hearing loss, cognitive decline & brain aging
TRANSCRIPT
Hearing Loss, Cognitive
Decline & Brain Aging
Frank R. Lin, M.D. Ph.D.
Associate Professor of Otolaryngology, Geriatric Medicine,
Mental Health, and Epidemiology
Johns Hopkins University
Baltimore, Maryland
Healthy Aging
Healthy Aging
Maintaining Physical
Mobility & Activity
Avoiding Injury
Health Resource
Utilization
Keeping Socially
Engaged & Active
Hearing Loss
Cognitive Vitality
& Avoiding Dementia
Projected Worldwide
Prevalence of
Dementia 2010-2050
Alzheimer’s Disease International, 2009
Hearing Loss & Cognition/Dementia Basic Questions
• Is HL independently associated with cognitive
decline/dementia?
• Does treating HL reduce the risk of cognitive
decline/dementia?
• How can HL be effectively addressed in the
community?
Hearing Loss & Dementia Common Cause or Modifiable Risk Factor
Hearing
Loss
Impaired
Cognition &
Dementia
Common
pathological process
?
“Effortful listening”
Inte
nsity
“Sunday”
Presbycusis &
Cochlear impairment
Decreased hearing
sensitivity & poor
frequency resolution
Hearing
Loss
Common
pathological process
Cognitive Load
Impaired
Cognition &
Dementia
Hearing Loss & Dementia Common Cause or Modifiable Risk Factor
Hearing Loss & Cognitive Load
Cognitive Resource Capacity
Available Cognitive
Resources
For Performance of Tasks
Age-Related
Decline
Auditory
Perceptual
Processing
Requirements
• Kahneman model of shared attention and
resource capacity (D. Kahneman, Attention & Effort,1973)
Hearing Loss & Cognitive Load
Poorer hearing is associated with:
A. Reduced language-driven activity in primary auditory pathways
B. Increased compensatory language-driven activity in pre-frontal cortical areas
Peelle et al, J. Neurosci, 2011
Grossman et al, Brain Lang, 2002
B
Hearing
Loss
Common
pathological process
Cognitive Load
Impaired
Cognition &
Dementia
Hearing Loss & Dementia Common Cause or Modifiable Risk Factor
Brain
structure/function
Does Peripheral Hearing Loss Affect
Brain Structure/Function?
In humans, hearing loss associated in cross-sectional studies with:
• Reduced cortical volumes in primary auditory cortex • Husain et al. 2010 Brain Research
• Peelle et al, 2011 J. Neuroscience
• Eckert et al. 2012 JARO
• Variation in central auditory white matter tract integrity on DTI • Chang et al. 2004 Neuroreport
• Lin et al. 2008 J. Magn Reson Imaging
In animals, cochlear impairments associated in longitudinal studies with:
• Tonotopic reorganization of auditory cortex • Kakigi et al 2000 Audiology
• Cheung et al 2009 J. Neurosci
• Morphologic changes in central neuronal structures • Groschel et al 2010 Neurotrauma
Structure/
Function
Alzheimer’s
Neuropathology
Microvascular
Disease
Hearing
Impairment
Double Hit Theoretical Model Hearing Loss & Brain Structure/Function
F. Lin & M. Albert, Aging & Mental Health, In press 2014
Hearing
Loss
Common
pathological process
Cognitive Load
Impaired
Cognition &
Dementia
Hearing Loss & Dementia Common Cause or Modifiable Risk Factor
Brain
structure/function
Social Isolation
Social Isolation
Impaired
Cognition &
Dementia
Health Behavioral
Pathways • Smoking
• Adherence to medical tx
• Diet
• Exercise
Physiologic
Pathways • HPA axis response
• Immune system fxn
• Cardiovascular reactivity
Psychological
Pathways • Self-esteem
• Self-efficacy
• Coping
• Sense of well-being
Social isolation is
associated with
upregulation of pro-
inflammatory genes
& increased
inflammation Cole & Cacioppo, Genome Biology, 2007
Cole & Cacioppo, PNAS, 2011
Hearing
Loss
Common
pathological process
Cognitive Load
Impaired
Cognition &
Dementia
Hearing Loss & Dementia Common Cause or Modifiable Risk Factor
Brain
structure/function
Social Isolation
Hearing Loss & Cognition/Dementia Datasets for Epidemiologic Analyses
• NHANES: National Health and Nutritional Examination Surveys
• Cross-sectional, representative sample of U.S. population
• BLSA: Baltimore Longitudinal Study of Aging
• Ongoing prospective study of older adults since 1958
• HealthABC: Health, Aging, & Body Composition Study
• Prospective, population-based study of ~3000 adults 70 years and older
Hearing Loss & Cognition/Dementia Epidemiologic Analyses
• Predictor variable • Speech-frequency pure tone average (0.5 – 4 kHz) in the
in the better-hearing ear
• Dependent Variable • Neurocognitive tests; Adjudicated diagnoses of dementia
• Covariates • Age, diabetes, smoking, hypertension, stroke, sex,
education, etc.
Hearing Loss & Cognition/Dementia Neurocognitive Testing
– Memory
• Free and cued selective reminding test (FCSRT)
– Executive Function
• Trail Making B
• Stroop Mixed
• Digit symbol substitution
– Psychomotor/processing speed
– Verbal function & language
These tests are
not dependent
on hearing.
Hearing Loss & Cognition Executive Function: Trail Making B
Trail Making B
1
8
7
6
5
1
4
3
2
D
C
A
H
B
E
G
F
Hearing Loss & Cognition Executive Function: Stroop Mixed
1
GREEN
RED
RED
GREEN
BLUE
BLUE
GREEN
Stroop
Mixed
RED
YELLOW
BLUE
BLUE
GREEN
YELLOW
BLACK
Hearing Loss & Cognition Executive Function: Digit Symbol Substitution Test (DSS)
DSS: Digit
Symbol
Substitution
Test
N = 605 adults 60-69 years Lin, J. Geront. Med. Sci., 2011 NHANES
BLSA N = 347 adults >60 years
Hearing Loss and Cognition Cross-Sectional Studies
Models adjusted for age, sex, race, education, diabetes, smoking, hypertension
Lin et al., Neuropsych., 2011
Hearing Loss & Cognitive Decline Adjusted 3MS & DSS scores by years of follow-up and hearing
loss status in 1,966 adults > 70 years followed for 6 years
Lin et al. JAMA Int Med. 2013
Adjusted for age, sex, race, education, study site, smoking status, hypertension,
diabetes, and stroke history
41% faster rate
of cognitive
decline in 3MS
scores in HL
vs. NH
32% faster rate
of cognitive
decline in DSS
scores in HL
vs. NH
Hearing Loss & Incident Dementia Dementia incidence in 639 adults followed for >10 years in
the BLSA
Lin et al., Arch Neuro., 2011
HR 95% CI p
Mild 1.89 1.00 – 3.58 0.05
Moderate 3.00 1.43 – 6.30 .004
Severe 4.94 1.09 – 22.4 .04
Risk of incident all-
cause dementia
(compared to normal
hearing)a
a Adjusted for age, sex, race, education,
DM, smoking, & hypertension
Does Peripheral Hearing Loss Affect
Brain Structure/Function?
Cognitive
Function
Alzheimer’s
Neuropathology
Microvascular
Disease
Hearing
Impairment
F. Lin & M. Albert, Aging & Mental Health, In press 2014
Hearing Loss & Brain Structure
Poorer hearing is associated with reduced gray
matter in the auditory cortices
Peelle et al, J. Neurosci, 2011
Hearing Loss & Accelerated
Brain Volume Decline
BLSA
• Hypothesis: Hearing loss is associated with
accelerated atrophy in the superior, middle,
and inferior temporal gyri
• 126 participants (56-86 yrs) in
the neuroimaging substudy of
the BLSA • Mean follow-up duration of 6.4 years
• 1.5T MRI performed annually
+ < .05; * < .01; ** <.001
Estimated
Annual
Rates of
Change in
Brain
Volume
(cm3/year)
Lin et al., Neuroimage 2014
Voxel-Based
Analyses
Difference in
mean gray
matter volume
change in those
with HL vs. NH
Faster decline in
brain volume in
HL vs. NH
Lin et al., Neuroimage 2014
L
Hearing
Loss
Common
pathological process
Cognitive Load
Impaired
Cognition &
Dementia
Hearing Loss & Dementia Common Cause or Modifiable Risk Factor
Brain
structure/function
Social Isolation
Hearing Loss & Cognition/Dementia Basic Questions
• Is HL independently associated with cognitive
decline/dementia?
• Does treating HL reduce the risk of cognitive
decline/dementia?
• How can HL be effectively addressed in the
community?
The question of whether treating hearing
loss could delay cognitive decline or
dementia remains unknown
There has never been a randomized clinical trial of
treating hearing loss to explore effects on
reducing the risk of cognitive decline/dementia
Best-Practices Hearing
Rehabilitative Treatment
Cognitive Functioning
Enhanced Verbal Communication & Social Engagement
Audibility of speech & environmental
sounds
Intervention Proximal/Mediating
Outcomes
Primary
Outcome
Secondary
Outcomes
HRQL
Social/Leisure Activities
Daily
Functioning
Mobility
Brain structure (MRI)
Conceptual Model for HL-Cognition RCT In collaboration with Marilyn Albert, Joe Coresh, Richey Sharrett, George
Rebok, ARIC Study Team (T. Mosley, D. Knopman, L, Coker, C. Jack), and U.
South Florida (T. Chisolm, A. Eddins)
HL-Cognition RCT Characteristics
• Trial to be nested within an ongoing observational study –
Atherosclerosis Risk in Communities Neurocognitive Study • Cohort of ~16,000 adults in 4 US cities followed for over 25 years
• Sample size ~ 800 individuals with normal cognition age 70-
79 with mild-moderate HL • Possible additional cohort of 500 individuals with Mild Cognitive Impairment
• Powered to detect 0.25 effect size difference in rate of
cognitive decline over 3-5 years between treatment &
control group
• Timeline:
• NIA planning grant — 2014-2015
• Study recruitment — 2016-17
• 3-5 years follow-up — 2017-2021
Hearing Loss & Cognition/Dementia Basic Questions
• Is HL independently associated with cognitive
decline/dementia?
• Does treating HL reduce the risk of cognitive
decline/dementia?
• How can HL be effectively addressed in the
community?
RCTs are great but what can be done now?
How can ARHL be effectively addressed
in the community? Future Trends
• Innovations in hearing health care HHC services &
technology
• Accessible & affordable options are needed
• Hearing loss - Potentially modifiable late life risk factor for cognitive decline/dementia
Both for 1° and 2°/3° prevention of cognitive decline
• Limitations of current (only) gold-standard model of hearing healthcare:
Hearing Health Care & Dementia Potential & Limitations
Gold
Standard
Audiology
Care
$$$$
3-6 months
Current Model of
Hearing Health
Care
Innovations in Hearing Health Care Affordable & Accessible “Stepping Stones” are Needed
for Hearing Health Care
• Technology – Personal sound amplifiers
– Over-the-counter “hearing aids”
– Incorporation of Bluetooth allowing for integration with
smart phones & wireless sound transmission
– Cost USD $100-300
• Services - Community health care workers
– Community-based hearing screening
– Counseling, education, & provision of sound amplifiers &
other assistive technologies
– Referral as needed
Gold
Standard
Audiology
Care
$$$$
3-6 months
Additional Models
of Hearing Health
Care are Needed
Personal Sound
Amplifiers
$
3 hours
Community
Health Worker
$$
1 day
Hearing Aid
Dispenser
$$$
1-2 months
Pilot Study of CHW Model to Provide HHC
Services In collaboration with HLAA, C. Compton-Conley, T. Chisolm, N. Marrone
Individuals &
communication
partner
One-hour HL Intervention
1) Hearing assessment
2) Counseling/Education
- Expectation management
- Communication Strategies
3) Device Orientation
- Self-fit amplification device
- Assisted listening device
Johns Hopkins
Memory Clinic
Recruited over 6
months
Pilot
Intervention
Study
RCT &
Nonprofit
501c3
Implementation
& Dissemination
Studies
2015-18 2015 2014
Outcomes at BL & 1 month
in patient & care provider
Daily functioning
Caregiver burden
Total
Intervention
Cost: $150
How can HL be effectively addressed in
the community? Future Trends
• Innovations in hearing health care HHC services &
technology
• Accessible & affordable options are needed
• Understanding & approaching hearing loss in the
context of healthy aging/public health
Institute of Medicine Workshop
IOM Workshop on
Hearing Loss & Healthy Aging January 13-14, 2014 Washington, D.C.
• Two-day workshop addressing: – Implications of HL for healthy aging/public health & needed
areas of research
– Developing innovative models of care & technologies to address
HL
– Short & long-term collaborative strategies to approach HL as a
public health priority in the U.S.
www.iom.edu/hearingloss-aging
• Hypertension Heart attack & stroke
– Intervention: Medication, Lifestyle modification
• Hearing loss Cognitive decline, dementia
– Intervention: Comprehensive hearing tx?
• What are the consequences of hearing
loss for older adults?
• What is the impact of treating hearing
loss on older adults?
• How can hearing loss be effectively
addressed in the community?
“Are you telling me that I’m
going to develop
dementia?”
Acknowledgments
• NIDCD K23DC011279
• Triological Society &
American College of
Surgeons Clinician
Scientist Award
• Eleanor Schwartz
Charitable Foundation
• NIA Pepper OAIC
Career Development
Award
• NIA Intramural
Research Program
• Johns Hopkins
• George Rebok
• Joe Coresh
• Marilyn Albert
• Josh Betz
• Richey Sharrett
• BLSA
• Luigi Ferrucci
• Susan Resnick
• Jeff Metter
• Yang An
• Josh Goh
• HealthABC
• Tamara Harris
• Eleanor Simonsick
• Kristine Yaffe
