Healthy Older Adults Research Articles

Age-related Differences in Response Inhibition Are Mediated by Frontoparietal White Matter but Not Functional Activity.

Healthy older adults often exhibit lower performance but increased functional recruitment of the frontoparietal control network during cognitive control tasks. According to the cortical disconnection hypothesis, age-related changes in the microstructural integrity of white matter may disrupt inter-regional neuronal communication, which in turn can impair behavioral performance. Here, we use fMRI and diffusion-weighted imaging to determine whether age-related differences in white matter microstructure contribute to frontoparietal over-recruitment and behavioral performance during a response inhibition (go/no-go) task in an adult life span sample (n = 145). Older and female participants were slower (go RTs) than younger and male participants, respectively. However, participants across all ages were equally accurate on the no-go trials, suggesting some participants may slow down on go trials to achieve high accuracy on no-go trials. Across the life span, functional recruitment of the frontoparietal network within the left and right hemispheres did not vary as a function of age, nor was it related to white matter fractional anisotropy (FA). In fact, only frontal FA and go RTs jointly mediated the association between age and no-go accuracy. Our results therefore suggest that frontal white matter cortical "disconnection" is an underlying driver of age-related differences in cognitive control, and white matter FA may not fully explain functional task-related activation in the frontoparietal network during the go/no-go task. Our findings add to the literature by demonstrating that white matter may be more important for certain cognitive processes in aging than task-related functional activation.

Jazz Piano Training Modulates Neural Oscillations and Executive Functions in Older Adults

Musical improvisation is one of the most complex forms of creative behavior, often associated with increased executive functions. However, most traditional piano programs do not include improvisation skills. This research examined the effects of music improvisation in a novel jazz piano training intervention on executive functions and neural oscillatory activity in healthy older adults. Forty adults were recruited and randomly assigned to either jazz piano training (n = 20, 10 females) or a control group (n = 20, 13 females). The jazz piano training program included aural skills, basic technique, improvisation, and repertoire with 30 hours of training over 10 days. All participants at pre- and post-testing completed a battery of standardized cognitive measures (i.e., processing speed, inhibition, verbal fluency), and neurophysiological data was recorded during resting state and a musical improvisation task using electroencephalography (EEG). Results showed significantly enhanced processing speed and inhibition performance for those who received jazz piano training as compared to controls. EEG data revealed changes in frontal theta power during improvisation in the training group compared to controls. Learning to improvise may contribute to cognitive performance.

Impaired performance of rapid grip in people with Parkinson's disease and motor segmentation

Bradykinesia, or slow movement, is a defining symptom of Parkinson's disease (PD), but the underlying neuromechanical deficits that lead to this slowness remain unclear. People with PD often have impaired rates of motor output accompanied by disruptions in neuromuscular excitation, causing abnormal, segmented, force-time curves. Previous investigations using single-joint models indicate that agonist electromyogram (EMG) silent periods cause motor segmentation. It is unknown whether motor segmentation is evident in more anatomically complex and ecologically important tasks, such as handgrip tasks. Aim 1 was to determine how handgrip rates of force change compare between people with PD and healthy young and older adults. Aim 2 was to determine whether motor segmentation is present in handgrip force and EMG measures in people with PD. Subjects performed rapid isometric handgrip pulses to 20–60% of their maximal voluntary contraction force while EMG was collected from the grip flexors and extensors. Dependent variables included the time to 90% peak force, the peak rate of force development, the duration above 90% of peak force, the number of segments in the force-time curve, the number of EMG bursts, time to relaxation from 90% of peak force, and the peak rate of force relaxation. People with PD had longer durations and lower rates of force change than young and older adults. Six of 22 people with PD had motor segmentation. People with PD had more EMG bursts compared to healthy adults and the number of EMG bursts covaried with the number of segments. Thus, control of rapid movement in Parkinson's disease can be studied using isometric handgrip. People with PD have impaired rate control compared to healthy adults and motor segmentation can be studied in handgrip.

Within- and between-person associations of time-varying determinants with snacking in older adults: an EMA study.

Promoting healthy snacking is important in addressing malnutrition, overweight and obesity among an ageing population. However, little is known about the factors underlying snacking behaviour in older adults. The present study aimed to explore within- and between-person associations between determinants (i.e. intention, visibility of snacks, social modelling and emotions) and snacking behaviours (i.e. decision to snack, health factor of the snack and portion size) in older adults (60+). Conducting a two-part intensive longitudinal design, data was analysed from 48 healthy older adults consisting of (1) an event-based self-report ecological momentary assessment (EMA) diary every time they had a snack and (2) a time-based EMA questionnaire on their phone 5 times per day. Analysis through generalised linear mixed models indicated that higher intention to snack healthily leads to healthier snacking while higher levels of social modelling and cheerfulness promote unhealthier choices within individuals. At the between-person level, similar results were found for intention and social modelling. Visibility of a snack increased portion size at both a within- and between-person level, while the intention to eat a healthy snack only increased portion size at the between-person level. No associations were found between the decision to snack and all determinants. This is the first study to investigate both within- and between-person associations between time-varying determinants and snacking in older adults. Such information holds the potential for incorporation into just-in-time adaptive interventions, allowing for personalised tailoring, more effective promotion of healthier snacking behaviours and thus, pursuing the challenge of healthy ageing.

Exercise-induced cortical disinhibition mediates the relationship between fitness and memory in older adults.

Regular exercise benefits learning and memory in older adults, but the neural mechanisms mediating these effects remain unclear. Evidence in young adults indicates that acute exercise creates a favourable environment for synaptic plasticity by enhancing cortical disinhibition. As such, we investigated whether plasticity-related disinhibition mediated the relationship between cardiorespiratory fitness and memory function in healthy older adults (n=16, mean age=66.06). Participants completed a graded maximal exercise test and assessments of visual and verbal memory, followed by two counterbalanced sessions involving 20min of either high-intensity interval training exercise or rest. Disinhibition was measured following intermittent theta burst stimulation via paired-pulse transcranial magnetic stimulation. In line with our hypotheses, we observed a positive correlation between cardiorespiratory fitness and verbal memory, which was mediated by plasticity-related cortical disinhibition. Our novel finding implicates cortical disinhibition as a mechanism through which the effects of acute bouts of exercise may translate to improved memory in older adults. This finding extends current understanding of the physiological mechanisms underlying the positive influence of cardiorespiratory fitness for memory function in older adults, and further highlights the importance of promoting exercise engagement to maintain cognitive health in later life. KEY POINTS: There are well established benefits of regular exercise for memory function in older adults, but the mechanisms are unclear. Cortical disinhibition is important for laying down new memories, and is enhanced following acute exercise in young adults, suggesting it is a potential mechanism underlying these benefits in ageing. Older adults completed a fitness test and assessments of memory, followed by two sessions involving either 20min of exercise or rest. Disinhibition was measured following intermittent theta burst stimulation via paired-pulse transcranial magnetic stimulation. Cardiorespiratory fitness was positively associated with memory performance. Higher fitness was associated with enhanced cortical disinhibition following acute exercise. Cortical disinhibition completely mediated the relationship between fitness and memory. This novel finding provides a mechanistic account for the positive influence of cardiorespiratory fitness on memory in later life, and emphasises the importance of regular exercise for cognitive health in older populations.

Multi-night acoustic stimulation is associated with better sleep, amyloid dynamics, and memory in older adults with cognitive impairment.

Sleep is a potential early, modifiable risk factor for cognitive decline and dementia. Impaired slow wave sleep (SWS) is pronounced in individuals with cognitive impairment (CI). Cognitive decline and impairments of SWS are bi-directionally linked in a vicious cycle. SWS can be enhanced non-invasively using phase-locked acoustic stimulation (PLAS), potentially breaking this vicious cycle. Eighteen healthy older adults (HC, agemean±sd, 68.3 ± 5.1) and 16 older adults (agemean±sd, 71.9 ± 3.9) with CI (Montreal Cognitive Assessment ≤ 25) underwent one baseline (sham-PLAS) night and three consecutive stimulation nights (real-PLAS). EEG responses and blood-plasma amyloid beta Aβ42/Aβ40 ratio were measured pre- and post-intervention, as was episodic memory. The latter was again evaluated 1week and 3months after the intervention. In both groups, PLAS induced a significant electrophysiological response in both voltage- and time-frequency analyses, and memory performance improved in association with the magnitude of this response. In the CI group, both electrophysiological and associated memory effects were delayed compared to the healthy group. After 3 intervention nights, electrophysiological response to PLAS was no longer different between CI and HC groups. Only in the CI sample, stronger electrophysiological responses were significantly associated with improving post-intervention Aβ42/Aβ40 ratios. PLAS seems to improve SWS electrophysiology, memory, and amyloid dynamics in older adults with CI. However, effects on memory require more time to unfold compared to healthy older adults. This indicates that PLAS may become a potential tool to ameliorate cognitive decline, but longer interventions are necessary to compensate for declining brain integrity. This study was pre-registered (clinicaltrials.gov: NCT04277104).

The Association of Circulating Glucagon-Like Peptide-1 with Cognitive Functions and Biomarkers in Alzheimer's Disease.

Alzheimer's disease (AD) is an age-related neurodegenerative disease that is clinically characterized by progressive cognitive decline. Glucagon-like peptide-1 (GLP-1) is a hormone that belongs to the incretin family and is released in response to nutrient intake. It plays a role in maintaining metabolic homeostasis and has been suggested to be involved in maintaining the brain microenvironment. However, the role of GLP-1 in AD pathogenesis has not been fully illustrated. This study aims to investigate the clinical relevance of GLP-1 in AD and the effects of GLP-1 in amyloid-β (Aβ) metabolism in vitro. In this study, 39 AD patients and 120 cognitively intact controls were included. Plasma levels of GLP-1 were measured using ELISA. SH-SY5Y cells overexpressing human amyloid precursor protein (APP) were treated with GLP-1. Western blot analysis was used to assess the effects of GLP-1 on the metabolism of Aβ. Plasma GLP-1 levels were decreased with aging. Plasma GLP-1 levels were lower in AD patients in comparison with healthy older adults. Plasma GLP-1 levels were positively associated with Mini-Mental State Examination scores but negatively associated with plasma pTau181 levels. GLP-1 dose-dependently increased the area fraction of mitochondrial staining in vitro. Furthermore, GLP-1 dose-dependently promoted the α-cleavage of APP, thus reducing the generation of Aβ. GLP-1 has neuroprotective effects in AD, and therefore the decrease in GLP-1 levels during aging might contribute to the development of AD.

Association between executive functions and COMT Val108/158Met polymorphism among healthy younger and older adults: A preliminary study.

Genetic variability in the dopaminergic system could contribute to age-related impairments in executive control. In this study, we examined whether genetic polymorphism for catechol-O-methyltransferase (COMT Val158Met) is related to performance on updating, shifting and inhibition tasks. We administered a battery of executive tasks assessing updating, shifting and inhibition functions to 45 older and 55 younger healthy participants, and created composite z-scores associated to each function. Six groups were created based on genetic alleles (Val/Val, Val/Met, Met/Met) derived from the COMT gene and age (younger, older). Age and genotype effects were assessed with t-test and ANOVA (p<0.05). A lower performance was observed in the older group for the three executive processes, and more particularly for inhibition. Moreover, older participants homozygous for the Val allele have a lower performance on the inhibition composite in comparison to younger Val/Val. These results confirm presence of executive performance decrease in healthy aging. With regard to genetic effect, older participants seem particularly disadvantaged when they have a lower baseline dopamine level (i.e., Val/Val homozygous) that is magnified by aging, and when the executive measure emphasize the need of stable representations (as in inhibition task requiring to maintain active the instruction to not perform an automated process).

Computerized assessment of executive functioning: Validation of the CNS Vital Signs executive functioning scores in a sample of community-dwelling older adults

Objective: Computerized assessment of cognitive functioning has gained significant popularity over recent years, yet options for clinical assessment of executive functioning (EF) are lacking. One computerized testing platform, CNS Vital Signs (CNS-VS), offers tests designed to measure EF but requires further validation. The goal of the present study was to validate CNS-VS executive scores against standard clinical measures of EF. We also sought to determine whether a modified CNS-VS composite score that included variables purported to measure inhibition, switching, and working memory would outperform the currently available CNS-VS Executive Function Index. Method: A sample of 73 cognitively healthy older adults completed four tests from the Delis-Kaplan Executive Function System, the Digit Span subtest from the Wechsler Adult Intelligence Scale-fourth edition, and three CNS-VS tasks purported to measure inhibition, switching, and working memory. Results: Performances on the CNS-VS tests were predicted by performances on standard paper-and-pencil measures. Although the currently available CNS-VS Executive Function Index predicted unique variance in a well-validated paper-and-pencil EF composite score, our Modified CNS-VS EF composite accounted for unique variance above and beyond the original CNS-VS Executive Function Index, while the reverse was not true. Conclusions: The present results support the construct validity of CNS-VS EF tests but also suggest that modifications to their current composite scores would improve the prediction of EF performance.

The association between adherence to the EAT-Lancet diet and cognitive ageing.

The EAT-Lancet commission has proposed a dietary pattern that is both sustainable and healthy. However, the impact of this diet on cognition in older adults remains unexplored. Therefore, we examined the association between adherence to the EAT-Lancet diet and cognitive ageing. We used data from a previous intervention study involving cognitively healthy community-dwelling adults aged ≥65years. Adherence to the EAT-Lancet diet was calculated using a recently published index and a 190-item food frequency questionnaire. Global and domain-specific cognitive functioning were assessed at baseline and after 2 years using a neuropsychological test battery. Multivariate-adjusted linear regression was conducted to examine associations between EAT-Lancet diet adherence and cognitive functioning (n = 630) and 2-year change (n = 302). Greater adherence to the EAT-Lancet diet was associated with better global cognitive functioning (β per SD = 3.7 points [95% CI]: 0.04 [0.00, 0.08]) and slower rate of decline (β per SD [95% CI]: 0.05 [0.02, 0.08]). With respect to domain-specific functioning, beneficial associations were observed cross-sectionally for executive functioning (P < 0.01), and longitudinally for change in executive functioning (P < 0.01) and attention and working memory (P < 0.01). The degree of adherence to the EAT-Lancet was not associated with (changes in) information processing speed or episodic memory. We demonstrated that greater adherence to the EAT-Lancet diet is associated with better global cognitive functioning and slower cognitive decline among cognitively healthy older adults. Further research is needed to confirm these findings and assess the potential benefits of the EAT-Lancet diet for the ageing population in a broader context.

Stride width and postural stability in frontal gait disorders and Parkinson's disease.

Older adults, as well as those with certain neurological disorders, may compensate for poor neural control of postural stability by widening their base of foot support while walking. However, the extent to which this wide-based gait improves postural stability or affects postural control strategies has not been explored. People with idiopathic Parkinson's disease (iPD, n = 72), frontal gait disorders (FGD, n = 16), and healthy older adults (n = 32) performed walking trials at their preferred speed over an 8-m-long, instrumented walkway. People with iPD were tested in their OFF medication state. Analyses of covariance were performed to determine the associations between stride width and measures of lateral stability control. People with FGD exhibited a wide-based gait compared to both healthy older adults and iPD. An increased stride width was associated with an increase in lateral margin of stability in FGD. Unlike healthy older adults or iPD, people with FGD did not externally rotate their feet (toe-out angle) or shift their center of pressure laterally to aid lateral dynamic stability during walking but slowed their gait instead to increase stability. By adopting a slow, wide-based gait, people with FGD take advantage of the passive, pendular mechanics of walking.

Effects of inspiratory muscle training on thoracoabdominal volume regulation in older adults: A randomised controlled trial

ObjectivesWe investigated the effect of inspiratory muscle training (IMT) on inspiratory muscle strength, functional capacity and respiratory muscle kinematics during exercise in healthy older adults. Methods24 adults were randomised into an IMT or SHAM-IMT group. Both groups performed 30 breaths, twice daily, for 8 weeks, at intensities of ∼50 % maximal inspiratory pressure (PImax; IMT) or <15 % PImax (SHAM-IMT). Measurements of PImax, breathing discomfort during a bout of IMT, six-minute walk distance, physical activity levels, and balance were assessed pre- and post-intervention. Respiratory muscle kinematics were assessed via optoelectronic plethysmography (OEP) during constant work rate cycling. ResultsPImax was significantly improved (by 20.0±11.9 cmH2O; p=0.001) in the IMT group only. Breathing discomfort ratings during IMT significantly decreased (from 3.5±0.9–1.7±0.8). Daily sedentary time was decreased (by 28.0±39.8 min; p=0.042), and reactive balance significantly improved (by 1.2±0.8; p<0.001) in the IMT group only. OEP measures showed a significantly greater contribution of the pulmonary and abdominal rib cage compartments to total tidal volume expansion post-IMT. ConclusionsIMT significantly improves inspiratory muscle strength and breathing discomfort in this population. IMT induces greater rib cage expansion and diaphragm descent during exercise, thereby suggesting a less restrictive effect on thoracic expansion and increased diaphragmatic power generation.

Educational Attainment Moderates Task-state Control Network Connectivity Relations to Response Conflict Among Healthy Older Adults.

Older adult executive function varies widely due to brain and cognitive aging. Variance in older adult executive function is linked to increased response conflict from cognitive and brain aging. Cognitive Reserve (CR) is a theoretical protective mechanism that lessens brain aging's impact on cognition and is associated with greater educational attainment. Recent work in rest-state fMRI suggests CR proxies moderate the relationship between functional connectivity (FC) and cognitive performance. Brain network FC in "control networks", including the salience (SN), dorsal attention (DAN) and frontoparietal (FPN) networks, are associated with cognitive processes in older adults. CR is hypothesized to maintain cognitive processing in part through changes in how brain networks respond to cognitive demands. However, it is unclear how CR proxies like educational attainment are related to control network FC during performance when cognitive demands are increased relative to rest. Because CR is expressed more in those with higher education, we hypothesized stronger control network FC would relate to better performance, where this relationship would be strongest among the most educated. We collected flanker task data during fMRI to assess the impact of a CR-proxy (i.e., educational attainment) on response conflict among older adult subjects (n=42, age=65-80). Linear mixed effects models showed more educated older adults with greater SN-FC had a smaller flanker effect (i.e., less influence of distractors; p<.001) during task performance. For the first time, we show that educational attainment moderates the relationship between task-state SN-FC and executive function among older adults.

Association between physical fitness and executive functions in cognitively healthy female older adults: a cross-sectional study

Association between physical fitness and executive functions in cognitively healthy female older adults: a cross-sectional study

Virtual reality-based training may improve visual memory and some aspects of sustained attention among healthy older adults – preliminary results of a randomized controlled study

Background/AimsOlder age and cognitive inactivity have been associated with cognitive impairment, which in turn is linked to economic and societal burdens due to the high costs of care, especially for care homes and informal care. Emerging non-pharmacological interventions using new technologies, such as virtual reality (VR) delivered on a head-mounted display (HMD), might offer an alternative to maintain or improve cognition. The study aimed to evaluate the efficacy and safety of a VR-based Digital Therapeutics application for improving cognitive functions among healthy older adults.MethodsSeventy-two healthy seniors (experimental group N = 35, control group N = 37), aged 65–85 years, were recruited by the Medical University of Lodz (Poland). Participants were randomly allocated to the experimental group (a VR-based cognitive training which consists of a warm-up module and three tasks, including one-back and dual-N-back) or to the control group (a regular VR headset app only showing nature videos). The exercises are performed in different 360-degree natural environments while listening to a preferred music genre and delivered on a head-mounted display (HMD). The 12-week intervention of 12 min was delivered at least three times per week (36 sessions). Compliance and performance were followed through a web-based application. Primary outcomes included attention and working memory (CNS-Vital Signs computerized cognitive battery). Secondary outcomes comprised other cognitive domains. Mixed linear models were constructed to elucidate the difference in pre- and post-intervention measures between the experimental and control groups.ResultsThe users performed, on average, 39.8 sessions (range 1–100), and 60% performed more than 36 sessions. The experimental group achieved higher scores in the visual memory module (B = 7.767, p = 0.011) and in the one-back continuous performance test (in terms of correct responses: B = 2.057, p = 0.003 and omission errors: B = -1.950, p = 0.007) than the control group in the post-test assessment. The results were independent of participants’ sex, age, and years of education. The differences in CNS Vital Signs’ global score, working memory, executive function, reaction time, processing speed, simple and complex attention, verbal memory, cognitive flexibility, motor speed, and psychomotor speed were not statistically significant.ConclusionsVR-based cognitive training may prove to be a valuable, efficacious, and well-received tool in terms of improving visual memory and some aspect of sustainability of attention among healthy older adults. This is a preliminary analysis based on part of the obtained results to that point. Final conclusions will be drawn after the analysis of the target sample size.Trial registrationClinicaltrials.gov ID NCT05369897.

Development of a 12-Word Version of a Verbal Learning Test for Persian-Speaking Older Adults: Reliability, Construct Validity, and Normative Standards.

As people enter old age, they develop diseases, challenges, and cognitive and behavioral deficits that are associated with decreased abilities. Memory abilities and deficiencies and impaired models can be assessed using neuropsychological instruments, and a rehabilitation program can be developed based on the individuals' memory deficits. The present cross-sectional research aims to develop a new test (henceforth known as the Persian Verbal Learning Test, or PVLT) that is appropriate for Persian-speaking older adults. For normative data, we administered PVLT to a group of 374 Persian-speaking healthy older adults consisting of both genders (190 women and 184 men) who were aged 60-89years old. To determine reliability and validity, we evaluated neurologically healthy older adults and analyzed the results using intraclass correlation coefficient (ICC) and Pearson's correlation coefficient. The present findings showed that age, education, and gender significantly affect subtests of the PVLT. In the evaluation of reliability, significant positive correlations were observed between the variables of the PVLT in the standard/standard form. Furthermore, moderate correlations were observed between PVLT variables (immediate recall, short-delay recall, long-delay recall, and recognition), and the Immediate and Delayed Logical Memory subtests of Wechsler Memory Scale-Revised (WMS-R). However, subtests of the PVLT also showed significantly positive correlations with MoCA and non-verbal variables of WMS-R. According to the results of this study and given the good psychometric properties obtained, PVLT can potentially be used as a more appropriate tool than the SVLT for Persian-speaking older adults.

Normative Values of Echocardiographic Chamber Size and Function in Older Healthy Adults: The Multi-Ethnic Study of Atherosclerosis.

Echocardiographic (2-dimensional echocardiography) thresholds indicating disease or impaired functional status compared with normal physiological aging in individuals aged ≥65 years are not clearly defined. In the present study, we sought to establish standard values for 2-dimensional echocardiography parameters related to chamber size and function in older adults without cardiopulmonary or cardiometabolic conditions. In this cross-sectional study of 3032 individuals who underwent 2-dimensional echocardiography at exam 6 in the MESA (Multi-Ethnic Study of Atherosclerosis), 608 participants fulfilled our inclusion criteria of healthy aging, with normative values defined as the mean ± 1.96 standard deviation and compared across sex and race and ethnicity. Functional status measures included NT-proBNP (N-terminal pro-B-type natriuretic peptide), 6-minute walk distance, and Kansas City Cardiomyopathy Questionnaire. Prognostic performance using MESA cutoffs was compared with established guideline cutoffs using time-to-event analysis. The normative aging cohort (69.5±7.0 years, 46.2% male, 47.5% White) had lower NT-proBNP, higher 6-minute walk distance, and higher (better) Kansas City Cardiomyopathy Questionnaire summary values. Women had significantly smaller chamber sizes and better biventricular systolic function. White participants had the largest chamber dimensions, whereas Chinese participants had the smallest, even after adjustment for body size. Current guidelines identified 81.6% of healthy older adults in MESA as having cardiac abnormalities. Among a large, diverse group of healthy older adults, we found significant differences in cardiac structure and function by sex and race/ethnicity, which may signal sex-specific cardiac remodeling with advancing age. It is crucial for existing guidelines to consider the observed and clinically significant differences in cardiac structure and function associated with healthy aging. Our study highlights that existing guidelines, which grade abnormalities in echocardiographic cardiac chamber size and function based on younger individuals, may not adequately address the anticipated changes associated with normal aging.

Thalamic nuclei segmentation from T1-weighted MRI: Unifying and benchmarking state-of-the-art methods

Abstract The thalamus and its constituent nuclei are critical for a broad range of cognitive, linguistic, and sensorimotor processes, and are implicated in many neurological and neurodegenerative conditions. However, the functional involvement and specificity of thalamic nuclei in human neuroimaging work is underappreciated and not well studied due, in part, to technical challenges of accurately identifying and segmenting nuclei. This challenge is further exacerbated by a lack of common nomenclature for comparing segmentation methods. Here, we use data from healthy young (Human Connectome Project, n = 100) and older healthy adults, plus those with mild cognitive impairment and Alzheimer’s disease (Alzheimer’s Disease Neuroimaging Initiative, n = 540), to benchmark four state-of-the-art thalamic segmentation methods for T1 MRI (FreeSurfer, histogram-based polynomial synthesis [HIPS]-THOMAS, synthesized contrast segmentation [SCS]-convolutional neural network [CNN], and T1-THOMAS) under a single segmentation framework. Segmentations were compared using overlap and dissimilarity metrics to the Morel stereotaxic atlas, a widely accepted thalamic atlas. We also quantified each method’s estimation of thalamic nuclear degeneration across Alzheimer’s disease progression, and how accurately early and late mild cognitive impairment, and Alzheimer’s disease could be distinguished from healthy controls. We show that the HIPS-THOMAS approach produced the most effective segmentations of individual thalamic nuclei relative to the Morel atlas, and was also most accurate in discriminating healthy controls from those with mild cognitive impairment and Alzheimer’s disease using individual nucleus volumes. This latter result was different when using whole thalamus volumes, where the SCS-CNN approach was the most accurate in classifying healthy controls. This work is the first to systematically compare the efficacy of anatomical thalamic segmentation approaches under a unified nomenclature. We also provide recommendations of which segmentation method to use for studying the functional relevance of specific thalamic nuclei, based on their overlap and dissimilarity with the Morel atlas.

Glucose Targets Using Continuous Glucose Monitoring Metrics in Older Adults With Diabetes: Are We There Yet?

The older population is increasing worldwide and up to 30% of older adults have diabetes. Older adults with diabetes are at risk of glucose-related acute and chronic complications. Recently, mostly in type 1 diabetes (T1D), continuous glucose monitoring (CGM) devices have proven beneficial in improving time in range (TIR glucose, 70-180 mg/dL or glucose 3.9-10 mmol/L), glycated hemoglobin (HbA1c), and in lowering hypoglycemia (time below range [TBR] glucose <70 mg/dL or glucose <3.9 mmol/L). The international consensus group formulated CGM glycemic targets relating to older adults with diabetes based on very limited data. Their recommendations, based on expert opinion, were aimed at mitigating hypoglycemia in all older adults. However, older adults with diabetes are a heterogeneous group, ranging from healthy to very complex frail individuals based on chronological, biological, and functional aging. Recent clinical trial and real-world data, mostly from healthy older adults with T1D, demonstrated that older adults often achieve CGM targets, including TIR recommended for non-vulnerable groups, but less often meet the recommended TBR <1%. Existing data also support that hypoglycemia avoidance may be more strongly related to minimization of glucose variability (coefficient of variation [CV]) rather than lower TIR. Very limited data are available for glucose goals in older adults adjusted for the complexity of their health status. Herein, we review the bidirectional associations between glucose and health status in older adults with diabetes; use of diabetes technologies, and their impact on glucose control; discuss current guidelines; and propose a new set of CGM targets for older adults with insulin-treated diabetes that are individualized for health and living status.

Investigating the effects of synbiotic supplementation on functional movement, strength and muscle health in older Australians: a study protocol for a double-blind, randomized, placebo-controlled trial

BackgroundAging has been associated with a progressive loss of skeletal muscle quality, quantity and strength, which may result in a condition known as sarcopenia, leading to a decline in physical performance, loss of independence and reduced quality of life. While the cause of impaired physical functioning observed in elderly populations appears to be multifactorial, recent evidence suggests that age-associated alterations in gut microbiota could be a contributing factor. The primary objective will be to assess the effects of a dietary synbiotic formulation on sarcopenia-related functional outcomes such as handgrip strength, gait speed and physical performance within older individuals living independently. The secondary objective will be to examine associations between changes in gut microbiota composition, functional performance and lean muscle mass.MethodsSeventy-four elderly (60–85 years) participants will be randomized in a double-blind, placebo-controlled fashion to either an intervention or control group. The intervention group (n = 37) will receive oral synbiotic formulation daily for 16 weeks. The control group (n = 37) will receive placebo. Assessments of physical performance (including Short Physical Performance Battery, handgrip strength and timed up-and-go tests) and muscle ultrasonography will be performed at 4 time points (baseline and weeks 8, 16 and 20). Likewise, body composition via bioelectric impedance analysis and blood and stool samples will be collected at each time point. Dual-energy X-ray absorptiometry will be performed at baseline and week 16. The primary outcomes will be between-group changes in physical performance from baseline to 16 weeks. Secondary outcomes include changes in body composition, muscle mass and architecture, fecal microbiota composition and diversity, and fecal and plasma metabolomics.DiscussionGut-modulating supplements appear to be effective in modifying gut microbiota composition in healthy older adults. However, it is unclear whether these changes translate into functional and/or health improvements. In the present study, we will investigate the effects of a synbiotic formulation on measures of physical performance, strength and muscle health in healthy older populations.Trial registrationThis study was prospectively registered with the Australian New Zealand Clinical Trials Registry (ACTRN12622000652774) in May 2022.