Y P Aging, O cognitive-motor C function, and tCS T O N Brad Manor, PhD O D October 31, 2017 E S A E L P
Y P O Disclosures C T - NIH / NIA O - Michael J. Fox Foundation N - U.S.-Israel Binational Science Foundation O - Marcus Applebaum Research Award D - Harvard Football Players Health Study E - Neuroelectrics, Inc. S A E L P
Y P Aging is associated w ith progressive decline in O mobility and mental function. C 1 in 3 older adults dies with Alzheimer’s T disease or related dementia. O 1 in 3 older adults fall N each year. O D E S A E L P Are they separate problems?
Y P O Mobility and mental function are intertw ined. C n = 256 T O N O D E S A E L • Lowest quartile = 3x more likely to suffer a fall P • Highest quartile = Less likely to fall than all others Herman et al, J Gerontol, 2010
Y P O Mobility and mental function are intertw ined. C n = 26,000 After adjusting for age, sex, T education and cohort source: O N • Cognitive complaints alone: 9% more likely O D • Slow gait alone: E 40% more likely S A • Both: E 72% more likely L P Verghese et al, Neurology, 2014
Y P O Why does measuring one predict the other? C Motor output and coordination T Sensation O Sensory integration N Cognition O Mood D E S A E L P
Y P Do w e ever just stand or w alk? O C Cognitive dual tasking is the norm… T O and it disrupts our balance! N O D E S A E L P
Y P 500, 497, Standing Standing + Counting Dual Task O 494… Paradigm C T O N O D E S A Dual task “cost” E L P
Y P We can also measure the dual task cost to O w alking. C T Standing O N O D E Standing + Counting S A E L P
Y P Dual task cost: A functionally relevant measure of O cognitive reserve. C Cognitive Resources T O Balance control system N Attention, Reserve Decision O Making D E Standing Counting S A Proprioceptio E n Dual task cost L P
Y P O C T O N O D E tCS can help understand and enhance mobility and mental function in aging. S A Question 1: Can tDCS improve dual task standing and walking E in older adults? L P
Y P O Where should w e target? C T O N O D E Single task: Auditory Single task: Tactile S Dual task A E Dual tasking depends upon the activation of numerous brain regions, including L the left dorsolateral prefrontal cortex (dlPFC). P Deprez et al, Neuropsychologia, 2013
Y P Single sessions of tDCS targeting the left dlPFC O mitigate dual task costs. C T tDCS characteristics O N - Two, 5x7cm sponge electrodes - Anode: F3 on 10-20 EEG system O - Cathode: Contralateral orbit - 2 mA D - 20 minutes - Participant at rest E S A E Dual task Dual task tDCS Assessment (Real or Sham) Assessment L P Manor, Pascual-Leone et al, European Journal of Neuroscience, 2014
Y P 79 year-old female w ith previous falls O A: Post Sham tDCS C Single-Task Standing Dual-Task Standing Dual Task Cost 4 20 T Displacement (cm) Anterioposterior O 0 0 N O -4 -20 Cost D (% Change in Area) B: Post Real tDCS 20 4 E Displacement (cm) Anterioposterior S A 0 0 E L -4 -20 P -20 0 20 -20 0 20 -20 0 20 0 4 -4 0 4 -4 0 4 -4 Mediolateral Mediolateral Mediolateral Displacement (cm) Displacement (cm) Displacement (cm)
Y P Single sessions of tDCS targeting the left dlPFC O mitigate dual task costs. C T O N O D E S A E L P Manor et al, European Journal of Neuroscience, 2014; Journal of Cognitive Neuroscience, 2016
Y P Single sessions of tDCS targeting the left dlPFC O mitigate dual task costs. C T 37 healthy adults aged 65 and older O N O D E S A E L P Manor et al, European Journal of Neuroscience, 2014; Journal of Cognitive Neuroscience, 2016
Y P The functional implications are potentially O significant! C T • How long does the effect of one session last? O N • What about multiple sessions? O Which population? D • Functionally-limited adults? E S • Applications to sports, mobility, falls… A E L P
Y P Slow gait, executive dysfunction, and depression O are common in older adults. C T MOBILIZE Boston Study (Lipsitz): 765 older adults O • Gait speed: 34%: preferred speed < 0.9 m/s N • Executive function: 31%: TMT-B < 1.5 SD below age/education means O • Depression: 29%: CES-D > 11 D • Likelihood of having all 3? E • If random: 3% S • In cohort: 17% A E A common pathway? L P Hajjar, Lipsitz et al; JGMS; 2009; 64; 994-1001
Y P All 3 symptoms have been linked to reduced O functional activation of the prefrontal cortex. C N-back cognitive test T Transcranial Doppler O Ultrasound N O D E Fast walkers S Slow walkers A E L P Sorond, Lipsitz et al, Ann Neurol 2011;70:213-20
Y P Can tDCS improve outcomes in those w ith slow O gait, executive dysfunction and depression? C T Pilot, randomized, sham-controlled trial in adults aged 65 O years and older: n = 20 N Inclusion Exclusion O Walking speed ≤ 1.0 m/s Inability to stand/walk unassisted D Mild-to-moderate executive Severe dementia dysfunction E Evidence of mildly-depressed affect Severe depression S Diabetes A History of stroke E Parkinson’s, other neurological disease L Contraindications to MRI or tDCS P
Y P Study procedures: O C • Behavioral assessment (cognition/mood/mobility/dual task) T V1 O • MRI (structural, resting state) N V2 O V3-12 • tDCS intervention (10 sessions) D E • Behavioral assessment V13 S A • MRI V14 E L • Behavioral assessment (2 week follow-up) P V15
Y P Individuals w ere randomized to tDCS targeting the O left dlPFC or inactive sham stimulation. C T O N O D E S A Left dorsolateral prefrontal cortex E Image courtesy of Neuroelectrics, Inc L P
Y P We successfully recruited a small cohort w ith O concomitant functional limitations. C Table 1: Catalyst sample characteristics (mean±SD) T Real tDCS Sham tDCS P value O Sample (n) 10 10 N Age (years) 83 ± 10 79 ± 10 0.35 Gender (women; 5; 5 6; 4 O men) 4m gait speed (m/s) 0.73 ± 0.17 0.72 ± 0.14 0.96 D Trail Making Test B 142 ± 64 152 ± 78 0.68 E (sec) Geriatric 3.4 ± 3.0 4.0 ± 2.5 0.47 S Depression Scale A (scale 0-12) Mini Mental State E 24.1 ± 3.4 25.5 ± 3.3 0.38 Examination L (MMSE) P No unexpected adverse events; excellent compliance & blinding
Y P Multiple sessions of tDCS induced lasting O improvements in dual task performance. C T 500, 497, (3 days) (2 weeks) 494… O N Dual task cost to standing postural sway speed (%) O D E S A E L Trends (p < 0.1) towards increased performance were also observed in: P - Timed Up-and-Go (TUG) test of mobility - Preferred gait speed
Y P Multiple sessions of tDCS induced lasting O improvements in cognitive function. C T O N O D E S A E tDCS-related improvements were limited to the “executive function” sub-score. L To do: Are tDCS-related improvements linked to changes in brain function? P
Y P Is the left dlPFC really the best target? O C T O N O D E S A E L P Image courtesy of Neuroelectrics
Y P Is the left dlPFC really the best target? O C 25 older adults with a recent history of falling T O Multi-target Single-target Sham N O D E S A E L Inter-subject variability in effectiveness is still high. P
Y P What’s causing such high inter-subject variability? O C Electrode size Anatomy: T - Skin O Placement - Skull N - CSF Direction of flow O - gray mater - White mater D Current intensity E Brain physiology S Current duration A Brain state E - Off-line (resting) Biological aging—especially in the presence of - On-line L disease—alters brain structure and function, and P thus, the flow and effects of tDCS.
Y P Brain anatomy can be very different! O C 68 year old male: - No diagnosed disease T - Fast gait O - Normal executive function N - Regular exercise O D E 79 year old male: S - No diagnosed disease A - Slow gait E - Poor executive function L - Sedentary P Images courtesy of Neuroelectrics
Y P Brain anatomy can be very different! O C 68 year old: 79 year old: T O N O D E S A E L P Images courtesy of Neuroelectrics
Y P Brain anatomy can be very different! O C 68 year old: 79 year old: T O N O D E S A E L P Images courtesy of Neuroelectrics
Y P Brain anatomy can be very different! O C 68 year old: 79 year old: T O N O D E S A E L P Images courtesy of Neuroelectrics
Y P Vastly different montage and current parameters O are required to optimize flow to a given region. C 68 year old: 79 year old: T O 79 year old: N O D E S A E L P Images courtesy of Neuroelectrics
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