Detecting cognitive decline in high-functioning older adults: The relationship between subjective cognitive concerns, frequency of high neuropsychological test scores, and the frontoparietal control network.

OBJECTIVE: Neuropsychologists have difficulty detecting cognitive decline in high-functioning older adults because greater neurological change must occur before cognitive performances are low enough to indicate decline or impairment. For high-functioning older adults, early neurological changes may correspond with subjective cognitive concerns and an absence of high scores. This study compared high-functioning older adults with and without subjective cognitive concerns, hypothesizing those with cognitive concerns would have fewer high scores on neuropsychological testing and lower frontoparietal network volume, thickness, and connectivity. METHOD: Participants had high estimated premorbid functioning (e.g., estimated intelligence ≥75th percentile or college-educated) and were divided based on subjective cognitive concerns. Participants with cognitive concerns (n = 35; 74.0 ± 9.6 years old, 62.9% female, 94.3% White) and without cognitive concerns (n = 33; 71.2 ± 7.1 years old, 75.8% female, 100% White) completed a neuropsychological battery of memory and executive function tests and underwent structural and resting-state magnetic resonance imaging, calculating frontoparietal network volume, thickness, and connectivity. RESULTS: Participants with and without cognitive concerns had comparable numbers of low test scores (≤16th percentile), p = .103, d = .40. Participants with cognitive concerns had fewer high scores (≥75th percentile), p = .004, d = .71, and lower mean frontoparietal network volumes (left: p = .004, d = .74; right: p = .011, d = .66) and cortical thickness (left: p = .010, d = .66; right: p = .033, d = .54), but did not differ in network connectivity. CONCLUSIONS: Among high-functioning older adults, subjective cognitive decline may correspond with an absence of high scores on neuropsychological testing and underlying changes in the frontoparietal network that would not be detected by a traditional focus on low cognitive test scores.

Implementation and evaluation of a community-based mindful walking randomized controlled trial to sustain cognitive health in older African Americans at risk for dementia.

BACKGROUND: With an increasing proportion of older adults and the associated risk of Alzheimer's Disease and Related Dementias (ADRD) around the globe, there is an urgent need to engage in ADRD risk reduction efforts. African American (AA) older adults in the U.S. are disproportionally impacted by ADRD compared to other races and ethnicities. Mindful walking integrates two potentially protective factors of ADRD by elevating mindfulness and physical activity (i.e., walking), resulting in a synergistic behavioral strategy that is feasible and safe for older adults. However, the efficacy of applying this intervention for cognitive health outcomes has not been evaluated using experimental designs. METHODS: This paper documents the goal and protocol of a community-based, mindful walking randomized controlled trial to examine the short- and longer-term efficacy on cognitive and other health-related outcomes in ADRD at-risk AA older adults. The study outcomes include various brain health determinants, including cognitive function, quality of life, psychological well-being, physical activity, mindfulness, sleep, and overall health status. In addition, the estimated costs of program implementation are also collected throughout the study period. This study will recruit 114 older adults (ages 60+ years) with elevated ADRD risk from the Midlands region of South Carolina. Older adults are randomly assigned to participate in 24 sessions of outdoor mindful walking over three months or a delayed mindful walking group (n=57 in each group). Participants in both groups follow identical measurement protocols at baseline, after 12 weeks, after 18 weeks, and after 24 weeks from baseline. The outcome measures are administered in the lab and in everyday settings. Costs per participant are calculated using micro-costing methods. The eliciting participant costs for mindful walking engagement with expected results are reported using the payer and the societal perspectives. DISCUSSION: This study will generate evidence regarding the efficacy of mindful walking on sustaining cognitive health in vulnerable older adults. The results can inform future large-scale effectiveness trials to support our study findings. If successful, this mindful walking program can be scaled up as a low-cost and viable lifestyle strategy to promote healthy cognitive aging in diverse older adult populations, including those at greatest risk. TRIAL REGISTRATION: ClinicalTrials.gov number NCT06085196 (retrospectively registered on 10/08/2023).

Documenting Compliance and Symptom Reactivity for Ambulatory Assessment Methodology Following Concussion in Adolescents and Young Adults: Feasibility of the Mobile Neurocognitive Health (MNCH) Project.

OBJECTIVE: Evaluate compliance, symptom reactivity, and acceptability/experience ratings for an ecological momentary assessment (EMA) protocol involving ultra-brief ambulatory cognitive assessments in adolescent and young adult patients with concussion. SETTING: Outpatient concussion clinic. PARTICIPANTS: 116 patients aged 13 to 25 years with concussion. DESIGN: Prospective research design was used to examine compliance, symptom reactivity, and acceptability/experience for the Mobile Neurocognitive Health Project (MNCH); an EMA study of environmental exposures, symptoms, objective cognitive functioning, and symptom reactivity involving 4, daily EMA surveys (7:30 am, 10:30 am, 3:00 pm, 8:00 pm) for a period of 7 days following concussion. Overall compliance rates, symptom reactivity scores, and participant acceptability/experience ratings were described. A series of non-parametric Friedman Tests with post-hoc Wilcoxon signed-rank tests were used to examine differences in compliance and reactivity related to time of day and over the course of the protocol (first 3 days [Early Week] vs last 4 days [Late Week]). MAIN MEASURES: Compliance rates, symptom reactivity scores, participant experience/acceptability. RESULTS: Overall median compliance was 71%, and there were significantly fewer 7:30 am surveys completed compared to the 10:30 am (Z = -4.88,P ≤ .001), 3:00 pm (Z = -4.13,P ≤ .001), and 8:00 pm (Z = -4.68, P ≤ .001) surveys. Compliance for Early Week surveys were significantly higher than Late Week (Z = -2.16,P = .009). The median symptom reactivity score was 34.39 out of 100 and was significantly higher for Early Week compared to Late Week (Z = -4.59,P ≤ .001). Ninety-nine percent (89/90) of the sample agreed that the app was easy to use, and 18% (16/90) indicated that the app interfered with their daily life. CONCLUSION: Adolescents and young adults with concussion were compliant with the MNCH EMA protocol. Symptom reactivity to the protocol was low and the majority of participants reported that the app and protocol were acceptable. These findings support further investigation into applications of EMA for use in concussion studies.

Sometimes you just can't: within-person variation in working memory capacity moderates negative affect reactivity to stressor exposure.

The executive hypothesis of self-regulation places cognitive information processing at the center of self-regulatory success/failure. While the hypothesis is well supported by cross-sectional studies, no study has tested its primary prediction, that temporary lapses in executive control underlie moments of self-regulatory failure. Here, we conducted a naturalistic experiment investigating whether short-term variation in executive control is associated with momentary self-regulatory outcomes, indicated by negative affect reactivity to everyday stressors. We assessed working memory capacity (WMC) through ultra-brief, ambulatory assessments on smart phones five times per day in a 7-day ecological momentary assessment (EMA) study involving college-aged adults. We found that participants exhibited more negative affect reactivity to stressor exposures during moments when they exhibited lower than usual WMC. Contrary to previous findings, we found no between-person association between WMC and average stress reactivity. We interpret these findings as reflecting the role of executive control in determining one's effective capacity to self-regulate.

Cognitive Control Moderates the Health Benefits of Trait Self-Regulation in Young Adults.

Separate lines of epidemiological research suggest that individuals with high trait self-regulation (e.g. conscientious individuals) and individuals with higher cognitive ability (e.g. executive control/intelligence) each tend to enjoy superior health and well-being outcomes. However, it remains largely unexplored whether these personological and cognitive contributions to physical health are shared, independent, or interdependent. In the current study, we examined associations between trait self-regulation, cognitive control, self-reported physical health, and subjective well-being. A domain-general model revealed little shared variance between trait self-regulation and cognitive control but revealed significant unique relationships between each predictor and physical health. Results of a latent moderation analysis suggested that cognitive control moderated the contribution of self-regulation to health but not subjective well-being. This moderation effect was characterized by a strengthened relationship between trait self-regulation and health with decreases in cognitive control. Together, our results suggest that self-regulation and cognitive control may independently contribute to health outcomes in young adults and that self-regulation may be increasingly important for individuals lower in cognitive control.

Neural Mechanisms for the Benefits of Stimulus-Driven Attention.

Stimulus-driven attention can improve working memory (WM) when drawn to behaviorally relevant information, but the neural mechanisms underlying this effect are unclear. The present study used functional magnetic resonance imaging (fMRI) to test competing hypotheses regarding the nature of the benefits of stimulus-driven attention to WM: that stimulus-driven attention benefits WM directly via salience detection, that stimulus-driven attention benefits WM incidentally via cognitive control mechanisms recruited to reduce interference from salient features, or that both mechanisms are co-involved in enhancing WM for salient information. To test these hypotheses, we observed activation in brain regions associated with cognitive control and salience detection. We found 2 cognitive control regions that were associated with enhanced memory for salient stimuli: a region in the right superior parietal lobule and a region in the right inferior frontal junction. No regions associated with salience detection were found to show this effect. These fMRI results support the hypothesis that benefits to WM from stimulus-driven attention occur primarily as a result of cognitive control and top-down factors rather than pure bottom-up aspects of stimulus-driven attention.

Dynamic range of frontoparietal functional modulation is associated with working memory capacity limitations in older adults.

Older adults tend to over-activate regions throughout frontoparietal cortices and exhibit a reduced range of functional modulation during WM task performance compared to younger adults. While recent evidence suggests that reduced functional modulation is associated with poorer task performance, it remains unclear whether reduced range of modulation is indicative of general WM capacity-limitations. In the current study, we examined whether the range of functional modulation observed over multiple levels of WM task difficulty (N-Back) predicts in-scanner task performance and out-of-scanner psychometric estimates of WM capacity. Within our sample (60-77years of age), age was negatively associated with frontoparietal modulation range. Individuals with greater modulation range exhibited more accurate N-Back performance. In addition, despite a lack of significant relationships between N-Back and complex span task performance, range of frontoparietal modulation during the N-Back significantly predicted domain-general estimates of WM capacity. Consistent with previous cross-sectional findings, older individuals with less modulation range exhibited greater activation at the lowest level of task difficulty but less activation at the highest levels of task difficulty. Our results are largely consistent with existing theories of neurocognitive aging (e.g. CRUNCH) but focus attention on dynamic range of functional modulation asa novel marker of WM capacity-limitations in older adults.

Ventral fronto-parietal contributions to the disruption of visual working memory storage.

The ability to maintain information in visual working memory (VWM) in the presence of ongoing visual input allows for flexible goal-directed behavior. Previous evidence suggests that categorical overlap between visual distractors and the contents of VWM is associated with both the degree to which distractors disrupt VWM performance and activation among fronto-parietal regions of cortex. While within-category distractors have been shown to elicit a greater response in ventral fronto-parietal regions, to date, no study has linked distractor-evoked response of these regions to VWM performance costs. Here we examined the contributions of ventral fronto-parietal cortex to the disruption of VWM storage by manipulating memoranda-distractor similarity. Our results revealed that the degree of activation across cortex was graded in a manner suggesting that similarity between the contents of VWM and visual distractors influenced distractor processing. While abrupt visual onsets failed to engage ventral fronto-parietal regions during VWM maintenance, objects sharing categorical- (Related objects) and feature-overlap (Matched objects) with VWM elicited a significant response in the right TPJ and right AI. Of central relevance, the magnitude of activation in the right AI elicited by both types of distractor objects subsequently predicted costs to binding change detection accuracy. In addition, Related and Matched distractors differentially affected ventral-dorsal connectivity between the right AI and dorsal parietal regions, uniquely contributing to disruption of VWM storage. Together, our current results implicate activation of ventral fronto-parietal cortex in disruption of VWM storage, and disconnection between ventral frontal and dorsal parietal cortices as a mechanism to protect the contents of VWM.

Cardiorespiratory fitness modifies the relationship between myocardial function and cerebral blood flow in older adults.

A growing body of evidence indicates that cardiorespiratory fitness attenuates some age-related cerebral declines. However, little is known about the role that myocardial function plays in this relationship. Brain regions with high resting metabolic rates, such as the default mode network (DMN), may be especially vulnerable to age-related declines in myocardial functions affecting cerebral blood flow (CBF). This study explored the relationship between a measure of myocardial mechanics, global longitudinal strain (GLS), and CBF to the DMN. In addition, we explored how cardiorespiratory affects this relationship. Participants were 30 older adults between the ages of 59 and 69 (mean age=63.73years, SD=2.8). Results indicated that superior cardiorespiratory fitness and myocardial mechanics were positively associated with DMN CBF. Moreover, results of a mediation analysis revealed that the relationship between GLS and DMN CBF was accounted for by individual differences in fitness. Findings suggest that benefits of healthy heart function to brain function are modified by fitness.

Design and methods of the mobile assessment of cognition, environment, and sleep (MACES) feasibility study in newly diagnosed breast cancer patients.

Endocrine therapy (ET) for breast cancer treatment is associated with cognitive complaints, but their etiology is poorly understood. To address this, we developed and implemented an ambulatory assessment protocol consisting of wearable activity monitors, brief surveys of affect, context, and perceived impairments, and ultra-brief performance-based measures of cognition. Newly diagnosed, ER/PR+, stage 0-III, female breast cancer patients, were recruited. Ambulatory assessments were conducted on smart phones and wearable activity monitors were used to monitor sleep and physical activity. Participants were asked to complete five 7-day measurement bursts (one before starting ET and one each month for 4 consecutive months while on ET). We observed a consent rate of 36%, 27 women completed the study. Of the women that withdrew, 91% dropped prior to the midpoint of follow up. There were no significant differences in demographics, clinical breast cancer characteristics, sleep or physical activity patterns, or measures of cognition between women who completed versus withdrew. Women who did not complete the study provided fewer valid days of baseline data. In conclusion, while some women may be overwhelmed with their cancer diagnosis, we did not identify any predictive characteristics of women whom did not complete the study. This novel method enables the prospective study of psychological changes associated with cancer treatment, capturing a wide array of information about behavior, experience, and cognition, thus providing a picture of the lived experiences of cancer patients before and during exposure to ET.

Ultra-brief Assessment of Working Memory Capacity: Ambulatory Assessment Study Using Smartphones.

BACKGROUND: The development of mobile technology with substantial computing power (ie, smartphones) has enabled the adaptation of performance-based cognitive assessments to remote administration and novel intensive longitudinal study designs (eg, measurement burst designs). Although an "ambulatory" cognitive assessment paradigm may provide new research opportunities, the adaptation of conventional measures to a mobile format conducive to intensive repeated measurement involves balancing measurement precision, administration time, and procedural consistency. OBJECTIVE: Across 3 studies, we adapted "complex span" tests of working memory capacity (WMC) for ultra-brief, smartphone-based administration and examined their reliability, sufficiency, and associations with full-length, laboratory-based computerized administrations. METHODS: In a laboratory-based setting, study 1 examined associations between ultra-brief smartphone adaptations of the operation span, symmetry span, and rotation span tasks and full-length computerized versions. In study 2, we conducted a 4-day ecological momentary assessment (EMA) study (4 assessments per day), where we examined the reliability of ultra-brief, ambulatory administrations of each task. In study 3, we conducted a 7-day EMA study (5 assessments per day) involving the ultra-brief rotation span task, where we examined reliability in the absence of extensive onboarding and training. RESULTS: Measurement models in study 1 suggest that comparable estimates of latent WMC can be recovered from ultra-brief complex span task performance on smartphones. Significant correlations between the ultra-brief tasks and respective full-length versions were observed in study 1 and 2, ranging from r=0.4 to r=0.57. Results of study 2 and study 3 suggest that reliable between-person estimates of operation span, symmetry span, rotation span, and latent WMC can be obtained in 2-3 ultra-brief administrations (equivalent to <1 day of testing in an EMA study design). The results of study 3 replicated our findings, showing that reliable between-person estimates of rotation span may be obtained in as few as 2 ultra-brief administrations in the absence of extensive onboarding and training. In addition, the modification of task parameterization for study 3 improved the estimates of reliability of within-person change. CONCLUSIONS: Ultra-brief administration of complex span tasks on smartphones in a measurement burst design can generate highly reliable cross-sectional estimates of WMC. Considerations for future mobile cognitive assessment designs and parameterizations are discussed.

Multicultural Healthy Diet to Reduce Cognitive Decline & Alzheimer's Disease Risk: Study protocol for a pilot randomized controlled trial.

BACKGROUND: Emerging evidence indicates that healthy dietary patterns are associated with higher cognitive status; however, few clinical trials have explored this association in diverse middle-aged adults before the onset of cognitive decline. We use novel ambulatory methods to assess cognition in natural settings in tandem with diet recording. AIMS: We investigate whether the Multicultural Healthy Diet Study to Reduce Cognitive Decline & Alzheimer's Disease Risk, a pilot randomized controlled trial of an anti-inflammatory dietary pattern compared to usual diet, can mitigate cognitive decline and Alzheimer's Disease risk in a diverse population of 40-65 year old adults in Bronx, New York. METHODS: Primary cognitive outcomes assessed at nine months are collected in an ecological momentary assessment "measurement burst" design, over the course of participants' daily lives. These ultra-brief, ambulatory cognitive assessments examine processing speed, visuospatial working memory, short-term associative memory binding, long-term associative memory, and working memory capacity. Key secondary outcomes relate to comparing dietary intake between study arms with respect to cognitive outcomes. We assess diet with food records using the National Cancer Institute's Automated Self-Administered 24-h record and serum biomarkers. We further investigate the association of self-reported diet and dietary biomarkers with inflammatory-based biomarkers. CONCLUSION: This randomized controlled trial of diet and cognition for the first time combines novel measures of ambulatory cognitive assessment with web-based assessment of dietary intake recording. This new approach enabled the study to continue in the midst of the COVID-19 pandemic in remote format.

Frontostriatal and limbic contributions to cognitive decline in Parkinson's disease.

BACKGROUND AND PURPOSE: The circuitry underlying heterogenous cognitive profiles in Parkinson's disease (PD) remains unclear. The purpose of this study is to investigate whether structural changes in frontostriatal and limbic pathways contribute to different cognitive trajectories in PD. METHODS: We obtained clinical and multimodal MRI data from 120 control and 122 PD subjects without dementia or severe motor disability. T1/T2-weighted images estimated volume, and diffusion imaging evaluated fractional anisotropy (FA) of frontostriatal (striatum and frontostriatal white matter [FSWM]) and limbic (hippocampus and fornix) structures. Montreal Cognitive Assessment (MoCA) gauged total and domain-specific (attention/executive and memory) cognitive function. Linear mixed-effects models were used to compare MRI and cognitive progression over 4.5 years between controls and PD and evaluate associations between baseline MRI and cognitive changes in PD. RESULTS: At baseline, control and PD groups were comparable, except PD participants had smaller striatal volume (p < 0.001). Longitudinally, PD showed faster decline in hippocampal volume, FSWM FA, and fornix FA (ps < .016), but not striatal volume (p = .218). Total and domain-specific MoCA scores declined faster in PD (ps < .030). In PD, lower baseline hippocampal volume (p = .005) and fornix FA (p = .032), but not striatal volume (p = .662) or FSWM FA (p = .143), were associated with faster total MoCA decline. Baseline frontostriatal metrics of striatal volume and FSWM FA were associated with faster attention/executive decline (p < .038), whereas lower baseline hippocampal volume was associated with faster memory decline (p = .005). CONCLUSION: In PD, frontostriatal structural metrics are associated with attention/executive tasks, whereas limbic changes correlated with faster global cognitive decline, particularly in memory tasks.

Dopamine D1 Agonists: First Potential Treatment for Late-Stage Parkinson's Disease.

Current pharmacotherapy has limited efficacy and/or intolerable side effects in late-stage Parkinson's disease (LsPD) patients whose daily life depends primarily on caregivers and palliative care. Clinical metrics inadequately gauge efficacy in LsPD patients. We explored if a D1/5 dopamine agonist would have efficacy in LsPD using a double-blind placebo-controlled crossover phase Ia/b study comparing the D1/5 agonist PF-06412562 to levodopa/carbidopa in six LsPD patients. Caregiver assessment was the primary efficacy measure because caregivers were with patients throughout the study, and standard clinical metrics inadequately gauge efficacy in LsPD. Assessments included standard quantitative scales of motor function (MDS-UPDRS-III), alertness (Glasgow Coma and Stanford Sleepiness Scales), and cognition (Severe Impairment and Frontal Assessment Batteries) at baseline (Day 1) and thrice daily during drug testing (Days 2-3). Clinicians and caregivers completed the clinical impression of change questionnaires, and caregivers participated in a qualitative exit interview. Blinded triangulation of quantitative and qualitative data was used to integrate findings. Neither traditional scales nor clinician impression of change detected consistent differences between treatments in the five participants who completed the study. Conversely, the overall caregiver data strongly favored PF-06412562 over levodopa in four of five patients. The most meaningful improvements converged on motor, alertness, and functional engagement. These data suggest for the first time that there can be useful pharmacological intervention in LsPD patients using D1/5 agonists and also that caregiver perspectives with mixed method analyses may overcome limitations using methods common in early-stage patients. The results encourage future clinical studies and understanding of the most efficacious signaling properties of a D1 agonist for this population.

Do brain activation changes persist in athletes with a history of multiple concussions who are asymptomatic?

PRIMARY OBJECTIVE: To evaluate brain activation patterns of asymptomatic athletes with a history of two or more concussions. RESEARCH DESIGN: A paired case-control design was used to evaluate brain activation patterns during cognitive performance in 14 athletes with a history of two or more concussions and 14 age- and sex-matched controls with no previous concussion. METHODS AND PROCEDURES: Percentage Blood-Oxygen-Level-Dependent (BOLD) change during an N-back working memory task was assessed in all participants. Performance on the Trail-Making Test Form A and B, Symbol-Digit Modalities Test and the Immediate Post-concussion Assessment and Cognitive Test (ImPACT) was also compared between groups. MAIN RESULTS: As expected, brain regions activated during the performance of the N-back were equivalent between groups. The groups performed similarly on the neurocognitive measures. The history of concussion group was less accurate than controls on the 1-, 2- and 3-back conditions of the N-back. CONCLUSIONS: Following the complete resolution of symptoms, a history of two or more concussions is not associated with changes in regional brain activation during the performance of working memory task. Compensatory brain activation may only persist during the typically brief time athletes experience symptoms following concussion.

Ambulatory Assessment in Concussion Clinical Care and Rehabilitation.

Concussion is a mild traumatic brain injury that is characterized by a wide range of physical, emotional, and cognitive symptoms as well as neurocognitive, vestibular, and ocular impairments that can negatively affect daily functioning and quality of life. Clinical consensus statements recommend a targeted, clinical profile-based approach for management and treatment. This approach requires that clinicians utilize information obtained via a clinical interview and a multi-domain assessment battery to identify clinical profile(s) (e.g., vestibular, mood/anxiety, ocular, migraine, cognitive fatigue) and prescribe a corresponding treatment/rehabilitation program. Despite this comprehensive approach, the clinical picture can be limited by the accuracy and specificity of patient reports (which often conflate timing and severity of symptomology), as well as frequency and duration of exposure to symptom exacerbating environments (e.g., busy hallways, sitting in the back seat of a car). Given that modern rehabilitation programs leverage the natural environment as a tool to promote recovery (e.g., expose-recover approach), accurate characterization of the patient clinical profile is essential to improving recovery outcomes. Ambulatory assessment methodology could greatly benefit concussion clinical care by providing a window into the symptoms and impairments experienced by patients over the course of their daily lives. Moreover, by evaluating the timing, onset, and severity of symptoms and impairments in response to changes in a patient's natural environment, ambulatory assessments can provide clinicians with a tool to confirm clinical profiles and gauge effectiveness of the rehabilitation program. In this perspective report, we review the motivations for utilizing ambulatory assessment methodology in concussion clinical care and report on data from a pilot project utilizing smart phone-based, ambulatory assessments to capture patient reports of symptom severity, environmental exposures, and performance-based assessments of cognition for 7 days following their initial evaluation.

Accounting for retest effects in cognitive testing with the Bayesian double exponential model via intensive measurement burst designs.

Monitoring early changes in cognitive performance is useful for studying cognitive aging as well as for detecting early markers of neurodegenerative diseases. Repeated evaluation of cognition via a measurement burst design can accomplish this goal. In such design participants complete brief evaluations of cognition, multiple times per day for several days, and ideally, repeat the process once or twice a year. However, long-term cognitive change in such repeated assessments can be masked by short-term within-person variability and retest learning (practice) effects. In this paper, we show how a Bayesian double exponential model can account for retest gains across measurement bursts, as well as warm-up effects within a burst, while quantifying change across bursts in peak performance. We also highlight how this approach allows for the inclusion of person-level predictors and draw intuitive inferences on cognitive change with Bayesian posterior probabilities. We use older adults' performance on cognitive tasks of processing speed and spatial working memory to demonstrate how individual differences in peak performance and change can be related to predictors of aging such as biological age and mild cognitive impairment status.

Fornix white matter microstructure differentially predicts false recollection rates in older and younger adults.

Healthy aging is accompanied by increased false remembering in addition to reduced successful remembering in older adults. Neuroimaging studies implicate age-related differences in the involvement of medial temporal lobe and fronto-parietal regions in mediating highly confident false recollection. However, no studies have directly examined the relationship between white matter microstructure and false recollection in younger and older adults. Using diffusion-weighted imaging and probabilistic tractography, we examined how white matter microstructure within tracts connecting the hippocampus and the fronto-parietal retrieval network contribute to false recollection rates in healthy younger and older adults. We found only white matter microstructure within the fornix contributed to false recollection rates, and this relationship was specific to older adults. Fornix white matter microstructure did not contribute to true recollection rate, nor did common white matter contribute to false recollection, suggesting fornix microstructure is explicitly associated with highly confident false memories in our sample of older adults. These findings underlie the importance of examining microstructural correlates associated with false recollection in younger and older adults.

Mindful walking and cognition in older adults: A proof of concept study using in-lab and ambulatory cognitive measures.

Mindfulness practice and walking have been linked individually to sustain cognition in older adults. This early-phase study aimed to establish proof-of-concept by evaluating whether an intervention that integrates light-intensity walking with mindfulness practices shows promising signs of improving cognition in older adults. Participants (N = 25, Mage = 72.4 ± 6.45) were community-dwelling older adults who engaged in a supervised mindful walking program over one month (8 sessions total, 2 sessions per week, 30-minute slow walking containing mindfulness skills). They completed performance-based and subjective ratings of cognitive measures in field before and after two mindful walking bouts using a smartphone app. They also completed in-lab performance-based and self-report cognitive measures at baseline and after the entire program. Controlling for demographics, potential covariates, and time trends, short-term improvements in perceived cognition and processing speed were observed from pre- to post-mindful walking sessions (i.e., 30 min) across multiple ambulatory cognitive measures (Cohen's ds range = 0.46-0.66). Longer-term improvements in processing speed and executive function were observed between baseline and end of the program (i.e., one month) across various performance-based cognitive measures (ds range = 0.43-1.28). No significant changes were observed for other cognitive domains. This early-phase study (Phase IIa) provides preliminary support that mindful walking activity is promising for sustaining cognition in older adults. Our promising findings form the building blocks of evidence needed to advance this intervention to a fully powered randomized controlled trial that examines program efficacy with a comparator. Favorable outcomes will inform the development of this lifestyle behavioral strategy for promoting healthy brain aging in late adulthood.

Variability in Cognitive Performance on Mobile Devices Is Sensitive to Mild Cognitive Impairment: Results From the Einstein Aging Study.

Background and Objective: Within-person variability in cognitive performance has emerged as a promising indicator of cognitive health with potential to distinguish normative and pathological cognitive aging. We use a smartphone-based digital health approach with ecological momentary assessments (EMA) to examine differences in variability in performance among older adults with mild cognitive impairment (MCI) and those who were cognitively unimpaired (CU). Method: A sample of 311 systematically recruited, community-dwelling older adults from the Einstein Aging Study (Mean age = 77.46 years, SD = 4.86, Range = 70-90; 67% Female; 45% Non-Hispanic White, 40% Non-Hispanic Black) completed neuropsychological testing, neurological assessments, and self-reported questionnaires. One hundred individuals met Jak/Bondi criteria for MCI. All participants performed mobile cognitive tests of processing speed, visual short-term memory binding, and spatial working memory on a smartphone device up to six times daily for 16 days, yielding up to 96 assessments per person. We employed heterogeneous variance multilevel models using log-linear prediction of residual variance to simultaneously assess cognitive status differences in mean performance, within-day variability, and day-to-day variability. We further tested whether these differences were robust to the influence of environmental contexts under which assessments were performed. Results: Individuals with MCI exhibited greater within-day variability than those who were CU on ambulatory assessments that measure processing speed (p < 0.001) and visual short-term memory binding (p < 0.001) performance but not spatial working memory. Cognitive status differences in day-to-day variability were present only for the measure of processing speed. Associations between cognitive status and within-day variability in performance were robust to adjustment for sociodemographic and contextual variables. Conclusion: Our smartphone-based digital health approach facilitates the ambulatory assessment of cognitive performance in older adults and the capacity to differentiate individuals with MCI from those who were CU. Results suggest variability in mobile cognitive performance is sensitive to MCI and exhibits dissociative patterns by timescale and cognitive domain. Variability in processing speed and visual short-term memory binding performance may provide specific detection of MCI. The 16-day smartphone-based EMA measurement burst offers novel opportunity to leverage digital technology to measure performance variability across frequent assessments for studying cognitive health and identifying early clinical manifestations of cognitive impairment.