Heart rate variability and risk of agitation in Alzheimer's disease: the Atherosclerosis Risk in Communities Study.

Agitation in Alzheimer's disease is common and may be related to impaired emotion regulation capacity. Heart rate variability, a proposed index of autonomic and emotion regulation neural network integrity, could be associated with agitation propensity in Alzheimer's disease. We used the Atherosclerosis Risk in Communities Study cohort data, collected over seven visits spanning over two decades, to investigate whether heart rate variability (change) was associated with agitation risk in individuals clinically diagnosed with dementia due to Alzheimer's disease. Agitation (absence/presence) at Visit 5, the primary outcome, was based on the Neuropsychiatric Inventory agitation/aggression subscale, or a composite score comprising the total number of agitation/aggression, irritability, disinhibition and aberrant motor behaviour subscales present. Visit 1-5 heart rate variability measures were the log-transformed root mean square of successive differences in R-R intervals and standard deviation of normal-to-normal R-R intervals obtained from resting, supine, standard 12-lead ECGs. To aid interpretability, heart rate variability data were scaled such that model outputs were expressed for each 0.05 log-unit change in heart rate variability (which approximated to the observed difference in heart rate variability with every 5 years of age). Among 456 participants who had dementia, 120 were clinically classified to have dementia solely attributable to Alzheimer's disease. This group showed a positive relationship between heart rate variability and agitation risk in regression models, which was strongest for measures of (potentially vagally mediated) heart rate variability change over the preceding two decades. Here, a 0.05 log-unit of heart rate variability change was associated with an up to 10-fold increase in the odds of agitation and around a half-unit increase in the composite agitation score. Associations persisted after controlling for participants' cognitive status, heart rate (change), sociodemographic factors, co-morbidities and medications with autonomic effects. Further confirmatory studies, incorporating measures of emotion regulation, are needed to support heart rate variability indices as potential agitation propensity markers in Alzheimer's disease and to explore underlying mechanisms as targets for treatment development.

Improving comparability across cognitive training trials for brain aging: A focus on interoperability.

Cognitive training may promote healthy brain aging and prevent dementia, but results from individual studies are inconsistent. There are disagreements on how to evaluate cognitive training interventions between clinical and basic scientists. Individual labs typically create their own assessment and training materials, leading to difficulties reproducing methods. Here, we advocate for improved interoperability: the exchange and cooperative development of a consensus for cognitive training design, analysis, and result interpretation. We outline five guiding principles for improving interoperability: (i) design interoperability, developing standard design and analysis models; (ii) material interoperability, promoting sharing of materials; (iii) interoperability incentives; (iv) privacy and security norms, ensuring adherence to accepted ethical standards; and (v) interpretability prioritization, encouraging a shared focus on neurobiological mechanisms to improve clinical relevance. Improving interoperability will allow us to develop scientifically optimized, clinically useful cognitive training programs to slow/prevent brain aging. HIGHLIGHTS: Interoperability facilitates progress via resource sharing and comparability.Better interoperability is needed in cognitive training for brain aging research.We adapt an interoperability framework to cognitive training research.We suggest five guiding principles for improved interoperability.We propose an open-source pipeline to facilitate interoperability.

Autonomic nervous system flexibility for understanding brain aging.

A recent call was made for autonomic nervous system (ANS) measures as digital health markers for early detection of Alzheimer's disease and related dementia (AD/ADRD). Nevertheless, contradictory or inconclusive findings exist. To help advance understanding of ANS' role in dementia, we draw upon aging and dementia-related literature, and propose a framework that centers on the role of ANS flexibility to guide future work on application of ANS function to differentiating the degree and type of dementia-related brain pathologies. We first provide a brief review of literature within the past 10 years on ANS and dementia-related brain pathologies. Next, we present an ANS flexibility model, describing how the model can be applied to understand these brain pathologies, as well as differentiate or even be leveraged to modify typical brain aging and dementia. Lastly, we briefly discuss the implication of the model for understanding resilience and vulnerability to dementia-related outcomes.

Effect of online tDCS to left somatomotor cortex on neuropsychiatric symptoms among older adults at risk for dementia.

BACKGROUND: Neuropsychiatric symptoms (NPS) in mild cognitive impairment (MCI) cause distress to patients and caregivers, and accelerate progression to dementia. Transcranial direct current stimulation (tDCS) is a promising non-invasive treatment for NPS. OBJECTIVE/HYPOTHESIS: This pilot study assessed behavioral and neural effects of a 4-week anodal tDCS intervention targeting left sensorimotor cortex (LSMC: left precentral/postcentral gyri) during visual attention (compared to online sham tDCS), in 40 older adults (24 females, mean age = 71) with MCI. METHODS: A phase 0 double-blinded randomized control trial was conducted. NPS (patient-reported mood symptoms plus a caregiver-reported questionnaire) and fMRI were measured at baseline and immediately post-intervention. RESULTS: Generalized Estimating Equations found no significant group by time interactions for either NPS measure. However, there was evidence of decreased patient-reported NPS (Wald's χ2 = 3.80, p = .051), decreased LSMC activation during visual attention (Wald's χ2 = 2.93, p = .087), and increased LSMC-amygdala resting-state functional connectivity (rsFC; Wald's χ2 = 3.13, p = .077) in intervention group from pre-to post-intervention. Decrease in LSMC activation (Wald's χ2 = 9.20, p = .002) and increase in LSMC-amygdala rsFC (Wald's χ2 = 4.72, p = .030) related to decreased patient-reported NPS. Increased positive valence across sessions was significantly associated with intervention-related NPS improvement (Wald's χ2 = 22.92, p < .001). There were no findings for caregiver-reported NPS. Effects were stronger for left postcentral compared to left precentral gyrus. CONCLUSION: We found tentative evidence that tDCS applied to LSMC during visual attention in older adults with MCI improved NPS via changes in LSMC activation and LSMC-amygdala rsFC, suggesting improved emotion regulation. Patient-reported NPS was more sensitive to these changes than caregiver-reports, and effects were strongest for left postcentral gyrus. Follow-up studies should perform precise mechanistic investigation and efficacy testing.

A Multi-Dimensional Model of Fatigue in Old Age: Implications for Brain Aging.

As the most reported symptom in old age, fatigue is understudied in terms of both mechanisms and measures. Population heterogeneity and methodological inconsistency makes understanding the relationship between fatigue and brain aging challenging. The present article comprehensively reviews existing conceptual and operational frameworks of fatigue, as well as mechanistic heterogeneities of fatigue that exist in the aging literature. Then, I propose a Multi-Dimensional Model of fatigue to provide theoretical cohesion to the study of fatigue in old age, along with a "fatigue circuit" addressing brain profiles across dimensions of fatigue. The potential relationships between fatigue dimensions, the fatigue circuit, and brain aging are discussed to inform the direction of future research.

A Novel Explainability Approach for Technology-Driven Translational Research on Brain Aging.

Brain aging leads to difficulties in functional independence. Mitigating these difficulties can benefit from technology that predicts, monitors, and modifies brain aging. Translational research prioritizes solutions that can be causally linked to specific pathophysiologies at the same time as demonstrating improvements in impactful real-world outcome measures. This poses a challenge for brain aging technology that needs to address the tension between mechanism-driven precision and clinical relevance. In the current opinion, by synthesizing emerging mechanistic, translational, and clinical research-related frameworks, and our own development of technology-driven brain aging research, we suggest incorporating the appreciation of four desiderata (causality, informativeness, transferability, and fairness) of explainability into early-stage research that designs and tests brain aging technology. We apply a series of work on electrocardiography-based "peripheral" neuroplasticity markers from our work as an illustration of our proposed approach. We believe this novel approach will promote the development and adoption of brain aging technology that links and addresses brain pathophysiology and functional independence in the field of translational research.

Enhancing cortical network-level participation coefficient as a potential mechanism for transfer in cognitive training in aMCI.

Effective cognitive training must improve cognition beyond the trained domain (show a transfer effect) and be applicable to dementia-risk populations, e.g., amnesic mild cognitive impairment (aMCI). Theories suggest training should target processes that 1) show robust engagement, 2) are domain-general, and 3) reflect long-lasting changes in brain organization. Brain regions that connect to many different networks (i.e., show high participation coefficient; PC) are known to support integration. This capacity is 1) relatively preserved in aMCI, 2) required across a wide range of cognitive domains, and 3) trait-like. In 49 individuals with aMCI that completed a 6-week visual speed of processing training (VSOP) and 28 active controls, enhancement in PC was significantly more related to transfer to working memory at global and network levels in VSOP compared to controls, particularly in networks with many high-PC nodes. This suggests that enhancing brain integration may provide a target for developing effective cognitive training.

Brain Small-Worldness Properties and Perceived Fatigue in Mild Cognitive Impairment.

BACKGROUND: Perceived fatigue is among the most common complaints in older adults and is substantially influenced by diminished resources or impaired structure of widespread cortical and subcortical regions. Alzheimer's disease and its preclinical stage-mild cognitive impairment (MCI)-are considered a brain network disease. It is unknown, however, whether those with MCI will therefore perceive worse fatigue, and whether an impaired global brain network will worsen their experience of fatigue. METHODS: In this pilot case-control study of age-, sex-, and education-matched MCI and their cognitively healthy counterparts (HCs), perceived fatigue was measured using Multidimensional Fatigue Inventory, and diffusion tensor imaging tractography data were analyzed using graph theory methods to explore small-worldness properties: segregation and integration. RESULTS: Perceived fatigue was more severe in MCI than HCs. Despite a trend for greater network alterations in MCI, there were no significant group differences in integration or segregation. Greater perceived fatigue was related to higher segregation across groups; more perceived fatigue was related to higher segregation and lower integration in MCI but not HCs. CONCLUSION: Findings of this study support the notion that altered whole-brain small-worldness properties in brain aging or neurodegeneration may underpin perceived fatigue.

Functional brain mapping in patients with chronic back pain shows age-related differences.

ABSTRACT: Low back pain is the most common pain condition and cause for disability in older adults. Older adults suffering from low back pain are more disabled than their healthy peers, are more predisposed to frailty, and tend to be undertreated. The cause of increased prevalence and severity of this chronic pain condition in older adults is unknown. Here, we draw on accumulating data demonstrating a critical role for brain limbic and sensory circuitries in the emergence and experience of chronic low back pain (CLBP) and the availability of resting-state brain activity data collected at different sites to study how brain activity patterns predictive of CLBP differ between age groups. We apply a data-driven multivariate searchlight analysis to amplitude of low-frequency fluctuation brain maps to classify patients with CLBP with >70% accuracy. We observe that the brain activity pattern including the paracingulate gyrus, insula/secondary somatosensory area, inferior frontal, temporal, and fusiform gyrus predicted CLBP. When separated by age groups, brain patterns predictive of older patients with CLBP showed extensive involvement of limbic brain areas including the ventromedial prefrontal cortex, the nucleus accumbens, and hippocampus, whereas only anterior insula paracingulate and fusiform gyrus predicted CLBP in the younger patients. In addition, we validated the relationships between back pain intensity ratings and CLBP brain activity patterns in an independent data set not included in our initial patterns' identification. Our results are the first to directly address how aging affects the neural signature of CLBP and point to an increased role of limbic brain areas in older patients with CLBP.

Age-related changes in ongoing thought relate to external context and individual cognition.

Understanding how age-related changes in cognition manifest in the real world is an important goal. One means of capturing these changes involves "experience sampling" participant's self-reported thoughts. Research has shown age-related changes in ongoing thought: e.g., older adults have fewer thoughts unrelated to the here-and-now. However, it is currently unclear how these changes reflect cognitive aging or lifestyle changes. 78 younger adults and 35 older adults rated their thought contents along 20 dimensions and the difficulty of their current activity in their daily lives. They also performed cognitive tasks in the laboratory. In a set of exploratory analyses, we found that older adults spent more time thinking positive, wanted thoughts, particularly in demanding contexts, and less time mind wandering about their future selves. Past-related thought related to episodic memory differently in older and younger adults. These findings inform the use of experience sampling to understand cognitive aging.

Targeting autonomic flexibility to enhance cognitive training outcomes in older adults with mild cognitive impairment: study protocol for a randomized controlled trial.

IMPORTANCE: Cognitive training with components that can further enhance the transferred and long-term effects and slow the progress of dementia is needed for preventing dementia. OBJECTIVE: The goal of the study is to test whether improving autonomic nervous system (ANS) flexibility via a resonance frequency breathing (RFB) training will strengthen the effects of a visual speed of processing (VSOP) cognitive training on cognitive and brain function, and slow the progress of dementia in older adults with mild cognitive impairment (MCI). DESIGN: Stage II double-blinded randomized controlled trial. The study was prospectively registered at ClinicalTrials.gov, with registration approved on 21 August 2020 (No. NCT04522791). SETTING: Study-related appointments will be conducted on-site at University of Rochester Medical Center locations. Data collection will be conducted from August 2020 to February 2025. PARTICIPANTS: Older adults with MCI (n = 114) will be randomly assigned to an 8-week combined intervention (RFB+VSOP), VSOP with guided imagery relaxation (IR) control, and a IR-only control, with periodical booster training sessions at follow-ups. Mechanistic and distal outcomes include ANS flexibility, measured by heart rate variability, and multiple markers of dementia progress. Data will be collected across a 14-month period. DISCUSSION: This will be among the first RCTs to examine in older persons with MCI a novel, combined intervention targeting ANS flexibility, an important contributor to overall environmental adaptation, with an ultimate goal for slowing neurodegeneration. TRIAL REGISTRATION: ClinicalTrials.gov NCT04522791 . Registered on 21 August 2020 Protocol version: STUDY00004727; IRB protocol version 2, approved on 30 July 2020.

Longitudinal stability of medial temporal lobe connectivity is associated with tau-related memory decline.

The relationship between Alzheimer's disease (AD) pathology and cognitive decline is an important topic in the aging research field. Recent studies suggest that memory deficits are more susceptible to phosphorylated tau (Ptau) than amyloid-beta. However, little is known regarding the neurocognitive mechanisms linking Ptau and memory-related decline. Here, we extracted data from Alzheimer's Disease Neuroimaging Initiative (ADNI) participants with cerebrospinal fluid (CSF) Ptau collected at baseline, diffusion tensor imaging measure twice, 2 year apart, and longitudinal memory data over 5 years. We defined three age- and education-matched groups: Ptau negative cognitively unimpaired, Ptau positive cognitively unimpaired, and Ptau positive individuals with mild cognitive impairment. We found the presence of CSF Ptau at baseline was related to a loss of structural stability in medial temporal lobe connectivity in a way that matched proposed disease progression, and this loss of stability in connections known to be important for memory moderated the relationship between Ptau accumulation and memory decline.

Decoding individual identity from brain activity elicited in imagining common experiences.

Everyone experiences common events differently. This leads to personal memories that presumably provide neural signatures of individual identity when events are reimagined. We present initial evidence that these signatures can be read from brain activity. To do this, we progress beyond previous work that has deployed generic group-level computational semantic models to distinguish between neural representations of different events, but not revealed interpersonal differences in event representations. We scanned 26 participants' brain activity using functional Magnetic Resonance Imaging as they vividly imagined themselves personally experiencing 20 common scenarios (e.g., dancing, shopping, wedding). Rather than adopting a one-size-fits-all approach to generically model scenarios, we constructed personal models from participants' verbal descriptions and self-ratings of sensory/motor/cognitive/spatiotemporal and emotional characteristics of the imagined experiences. We demonstrate that participants' neural representations are better predicted by their own models than other peoples'. This showcases how neuroimaging and personalized models can quantify individual-differences in imagined experiences.

Autonomic flexibility reflects learning and associated neuroplasticity in old age.

Effective learning in old age, particularly in those at risk for dementia, is essential for prolonging independent living. Individual variability in learning, however, is remarkable; that is, months of cognitive training to improve learning may be beneficial for some individuals but not others. So far, little is known about which neurophysiological mechanisms account for the observed variability in learning induced by cognitive training in older adults. By combining Lövdén et al.'s (2010, A theoretical framework for the study of adult cognitive plasticity. Psychological Bulletin, 136, 659-676) framework proposing the role of adaptation capacity in neuroplasticity and a neurovisceral integration model of the relationship between autonomic nervous system (ANS) and brain with a novel shapelet analytical approach that allows for accurate and interpretable analysis of time series data, we discovered an acute, ECG-derived ANS segment in response to cognitive training tasks at baseline that predicted learning outcomes from a 6-week cognitive training intervention. The relationship between the ANS segment and learning was robust in both cross-participant and cross-task analyses among a group of older adults with amnestic mild cognitive impairment. Furthermore, the revealed ANS shapelet significantly predicted training-induced neuroplasticity in the dorsal anterior cingulate cortex and select frontal regions during task fMRI. Across outcome measures, individuals were less likely to prospectively benefit from the cognitive training if their ECG data were more similar to this particular ANS segment at baseline. Our findings are among the first empirical evidence to confirm that adaptation capacity, indexed by ANS flexibility, predicts individual differences in learning and associated neuroplasticity beyond individual characteristics (e.g., age, education, neurodegeneration, total training).

Processing speed and attention training modifies autonomic flexibility: A mechanistic intervention study.

Adaptation capacity is critical for maintaining cognition, yet it is understudied in groups at risk for dementia. Autonomic nervous system (ANS) is critical for neurovisceral integration and is a key contributor to adaptation capacity. To determine the central nervous system's top-down regulation of ANS, we conducted a mechanistic randomized controlled trial study, using a 6-week processing speed and attention (PS/A)-targeted intervention. Eighty-four older adults with amnestic mild cognitive impairment (aMCI) were randomized to a 6-week PS/A-targeted intervention or an active control without PS/A. Utilizing repeated measures (i.e., PS/A test different from the intervention, resting and cognitive task-based ECG, and resting fMRI) at baseline, immediately post-intervention (post-test), and 6-month follow-up, we aimed to test whether PS/A causally influences vagal control of ANS via their shared central neural pathways in aMCI. We indexed vagal control of ANS using high-frequency heart rate variability (HF-HRV) extracted from ECG data. Functional brain connectivity patterns were extracted from fMRI using advanced statistical tools. Compared to the control group, the intervention group showed significant improvement in PS/A, HF-HRV, salience network (SN), central executive network (CEN), and frontal parietal network (FPN) connectivity at post-test; the effect on SN, CEN, and FPN remained at 6-month follow-up. Changes in PS/A and SN connectivity significantly predicted change in HF-HRV from baseline to post-test and/or 6-month-follow-up. Age, neurodegeneration, nor sex did not affect these relationships. This work provides novel support for top-down regulation of PS/A and associated SN on vagal control of ANS. Intervening PS/A may be a viable approach for promoting adaptation capacity in groups at risk for dementia.

Longitudinal Relationship Between Frailty and Cognition in Patients 50 Years and Older with Breast Cancer.

OBJECTIVES: To evaluate relationships between frailty and cognition longitudinally in adults 50 years and older with breast cancer receiving chemotherapy. DESIGN: Secondary analysis of a prospective longitudinal observational study. SETTING: University of Rochester NCI Community Oncology Research Program community oncology clinics. PARTICIPANTS: Patients with breast cancer age 50 and older receiving adjuvant/neoadjuvant chemotherapy (n = 376) and age-matched controls without cancer (n = 234). MEASUREMENTS: Frailty was assessed using a modified frailty score from self-reported assessments (weakness, exhaustion, physical activity, and gait speed). Cognition was assessed by patient report (Functional Assessment of Cancer Therapy-Cognition [FACT-Cog]) and objective measures. Frailty and cognition were measured at three time points (prechemotherapy [A1], postchemotherapy [A2], and 6 months postchemotherapy [A3]; similar time interval for controls). Linear regression models evaluated associations between frailty and cognition adjusting for covariates. RESULTS: The average age was 59 years (standard deviation = 6.4 y). At baseline, patients with cancer had a higher mean frailty score (1.21 vs .73; P < .001) and lower mean FACT-Cog score (158.4 vs 167.3; P < .001) compared with controls. Objective cognitive measures were not statistically different. Longitudinal decline in FACT-Cog between A1 and A2 (P < .05) and between A1 and A3 (P < .01) was associated with increased frailty score in patients compared with controls. Longitudinal worsening in Controlled Oral Word Association (P < .05) and Trail-Making Test (P < .01) were associated with an increase in frailty between A1 and A2 in patients compared with controls; longitudinal decline in the Delayed Match to Sample test was associated with an increase in frailty between A1 and A3 (P < .05) in patients compared with controls. This finding remained significant for a subset analysis of those aged 65 and older. CONCLUSION: In patients with breast cancer aged 50 and older, longitudinal decline in FACT-Cog and objective measures of attention and memory were associated with increased frailty during treatment and up to 6 months posttreatment. Overall, our study suggests cognition and frailty are both important factors to assess in breast cancer patients. J Am Geriatr Soc 67:928-936, 2019.

Cognitive and physical factors affecting daily function in Alzheimer's disease: A cross-sectional analysis.

Understanding the factors affecting activities of daily living (ADL) is important in Alzheimer's disease (AD), because decline in ADL contributes to many poor health outcomes. Existing studies often investigate the factors in isolation without a theoretical framework. The purpose of the present study was to provide preliminary results on how cognition, physical performance, and behavioral and psychological symptoms of dementia mediate the relationship of aerobic fitness and ADL in AD. A cross-sectional analysis was used (n = 28: average age 78 [8] years, education 16 (3) years, Mini-Mental State Examination scores 20 [4]). The results showed that aerobic fitness is not linked to ADL directly, and its association with ADL was mediated by physical performance and global cognition. Our findings provide preliminary support for aerobic fitness as a potential therapeutic target, as enhanced aerobic fitness could simultaneously modify other factors affecting ADL. Nurses are in a unique position for coordinating exercise safety assessment and prescription and educating older adults with AD about exercise participation.

Noncognitive Behavioral Changes Associated With Alzheimer's Disease: Implications of Neuroimaging Findings.

Alzheimer's disease (AD) is commonly associated with noncognitive behavioral changes (NCBCs). The authors systematically reviewed whether neuroimaging has helped with understanding the pathophysiology, diagnosis, or management of NCBCs associated with AD, including depression, aggression or agitation, anxiety, apathy, psychosis, and sleep disorder. The authors identified dissociable neural substrates with multimodal imaging: depression implicates the lateral and superior prefrontal cortex; apathy and agitation implicate the dorsal anterior cingulate; psychosis implicates right lateralized frontal and medial temporal areas; and anxiety implicates mesial temporal regions. Frontal white matter changes appear to underlie many NCBCs, emphasizing the preventative management of vascular risk factors. Further delineation of underlying neurocircuitry and pathophysiology in larger data sets might lead to biomarker identification for diagnosis and optimizing treatment targets.

Identification of Successful Cognitive Aging in the Alzheimer's Disease Neuroimaging Initiative Study.

The present prospective observational study aimed to identify the existence of successful cognitive agers among a group of well-defined cognitively healthy older adults (n = 354, mean age = 75 years), and to examine baseline individual-level predictors and associated health outcomes over time. Episodic memory (EM) and executive function (EF) composite scores and multiple health outcomes were obtained annually over 5 years. Potential individual-level predictors that were related to Alzheimer's disease pathology or genetic risk, neurodegeneration, and vascular risks were collected at baseline. Three latent classes with matched age and education were identified using growth mixture modeling: a group of participants who exhibited high, stable EM and EF (40.7% of the sample, "successful agers"); a group who had initial high cognitive performance that declined over time (21.2%, "declining agers"); and a group who had normal (EM) or poor (EF) but stable cognitive performance over time (38.1%, "low stable agers"). The group classification predicted significant differences in the incidence of global cognitive impairment, the development of at least one depressive symptom, and everyday functional impairment. Sex, apolipoprotein E allele 4, amyloid-ß1-42, and t-tau significantly contributed to the difference in cognitive trajectories between the successful agers and the other two groups. Characterizing successful cognitive agers who are relatively resistant to both tau and amyloid pathology provides potential pathways for promoting successful cognitive aging and preventing cognitive decline.

Activity engagement and physical function in old age sample.

OBJECTIVES: To describe the patterns of engagement in mental, physical, and social activity (MA, PA, and SA) and to examine the relationship between combined activity engagement and physical function among community-dwelling older adults. DESIGN: Cross-sectional correlational study. SETTING: Multiple communities. PARTICIPANTS: A total of 466 individuals aged 55 years or older. MEASUREMENTS: Physical function was assessed using grip strength and gait speed. Engagement in PA, MA and SA was obtained from self-report questionnaires. RESULTS: We identified four classes ("Active PA and MA", "Active MA", "Active PA", and "Inactive") that significantly differed in the frequency of engagement in MA and PA using latent class analysis. SA didn't differ across classes. Controlling for age, the "Active PA and MA", "Active MA", "Active PA" groups displayed similar grip strength that was superior to the "Inactive" group. "Active PA and MA" group had best gait speed relative to other groups, especially "Active MA" and "Inactive" group, while the "Active PA", "Active MA", and "Inactive" group were similar in gait speed. CONCLUSION: Combined physical and mental activity engagement was associated with better physical function, especially in gait speed. Future interventional research should investigate the combination of both physical and cognitive training to prevent decline of physical function in older adults.