Healthy Older Subjects Research Articles

Leg cycling efficiency is unaltered in healthy aging regardless of sex or training status.

Muscular efficiency during exercise has been used to interrogate aspects of human muscle energetics, including mitochondrial coupling and biomechanical efficiencies. Typically, assessments of muscular efficiency have involved graded exercises. Results of previous studies have been interpreted to indicate a decline in exercise efficiency with aging owing to decreased mitochondrial function. However, discrepancies in variables such as exercise stage duration, cycling cadence, and treadmill walking mechanics may have affected interpretations of results. Furthermore, recent data from our lab examining the ATP to oxygen ratio (P:O) in mitochondrial preparations isolated from NIA mouse skeletal muscle showed no change with aging. Thus, we hypothesized that delta efficiency (Δ€) during steady-rate cycling exercise would not be altered in older healthy subjects compared with young counterparts regardless of biological sex or training status. Young (21-35 yr) and older (60-80 yr) men (n = 21) and women (n = 20) underwent continual, progressive leg cycle ergometer tests pedaling at 60 RPM for three stages (35, 60, 85 W) lasting 4 min. Δ€was calculated as: (Δ work accomplished/Δ energy expended). Overall, cycling efficiencies were not significantly different in older compared with young subjects. Similarly, trained subjects did not exhibit significantly different exercise efficiencies compared to untrained. Moreover, there were no differences between men and women. Hence, our results obtained on healthy young and older subjects are interpreted to mean that previous reports of decreased efficiency in older individuals were attributable to metabolic or biomechanical comorbidities, not aging per se.NEW & NOTEWORTHY Muscular power is reduced, but the efficiency of movement is unaltered in healthy aging.

Efficacy and Safety of Coenzyme Q10 Supplementation in Neonates, Infants and Children: An Overview.

To date, there have been no review articles specifically relating to the general efficacy and safety of coenzyme Q10 (CoQ10) supplementation in younger subjects. In this article, we therefore reviewed the efficacy and safety of CoQ10 supplementation in neonates (less than 1 month of age), infants (up to 1 year of age) and children (up to 12 years of age). As there is no rationale for the supplementation of CoQ10 in normal younger subjects (as there is in otherwise healthy older subjects), all of the articles in the medical literature reviewed in the present article therefore refer to the supplementation of CoQ10 in younger subjects with a variety of clinical disorders; these include primary CoQ10 deficiency, acyl CoA dehydrogenase deficiency, Duchenne muscular dystrophy, migraine, Down syndrome, ADHD, idiopathic cardiomyopathy and Friedreich's ataxia.

Hybrid representation learning for cognitive diagnosis in late-life depression over 5 years with structural MRI

Late-life depression (LLD) is a highly prevalent mood disorder occurring in older adults and is frequently accompanied by cognitive impairment (CI). Studies have shown that LLD may increase the risk of Alzheimer’s disease (AD). However, the heterogeneity of presentation of geriatric depression suggests that multiple biological mechanisms may underlie it. Current biological research on LLD progression incorporates machine learning that combines neuroimaging data with clinical observations. There are few studies on incident cognitive diagnostic outcomes in LLD based on structural MRI (sMRI). In this paper, we describe the development of a hybrid representation learning (HRL) framework for predicting cognitive diagnosis over 5 years based on T1-weighted sMRI data. Specifically, we first extract prediction-oriented MRI features via a deep neural network, and then integrate them with handcrafted MRI features via a Transformer encoder for cognitive diagnosis prediction. Two tasks are investigated in this work, including (1) identifying cognitively normal subjects with LLD and never-depressed older healthy subjects, and (2) identifying LLD subjects who developed CI (or even AD) and those who stayed cognitively normal over five years. We validate the proposed HRL on 294 subjects with T1-weighted MRIs from two clinically harmonized studies. Experimental results suggest that the HRL outperforms several classical machine learning and state-of-the-art deep learning methods in LLD identification and prediction tasks.

Directed functional connectivity of the default-mode-network of young and older healthy subjects

Alterations in the default mode network (DMN) are associated with aging. We assessed age-dependent changes of DMN interactions and correlations with a battery of neuropsychological tests, to understand the differences of DMN directed connectivity between young and older subjects. Using a novel multivariate analysis method on resting-state functional MRI data from fifty young and thirty-one healthy older subjects, we calculated intra- and inter-DMN 4-nodes directed pathways. For the old subject group, we calculated the partial correlations of inter-DMN pathways with: psychomotor speed and working memory, executive function, language, long-term memory and visuospatial function. Pathways connecting the DMN with visual and limbic regions in older subjects engaged at BOLD low frequency and involved the dorsal posterior cingulate cortex (PCC), whereas in young subjects, they were at high frequency and involved the ventral PCC. Pathways combining the sensorimotor (SM) cortex and the DMN, were SM efferent in the young subjects and SM afferent in the older subjects. Most DMN efferent pathways correlated with reduced speed and working memory. We suggest that the reduced sensorimotor efferent and the increased need to control such activities, cause a higher dependency on external versus internal cues thus suggesting how physical activity might slow aging.

Increased dual-task interference during upper limb movements in stroke exceeding that found in aging - a systematic review and meta-analysis.

To determine whether dual-task interference during upper limb tasks is increased in patients after stroke compared to healthy older subjects and to compare magnitude of stroke-induced change in interference to that explained by aging. We conducted a systematic literature search in MEDLINE, CINAHL, Google Scholar and PEDro databases up to October 2023 for studies on upper limb dual-tasks in stroke and elderly healthy subjects. Eleven upper limb dual-task studies in stroke patients and 11 studies in healthy older subjects were identified and systematically reviewed. A meta-analysis was performed on seven stroke studies and on five studies in healthy older subjects that included control groups. Most stroke studies investigated proximal arm movements with kinematic measures, but few studies evaluated manual dexterity. In contrast, studies in healthy older subjects used more distal (finger tapping) tasks. The meta-analysis showed that stroke patients had on average a 19% (CI 95% = 1.0-37.3) increase in dual-task interference compared to age-matched healthy controls (Z = 2.06, p = 0.04). Older healthy subjects showed greater dual-task interference compared to younger subjects (19% greater, CI 95% = 6.5-31.2, Z = 2.98, p = 0.003). Meta-analysis revealed an increase in dual-task interference during upper limb movements in stroke patients, exceeding age-related changes, supporting the presence of subclinical impairments in divided attention post-stroke that may impede motor recovery.

Aging modulates frontal lobes involvement in emotion regulation processing.

Emotion regulation (ER) is the process by which individuals can modulate the intensity of their emotional experience and it plays a crucial role in daily life. So far, behavioral analyses seem to suggest that ER ability remains stable throughout the lifespan. However, imaging studies evaluating the neural correlates of ER performance during the aging process have shown mixed results. In this study, we used the "Cambridge Centre for Ageing and Neuroscience cohort sample" to investigate: (1) ER behavioral performance and (2) the differential association between brain measures (based on both structural and functional connectivity data) and ER performance, in a group of younger/middle-aged participants (N = 159; age range: 18y < x < 58y) relative to a group of older healthy subjects (N = 136; age range: 58y < =x < 89y). Whereas we found no group-related differences either in ER behavioral data or the association between ER performance and structural data, we did observe that ER performance was differentially correlated in our two study groups to functional connectivity measures in the fronto-insular-temporal network, which has been shown to be involved in emotional processing. Group-related differences were specifically localized in a cluster of voxels within the anterior cingulate areas which revealed a reverse pattern between our study groups: in younger/middle-aged participants better ER performance was associated with increase connectivity, whereas among older participants better ER performance was related to reduced connectivity. Based on our results, we suggest that a de-differentiation mechanism, known to affect the frontal lobes brain activity and connectivity in older subjects, might explain our findings.

Brain connectome correlates of short-term motor learning in healthy older subjects

The motor learning process entails plastic changes in the brain, especially in brain network reconfigurations. In the current study, we sought to characterize motor learning by determining changes in the coupling behaviour between the brain functional and structural connectomes on a short timescale. 39 older subjects (age: mean (SD) = 69.7 (4.7) years, men:women = 15:24) were trained on a visually guided sequential hand grip learning task. The brain structural and functional connectomes were constructed from diffusion-weighted MRI and resting-state functional MRI, respectively. The association of motor learning ability with changes in network topology of the brain functional connectome and changes in the correspondence between the brain structural and functional connectomes were assessed. Motor learning ability was related to decreased efficiency and increased modularity in the visual, somatomotor, and frontoparietal networks of the brain functional connectome. Between the brain structural and functional connectomes, reduced correspondence in the visual, ventral attention, and frontoparietal networks as well as the whole-brain network was related to motor learning ability. In addition, structure–function correspondence in the dorsal attention, ventral attention, and frontoparietal networks before motor learning was predictive of motor learning ability. These findings indicate that, in the view of brain connectome changes, short-term motor learning is represented by a detachment of the brain functional from the brain structural connectome. The structure–function uncoupling accompanied by the enhanced segregation into modular structures over the core functional networks involved in the learning process may suggest that facilitation of functional flexibility is associated with successful motor learning.

Age-associated changes in lower limb weight-bearing strategy during walking

BackgroundAs people age there is a proximal shift of joint moment generation from ankle plantarflexion and knee extension toward hip extension and flexion moments. This age-related redistribution has been documented in the context of propulsive force generation during the push-off phase with less evidence in the context of weight bearing. Additionally, these sagittal plane joint moments have been a primary focus of studies though the hip frontal plane moment also contributes to vertical support but has received less attention. Furthermore, how aging affects the relationships between changes in sagittal and frontal joint moments and changes in vertical support force as a function of walking speed remains unclear Research questionHow does aging affect the contributions of sagittal and frontal plane joint moments to weight-bearing across different walking speeds? MethodsGait analysis was performed on 24 young and 17 healthy older subjects walked on the treadmill at their preferred and 30 % faster speeds. Stepwise linear regression analysis was performed to determine the joint moments that predict the peak amplitudes of the vertical ground reaction force (VGRF) across different walking speeds. ResultsHip abduction and knee extension moments were the primary contributors to leading limb weight-bearing in young, whereas hip extension moment was the primary contributor in older adults. Ankle plantarflexion moment was the main contributor to trailing limb weight-bearing in young and hip flexion moment was the main contributor in older adults. From preferred to faster walking speed changes in knee extension moment were the primary contributor to changes in the trailing limb weight-bearing in young whereas changes in hip extension moment were the primary contributor in olderadults. SignificanceThese findings suggested that older and younger adults used different joint moment contributions to produce leading limb and trailing limb vertical support forces across different walking speeds.

Exploring Biomarkers of Mental Flexibility in Healthy Aging: A Computational Psychometric Study.

Mental flexibility (MF) has long been defined as cognitive flexibility. Specifically, it has been mainly studied within the executive functions domain. However, there has recently been increased attention towards its affective and physiological aspects. As a result, MF has been described as an ecological and cross-subject skill consisting of responding variably and flexibly to environmental cognitive-affective demands. Cross-sectional studies have mainly focused on samples composed of healthy individual and of patients with chronic conditions such as Mild Cognitive Impairment and Parkinson's, emphasizing their behavioral rigidity. Our study is the first to consider a sample of healthy older subjects and to outline physiological and psychological markers typical of mental flexibility, to identify functional biomarkers associated with successful aging. Our results reveal that biomarkers (respiratory and heart rate variability assessments) distinguished between individuals high vs. low in mental flexibility more reliably than traditional neuropsychological tests. This unveiled the multifaceted nature of mental flexibility composed of both cognitive and affective aspects, which emerged only if non-linear multi-variate analytic approaches, such as Supervised Machine Learning, were used.

Perceptual Integration Compensates for Attention Deficit in Elderly during Repetitive Auditory-Based Sensorimotor Task.

Sensorimotor integration (SI) brain functions that are vital for everyday life tend to decline in advanced age. At the same time, elderly people preserve a moderate level of neuroplasticity, which allows the brain's functionality to be maintained and slows down the process of neuronal degradation. Hence, it is important to understand which aspects of SI are modifiable in healthy old age. The current study focuses on an auditory-based SI task and explores: (i) if the repetition of such a task can modify neural activity associated with SI, and (ii) if this effect is different in young and healthy old age. A group of healthy older subjects and young controls underwent an assessment of the whole-brain electroencephalography (EEG) while repetitively executing a motor task cued by the auditory signal. Using EEG spectral power and functional connectivity analyses, we observed a differential age-related modulation of theta activity throughout the repetition of the SI task. Growth of the anterior stimulus-related theta oscillations accompanied by enhanced right-lateralized frontotemporal phase-locking was found in elderly adults. Their young counterparts demonstrated a progressive increase in prestimulus occipital theta power. Our results suggest that the short-term repetition of the auditory-based SI task modulates sensory processing in the elderly. Older participants most likely progressively improve perceptual integration rather than attention-driven processing compared to their younger counterparts.

Deep-learning-enabled brain hemodynamic mapping using resting-state fMRI

Cerebrovascular disease is a leading cause of death globally. Prevention and early intervention are known to be the most effective forms of its management. Non-invasive imaging methods hold great promises for early stratification, but at present lack the sensitivity for personalized prognosis. Resting-state functional magnetic resonance imaging (rs-fMRI), a powerful tool previously used for mapping neural activity, is available in most hospitals. Here we show that rs-fMRI can be used to map cerebral hemodynamic function and delineate impairment. By exploiting time variations in breathing pattern during rs-fMRI, deep learning enables reproducible mapping of cerebrovascular reactivity (CVR) and bolus arrival time (BAT) of the human brain using resting-state CO2 fluctuations as a natural “contrast media”. The deep-learning network is trained with CVR and BAT maps obtained with a reference method of CO2-inhalation MRI, which includes data from young and older healthy subjects and patients with Moyamoya disease and brain tumors. We demonstrate the performance of deep-learning cerebrovascular mapping in the detection of vascular abnormalities, evaluation of revascularization effects, and vascular alterations in normal aging. In addition, cerebrovascular maps obtained with the proposed method exhibit excellent reproducibility in both healthy volunteers and stroke patients. Deep-learning resting-state vascular imaging has the potential to become a useful tool in clinical cerebrovascular imaging.

Effect of APOE e4 allele on age‐related brain FDG‐PET uptake in older individuals at risk of dementia

AbstractBackgroundIn Alzheimer’s Disease (AD) patients, accumulating evidence suggests that the APOE‐e4 allele drives amyloid and tau pathology and decreases brain glucose metabolism. Similarly, in older healthy subjects, APOE‐e4 has been linked to brain hypometabolism. However, there are scarce clinical studies concerning the effect of APOE e4 and the age‐related cerebral glucose metabolism patterns of older individuals at‐risk for dementia.ObjectiveThis exploratory analysis aims to study the impact of carriage of the APOE‐e4 allele on age‐related brain glucose metabolism patterns of older individuals at‐risk for dementia.Method54 community‐dwelling older adults aged 60‐80 years with increased risk for AD due to cardiometabolic disorders (CMD, n = 32) or mild cognitive impairment (MCI, n = 22) who participated in a clinical trial. APOE genotyping was performed to identify carriers of the APOE‐e4 allele. 18F‐Fluoro‐2‐deoxy‐D‐glucose‐positron emission tomography/computed tomography (18F‐FDG PET/CT) was conducted and mean 18F‐FDG uptakes in brain regions of interest (ROI) from the atlas of anatomical labeling were obtained.Group differences by diagnosis (CMD,MCI) and APOE‐e4 status were examined using independent samples T‐tests. Linear regression models were conducted to evaluate the effect of age over mean 18F‐FDG uptake in each ROI. Age*APOE‐e4 interactions were examined, and the models were adjusted for diagnosis subgroup and gender effects. Adjusted models were corrected for multiple testing using the False Discovery Ratio (FDR).ResultMean 18F‐FDG uptake at each ROI was comparable between diagnosis and APOE‐e4 allele status groups. After correcting adjusted models for multiple testing, significant Age*APOE‐e4 interactions were found at the right inferior occipital gyrus (β ‐0.13, 95% CI ‐0.25 – 0.02, p = 0.035, FDR = 0.039), right paracentral lobule (β ‐0.14, 95% CI ‐0.25 – ‐0.03, p = 0.016, FDR = 0.024), and left superior parietal gyrus (β ‐0.11, 95% CI ‐0.20 – ‐0.02, p = 0.014, FDR = 0.021).ConclusionIn older individuals at risk of dementia, carriage of the APOE‐e4 allele was associated with an increased age‐related reduction in mean 18F‐FDG uptake in the right inferior occipital gyrus, right paracentral lobule, and left superior parietal gyrus. Knowledge of age‐ and APOE‐e4 allele‐related cerebral metabolic changes is critical to correctly interpreting brain 18F‐FDG PET/CT findings.

0273 Advanced assessment of sleep derived from hypnodensity

Abstract Introduction In a recent analysis of PSG studies with six, nine and twelve human scorers, we showed that sleep stage ambiguity is the rule rather than the exception, and that sleep stage probabilities (SSPs) calculated with artificial intelligence provide an excellent estimate of this ambiguity. Here we investigate clinical and demographic factors driving this ambiguity and evaluate potential benefits of using hypnodensity in addition to the traditional hypnogram for sleep assessment. Methods SSPs were determined in 195 healthy subjects aged 20–95 years and in 49 apnea patients aged 29–73 years (AHI: 5.8–105.5 events/hour). In addition to the recommended sleep parameters, we derived the percentage of ambiguous sleep stages (SSP ≤ 0.95), the mean amount of ambiguity per sleep stage (1-SSP), sleep stage continuity (absolute difference in SSP between two epochs) and sleep stage stability (two adjacent epochs belonging to the same sleep stage with SSP &amp;gt; 0.95 each) as well as NREM sleep depth (weighted average of NREM SSPs). Results The percentages of ambiguous NREM epochs (±SD) increased significantly with age (Pearson’s r=0.72; p&amp;lt; 0.01) from 40±9% in young healthy subjects (20-39 years, n=61) to 50±9% in middle-aged healthy subjects (40-59 years, n=59) and to 62±11% in older healthy subjects (≥ 60 years, n=75). The percentages of ambiguous REM epochs did not change significantly across age (r=0.1). Apnea patients showed an increased NREM ambiguity (77±15% compared to 53±10% in age- and sex-matched healthy controls; p&amp;lt; 0.01), while REM ambiguity was only slightly increased (p&amp;lt; 0.05). Furthermore, sleep stage continuity, stability, and NREM sleep depth decrease significantly with age and are significantly lower in apnea patients than in healthy controls (p&amp;lt; 0.01). Conclusion Artificial intelligence-based autoscoring shows ambiguity in 40% of NREM epochs in young healthy subjects, increasing to 77% in apnea patients. Assigning a single sleep stage to each epoch and presenting sleep architecture as a traditional hypnogram may be misleading, especially for older subjects and patients with sleep-disordered breathing. A hypnodensity chart representing sleep stage probabilities reflects this sleep staging ambiguity, provides all the information contained in a hypnogram, and offers insights into sleep ambiguity, continuity, stability, and sleep depth. Support (if any)

CD34+ progenitor cells as diagnostic and therapeutic targets in Alzheimer's disease.

CD34+ progenitor cells as diagnostic and therapeutic targets in Alzheimer's disease.

Usefulness of salivary sampling for the molecular detection of a genetic variant associated with bipolar disorders.

Under certain conditions, the hyperthymic temperament traits associated with an increased risk of developing bipolar disorders may in fact produce adaptive responses. The purpose of this study is to see if the type of biological material used for genetic analysis (saliva or blood) affects the detection of mutations in the CACNA1C (RS1006737) gene. The first experimental group consisted of Sardinian migrants ("volunteers") in South American and European megacities. The second experimental group consisted of older healthy subjects with hyperactivity and novelty-seeking characteristics from Cagliari, Italy. The genetic procedure included DNA extraction, real-time PCR, and the Sanger method. Nonetheless, the authors believe that saliva is the most appropriate biological material, given its many advantages. In contrast to blood, saliva can be collected by any type of healthcare provider after following a few simple instructions.

Mechanisms of Cognitive Decline due to White Matter Lesions in Cognitively Intact Older Adults

AbstractBackgroundWhite matter hyperintensities (WMH) on FLAIR MRI are highly prevalent in older adults and are linked to cognitive deficits as well as dementia. Likely mechanisms underlying associations between WMH and cognitive deficits include widespread partial disconnection due to the diffuse nature of progressive WMH and/or tract‐specific disconnection syndromes. We used a virtual lesion approach to evaluate cognitive deficits in domains associated with three tracts: left arcuate fasciculus (LAF; verbal working memory), inferior longitudinal fasciculus (ILF; visual processing), and fornix (memory).MethodWMH were semi‐automatically segmented from FLAIR MRI data in 481 ADNI controls and applied as regions of avoidance for probabilistic fiber tracking on DTI data in 46 healthy older subjects from the Human Connectome Lifespan database. Correlations between overall WMH burden or individual tract disruption and global or tract‐domain‐specific cognitive tests were assessed. Tract disconnection was also compared in subgroups with enriched disruption of specific tracts with respect to global WMH burden, Amyloid beta deposition status, and best (&gt;Mean+1SD) versus worst (&lt;Mean‐1SD) test performance.ResultAll three tracts showed disconnections due to WMH and the mean tract disconnection increased significantly with overall WMH burden (ILF; p&lt;0.001, LAF: p&lt;0.001, Fornix; p=0.025) (Figure 1A). Also, both overall WMH burden and percent disconnection in ILF were associated with prolonged Trail A and Trail B times after correction for age and education (Table 1). In subgroup analyses, Amyloid beta positive status significantly moderated correlation of Trail B times with overall WMH burden (p=0.007) and ILF disconnection (p=0.020) (Figure 2). Subjects with enriched ILF disconnection (Figure 1B) also had prolonged Trail A times than the average group (34.3 vs 30.2, p=0.003). Based on cognitive tests performance, subjects with better scores on verbal category fluency or verbal logical memory tests had lower LAF (p=0.035) and fornix (Test I; p=0.003, Test II; 0.025) disconnection.ConclusionWhile overall WMH burden correlates with cognitive deficits in ADNI controls, significant correlations between specific tract disconnection and tract‐domain‐specific cognitive tests are also observed. Both mechanisms likely contribute to age‐associated cognitive decline. Furthermore, amyloid beta accumulation strengthens these relationships.

Effects of Sitting Callisthenic Balance and Resistance Exercise Programs on Cognitive Function in Older Participants.

Exercise training programs have the potential to improve cognitive function in older subjects. However, the majority of training programs are based on aerobic modality. In the current study, the influence of 3 months programs of sitting callisthenic balance (SCB) and resistance training (RT) on cognitive functioning and the mediating role that a change in the level of neurotrophic factors and strength in older, healthy participants plays were examined. Global cognitive function was examined using MoCA, short-term memory using Digit Span and Delayed Matching to Sample, set shifting using Trial Making Test Part B, speed of processing simple visual stimuli using Simple Reaction Time, decision making using Choice Reaction Time, visual attention with Visual Attention Test (VAT), tests. Strength of lower and upper limbs, neurotrophin level (irisin, brain-derived neurotrophic factor (BDNF), neurotrophin 3 (NT-3), neurotrophin 4/5 (NT 4/5) were examined. Improved scores in RT vs. SCB were noted in MoCA (p = 0.02), reaction time in SRT (p = 0.02), TMT B (p = 0.03), errors committed in CRT (p = 0.04) and VAT (p = 0.02) were observed. No significant changes in the level of neurotrophic factors were observed. Changes in upper limb strength were related to changes in the number of errors committed in the SRT (p = 0.03). Lower limb strength changes explained the dynamics of the number of correct answers (p = 0.002) and errors committed (p = 0.006) in VAT. Both SCB and RT influenced multiple cognitive domains. The RT program improved global cognitive functioning, while no improvement was noticed in the SCB group. Decision making, visual attention and global cognitive function were improved after the RT program. Set-shifting, short-term visual memory processing speed of simple visual stimuli were improved after the SCB program, while a decrease in the processing speed of simple visual stimuli was noted in the RT group. Changes in irisin were related to set-shifting and short-term memory, while in BDNF to an improvement in the processing speed of simple visual stimuli. Resistance exercise training programs could be applied to prevent age related declines of cognitive function in healthy older subjects.

Use of the Kinect sensor measured three-dimensional reachable workspace to assess the upper extremity function in older adults.

We explored the utility of Kinect sensor-based upper extremity reachable workspace measure in healthy adults aged over 65years. Forty-three healthy older subjects (19 men and 24 women) aged over 65years and 22 healthy young subjects (11 men and 11 women) were included. All participants were ambulatory and perform the activities of daily living independently. Three-dimensional reachable workspace data were acquired for both arms using the Kinect sensor. We evaluated hand grip strength, manual muscle shoulder strength, and the active shoulder ranges of motion of the dominant and non-dominant sides. We assessed upper limb function using the Disabilities of Arm, Shoulder, and Hand (DASH) instrument and the health-related quality of life employing the descriptive EQ-5D-5L system. The quadrant 3 relative surface area in older adults was significantly smaller than that of young adults (both dominant and non-dominant sides), while the total and quadrants 1, 2, and 4 relative surface areas did not differ between older and young adults. However, the quadrant 3 relative surface area did not correlate with the DASH or EQ5D scores. The total and quadrant 1, 2, and 4 relative surface areas of the dominant side significantly correlated with the DASH score. The quadrant 4 relative surface area of the dominant side significantly correlated with the EQ5D score. Kinect sensor-based, three-dimensional, reachable workspace analysis may be useful to evaluate upper limb function in older adults.

Diminishing accelerated long-term forgetting in mild cognitive impairment: Study protocol for a prospective, double-blind, placebo-controlled, randomized controlled trial

BackgroundHarnessing the lifelong potential of the human brain for neuroplasticity may serve to maintain the viability of neural structures and postpone the onset of cognitive decline. The absence of effective pharmacological interventions to counter memory decline has encouraged scientists to test the possibility that noninvasive electrical stimulation may serve as an additional tool to improve memory abilities.Previous research showed that electrical stimulation of the greater occipital nerve enhances memory recall performance in young and older healthy subjects. This study aims to extend these findings to determine the effect of transcutaneous electrical stimulation of the greater occipital nerve on the improvement of episodic memory in individuals with amnestic Mild Cognitive Impairment (aMCI). Methods/designThis study is a prospective, double-blind, placebo-controlled, randomized parallel-group study. A total of 100 individuals with a diagnosis of aMCI according to NIA/AA will be recruited. Participants will be randomly assigned to one of four groups. One group will receive active non-invasive transcutaneous electrical stimulation of greater occipital nerve (NITESGON), while three groups will serve as controls (i.e., sham NITESGON, active NITESGON with local anesthesia, and active NITESGON on the C5/C6 nerve). The primary outcome, i.e., memory recall, will be determined by a word association task, and will be recorded at baseline, 7 days after NITESGON, and 28 days after NITESGON. The secondary outcome is neurophysiological changes determined by resting state EEG and will be assessed immediately before and after NITESGON. DiscussionThe results will add new insights into improving episodic memory in individuals with aMCI. Trial registration#NCT05289804 (clinicaltrial.gov) Protocol approval id#SPREC102021-23 (Ethics Committee at Trinity College Dublin, School of Psychology)

TLR9 Mediates Periodontal Aging by Fostering Senescence and Inflammaging

TLR9 is a critical nucleic acid sensing receptor in mediating periodontitis and periodontitis-associated comorbidities. Emerging evidence implicates TLR9 as a key sensor during aging, although its participation in periodontal aging is unexplored. Here, we investigated whether TLR9-mediated host responses can promote key hallmarks of aging, inflammaging, and senescence, in the course of periodontitis using a multipronged approach comprising clinical and preclinical studies. In a case-control model, we found increased TLR9 gene expression in gingival tissues of older (≥55 y) subjects with periodontitis compared to older healthy subjects as well as those who are younger (<55 y old) with and without the disease. Mechanistically, this finding was supported by an in vivo model in which wild-type (WT) and TLR9–/– mice were followed for 8 to 10 wk (young) and 18 to 22 mo (aged). In this longitudinal model, aged WT mice developed severe alveolar bone resorption when compared to their younger counterpart, whereas aged TLR9–/– animals presented insignificant bone loss when compared to the younger groups. In parallel, a boosted inflammaging milieu exhibiting higher expression of inflammatory/osteoclast mediators (Il-6, Rankl, Cxcl8) and danger signals (S100A8, S100A9) was noted in gingival tissues of aged WT mice compared to the those of aged TLR9–/– mice. Consistently, WT aged mice displayed an increase in prosenescence balance as measured by p16 INK4a /p19 ARF ratio compared to the younger groups and aged TLR9–/– animals. Ex vivo experiments with bone marrow–derived macrophages primed by TLR9 ligand (ODN 1668) further corroborated in vivo and clinical data and showed enhanced inflammatory-senescence circuit followed by increased osteoclast differentiation. Together, these findings reveal first systematic evidence implicating TLR9 as one of the drivers of periodontitis during aging and functioning by boosting a deleterious inflammaging/senescence environment. This finding calls for further investigations to determine whether targeting TLR9 will improve periodontal health in an aging population.