Early prediction of Alzheimers's disese using null longitudinal model-based classifiers

Incipient Alzheimer's Disease (AD) is characterized by a slow onset of clinical symptoms, with pathological brain changes starting several years earlier. Consequently, it is necessary to first understand and differentiate age-related changes in brain regions in the absence of disease, and then to support early and accurate AD diagnosis. However, there is poor understanding of the initial stage of AD; seemingly healthy elderly brains lose matter in regions related to AD, but similar changes can also be found in non-demented subjects having mild cognitive impairment (MCI). By using a Linear Mixed Effects approach, we modelled the change of 166 Magnetic Resonance Imaging (MRI)-based biomarkers available at a 5-year follow up on healthy elderly control (HC, n = 46) subjects. We hypothesized that, by identifying their significant variant (vr) and quasi-variant (qvr) brain regions over time, it would be possible to obtain an age-based null model, which would characterize their normal atrophy and growth patterns as well as the correlation between these two regions. By using the null model on those subjects who had been clinically diagnosed as HC (n = 161), MCI (n = 209) and AD (n = 331), normal age-related changes were estimated and deviation scores (residuals) from the observed MRI-based biomarkers were computed. Subject classification, as well as the early prediction of conversion to MCI and AD, were addressed through residual-based Support Vector Machines (SVM) modelling. We found reductions in most cortical volumes and thicknesses (with evident gender differences) as well as in sub-cortical regions, including greater atrophy in the hippocampus. The average accuracies (ACC) recorded for men and women were: AD-HC: 94.11%, MCI-HC: 83.77% and MCI converted to AD (cAD)-MCI non-converter (sMCI): 76.72%. Likewise, as compared to standard clinical diagnosis methods, SVM classifiers predicted the conversion of cAD to be 1.9 years earlier for females (ACC:72.5%) and 1.4 years earlier for males (ACC:69.0%)

Structural integrity of the contralesional hemisphere predicts cognitive impairment in chronic stroke

After stroke, white matter integrity can be affected both locally and distally to the primary lesion location. It has been shown that tract disruption in mirror's regions of the contralateral hemisphere is associated with degree of functional impairment. Fourteen patients suffering right hemispheric focal stroke (S) and eighteen healthy controls (HC) underwent Diffusion Weighted Imaging (DWI) and neuropsychological assessment. The stroke patient group was divided into poor (SP; n = 8) and good (SG; n = 6) cognitive recovery groups according to their cognitive improvement from the acute phase (72 hours after stroke) to the subacute phase (3 months post-stroke). Whole-brain DWI data analysis was performed by computing Diffusion Tensor Imaging (DTI) followed by Tract Based Spatial Statistics (TBSS). Assessment of effects was obtained computing the correlation of the projections on TBSS skeleton of Fractional Anisotropy (FA) and Radial Diffusivity (RD) with cognitive test results. Significant decrease of FA was found only in right brain anatomical areas for the S group when compared to the HC group. Analyzed separately, stroke patients with poor cognitive recovery showed additional significant FA decrease in several left hemisphere regions; whereas SG patients showed significant decrease only in the left genu of corpus callosum when compared to the HC. For the SG group, whole brain analysis revealed significant correlation between the performance in the Semantic Fluency test and the FA in the right hemisphere as well as between the performance in the Grooved Pegboard Test (GPT) and theTrail Making Test-part A and the FA in the left hemisphere. For the SP group, correlation analysis revealed significant correlation between the performance in the GPT and the FA in the right hemisphere

Genetic Variants at the 9p21.3 Locus Are Associated with Risk for Non-Compressible Artery Disease: Results from the ARTPER Study

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 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

Effects of Aerobic Exercise, Cognitive and Combined Training on Cognition in Physically Inactive Healthy Late-Middle-Aged Adults: The Projecte Moviment Randomized Controlled Trial

Background: Lifestyle interventions are promising strategies to promote cognitive health in aging. Projecte Moviment examines if aerobic exercise (AE), computerized cognitive training (CCT), and their combination (COMB) improves cognition, psychological health, and physical status compared to a control group. We assessed the moderating role of age and sex and the mediating effects of cardiorespiratory fitness (CRF), physical activity (PA), and psychological health on intervention-related cognitive benefits. Methods: This was a 12-week multi-domain, single-blind, proof-of-concept randomized controlled trial (RCT). 96 healthy adults aged 50-70 years were assigned to AE, CCT, COMB, and a wait-list control group. The per protocol sample, which completed the intervention with a level of adherence > 80%, consisted of 82 participants (62% female; age = 58.38 ± 5.47). We assessed cognition, psychological health, CRF, and energy expenditure in PA at baseline and after the intervention. We regressed change in each outcome on the treatment variables, baseline score, sex, age, and education. We used PROCESS Macro to perform the mediation and moderation analyses. Results: AE benefited Working Memory (SMD = 0.29, p = 0.037) and Attention (SMD = 0.33, p = 0.028) including the Attention-Speed (SMD = 0.31, p = 0.042) domain, compared to Control. COMB improved Attention (SMD = 0.30, p = 0.043), Speed (SMD = 0.30, p = 0.044), and the Attention-Speed (SMD = 0.30, p = 0.041) domain. CTT group did not show any cognitive change compared to Control. Sportive PA (S-PA) and CRF increased in AE and COMB. Age and sex did not moderate intervention-related cognitive benefits. Change in S-PA, but not in CRF, significantly mediated improvements on Attention-Speed in AE. Conclusion: A 12-week AE program improved Executive Function and Attention-Speed in healthy late-middle-aged adults. Combining it with CCT did not provide further benefits. Our results add support to the clinical relevance of even short-term AE as an intervention to enhance cognition and highlight the mediating role of change in S-PA in these benefits

Physical activity is associated with reduced Implicit learning but enhanced relational memory and executive functioning in young adults

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

Neuropsychological Impairment in Post-COVID condition individuals with and without cognitive complaints

One of the most prevalent symptoms of post-COVID condition is cognitive impairment, which results in a significant degree of disability and low quality of life. In studies with large sample sizes, attention, memory, and executive function were reported as long-term cognitive symptoms. This study aims to describe cognitive dysfunction in large post-COVID condition individuals, compare objective neuropsychological performance in those post-COVID condition individuals with and without cognitive complaints, and identify short cognitive exams that can differentiate individuals with post-COVID symptoms from controls. To address these aims, the Nautilus project was started in June 2021. During the first year, we collected 428 participants' data, including 319 post-COVID and 109 healthy controls (18-65 years old) from those who underwent a comprehensive neuropsychological battery for cognitive assessment. Scores on tests assessing global cognition, learning and long-term memory, processing speed, language and executive functions were significantly worse in the post-COVID condition group than in healthy controls. Montreal Cognitive Assessment, digit symbol test, and phonetic verbal fluency were significant in the binomial logistic regression model and could effectively distinguish patients from controls with good overall sensitivity and accuracy. Neuropsychological test results did not differ between those with and without cognitive complaints. Our research suggests that patients with post-COVID conditions experience significant cognitive impairment and that routine tests like the Montreal Cognitive Assessment, digit symbol, and phonetic verbal fluency test might identify cognitive impairment. Thus, the administration of these tests would be helpful for all patients with post-COVID-19 symptoms, regardless of whether cognitive complaints are present or absent

Cardiovascular risk and white matter lesions after endocrine control of Cushing's syndrome

Objective: Cushing's syndrome (CS) is associated with high cardiovascular risk. White matter lesions (WML) are common on brain magnetic resonance imaging (MRI) in patients with increased cardiovascular risk. AIM: To investigate the relationship between cardiovascular risk, WML, neuropsychological performance and brain volume in CS. Design/methods: Thirty-eight patients with CS (23 in remission, 15 active) and 38 controls sex-, age- and education-level matched underwent a neuropsychological and clinical evaluation, blood and urine tests and 3Tesla brain MRI. WML were analysed with the Scheltens scale. Ten-year cardiovascular risk (10CVR) and vascular age (VA) were calculated according to an algorithm based on the Framingham heart study. Results: Patients in remission had a higher degree of WML than controls and active patients (P<0.001 and P=0.008 respectively), which did not correlate with cognitive performance in any group. WML severity positively correlated with diastolic blood pressure (r=0.659, P=0.001) and duration of hypertension (r=0.478, P=0.021) in patients in remission. Both patient groups (active and in remission) had higher 10CVR (P=0.030, P=0.041) and VA than controls (P=0.013, P=0.039). Neither the 10CVR nor the VA correlated with WML, although both negatively correlated with cognitive function and brain volume in patients in remission (P<0.05). Total brain volume and grey matter volume in both CS patient groups were reduced compared to controls (total volume: active P=0.006, in remission P=0.012; grey matter: active P=0.001, in remission P=0.003), with no differences in white matter volume between groups. Conclusions: Patients in remission of Cushing's syndrome (but not active patients) have more severe white matter lesions than controls, positively correlated with diastolic pressure and duration of hypertension. Ten-year cardiovascular risk and vascular age appear to be negatively correlated with the cognitive function and brain volume in patients in remission of Cushing's syndrome

Effects and mechanisms of mindfulness training and physical exercise on cognition, emotional wellbeing, and brain outcomes in chronic stroke patients: Study protocol of the MindFit project randomized controlled trial

Background: Post-stroke cognitive and emotional complications are frequent in the chronic stages of stroke and have important implications for the functionality and quality of life of those affected and their caregivers. Strategies such as mindfulness meditation, physical exercise (PE), or computerized cognitive training (CCT) may benefit stroke patients by impacting neuroplasticity and brain health. Materials and methods: One hundred and forty-one chronic stroke patients are randomly allocated to receive mindfulness-based stress reduction + CCT (n = 47), multicomponent PE program + CCT (n = 47), or CCT alone (n = 47). Interventions consist of 12-week home-based programs five days per week. Before and after the interventions, we collect data from cognitive, psychological, and physical tests, blood and stool samples, and structural and functional brain scans. Results: The effects of the interventions on cognitive and emotional outcomes will be described in intention-to-treat and per-protocol analyses. We will also explore potential mediators and moderators, such as genetic, molecular, brain, demographic, and clinical factors in our per-protocol sample. Discussion: The MindFit Project is a randomized clinical trial that aims to assess the impact of mindfulness and PE combined with CCT on chronic stroke patients' cognitive and emotional wellbeing. Furthermore, our design takes a multimodal biopsychosocial approach that will generate new knowledge at multiple levels of evidence, from molecular bases to behavioral changes. Clinical trial registration: www.ClinicalTrials.gov, identifier NCT04759950

Neurocognitive profile of the post-COVID condition in adults in Catalonia. A mixed method prospective cohort and nested case-control study: Study Protocol

The diagnosis of the post-COVID condition is usually achieved by excluding other diseases; however, cognitive changes are often found in the post-COVID disorder. Therefore, monitoring and treating the recovery from the post-COVID condition is necessary to establish biomarkers to guide the diagnosis of symptoms, including cognitive impairment. Our study employs a prospected cohort and nested case-control design with mixed methods, including statistical analyses, interviews, and focus groups. Our main aim is to identify biomarkers (functional and structural neural changes, inflammatory and immune status, vascular and vestibular signs and symptoms) easily applied in primary care to detect cognitive changes in post-COVID cases. The results will open up a new line of research to inform diagnostic and therapeutic decisions with special considerations for cognitive impairment in the post-COVID condition

Exercise and fitness neuroprotective effects: molecular, brain volume and psychological correlates and their mediating role in healthy late-middle-aged women and men

Background: Although exercise is known to have a neuroprotective effect in aging, the mediators underlying the exercise-cognition association remain poorly understood. In this paper we aimed to study the molecular, brain, and behavioral changes related to physical activity and their potential role as mediators. Methods: We obtained demographic, physical activity outcomes [sportive physical activity and cardiorespiratory fitness (CRF)], plasma biomarkers (TNF-a, ICAM-1, HGF, SDF1-a, and BDNF), structural-MRI (brain volume areas), psychological and sleep health (mood, depressive and distress symptoms, and sleep quality), and multi-domain cognitive data from 115 adults aged 50-70 years. We conducted linear regression models and mediation analyses stratifying results by sex in a final sample of 104 individuals [65 women (age = 56.75 ± 4.96) and 39 men (age = 58.59 ± 5.86)]. Results: Women engaging in greater amounts of exercising showed lower TNF-a levels and greater dorsolateral prefrontal cortex and temporal lobe volumes. Men engaging in greater amounts of exercise showed greater temporal lobe volumes. CRF levels were not related to any of the analyzed outcomes in women but inmen higher CRF was associated with lower TNF-a, HGF and ventricle volumes, greater volume of temporal and parietal lobes and fewer depressive symptoms and better mood. In men, reduced TNF-a and HGF levels mediated brain and cognitive CRF-related benefits. Conclusion: Our results show that exercise is a promising approach for influencing inflammation and brain volume and also contributes to ongoing discussions about the physiological mediators for the association between CRF and cognition in men