Language Functions in the Aging Brain:
A Pathophysiological Exploration
Dalia Cahana-Amitay
VA Boston Healthcare System & Boston University School of Medicine
LSA 2013 Language & Aging Workshop
Gap:
Neurobiological Mechanisms
1
What Do we Know?
 Cardiovascular and metabolic changes in the brain are
factors underlying some of the language changes
observed with age
 Evidence from studies examining effects of
 Hypertension
 Diabetes
 The metabolic syndrome
2
Effects of Hypertension (HTN) and Diabetes
Mellitus (DM) on Lexical Retrieval (Albert et al., 2009, JAGS)
Percentage Difference in Naming Accuracy from Participants
with HTN and DM
1.00
% Difference
0.50
0.00
-0.50
-1.00
ANT
BNT
+
*
HTN
ANT
DM
+
-1.50
*
-2.00
-2.50
* - p<.05
+ - p<.10
BNT
3
Unadjusted
Adjusted for
Demographics
Effects of HTN and DM on Sentence
Processing in Aging
(Cahana-Amitay et al., 2013, JGPS)
4
Effect of Metabolic Syndrome on
Lexical Retrieval AND Sentence Processing
Percent difference in Accuracy on Naming and Sentence Comprehension Tasks in
those with Metabolic Syndrome
0
-0.5
ANT
ES
-1
-1.5
Percentage
Difference
*
-2
-2.5
-3
-3.5
*
-4
* - p<.05
5
BNT
MN
Vascular and Metabolic Health:
Pathophysiologic Consequences
 Decline in vascular health and occurrence of
metabolic diseases, can result from chronic
multisystem physiologic dysregulation (McEwen & Stellar, 1993;
McEwen, 1998; Glei et al., 2005; Piazza et al., 2010).
 Physiologic dysregulation: the long-term effects of
over/under-activation of physiological systems, in
response to environmental stressors, often
interpreted as “aging effects”
6
Biological Systems Affected
Systems
 The hypothalamicpituitary-adrenal (HPA)
axis,
 The sympathetic nervous
system (SNS),
 The immune system,
 Cardiovascular and
metabolic processes
Biomarkers
 Cardiovascular
 Metabolic
 Inflammatory
 Example: glucocorticoids,
such as cortisol, related
to HPA system
7
Cognitive effects of
Physiologic Dysregulation
 Studied mostly in relation to memory
 Chronically elevated levels of cortisol among older
adults are associated with impaired memory (e.g., Lupien et
al., 2005; Lupien et al., 2007; MacLullich et al., 2005)
 Chronicity accelerates neural changes that “age” the
brain
8
Cumulative Effects
 Not all biomarkers of physiologic dysregulation carry equal
weight in predicting functional changes among older
adults (Karlamangla et al., 2002)
 Cumulative effect among older adults associated with:




Physical decline
Cognitive impairment
Mood changes
Increased risk of mortality
(Goldman et al., 2006; Juster, McEwen, & Lupien, 2010; Seeman et al., 2010)
9
Effects on Language? Unexplored
 BUT some
 Impairments in recall of confrontation naming (Seeman et
al., 2010)
 Reduced category fluency (Greendale et al., 2000; MacLullich et al., 2005;
Beluche et al., 2010)
10
Why Look at Language and
Physiologic Dysregulation?
Age-related language decrements are associated with
vascular and metabolic changes in brain regions which
are also a prime target of stress-induced
pathophysiological processes
11
The Neural Correlates of Cortisol
Regulation in Response to Stress
Dedovic, Duchesne, Andrews, Engert, & Pruessner, 2009, NeuroImage)
12
Research Questions
 (1) Does stress-induced physiologic dysregulation
(measured by a summary index of biomarkers and
self-ratings of stress) adversely affect lexical retrieval
and sentence processing abilities (measured in terms
of poorer accuracy)?
 (2) If so, are these effects independent of age
effects?
13
Biomarkers for
Physiologic Dysregulation Index
Cardiovascular/
Respiratory
Systolic Blood
Pressure
Diastolic Blood
Pressure
Heart Rate
FVC
FEV1
Anthropometry
Metabolic
Body mass index
(BMI)
Waist circumference
Waist/Hip Ratio
Fasting Glucose
High-Sensitivity CInsulin
Reactive Protein
HbA1c
White blood cell count
Triglycerides
Low Density Lipoprotein
high Density Lipoprotein
Homocysteine
Albumin
Creatinine
14
Inflammation
Perceived Stress Measures
Measure
Perceived Stress
Scale (PSS)
(Rohleder et al., 2004)
Perceived Stress
Reactivity Scale
(PSRS)
(Kirschbaum &
Hellhammer, 1994)
Chronic Stress
Screening Scale
(CSSS)
(Rohleder et al., 2009)
Description
Related with basal HPA axis activity. The PSS is a 10-item questionnaire probing
participants’ feelings and thoughts experienced during the last month. The participants
are asked to rate how often they have felt or thought in a certain way. Participants with
higher PSS scores have been found to have lower Mini-Mental scores (Wolf et al,. 2005).
Related to Sympathetic Nervous System (salivary alpha-amylase (sAA)). A 23-item
questionnaire consisting of 1 overall scale and 5 subscales, designed to assess
participants’ subjective perception of stress in dealing with different situations they may
have encountered in the past. The test has been shown to have high consistency and has
been associated with self-efficacy, neuroticism, chronic stress and perceived stress.
Related to Sympathetic Nervous System (salivary alpha-amylase (sAA)). The CSSS is a 12item scale derived from the Trier Inventory for the Assessment of Chronic Stress a large
chronic stress inventory.
15
Predictions
 Those with greater degree of physiologic
dysregulation and perceived stress will evidence
worse language performance
 These effects will be independent of age
16
Stress-Induced Pathophysiology of
Language in the Aging Brain
Cognition
Health
Aging Brain
Language
Stress
Existing evidence
Aim 1
17
Aim 2