Decoding the Disparity: An Analysis of the Functional Connectivity Profile of Elderly African Americans with and without Alzheimer’s Disease

African Americans are twice as likely as non-Hispanic Whites to develop Alzheimer’s Disease. Current approaches to studying Alzheimer’s disease do not include a sufficient minority population needed to understand the nature of this disparity. Evidence from epidemiological and cerebrospinal fluid biomarker studies suggests that African Americans do indeed represent a unique phenotype of Alzheimer’s disease, partly driven by an elevated presence of risk factors. These risk factors include, but are not limited to an elevated presence of vascular disease which can manifest in the brain in the form of White Matter Hyperintensities (WMH). Functional magnetic resonance imaging is a method of detecting brain activity, and has been used to detect neurological changes within Alzheimer’s Disease in the form of functional connectivity (FC). FC is a measure of the correlation of activity between brain regions. In our first aim, we examined connectivity between a well-studied network, the default mode network and how race modifies the relationship between AD biomarkers and connectivity, and whether WMH in this network accounts for these racial differences. We found that race does modify the relationship between CSF t-Tau, Aβ42, and cognitive performance between the midline core and dorsomedial subsystems, but that WMH did not account for these differences. In our second aim, we analyzed connectivity between regions not typically associated with AD including the anterior putamen, pre and post central gyri, and superior and middle frontal gyri. We found that, independent of race, anterior putamen to pre and post central gyri increased as CSF Aβ42 decreased, but the connectivity decreased as regional WMH volume increased. Within African Americans, connectivity between the middle and superior frontal connectivity decreased as CSF Aβ42 decreased, and as regional WMH volume increased. This work further characterizes the AA dementia profile, and provides novel regions of exploration that may be affected by AD. Furthermore, we provide neurological support for the claim that in studies of individuals with Alzheimer’s disease, race should be considered as an important factor of interest in analyses

Effects of Transcranial Magnetic Stimulation on the Default Mode Network in Minimal Cognitive Impairment and Alzheimer's disease: An ALE meta-analysis and systematic review

openObjective: This systematic review and meta-analysis sought to comprehensively assess the efficacy of repetitive transcranial magnetic stimulation (rTMS) on the default mode network (DMN) through functional magnetic resonance imaging (fMRI) among individuals diagnosed with mild cognitive impairment (MCI) and Alzheimer's disease (AD). The primary objective was to unravel the neuroimaging mechanisms underpinning cognitive intervention. Methods: A search encompassing English articles published until July 30, 2023, was conducted across prominent databases, including PubMed, Web of Science, Embase, and Cochrane Library. The study specifically focused on randomized controlled trials utilizing resting-state fMRI to investigate the impact of rTMS within the MCI and AD populations. The analysis of fMRI data was executed using GingerALE. Results: Our meta-analysis encompassed a total of seven studies focusing on AD, collectively 116 patients in the treatment group and 90 patients in the sham group. Additionally, in MCI group comprised 34 patients in the treatment groups and 39 patients in the sham group. The combined ALE quantitative analyses on group contrasts between Alzheimer's patients and the sham group showed no significant clusters of convergence. A similar outcome was observed when conducting meta-analyses of the MCI group. The restricted pool of eligible studies may have hindered our ability to detect meaningful clusters of convergence. Conclusions: The outcomes of this meta-analysis and systematic review collectively underscore the potential effectiveness and safety of rTMS intervention in addressing the needs of patients coping with MCI and AD. These improvements could likely be attributed to the favorable modulation that rTMS imparts upon spontaneous neural activity and cognitive networks. By elucidating the intricate neural mechanisms involved, this study contributes insights into the burgeoning field of cognitive intervention strategie

Negative affective burden is associated with higher resting-state functional connectivity in subjective cognitive decline

Publisher Copyright: © 2022, The Author(s).Subjective cognitive decline (SCD), as expressed by older adults, is associated with negative affect, which, in turn, is a likely risk factor for Alzheimer’s Disease (AD). This study assessed the associations between negative affective burden, cognitive functioning, and functional connectivity in networks vulnerable to AD in the context of SCD. Older participants (60–90 years) with SCD (n = 51) and healthy controls (n = 50) were investigated in a cross-sectional study. Subclinical negative affective burden, quantified through a composite of self-reported negative affective factors, was related to cognitive functioning (self-perceived and objective) and functional connectivity. Seed-to-voxel analyses were carried out in default mode network (DMN) and salience network (SAL) nodes using resting-state functional magnetic resonance imaging. Greater negative affective burden was associated with lower self-perceived cognitive functioning and lower between-network functional connectivity of DMN and SAL nodes in the total sample. In addition, there was a significant moderation of SCD status. Greater negative affective burden related to higher functional connectivity within DMN (posterior cingulate-to-precuneus) and within SAL (anterior cingulate-to-insula) nodes in the SCD group, whereas in controls the inverse association was found. We show that negative affective burden is associated with functional brain alterations in older adults, regardless of SCD status. Specifically in the SCD phenotype, greater negative affective burden relates to higher functional connectivity within brain networks vulnerable to AD. Our findings imply that negative affective burden should be considered a potentially modifiable target for early intervention.Peer reviewe

Brain Hemodynamic Intermediate Phenotype Links Vitamin B12 to Cognitive Profile of Healthy and Mild Cognitive Impaired Subjects

Vitamin B12, folate, and homocysteine are implicated in pivotal neurodegenerative mechanisms and partake in elders’ mental decline. Findings on the association between vitamin-related biochemistry and cognitive abilities suggest that the structural and functional properties of the brain may represent an intermediate biomarker linking vitamin concentrations to cognition. Despite this, no previous study directly investigated whether vitamin B12, folate, and homocysteine levels are sufficient to explain individual neuropsychological profiles or, alternatively, whether the activity of brain regions modulated by these compounds better predicts cognition in elders. Here, we measured the relationship between vitamin blood concentrations, scores at seventeen neuropsychological tests, and brain activity of sixty-five elders spanning from normal to Mild Cognitive Impairment. We then evaluated whether task-related brain responses represent an intermediate phenotype, providing a better prediction of subjects’ neuropsychological scores, as compared to the one obtained considering blood biochemistry only. We found that the hemodynamic activity of the right dorsal anterior cingulate cortex was positively associated ( cluster corrected) with vitamin B12 concentrations, suggesting that elders with higher B12 levels had a more pronounced recruitment of this salience network region. Crucially, the activity of this area significantly predicted subjects’ visual search and attention abilities (), whereas B12 levels per se failed to do so. Our results demonstrate that the relationship between blood biochemistry and elders’ cognitive abilities is revealed when brain activity is included into the equation, thus highlighting the role of brain imaging as intermediate phenotype

The organization of functional neurocognitive networks in focal epilepsy correlates with domain-specific cognitive performance

Understanding and diagnosing cognitive impairment in epilepsy remains a prominent challenge. New etiological models suggest that cognitive difficulties might not be directly linked to seizure activity, but are rather a manifestation of a broader brain pathology. Consequently, treating seizures is not sufficient to alleviate cognitive symptoms, highlighting the need for novel diagnostic tools. Here, we investigated whether the organization of three intrinsic, resting-state functional connectivity networks was correlated with domain-specific cognitive test performance. Using individualized EEG source reconstruction and graph theory, we examined the association between network small worldness and cognitive test performance in 23 patients with focal epilepsy and 17 healthy controls, who underwent a series of standardized pencil-and-paper and digital cognitive tests. We observed that the specific networks robustly correlated with test performance in distinct cognitive domains. Specifically, correlations were evident between the default mode network and memory in patients, the central-executive network and executive functioning in controls, and the salience network and social cognition in both groups. Interestingly, the correlations were evident in both groups, but in different domains, suggesting an alteration in these functional neurocognitive networks in focal epilepsy. The present findings highlight the potential clinical relevance of functional brain network dysfunction in cognitive impairment.Peer reviewe

Cognitive reserve impacts on inter-individual variability in resting-state cerebral metabolism in normal aging

peer reviewedThere is a great deal of heterogeneity in the impact of aging on cognition and cerebral functioning. One potential factor contributing to individual differences among the elders is the cognitive reserve, which designates the partial protection from the deleterious effects of aging that lifetime experience provides. Neuroimaging studies examining task-related activation in elderly people suggested that cognitive reserve takes the form of more efficient use of brain networks and/or greater ability to recruit alternative networks to compensate for age-related cerebral changes. In this multi-centre study, we examined the relationships between cognitive reserve, as measured by education and verbal intelligence, and cerebral metabolism at rest (FDG-PET) in a sample of 74 healthy older participants. Higher degree of education and verbal intelligence was associated with less metabolic activity in the right posterior temporoparietal cortex and the left anterior intraparietal sulcus. Functional connectivity analyses of resting-state fMRI images in a subset of 41 participants indicated that these regions belong to the default mode network and the dorsal attention network respectively. Lower metabolism in the temporoparietal cortex was also associated with better memory abilities. The findings provide evidence for an inverse relationship between cognitive reserve and resting-state activity in key regions of two functional networks respectively involved in internal mentation and goal-directed attention

Brain hemodynamic intermediate phenotype links Vitamin B12 to cognitive profile of healthy and mild cognitive impaired subjects

Vitamin B12, folate, and homocysteine are implicated in pivotal neurodegenerative mechanisms and partake in elders' mental decline. Findings on the association between vitamin-related biochemistry and cognitive abilities suggest that the structural and functional properties of the brain may represent an intermediate biomarker linking vitamin concentrations to cognition. Despite this, no previous study directly investigated whether vitamin B12, folate, and homocysteine levels are sufficient to explain individual neuropsychological profiles or, alternatively, whether the activity of brain regions modulated by these compounds better predicts cognition in elders. Here, we measured the relationship between vitamin blood concentrations, scores at seventeen neuropsychological tests, and brain activity of sixty-five elders spanning from normal to Mild Cognitive Impairment. We then evaluated whether task-related brain responses represent an intermediate phenotype, providing a better prediction of subjects' neuropsychological scores, as compared to the one obtained considering blood biochemistry only. We found that the hemodynamic activity of the right dorsal anterior cingulate cortex was positively associated (p value < 0 05 cluster corrected) with vitamin B12 concentrations, suggesting that elders with higher B12 levels had a more pronounced recruitment of this salience network region. Crucially, the activity of this area significantly predicted subjects' visual search and attention abilities (p value = 0 0023), whereas B12 levels per se failed to do so. Our results demonstrate that the relationship between blood biochemistry and elders' cognitive abilities is revealed when brain activity is included into the equation, thus highlighting the role of brain imaging as intermediate phenotype.Vitamin B12, folate, and homocysteine are implicated in pivotal neurodegenerative mechanisms and partake in elders' mental decline. Findings on the association between vitamin-related biochemistry and cognitive abilities suggest that the structural and functional properties of the brain may represent an intermediate biomarker linking vitamin concentrations to cognition. Despite this, no previous study directly investigated whether vitamin B12, folate, and homocysteine levels are sufficient to explain individual neuropsychological profiles or, alternatively, whether the activity of brain regions modulated by these compounds better predicts cognition in elders. Here, we measured the relationship between vitamin blood concentrations, scores at seventeen neuropsychological tests, and brain activity of sixty-five elders spanning from normal to Mild Cognitive Impairment. We then evaluated whether task-related brain responses represent an intermediate phenotype, providing a better prediction of subjects' neuropsychological scores, as compared to the one obtained considering blood biochemistry only. We found that the hemodynamic activity of the right dorsal anterior cingulate cortex was positively associated (p value < 0 05 cluster corrected) with vitamin B12 concentrations, suggesting that elders with higher B12 levels had a more pronounced recruitment of this salience network region. Crucially, the activity of this area significantly predicted subjects' visual search and attention abilities (p value = 0 0023), whereas B12 levels per se failed to do so. Our results demonstrate that the relationship between blood biochemistry and elders' cognitive abilities is revealed when brain activity is included into the equation, thus highlighting the role of brain imaging as intermediate phenotype

Large-scale functional networks, cognition and brain structures supporting social cognition and theory of mind performance in prodromal to mild Alzheimer’s Disease

Impairment of social cognition (SC) skills such as recognition and attribution of intentions and affective states of others (Theory of Mind, ToM) has been evidenced in Alzheimer’s Disease (AD). This study investigated the neuropsychological, neuroanatomical and brain-functional underpinnings of SC processing to obtain an understanding of the social neurophenotype in early probable AD. Forty-six patients with mild cognitive impairment and mild probable AD underwent SC assessment including emotion recognition (Ekman-60-faces task) and cognitive and affective ToM (Reading-the-Mind-in-the-Eyes test and Story-based Empathy task). Linear models tested the association between SC scores and neuropsychological measures, grey matter maps and large-scale functional networks activity. The executive domain had the most predominant association with SC scores in the cognitive profile. Grey matter volume of the anterior cingulate, orbitofrontal, temporoparietal junction (TPJ), superior temporal, and cerebellar cortices were associated with ToM. Social cognition scores were associated with lower connectivity of the default-mode network with the prefrontal cortex. The right fronto-parietal network displayed higher inter-network connectivity in the right TPJ and insula while the salience network showed lower inter-network connectivity with the left TPJ and insula. Connectivity coupling alterations of executive-attentional networks may support default mode social-cognitive-associated decline through the recruitment of frontal executive mechanisms