Roee Holtzer

• Yeshiva University

UNSTRUCTURED We present the Wearable Cognitive Assessment and Augmentation Toolkit (WearCAAT), a cross-platform mobile application to conduct functional neuroimaging research with modern mobile devices. The need to observe human cognition in more natural environments, i.e., outside of sterile Laboratory Settings, is critical to understanding human...

Cortical lesions (CL) have been reported and characterized in multiple sclerosis (MS), but their presence and association with cognitive function in older adults with MS (OAMS) have not been evaluated. To quantify the presence of CL in OAMS and healthy controls. We hypothesized that compared to controls, OAMS would have more CL, and CL would be ass...

Objective To assess whether resting-state functional connectivity (RSFC) brain networks are associated with gait speed in a sample of older adults with and without multiple sclerosis (MS). Methods Older adults with MS (OAMS: n = 82, mean age = 64.4 ± 4.1 years) and controls (n = 85, mean age = 68.6 ± 7.1 years) underwent brain MRI, cognitive asses...

Objective This study introduces the Montefiore Einstein Robust Geriatric Normative Project (MERGER-NP), which provides robust normative data for older adults on the Repeatable Battery for Neuropsychological Status (RBANS) and other select neuropsychological tests. Method Age-stratified and regression-based demographic norms were derived from a rob...

Background/Objectives: Footfall placement variability is associated with falls in older adults and neurological diseases. Thus, the study of dual-task gait impairment in middle-aged to older-aged adults with multiple sclerosis (MS) is clinically relevant, particularly in environments that mimic the obstacles experienced in daily ambulation. Methods...

Functional near infrared spectroscopy (fNIRS) is being increasingly used to assess brain hemodynamic responses during active walking in older adults due to its wearability, and relative immunity to motion artifacts. Specifically, fNIRS allows for continuous monitoring of brain activations that vary in response to experimental manipulations of cogni...

White matter hyperintensities (WMH) are clinical markers of subcortical ischemic vascular cognitive impairment (SIVCI) associated with impaired postural balance and falls. Physical reserve (PR) is a recently established construct that reflects one’s capacity to maintain physical function despite brain pathology. This cross-sectional study aims to m...

Interdisciplinary research has demonstrated that cognitive and mobility performance and decline are inter-related and potentially coupled implicating the brain as a key common denominator shared by both domains of function. Novel studies in the current symposium utilize advanced neuroimaging methods to elucidate how structural and functional measur...

Cognitive and physical function are interrelated in aging co-occurring impairments in both domains can be debilitating and lead to increased risk of developing dementia. Amyloid beta (Aβ) deposition in the brain is linked to cognitive decline and is also associated with poorer physical function in older adults. However, significant inter-individual...

Objective We examined whether brain hemodynamic responses, gait, and cognitive performances under single- and dual-task conditions predict falls during longitudinal follow-up in older adults with multiple sclerosis (OAMS) with relapsing-remitting and progressive subtypes. Methods Participants with relapsing-remitting (n = 53, mean age = 65.02 ± 4....

Background Mobility and cognitive impairment are prevalent and co-occurring in older adults with multiple sclerosis (OAMS), yet there is limited research concerning the role of disability status in the cognitive control of gait among OAMS. Objective We investigated the levels of prefrontal cortex (PFC) activation, using oxygenated hemoglobin (HbO...

White matter hyperintensities (WMH) are markers of subcortical ischemic vascular cognitive impairment (SIVCI) associated with impaired postural balance. Physical reserve (PR) is a recently established construct that reflects one’s capacity to maintain physical function despite brain pathology. This cross-sectional study aims to map functional netwo...

White matter hyperintensities (WMH) are markers of subcortical ischemic vascular cognitive impairment (SIVCI) associated with impaired postural balance. Physical reserve (PR) is a recently established construct that reflects one’s capacity to maintain physical function despite brain pathology. This cross-sectional study aims to map functional netwo...

The peak prevalence of multiple sclerosis has shifted into older age groups, but co-occurring and possibly synergistic motoric and cognitive declines in this patient population are poorly understood. Dual-task-walking performance, subserved by the prefrontal cortex, and compromised in multiple sclerosis and aging, predicts health outcomes. Whether...

Objective Late-life depression is prevalent among older adults and the presence of depressive symptoms has been shown to be associated cross-sectionally with worse verbal fluency performance. There is limited and mixed evidence as to whether depressive symptoms impact change in verbal fluency performance over time, and whether gender impacts this r...

Objective Multiple sclerosis (MS), an inflammatory autoimmune disease of the central nervous system, is characterized by damage to white matter via myelin degeneration with resulting sclerotic plaques and lesions. Upwards of 70% of people with MS show cognitive changes in multiple domains including verbal memory. Advances in disease-modifying thera...

Objective Multiple sclerosis (MS) is a chronic neurodegenerative autoimmune disease of the central nervous system. Apathy is significantly higher in adults with MS compared to healthy populations. Apathy is a lack of motivation that can cause dysfunctions in each step of goal-directed behaviors. Apathy is associated with diminished ability to perfo...

Objective Research has shown that social support has protective effects against cognitive decline in older adults. No study to date has examined the relationship between social support and cognition in older adults with Multiple Sclerosis (MS). Advances in treatments for MS have resulted in a growing number of aging individuals with MS, making it i...

Evidence provides support for using functional near-infrared spectroscopy (fNIRS) to quantify brain activations, notably in the pre-frontal cortex (PFC), under different walking conditions. Dual-tasks that involve walking impose additional demands on attention resources relative to the single tasks, and Studies using fNIRS revealed increased HbO2 i...

Objective Pain is a mechanism for attention disruption due, in part, to a shared reliance on the prefrontal cortex (PFC). Amongst older adults, the experience of pain is both prevalent and functionally impactful. Dual-task walking (DTW) paradigms are a useful means of assessing the impact of pain on attentional control and known to be sensitive to...

Objective The decreasing rate of within-person word generation in verbal fluency (VF) tasks, here referred to as slope, is associated with mild cognitive impairment and with lower grey matter volume in select regions. While VF is sensitive to cognitive decline in Multiple Sclerosis (MS), VF slopes have yet to be assessed in older adults with MS. We...

Decline in gait features is common in older adults and an indicator of increased risk of disability, morbidity, and mortality. Under dual task walking (DTW) conditions, further degradation in the performance of both the gait and the secondary cognitive task were found in older adults which were significantly correlated to falls history. Cortical co...

Background Apathy is common in multiple sclerosis (MS) and neurological disease, but its presence and underlying brain mechanisms in older adults with MS (OAMS) have not been evaluated. Objective Examine apathy and its association with caudate nuclei volume in OAMS and controls. We hypothesized that compared to controls, OAMS would demonstrate: a)...

Objectives: To examine whether Subjective Cognitive Complaints (SCCs) predicted incident mild cognitive impairment (MCI). Design: Prospective Study. Setting: Central Control of Mobility and Aging (CCMA), a cohort study of community-residing older adults. Participants: Participants were dementia-free community-residing older adults. Measurem...

Objective: Increased intraindividual variability (IIV) in behavioral and cognitive performance is a risk factor for adverse outcomes but research concerning hemodynamic signal IIV is limited. Cortical thinning occurs during aging and is associated with cognitive decline. Dual-task walking (DTW) performance in older adults has been related to cogni...

Background: Mobility impairment is common in older persons with multiple sclerosis (MS), and further compounded by general age-related mobility decline but its underlying brain substrates are poorly understood. Objective: Examine fronto-striatal white matter (WM) integrity and lesion load as imaging correlates of mobility outcomes in older perso...

Music making is linked to improved cognition and related neuroanatomical changes in children and adults; however, this has been relatively under-studied in aging. The purpose of this study was to assess neural, cognitive, and physical correlates of music making in aging using a dual-task walking (DTW) paradigm. Study participants (N = 415) were hea...

Objective: The current study was designed to examine associations between depressive symptoms and longitudinal declines in category and letter fluency performance in a gender-stratified sample of older adults. Method: Participants were community-residing older adults (females: n = 289; males: n = 233) followed annually (2011-2018) as part of a c...

Background and objective Cognitive and physical functions correlate and delineate aging and disease trajectories. Whereas cognitive reserve (CR) is well-established, physical reserve (PR) is poorly understood. We, therefore, developed and evaluated a novel and more comprehensive construct, individual reserve (IR), comprised of residual-derived CR a...

The current study examined the relationship between gray matter volume (GMV) and rate of word generation over the course of three consecutive 20-sec intervals in 60-sec letter and category verbal fluency (VF) tasks. Attenuated rate of within-person word generation in VF provides incremental information beyond total scores and predicts increased ris...

Background Physical reserve (PR) refers to one’s ability to maintain physical functioning despite age, illness, or injury. The measurement and predictive utility of PR, however, are not well established. Aims We quantified PR using a residual measurement approach by extracting standardized residuals from gait speed, while accounting for demographi...

Background Cognitive Reserve (CR) protects against cognitive decline and dementia but its relation to mobility disability has not been established. To address this important gap in the literature, we conducted a longitudinal investigation to test the hypothesis that higher baseline CR was associated with a lower risk of developing mobility disabili...

What can muscles, gait, and brain activity tell us about cognitive decline? Are there certain markers we can track that are early predictors of cognitive status years later? In the current symposia, our goal is to address these questions with recent pilot, longitudinal and cross-sectional studies that measure potential markers of cognitive decline...

Walking and cognition are interrelated due to dependence on shared brain regions that include the prefrontal cortex (PFC). Limited literature indicates that asthma is associated with poor mobility in older adults but the mechanisms underlying this relationship are unknown. Therefore, we tested the hypothesis that asthma history was associated with...

Objective: We examined whether individual differences in positive and negative affective states predicted dual-task costs using an established Dual-Task Walking protocol in non-demented older adults. We hypothesized that positive and negative affect would be associated with smaller and larger dual-task costs, respectively. Methods: Participants (N...

Background: Cognitive reserve (CR) protects against cognitive decline and dementia but its relation to mobility impairment has not been established. To address this important gap in the literature, we conducted a longitudinal investigation to test the hypothesis that higher baseline CR was associated with a lower risk of developing mobility impair...

Background and Objectives Functional Near-Infrared Spectroscopy (fNIRS) studies provide direct evidence to the important role of the prefrontal cortex (PFC) during walking in aging and Parkinson's disease (PD). Most studies mainly explored mean HbO2 levels, while moment-to-moment variability measures have been rarely investigated. Variability measu...

Background Cognitive Reserve (CR) protects against cognitive decline, but whether CR influences the efficiency of cortical control of gait has not been reported. The current study addressed this important gap in the literature. Specifically, we determined the role of CR in moderating the efficiency of functional Near-Infrared-Spectroscopy (fNIRS)-d...

Background Decline in executive functions and related cognitive processes is associated with mobility decline, and these functions might be amenable to cognitive remediation. This study aimed to examine whether a computerised cognitive remediation programme would improve walking in adults aged 70 years and older.

Brain games – Do they improve cognition and mobility? Computerized cognitive remediation programs (‘brain games’) are widely available, and are marketed to the public to improve cognition, but the evidence-base to support prescription of this popular intervention is limited. Previous clinical trials examining the role of cognitive training to impr...

Objective Greater intraindividual variability (IIV) in behavioral and cognitive performance is a risk factor for adverse outcomes but research concerning IIV in neural signal is scarce. Using functional near-infrared spectroscopy (fNIRS), we showed that IIV in oxygenated hemoglobin (HbO2) levels in the prefrontal cortex increased from single task (...

Dual tasking, a defined facet of executive control processes, is subserved, in part, by the prefrontal cortex (PFC). Previous functional near-infrared spectroscopy (fNIRS) studies revealed elevated PFC oxygenated hemoglobin (HbO2) under Dual-Task-Walk (DTW) compared to Single-Task Walk (STW) conditions. Based on the concept of neural inefficiency (...

Background Among older adults, walking performance is a reliable indicator of adverse health outcomes including incident mobility impairment. Whereas, attention and executive functions have been implicated in cognitive control of locomotion, much less is known about the role of Cognitive Reserve (CR) in predicting mobility impairments among older a...

Objectives Literature regarding the association of fear of falling (FOF), a common concern in aging, and cognition is scarce. Moreover, whether frequency of FOF endorsement influences age-related cognitive decline has not been reported. Here we determined whether FOF status (no FOF, single-report FOF, recurrent FOF), predicted decline in global cog...

(1) Functional near-infrared spectroscopy (fNIRS) provides a useful tool for monitoring brain activation changes while walking in adults with neurological disorders. When combined with dual task walking paradigms, fNIRS allows for changes in brain activation to be monitored when individuals concurrently attend to multiple tasks. However, difference...

Decline in gait features is common in older adults and an indicator of disability and mortality. Cortical control of gait, specifically in the pre-frontal cortex as measured by functional near infrared spectroscopy (fNIRS), during dual task walking has shown to be moderated by age, gender, cognitive status, and various age-related disease condition...

Aging is accompanied by changes in cognitive, physical, and brain function. Research has found increased activation in the prefrontal cortex (PFC) in dual-task-walk (DTW) as compared to single-task walk (STW) due to increased cognitive demands in the former condition. Older adults have more difficulty with DTW than younger adults, and difficulty wi...

Physical resilience (PR), which denotes one’s ability to resist functional physical decline, can be operationalized through longitudinal assessments on the Short Physical Performance Battery (SPPB). Dual-task walking (DTW) is predictive of adverse outcomes but its role in predicting incident PR has not been assessed. Herein, we determined whether v...

Fear of Falling (FOF) is common and associated with poor mobility in aging but whether persistence of FOF endorsement influences cognitive decline has not been reported. Here we determined the effect of FOF, measured dichotomously and after accounting for persistence, on decline in global cognitive function (GCF), memory, and attention/executive fu...

Pain is prevalent and associated with adverse outcomes in older adults. The moderating effect of pain on cortical control of locomotion has not been assessed. This study examined the effects of subjective pain on changes in fNIRS-derived oxygenated hemoglobin (HbO2), gait velocity, and cognitive accuracy from single to dual-task walking conditions...

Aging populations are at increased risk to experience mobility disability, which is associated with falls, frailty, and mortality. Previous studies have not examined the concurrent associations of both positive and negative affect with gait velocity. We examined whether individual differences in positive and negative affect predicted dual-task perf...

Functional near infrared spectroscopy (fNIRS) studies utilized a limited and inconsistent number of processing algorithms to assess the prefrontal activity during active walking. To address this critical limitation, we have reanalyzed our large dataset of older adults (n=83) who underwent single and dual-task walking (STW and DTW) protocol by apply...

functional near infrared spectroscopy (fNIRS) has been increasingly used to assess changes in the hemodynamic response during active walking in aging and disease populations. Key findings revealed that HbO2 in the prefrontal cortex (PFC) increased from single-task-walk (STW) to dual-task-walk (DTW) due to the greater cognitive demands inherent in t...

Objective Pain is prevalent and functionally impactful in older adults. The prefrontal cortex is involved in pain perception, attentional control, and cortical control of locomotion. Although pain is a known moderator of attentional capacity, its moderating effect on cortical control of locomotion has not been assessed. This study aimed to examine...

Intraindividual variability in gait and cognitive performance is distinct from central-tendency measures and associated with clinical outcomes in aging. Knowledge concerning intraindividual variability in neural activity, however, has been relatively scarce, and no research to date has reported on such variability during active walking. The current...

Background: Functional near-infrared spectroscopy (fNIRS) is increasingly used in the field of posture and gait to investigate patterns of cortical brain activation while people move freely. fNIRS methods, analysis and reporting of data vary greatly across studies which in turn can limit the replication of research, interpretation of findings and c...

The current study aimed to determine whether word generation performance on individual within-task 20-second time intervals predicted conversion to Mild Cognitive Impairment (MCI) status. Longitudinal data (Mean follow-up=2.95±1.64 years) was collected from cognitively-healthy community-dwelling older adults (N=344; %female=56.1). Performance on le...

The presence of Mild Cognitive Impairments (MCI) is associated with worse gait performance. However, the effect of MCI on cortical control of gait, as assessed during active walking, is unknown. We hypothesized that MCI would be associated with attenuated activations and limited improvement in efficiency in the Prefrontal cortex (PFC) under cogniti...

While the growth hormone/insulin-like growth factor-1 (GH/IGF-1) pathway plays essential roles in growth and development, diminished signaling via this pathway in model organisms extends lifespan and health-span. In humans, circulating IGF-1 and IGF-binding proteins 3 and 1 (IGFBP-3 and 1), surrogate measures of GH/IGF-1 system activity, have not b...

Objective: Apathy symptoms are common in healthy older adults and may manifest independently of depressive symptoms. Perceived social support is considered a protective factor against adverse health outcomes in aging. We investigated the differential associations of apathy and depressive symptoms with perceived social support in older adults. Metho...

Functional near infrared spectroscopy (fNIRS) is a noninvasive optics-based neuroimaging modality successfully applied to real-life settings. The technology uses light in the near infrared range (650-950nm) to track changes in oxygenated (HbO2) and deoxygenated hemoglobin (Hb) obtained from measured light intensity using light-tissue interaction pr...

Objectives: Perceived social support (PSS) has a uniquely beneficial effect on physical and mental health in older adults, yet relatively little is known about patterns of change in PSS during late life. The purpose of this study was to identify risk factors related to individual-level change in PSS, with a focus on personality (specifically Neurot...

Offspring of parents with exceptional longevity (OPEL) manifest lower prevalence of cardiovascular disease (CVD), but the role of lifestyle factors in this unique cohort is not known. Our study tested whether OPEL have lesser prevalence of CVD independent of lifestyle factors. Prevalence of CVD and CVD risk factors was assessed in a population of c...

Older adults are less efficient at avoiding obstacles compared to young adults, especially under attention-demanding conditions. Using functional near-infrared-spectroscopy (fNIRS), recent studies implicated the prefrontal cortex (PFC) in cognitive control of locomotion, notably under dual-task walking conditions. The neural substrates underlying O...

Background: Gait impairments present while dual-tasking in older adults with multiple sclerosis (MS) have been associated with an increased risk of falls. Prior studies have examined prefrontal cortex (PFC) activity using functional near infrared spectroscopy (fNIRS) while dual-tasking in older adults with and without cognitive impairment. While t...

Objective: Although depressive symptoms are widely recognized as a predictor of functional decline among older adults, little is known about the predictive utility of apathy in this population. We prospectively examined apathy symptoms as predictors of incident slow gait, frailty, and disability among non-demented, community-dwelling older adults....

Multiple sclerosis (MS) is a chronic inflammatory and neurodegenerative disease affecting various neurological domains, such as postural control, cognition, fear of falling, depression-anxiety, and fatigue. This study examined the associations of cognitive functions, fear of falling, depression-anxiety, and fatigue with postural control in patients...

Background and purpose: Traditional neuroimaging techniques restrict movement and make it difficult to study the processes that require oral, upper limb, or lower limb motor execution. Functional near-infrared spectroscopy (fNIRS) is an optical neuroimaging modality that measures brain oxygenation and permits movement during data acquisition. A ke...

Objective: To determine whether brain activity over the prefrontal cortex measured in real time during walking predicts falls in high-functioning older adults. Method: We examined166 older persons (mean age 75 years, 51% women) enrolled in a prospective aging study. High-functioning status defined as the absence of dementia or disability with no...

The ability to walk is critical for functional independence and wellbeing. The pre-frontal cortex (PFC) plays a key role in cognitive control of locomotion, notably under attention-demanding conditions. Factors that influence brain responses to cognitive demands of locomotion, however, are poorly understood. Herein we evaluated the individual and c...

Mobility disabilities represent the most prevalent disability among seniors. Emerging evidence indicates that executive functions play an important role in maintaining mobility. However, the use of cognitive remediation programs to enhance mobility has not been investigated in a full-scale randomized control trial. The CREM study is a single-blind...

Introduction: Postural instability/gait difficulty (PIGD) and fear of falling (FoF) frequently co-exist, but their individual predictive values for falls have not been compared in aging. This study aims to determine both independent and combined effect of PIGD and FoF to falls in older adults without dementia. Methods: PIGD and other extrapyrami...

Objectives: Mild cognitive impairments (MCI) is a transitional state in aging associated with increased risk of incident dementia. The current study investigated whether MCI status moderated the effect of time on word generation during verbal fluency tasks. Specifically, the objective was to determine whether MCI status had differential effects on...

Mutations that reduce somatotropic signaling result in improved lifespan and health-span in model organisms and humans. However, whether reduced circulating insulin-like growth factor-I (IGF-I) level is detrimental to cognitive and muscle function in older adults remains understudied. A cross-sectional analysis was performed in Ashkenazi Jews with...

Mobility and cognitive impairments are common in persons with multiple sclerosis (MS), and are expected to worsen with increasing age. However, no studies, to date, in part due to limitations of conventional neuroimaging methods, have examined changes in brain activation patterns during active locomotion in older patients with MS. This study used f...

Research suggests a reciprocal relationship between late-life anxiety and cognition, particularly attention and executive functions. Whereas evidence supports a conceptual distinction between cognitive and somatic dimensions of anxiety, their differential relationship with cognitive outcomes has not been examined, particularly on tests of attention...

Background Fatigue adversely impacts quality of life in old age. The relationship between subjective and objective measurements of fatigue, however, is poorly understood. We examined whether subjective fatigue moderated the expression of objective fatigue during locomotion. Associations between objective and subjective measures of fatigue were pred...

Objective: To develop and validate a subjective measure of cognitive fatigue-the State-Trait Inventory of Cognitive Fatigue (STI-CF)-in community-dwelling older adults. Design: Scale development and test construction. Setting: Community-dwelling older adults enrolled in a longitudinal cohort aging study. Participants: Participants (N=175) we...

Objective: Cognitive dysfunction is prevalent in multiple sclerosis. As self-reported cognitive functioning is unreliable, brief objective screening measures are needed. Utilizing widely used full-length neuropsychological tests, this study aimed to establish the criterion validity of highly abbreviated versions of the Brief Visuospatial Memory Te...

Objectives: To examine the role of cognitive reserve in reducing delirium incidence and severity in older adults undergoing surgery. Design: Prospective cohort study. Setting: Hospital. Participants: Older adults (mean age 71.2, 65% women) undergoing elective orthopedic surgery (N = 142). Measurements: Incidence (Confusion Assessment Metho...

Background: Rett syndrome (RTT) is a severe neurological disease that primarily affects females. The level of brain derived neurotropic factor (BDNF) expression directly correlates with the severity of RTT related symptoms. Because Glatiramer acetate (GA) stimulates secretion of BDNF in the brain, we conducted the study with the objective to asses...

Poor social networks and decreased levels of social support are associated with worse mood, health, and cognition in younger and older adults. Yet, we know very little about the brain substrates associated with social networks and social support, particularly in older adults. This study examined functional brain substrates associated with social ne...

The posture first hypothesis suggests that under dual-task walking conditions older adults prioritize gait over cognitive task performance. Functional neural confirmation of this hypothesis, however, is lacking. Herein, we determined the functional neural correlates of the posture first hypothesis and hypothesized that the presence of neurological...

Objective: Despite the growing importance of slow gait as a universal screen of health, systematic investigation of risk factors for incident slow gait is lacking. Our objective was to identify potentially modifiable risk factors for incident slow gait. Design: Prospective cohort study. Setting: The Health and Retirement Study, a nationally re...

Research investigating multisensory integration (MSI) processes in aging is scarce, but converging evidence for larger behavioral MSI effects in older compared to younger adults exists. The current study employed a three-prong approach to determine whether inherent age-related sensory processing declines were associated with larger (i.e., worse) vi...

The Walking While Talking (WWT) dual-task paradigm is a mobility stress test that predicts major outcomes, including falls, frailty, disability, and mortality in aging. Certain personality traits, such as neuroticism, extraversion, and their combination, have been linked to both cognitive and motor outcomes. We examined whether individual differenc...

Objectives: Functional losses are common in healthy and cognitively impaired older adults. However, subtle declines in instrumental activities of daily living (IADLs) are not always detected in self-reports. Performance IADL measurements are financially and time burdensome, restricting their use in varied settings. To address these limitations, we...