Cognitive Control of Walking in Aging

• ¹ Villanova University, Electrical and Computer Engineering, United States
• ² Albert Einstein College of Medicine, Department of Neurology, United States

Introduction: In aging populations, decline in gait performance is common and can result in increased risk of morbidity and mortality, hospitalizations, and poorer quality of life (Verghese et.al., 2006, Montero-Odasso et.al., 2005, Holtzer et.al., 2014). The neural underpinnings of gait are not well understood even though recent epidemiological, cognitive, and neuroimaging studies suggest that gait is influenced by higher-order cognitive and cortical control mechanisms. Over the past decade, we have been investigating neural correlates of locomotion in elderly populations. Specifically, we have studied executive control of gait in a large cohort of elderly participants by monitoring their brain activity in the dorsolateral prefrontal cortex using functional near infrared spectroscopy (fNIRS) while they are performing real, on the ground walking tasks with or without a cognitive interference task of letter generation in a longitudinal study for five years. We have looked into various aspects of cognitive control of locomotion in healthy elderly individuals such as age effects in comparison to young individuals, gender differences, how stress or fatigue affect cognitive outcomes. We have also studied elderly populations with different disease conditions such as the ones with neurological gait abnormalities, diabetics or the ones with Parkinsonian syndromes or with multiple sclerosis (MS) and compared cognitive activity differences in these different diseased populations in comparison to healthy aging. Here, we would like to review and summarize those prior findings. Materials and Methods: In all the studies, community residing individuals of age 65 years and older who were enrolled in “Central Control of Mobility in Aging” (CCMA), a longitudinal study designed to determine cognitive and brain predictors of mobility in aging were involved. Each participant received comprehensive neuropsychological, cognitive, psychological, and mobility assessments as well as a structured neurological examination. CCMA participants are followed longitudinally at yearly intervals for five years. Written informed consents were obtained at clinic visits according to study protocols and approved by the institutional review board. Using the advantages of fNIRS technology of being noninvasive, portable, comfortable, wearable, and more immune to movement artifacts as compared to other neuroimaging technologies, in our studies we were able to monitor the cognitive activity of participants while they were performing real on the ground walking tasks. The overall task protocol involved two single tasks: 1) Normal Pace Walk (NW) and 2) Cognitive (Alpha) and one dual task condition (Walk While Talk, WWT). For the NW task, participants were asked to walk around the electronic walkway (Zenometrics system: A 4 x 14 foot Zeno electronic walkway where quantitative measures of gait including stride velocity and stride length can be assessed (Zenometrics, LLC; Peekskill, NY)) at their “normal pace” for three consecutive loops. For the Alpha task, participants were required to stand still on the electronic walkway while reciting out loud alternate letters of the alphabet starting with the letter B for 30 seconds. In WWT participants were instructed to walk around the walkway as in NW task while reciting alternate letters of the alphabet as in Alpha task. Participants were instructed to pay equal attention to both tasks. The three test conditions were presented in a counterbalanced order. We used the fNIRS Imager 1000 (fNIRS Devices, LLC, Potomac, MD) in our studies to monitor changes in hemodynamic activity in the PFC of participants during actual locomotion. The fNIRS system consisted of a flexible circuit board that was placed on the participants’ forehead using standard procedures, a control box for data acquisition at 2Hz sampling rate and a computer for data collection and storage. The fNIRS sensor consisted of 4 LED light sources and 10 photodetectors which cover the forehead using 16 voxels, with a source-detector separation of 2.5 cm. Results and Conclusion: In our initial pilot study on eleven young and eleven elderly participants, we have found that oxygenation levels are increased in the PFC in WWT compared to NW in young and old individuals where this effect was modified by age with young individuals showing greater increases in PFC oxygenation levels compared to the old participants (Holtzer et.al., 2011). This finding suggests that older adults may underutilize the PFC in attention demanding locomotion tasks. In our CCMA study on a large cohort of nondemented and ambulatory elderly adults (n=348), we have provided reproducible measurements of task-related changes in oxygenation levels where increased PFC activity was found in WWT compared to NW (Holtzer et.al., 2015, Verghese et.al., 2017, Chen et.al., 2017). In addition elevated PFC oxygenation levels were shown to be maintained throughout the course of WWT but not during NW. Consistent with compensatory reallocation models, increased oxygenation levels in the PFC were related to better gait and cognitive performance during WWT. In a follow up study, we determined the individual and combined effect of gender and perceived stress on gait velocity and PFC oxygenation levels during locomotion (Holtzer et.al, 2017a). We found that higher levels of perceived task-related stress were associated with more difficulties in negotiating the demands of dual-task walking as well as attenuation of brain oxygenation patterns under attention-demanding walking in older men. We have also examined subjective and objective measures of fatigue in the context of an established dual-task walking paradigm (Holtzer et.al., 2017b). Consistent with the study predictions, we have observed that gait velocity declined during the course of WWT but not during NW. Worse perceptions of fatigue were associated with an attenuated increase in oxygenation levels from NW to WWT. In addition to these findings in healthy aging, our studies identified differences in brain activity levels in elderly with various disease conditions such as diabetics or individuals with neurological gait abnormalities, Parkinsonian syndromes or with MS that we plan to summarize and discuss further (Holtzer et.al., 2016, 2018, Mahoney et.al., 2016, Hernandez et.al., 2016, Chaparro et.al., 2017). In conclusion, our findings have provided more information on neural underpinnings of mobility in aging with or without disease conditions which can provide implications on risk assessment and intervention of incident mobility impairments and falls.