Language Functions in the Aging Brain:

A Pathophysiological Exploration

Dalia Cahana-AmitayVA Boston Healthcare System & Boston University School of

Medicine

LSA 2013 Language & Aging Workshop

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Gap: Neurobiological

Mechanisms

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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

What Do we Know?

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Effects of Hypertension (HTN) and Diabetes Mellitus (DM) on Lexical Retrieval (Albert et al., 2009, JAGS)

ANT BNT ANT BNTHTN DM

-2.50

-2.00

-1.50

-1.00

-0.50

0.00

0.50

1.00

UnadjustedAdjusted for Demographics

% Difference

*

*

+

+

* - p<.05+ - p<.10

Percentage Difference in Naming Accuracy from Participants with HTN and DM

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Effects of HTN and DM on Sentence Processing in Aging (Cahana-Amitay et al., 2013, JGPS)

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Effect of Metabolic Syndrome on Lexical Retrieval AND Sentence

Processing

ANT ES BNT MN

-4

-3.5

-3

-2.5

-2

-1.5

-1

-0.5

0

Percentage Difference

* - p<.05

*

*

Percent difference in Accuracy on Naming and Sentence Comprehension Tasks in those with Metabolic Syndrome

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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”

Vascular and Metabolic Health: Pathophysiologic Consequences

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Biological Systems Affected

Systems The hypothalamic-

pituitary-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

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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

Cognitive effects of Physiologic Dysregulation

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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)

Cumulative Effects

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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)

Effects on Language? Unexplored

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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

Why Look at Language and Physiologic Dysregulation?

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The Neural Correlates of Cortisol Regulation in Response to Stress

Dedovic, Duchesne, Andrews, Engert, & Pruessner, 2009, NeuroImage)

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(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?

Research Questions

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Cardiovascular/Respiratory

Anthropometry Metabolic Inflammation

Systolic Blood PressureDiastolic Blood PressureHeart RateFVC FEV1

  

Body mass index (BMI)Waist circumference Waist/Hip Ratio 

Fasting GlucoseInsulin HbA1cTriglycerides Low Density Lipoprotein high Density LipoproteinHomocysteineAlbuminCreatinine

High-Sensitivity C-Reactive ProteinWhite blood cell count

Biomarkers for Physiologic Dysregulation Index

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Measure Description Perceived Stress Scale (PSS) (Rohleder

et al., 2004)

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).

Perceived Stress Reactivity Scale (PSRS)(Kirschbaum & Hellhammer, 1994)

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.

Chronic Stress Screening Scale (CSSS) (Rohleder et al., 2009)

Related to Sympathetic Nervous System (salivary alpha-amylase (sAA)). The CSSS is a 12-item scale derived from the Trier Inventory for the Assessment of Chronic Stress a large chronic stress inventory.

Perceived Stress Measures

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Those with greater degree of physiologic dysregulation and perceived stress will evidence worse language performance

These effects will be independent of age

Predictions

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Stress-Induced Pathophysiology of Language in the Aging Brain

Existing evidence Aim 1 Aim 2

Stress Language

Health Cognition

Aging Brain