Associations between subjective cognitive concern, brain network connectivity, and cognitive performance in cognitively normal older adults

Understanding the precise relation between functional connectivity and structural (white matter) connectivity and how these relationships account for cognitive changes in older adults are major challenges for neuroscience. We investigate these issues using an approach in which structural equation modeling (SEM) is employed to integrate functional and structural connectivity data from younger and older adults (n = 62), analyzed with a common framework based on regions connected by canonical tract groups (CTGs). CTGs (e.g., uncinate fasciculus) serve as a common currency between functional and structural connectivity matrices, and ensure equivalent sparsity in connectome information. We used this approach to investigate the neural mechanisms supporting memory for items and memory for associations, and how they are affected by healthy aging. We found that different structural and functional CTGs made independent contributions to source and item memory performance, suggesting that both forms of connectivity underlie age-related differences in specific forms of memory. Furthermore, the relationship between functional and structural connectivity was best explained by a general relationship between latent constructs—a relationship absent in any specific CTG group. These results provide insights into the relationship between structural and functional connectivity patterns, and elucidate their relative contribution to age-related differences in source memory performance.

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.

Effect of increasing cognitive activity participation on default mode network in older adults with subjective cognitive decline: a randomised controlled trial

BackgroundBuilding on our previous findings that increased participation in cognitive activities, such as calligraphy practice, improves working memory and strengthens functional connectivities within the Default Mode Network in older adults with Subjective Cognitive Decline, we conducted a secondary analysis to examine the effects on other functional brain networks.MethodA total of 112 participants (aged 55‐75 years, CDR 0 but with Subjective Cognitive Decline, practicing ≥1 hour of calligraphy per week) were randomly assigned to either the control group (continuing usual calligraphy practice) or the intervention group (doubling the practice time for 6 months) in a 1:1 ratio. Functional connectivities within the Salience Network and Central Executive Network were assessed using functional MRI before and after the intervention. This assessor‐blind randomized controlled trial was funded by the Research Grants Council in Hong Kong (grant number: 24114519).ResultThe intervention group showed stronger functional connectivities between core components of the Salience Network, including the anterior insula, supramarginal gyrus, and prefrontal cortex, over the 6‐month period, whereas the control group did not. No significant group differences were observed in the changes of functional connectivities within the Central Executive Network.ConclusionOur findings suggest that increasing participation enhances the ability of the Salience Network to integrate and process salient stimuli, potentially contributing to improved cognitive regulation. Engaging more in cognitive activities may serve as a safe and effective non‐pharmacological intervention for maintaining cognitive function and network integrity in older adults. Future research should explore the long‐term benefits and potential mechanisms underlying these network‐specific changes.

This study aimed to investigate the adequacy of the visual-motor inte-gration (VMI) scale for Korean elderly (VMIS-KE) compared to tradition-al measures, mini-mental state examination of Korean version (MMSE-KC) and Beery VMI for cognitive decline in diabetic older adults. For this explanatory research, data were collected from September 1 to Sep-tember 15, 2013, from 34 diabetic older adults and 31 nondiabetic older adults in Daegu and Gyeongsan of Korea. Mean differences between the two groups were analyzed with SPSS 18.0. The diabetic older adults showed significantly lower scores in the VMIS-KE (t=4.128, P<0.001) and MMSE-KC (t=2.231, P=0.029) compared with the nondiabetic older adults. In all subcategories of VMI-KE, figure cognition (t=5.342, P<0.001), memory (t=3.011, P=0.004) and spatial cognition (t=2.639, P=0.011), there were significant differences whereas no significant difference in the VMI-6th revision (t=0.994, P=0.325). VMIS-KE could be a sensitive indicator to assess cognitive change in older adults with diabetes and health care providers should periodically evaluate vulnerable groups such as them with it.

High-impact pain predicts subjective cognitive decline and interacts with APOE4 genotype in the development of objective cognitive impairment.

The decline in cognitive and motor functions with age affects the performance of the aging healthy population in many daily life activities. Physical activity appears to mitigate this decline or even improve motor and cognitive abilities in older adults. The current systematic review will focus mainly on behavioral studies that look into the dual effects of different types of physical training (e.g., balance training, aerobic training, strength training, group sports, etc.) on cognitive and motor tasks in older adults with no known cognitive or motor disabilities or disease. Our search retrieved a total of 1095 likely relevant articles, of which 41 were considered for full-text reading and 19 were included in the review after the full-text reading. Overall, observations from the 19 included studies conclude that improvements on both motor and cognitive functions were found, mainly in interventions that adopt physical-cognitive training or combined exercise training. While this finding advocates the use of multimodal exercise training paradigms or interventions to improve cognitive-motor abilities in older adults, the sizeable inconsistency among training protocols and endpoint measures complicates the generalization of this finding.

BackgroundApolipoprotein (APOE) ɛ4 positivity and subjective cognitive decline (SCD) both increase risk of Alzheimer’s disease (AD) development. However, few studies have examined the relationship between SCD and APOE status, especially using longitudinal data. The current study examined whether APOE is associated with the rate of cognitive change in SCD and mild cognitive impairment (MCI).MethodsA sample of 3494 older adults (1990 normal controls, NC, 775 SCD, and 729 MCI) with a mean follow-up of 9.09 years were included from the Rush Alzheimer’s Disease Center Research Sharing Hub. Linear mixed effects models examined the relationship between APOE status and cognitive change in older adults with SCD normal controls, and people with MCI.ResultsThe presence of at least one ɛ2 allele in SCD and MCI results in cognitive change rates similar to a NC with the ɛ3ɛ3 genotype. Older adult SCD-ɛ4 individuals exhibited increased rate of cognitive decline compared to all groups, including NC-ɛ4 and MCI-ɛ4.ConclusionPeople with SCD with at least one ɛ4 allele experience increased rates of cognitive decline compared to cognitively healthy older adults and people with MCI. These findings have important implications for treatments and interventions and can improve future research and clinical trials by targeting people in the preclinical AD phase (i.e., SCD) who also possess at least one APOE ɛ4 allele.

BackgroundBoth subjective cognitive decline (SCD) and amnestic mild cognitive impairment (aMCI) have a high risk of progression to Alzheimer's disease (AD). While most of the available evidence described changes in functional connectivity (FC) in SCD and aMCI, there was no confirmation of changes in functional connectivity density (FCD) that have not been confirmed. Therefore, the purpose of this study was to investigate the specific alterations in resting-state FCD in SCD and aMCI and further assess the extent to which these changes can distinguish the preclinical and early-stage AD.MethodsA total of 57 patients with SCD, 59 patients with aMCI, and 78 healthy controls (HC) were included. The global FCD, local FCD, and long-range FCD were calculated for each voxel to identify brain regions with significant FCD alterations. The brain regions with abnormal FCD were then used as regions of interest for FC analysis. In addition, we calculated correlations between neuroimaging alterations and cognitive function and performed receiver-operating characteristic analyses to assess the diagnostic effect of the FCD and FC alterations on SCD and aMCI.ResultsFCD mapping revealed significantly increased global FCD in the left parahippocampal gyrus (PHG.L) and increased long-range FCD in the left hippocampus for patients with SCD when compared to HCs. However, when compared to SCD, patients with aMCI showed significantly decreased global FCD and long-range FCD in the PHG.L. The follow-up FC analysis further revealed significant variations between the PHG.L and the occipital lobe in patients with SCD and aMCI. In addition, patients with SCD also presented significant changes in FC between the left hippocampus, the left cerebellum anterior lobe, and the inferior temporal gyrus. Moreover, changes in abnormal indicators in the SCD and aMCI groups were significantly associated with cognitive function. Finally, combining FCD and FC abnormalities allowed for a more precise differentiation of the clinical stages.ConclusionTo our knowledge, this study is the first to investigate specific alterations in FCD and FC for both patients with SCD and aMCI and confirms differential abnormalities that can serve as potential imaging markers for preclinical and early-stage Alzheimer's disease (AD). Also, it adds a new dimension of understanding to the diagnosis of SCD and aMCI as well as the evaluation of disease progression.

Subjective cognitive decline (SCD) is an early manifestation of the Alzheimer's disease (AD) continuum, and accurately diagnosing SCD to differentiate it from neurotypical aging in older adults is a common challenge for researchers. This review examines and summarizes relevant studies regarding the neuroimaging of the AD continuum, and comprehensively summarizes and outlines the SCD clinical features characterizing along with the corresponding neuroimaging changes involving structural, functional, and metabolic networks. The clinical characteristics of SCD include a subjective decline in self-perceived cognitive function, and there are significant imaging changes, such as reductions in gray matter volume in certain brain regions, abnormalities in the integrity of white matter tracts and diffusion metrics, alterations in functional connectivity between different sub-networks or within networks, as well as abnormalities in brain metabolic networks and cerebral blood flow perfusion. The 147 referenced studies in this paper indicate that exploring the structural, functional, and metabolic network changes in the brain related to SCD through neuroimaging aims to enhance the goals and mission of brain science development programs: "Understanding the Brain," "Protecting the Brain," and "Creating the Brain," thereby strengthening researchers' investigation into the mechanisms of brain function. Early diagnosis of SCD, along with prompt intervention, can reduce the incidence of AD spectrum while improving patients' quality of life, even integrating numerous scientific research achievements into unified and established standards and applying them in clinical practice by doctors, thus all encouraging researchers to further investigate SCD issues in older adults.

Associations between Physical Activity and Cognitive Functioning among Middle-Aged and Older Adults.

INTRODUCTIONNo studies in India have explored subjective cognitive decline (SCD), a hallmark of stage II of preclinical Alzheimer's disease. This study aims to assess the prevalence and correlates of SCD in a South Indian, urban, elderly population.METHODSWe screened 403 individuals 60 years of age and older using the Subjective Memory Complaints Questionnaire (SMCQ) and measured objective cognition with the Montreal Cognitive Assessment (MoCA). Physical health parameters were evaluated for all participants.RESULTSAmong the participants, 377 (93.5%) reported subjective memory complaints. Of the 26 individuals without SCD, 15(57.7%) had objective cognitive impairment (MoCA <25). A total of 182 participants (45.2%) were identified with SCD. Higher educational attainment was significantly associated with fewer SCD reports and better cognitive performance (p < 0.001).DISCUSSIONSubjective cognitive decline (SCD) is highly prevalent among older adults. Screening for SCD can help identify individuals at risk for Alzheimer's disease. SCD assessement combined with cost‐effective biomarkers that confirms AD will help individuals to be identified for disease‐modifying therapies.HighlightsNearly half of older adults population screened has reported subjective cognitive decline (SCD), highlighting the widespread occurrence of SCD in urban South India.Participants with higher educational attainment had significantly fewer memory complaints and performed better on cognitive assessments.SCD was prevalent even among individuals without major comorbid conditions such as diabetes and hypertension and those who were on regular treatment for metabolic and cardiovascular disorders.Identifying subjective cognitive decline (SCD) can facilitate early and accurate diagnosis of cognitive disorders and help delay progression to dementia. This highlights the importance of developing and implementing improved public health strategies to address these challenges.Further longitudinal studies are necessary to explore the progression of SCD to dementia, focusing on the interplay between cognitive health, biomarkers, and educational factors in the Indian population.

Accelerometer-assessed light physical activity is protective of future cognitive ability: A longitudinal study among community dwelling older adults

Gait abnormalities and postural instability have been linked to cognitive decline in older adults, however the causal relationships between cognitive capacity and gait is still an open problem. Emerging portable technologies may help elucidate these connections by enabling gait analysis in out-of-the-lab settings, with higher sensitivity than timed gait assessment tests. The purpose of this work was to evaluate the associations between cognitive ability (Montreal Cognitive As-sessment scores) and measures of gait and balance disturbance (spatiotemporal gait parameters, dynamic margin of stability) in a group of older adults, under a dual-task walking paradigm, using an integrated gait analysis system that features a mobile robot and in-shoe sensors. Results of hierarchical regression analyses adjusted for age and gender indicated that decline in cognitive ability in older adults is independently associated with more conservative overground gait patterns (i.e., smaller absolute values of the anteroposterior margin of stability) and increased gait variability (i.e., larger coefficients of variation in stride time and stride velocity) when performing dual-task walking. These results provide proof-of-concept validation of the applicability of integrated robotic and wearable sensors technologies to out-of-the-lab gait analysis in older adults.

Objective:Nonpathological aging has been linked to decline in both verbal and visuospatial memory abilities in older adults. Disruptions in resting-state functional connectivity within well-characterized, higherorder cognitive brain networks have also been coupled with poorer memory functioning in healthy older adults and in older adults with dementia. However, there is a paucity of research on the association between higherorder functional connectivity and verbal and visuospatial memory performance in the older adult population. The current study examines the association between resting-state functional connectivity within the cingulo-opercular network (CON), frontoparietal control network (FPCN), and default mode network (DMN) and verbal and visuospatial learning and memory in a large sample of healthy older adults. We hypothesized that greater within-network CON and FPCN functional connectivity would be associated with better immediate verbal and visuospatial memory recall. Additionally, we predicted that within-network DMN functional connectivity would be associated with improvements in delayed verbal and visuospatial memory recall. This study helps to glean insight into whether within-network CON, FPCN, or DMN functional connectivity is associated with verbal and visuospatial memory abilities in later life.Participants and Methods:330 healthy older adults between 65 and 89 years old (mean age = 71.6 ± 5.2) were recruited at the University of Florida (n = 222) and the University of Arizona (n = 108). Participants underwent resting-state fMRI and completed verbal memory (Hopkins Verbal Learning Test - Revised [HVLT-R]) and visuospatial memory (Brief Visuospatial Memory Test - Revised [BVMT-R]) measures. Immediate (total) and delayed recall scores on the HVLT-R and BVMT-R were calculated using each test manual’s scoring criteria. Learning ratios on the HVLT-R and BVMT-R were quantified by dividing the number of stimuli (verbal or visuospatial) learned between the first and third trials by the number of stimuli not recalled after the first learning trial. CONN Toolbox was used to extract average within-network connectivity values for CON, FPCN, and DMN. Hierarchical regressions were conducted, controlling for sex, race, ethnicity, years of education, number of invalid scans, and scanner site.Results:Greater CON connectivity was significantly associated with better HVLT-R immediate (total) recall (ß = 0.16, p = 0.01), HVLT-R learning ratio (ß = 0.16, p = 0.01), BVMT-R immediate (total) recall (ß = 0.14, p = 0.02), and BVMT-R delayed recall performance (ß = 0.15, p = 0.01). Greater FPCN connectivity was associated with better BVMT-R learning ratio (ß = 0.13, p = 0.04). HVLT-R delayed recall performance was not associated with connectivity in any network, and DMN connectivity was not significantly related to any measure.Conclusions:Connectivity within CON demonstrated a robust relationship with different components of memory function as well across verbal and visuospatial domains. In contrast, FPCN only evidenced a relationship with visuospatial learning, and DMN was not significantly associated with memory measures. These data suggest that CON may be a valuable target in longitudinal studies of age-related memory changes, but also a possible target in future non-invasive interventions to attenuate memory decline in older adults.