[PPT] - Y P Aging, O cognitive-motor C function, and tCS T O N Brad PowerPoint Presentation

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Aging, cognitive-motor function, and tCS

Brad Manor, PhD October 31, 2017

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NIH / NIA
Michael J. Fox Foundation
U.S.-Israel Binational Science Foundation
Marcus Applebaum Research Award
Harvard Football Players Health Study
Neuroelectrics, Inc.

Disclosures

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Aging is associated w ith progressive decline in mobility and mental function.

1 in 3 older adults fall each year. 1 in 3 older adults dies with Alzheimer’s disease or related dementia.

Are they separate problems?

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Herman et al, J Gerontol, 2010

Lowest quartile

= 3x more likely to suffer a fall

Highest quartile

= Less likely to fall than all others

Mobility and mental function are intertw ined.

n = 256

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Verghese et al, Neurology, 2014

After adjusting for age, sex, education and cohort source:

Cognitive complaints alone:
9% more likely
Slow gait alone:
40% more likely
Both:
72% more likely

Mobility and mental function are intertw ined.

n = 26,000

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Why does measuring one predict the other? Motor output and coordination Sensation Sensory integration Cognition Mood

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Cognitive dual tasking is the norm… and it disrupts our balance! Do w e ever just stand or w alk?

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Dual Task Paradigm Dual task “cost” Standing + Counting Standing 500, 497, 494…

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Standing + Counting Standing We can also measure the dual task cost to w alking.

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Dual task cost: A functionally relevant measure of cognitive reserve.

Standing Counting

Dual task cost

Cognitive Resources

Proprioceptio n

Attention, Decision Making

Balance control system Reserve

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tCS can help understand and enhance mobility and mental function in aging. Question 1: Can tDCS improve dual task standing and walking in older adults?

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Deprez et al, Neuropsychologia, 2013

Single task: Auditory Single task: Tactile Dual task Dual tasking depends upon the activation of numerous brain regions, including the left dorsolateral prefrontal cortex (dlPFC).

Where should w e target?

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Manor, Pascual-Leone et al, European Journal of Neuroscience, 2014

Dual task Assessment Dual task Assessment tDCS (Real or Sham)

tDCS characteristics

Two, 5x7cm sponge electrodes
Anode: F3 on 10-20 EEG system
Cathode: Contralateral orbit
2 mA
20 minutes
Participant at rest

Single sessions of tDCS targeting the left dlPFC mitigate dual task costs.

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Single-Task Standing Dual-Task Standing Dual Task Cost Anterioposterior Displacement (cm) Anterioposterior Displacement (cm) Mediolateral Displacement (cm) Mediolateral Displacement (cm) Mediolateral Displacement (cm) Cost (% Change in Area) A: Post Sham tDCS B: Post Real tDCS

79 year-old female w ith previous falls

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Manor et al, European Journal of Neuroscience, 2014; Journal of Cognitive Neuroscience, 2016

Single sessions of tDCS targeting the left dlPFC mitigate dual task costs.

P L E A S E D O N O T C O P Y

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37 healthy adults aged 65 and older

Manor et al, European Journal of Neuroscience, 2014; Journal of Cognitive Neuroscience, 2016

Single sessions of tDCS targeting the left dlPFC mitigate dual task costs.

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How long does the effect of one session last?
What about multiple sessions?
Functionally-limited adults?
Applications to sports, mobility, falls…

The functional implications are potentially significant! Which population?

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MOBILIZE Boston Study (Lipsitz): 765 older adults

Gait speed:

34%: preferred speed < 0.9 m/s

Executive function:

31%: TMT-B < 1.5 SD below age/education means

Depression:

29%: CES-D > 11

Likelihood of having all 3?
If random: 3%
In cohort: 17%

A common pathway?

Hajjar, Lipsitz et al; JGMS; 2009; 64; 994-1001

Slow gait, executive dysfunction, and depression are common in older adults.

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Sorond, Lipsitz et al, Ann Neurol 2011;70:213-20

All 3 symptoms have been linked to reduced functional activation of the prefrontal cortex.

Fast walkers Slow walkers

N-back cognitive test Transcranial Doppler Ultrasound

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Inclusion Exclusion

Walking speed ≤ 1.0 m/s Inability to stand/walk unassisted Mild-to-moderate executive dysfunction Severe dementia Evidence of mildly-depressed affect Severe depression Diabetes History of stroke Parkinson’s, other neurological disease Contraindications to MRI or tDCS

Pilot, randomized, sham-controlled trial in adults aged 65 years and older: n = 20 Can tDCS improve outcomes in those w ith slow gait, executive dysfunction and depression?

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V1

Behavioral assessment (cognition/mood/mobility/dual task)

V2

MRI (structural, resting state)

V3-12 • tDCS intervention (10 sessions) V13

Behavioral assessment

V14

MRI

V15

Behavioral assessment (2 week follow-up)

Study procedures:

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Individuals w ere randomized to tDCS targeting the left dlPFC or inactive sham stimulation.

Left dorsolateral prefrontal cortex Image courtesy of Neuroelectrics, Inc

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Table 1: Catalyst sample characteristics (mean±SD) Real tDCS Sham tDCS P value Sample (n) 10 10 Age (years) 83 ± 10 79 ± 10 0.35 Gender (women; men) 5; 5 6; 4 4m gait speed (m/s) 0.73 ± 0.17 0.72 ± 0.14 0.96 Trail Making Test B (sec) 142 ± 64 152 ± 78 0.68 Geriatric Depression Scale (scale 0-12) 3.4 ± 3.0 4.0 ± 2.5 0.47 Mini Mental State Examination (MMSE) 24.1 ± 3.4 25.5 ± 3.3 0.38

We successfully recruited a small cohort w ith concomitant functional limitations. No unexpected adverse events; excellent compliance & blinding

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500, 497, 494… Trends (p < 0.1) towards increased performance were also observed in:

Timed Up-and-Go (TUG) test of mobility
Preferred gait speed

Multiple sessions of tDCS induced lasting improvements in dual task performance.

(2 weeks) (3 days) Dual task cost to standing postural sway speed (%)

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Multiple sessions of tDCS induced lasting improvements in cognitive function.

tDCS-related improvements were limited to the “executive function” sub-score. To do: Are tDCS-related improvements linked to changes in brain function?

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Is the left dlPFC really the best target?

Image courtesy of Neuroelectrics

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Is the left dlPFC really the best target? 25 older adults with a recent history of falling

Inter-subject variability in effectiveness is still high.

Multi-target Single-target Sham

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What’s causing such high inter-subject variability?

Electrode size Placement Direction of flow Current intensity Current duration Anatomy:

Skin
Skull
CSF
gray mater
White mater

Brain physiology Brain state

Off-line (resting)
On-line

Biological aging—especially in the presence of disease—alters brain structure and function, and thus, the flow and effects of tDCS.

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Brain anatomy can be very different!

68 year old male:

No diagnosed disease
Fast gait
Normal executive function
Regular exercise

79 year old male:

No diagnosed disease
Slow gait
Poor executive function
Sedentary