.e., in older adults and children). However, it is unknown whether these associations hold for younger adults who are considered to be in their cognitive prime, or for implicit cognitive functions that do not depend on motor sequencing. Here we report the results of a study in which we examine the relationship between objectively measured physical activity and (1) explicit relational memory, (2) executive control, and (3) implicit probabilistic sequence learning in a sample of healthy, college-aged adults. The main finding was that physical activity was positively associated with explicit relational memory and executive control (replicating previous research), but negatively associated with implicit learning, particularly in females. These results raise the intriguing possibility that physical activity upregulates some cognitive processes, but downregulates others. Possible implications of this pattern of results for physical health and health habits are discussed.

Background: This study investigated the cross-sectional associations of personal and general views on aging, number of non-communicable diseases, and their interactions as cross-sectional predictors of vigorous physical activity. Methods: Participants were 1699 individuals aged 50 years and over (Mean age = 67.79) and living in the community in the UK; 70.8% were women. Participants completed measures assessing Awareness of Age-Related Gains and Losses (AARC-Gains; AARC-Losses; indicators of personal views on aging), Expectations Regarding Aging (ERA; indicator of general views on aging), vigorous physical activity in the last month, non-communicable disease status, and sociodemographic questions. Linear regression models were used. Results: After having adjusted for age, sex, education, marital status, and working status, higher AARC-Gains, lower AARC-Losses, more positive ERA, and fewer non-communicable diseases were cross-sectionally associated with greater likelihood of engagement with vigorous physical activity (Adjusted models Odds Ratio (OR) of 1.08; 0.86; and 1.06, respectively). The interactions of AARC-Gains and AARC-Losses with number of non-communicable diseases as cross-sectional predictors of likelihood of engagement with vigorous physical activity were not statistically significant. The interaction between ERA (i.e., General Views on Aging) and number of non-communicable diseases was a statistically significant cross-sectional predictor of likelihood of engagement with vigorous physical activity (OR = 0.99; p = 0.044). Conclusions: Having more positive and less negative views on aging may prompt vigorous physical activity engagement. Moreover, positive general views of aging may be particularly important for physical activity among those who have one or more non-communicable diseases. Although we cannot infer causality, promoting positive views on aging and decreasing negative views on aging could help fostering active aging, especially among those with physical health conditions.

Background: Normal pressure hydrocephalus (NPH) is associated with corpus callosum abnormalities. Objectives: To study the clinical and neuropsychological effect of callosal thinning in 18 patients with idiopathic NPH and to investigate the postsurgical callosal changes in 14 patients. Methods: Global corpus callosum size and seven callosal subdivisions were measured. Neuropsychological assessment included an extensive battery assessing memory, psychomotor speed, visuospatial and frontal lobe functioning. Results: After surgery, patients showed improvements in memory, visuospatial and frontal lobe functions, and psychomotor speed. Two frontal corpus callosum areas, the genu and the rostral body, were the regions most related to the clinical and neuropsychological dysfunction. After surgery, total corpus callosum and four of the seven subdivisions presented a significant increase in size, which was related to poorer neuropsychological and clinical outcome. Conclusion: The postsurgical corpus callosum increase might be the result of decompression, re-expansion and increase of interstitial fluid, although it may also be caused by differences in shape due to cerebral reorganisation.

Lifestyle interventions have positive neuroprotective effects in aging. However, there are still open questions about how changes in resting-state functional connectivity (rsFC) contribute to cognitive improvements. The Projecte Moviment is a 12-week randomized controlled trial of a multimodal data acquisition protocol that investigated the effects of aerobic exercise (AE), computerized cognitive training (CCT), and their combination (COMB). An initial list of 109 participants was recruited from which a total of 82 participants (62% female; age = 58.38 ± 5.47) finished the intervention with a level of adherence > 80%. Only in the COMB group, we revealed an extended network of 33 connections that involved an increased and decreased rsFC within and between the aDMN/pDMN and a reduced rsFC between the bilateral supplementary motor areas and the right thalamus. No global and especially local rsFC changes due to any intervention mediated the cognitive benefits detected in the AE and COMB groups. Projecte Moviment provides evidence of the clinical relevance of lifestyle interventions and the potential benefits when combining them.

Peripheral artery disease (PAD) and non-compressible artery disease (NCAD) constitute predictors of subclinical atherosclerosis easily assessed through the ankle brachial index (ABI). Although both diseases show substantial genetic influences, few genetic association studies have focused on the ABI and PAD, and none have focused on NCAD. To overcome these limitations, we assessed the role of several candidate genes on the ABI, both in its continuous distribution and in the clinical manifestations associated to its extreme values: PAD and NCAD. We examined 13 candidate genomic regions in 1606 participants from the ARTPER study, a prospective population-based cohort, with the ABI assessed through ultrasonography. Association analyses were conducted independently for individuals with PAD (ABI < 0.9) or with NCAD (ABI > 1.4) vs. healthy participants. After including potential covariates and correction for multiple testing, minor alleles in the genetic markers rs10757278 and rs1333049, both in the 9p21.3 region, were significantly associated with a decreased risk of NCAD. Associations with the ABI showed limited support to these results. No significant associations were detected for PAD. The locus 9p21.3 constitutes the first genetic locus associated with NCAD, an assessment of subclinical atherosclerosis feasible for implementation in primary healthcare settings that has been systematically neglected from genetic studies.

Background/Objectives: Stroke often leads to persistent cognitive and emotional impairments, which rehabilitation may mitigate. However, the biological mechanisms underlying such improvements remain unclear. This study investigated whether supplementing computerized cognitive training (CCT) with mindfulness-based stress reduction (MBSR) or physical exercise (PE) modulated biomarkers of neuroplasticity, inflammation, and stress in patients with chronic stroke compared to CCT alone. We also explored whether biomarker changes mediated or correlated with behavioral improvements. Methods: In a three-arm, single-blind, randomized controlled trial (NCT04759950), 141 patients with chronic stroke were randomized (1:1:1) to MBSR+CCT, PE+CCT, or CCT-only for 12 weeks. Plasma levels of brain-derived neurotrophic factor (BDNF), insulin-like growth factor-1 (IGF-1), vascular endothelial growth factor (VEGF), C-reactive protein (CRP), interleukin-6 (IL-6), and cortisol were measured at baseline and post-intervention. Cognitive, mental health, mindfulness, and fitness outcomes were also assessed. Between- and within-group changes were analyzed using ANCOVA and paired t-tests. Per-protocol and complete-case analyses were conducted. Results: Among the 109 participants with ≥80% adherence, the only significant between-group difference was for VEGF: it remained stable in the MBSR+CCT group but declined in PE+CCT and CCT-only. Within-group analyses showed significant decreases in cortisol in MBSR+CCT and PE+CCT, while IGF-1 levels declined across all groups. In contrast, BDNF, IL-6, and CRP did not show significant changes, and biomarker changes were not significantly associated with behavioral improvements. Complete-case analysis (n = 126) yielded similar findings. Conclusions: Our findings suggest that combining MBSR or PE with CCT may modulate certain biological processes relevant to stroke recovery. MBSR may help maintain VEGF levels, which could support vascular health, while MBSR and PE may contribute to lowering cortisol levels. However, since no clear association with behavioral improvements was found, further research is needed to determine the clinical relevance of these biomarker changes in stroke recovery.