Change of Cognitive function

and Learning ability

in Allergic Rhinitis

Department of Pediatrics

Kyung Hee Univ. Sch of Med

Choi, Sun Hee. M.D.

November 2011

The Korean Academy of Asthma, Allergy and Clinical Immunology

SYMPOSIUM II. Comorbidities of allergic rhinitis

Severity of Allergic Rhinitis

• Mild allergic rhinitis symptoms include the following:

a.Normal sleep

•Normal daily activities, sports and leisure

•Normal work and school

•No troublesome symptoms

Moderate-to severe allergic rhinitis symptoms must

include one or more of the following:

•Abnormal sleep

•Impairment of daily activities, sport and leisure

•Problems caused at work or school •Troublesome symptoms.

ARIA 2008

Cognitive function

High level functions carried out by the

human brain, including comprehension

and use of speech, visual perception and

construction, calculation ability, attention

(information processing), memory, and

executive functions such as planning,

problem-solving, and self-monitoring.

From Wikipedia, October 2011

Wilken JA, et al. Ann Allergy Asthma Immunol 2002;89:372-80.

Allergic rhinitis

• Each year affect between 1.4% and 39.7%

• Peak age of onset in adolescence

• Sleep problem affects on the cognition, esp in

Perennial allergic rhinitis

• Methods to test cognitive function need training

• This talk will be focused on ≥ adolescence and

childhood with seasonal allergic rhinitis

Scholastic achievement is cumulatively

retarded by its treatments and/or the

disorder until 1990’s !

CON: AR doesn’t affect on the

cognition

Kremer B, et al. Clin Exp Allergy 2002;32:1310-5.

• Cross-sectional study case-control study

• sAR patients during pollen allergen exposure in the spring and

summer or pAR patients during increased symptom burden in the

fall and winter

Cognitive performance for groups

Psychological wellbeing for groups

PRO: AR affect on the cognition!

-Evidences-

Effects of seasonal allergic rhinitis

on selected cognitive abilities

• Ragweed AR patients-control study: 20-54year old

1. Stenberg memory scanning

task

2. Hick paradigm choice reaction

time test

3. Conners continuous

performance test

4. Paced auditory serial addition

test

5. Busche selective reminding

test learning trials

6. Digit span forward and

backward test

7. Salthouse listening span task

8. Buschke selective reminding

test delayed recall

Mashall PS, et al. Ann Allergy Clin Immunol 2000;84:403-10.

Ragweed

Winter

Ragweed

Symptom

scores over

the

previous 3

days

Changes in Hick paradigm choice

reaction time test decision making

speed by group, season, and

reaction time test condition

Changes in Buschke selective

reminding test consistent long-

term retrieval score in and out of

ragweed seasons by group

P 0.06

P 0.05

Recent memory, attention, motor speed: not affected !

Prevalence of impaired scores on working memory test by season and group.

Higher percentage of allergy subjects were impaired on the SLST, and

Buschke!

*

Effects on Fatigue and Mood

• Allergic patients with ragweed AR, and control between

age of 23 to 50

• Ragweed season 1996, winter of 1997, ragweed season

1997.

• Symptom score, assessment of mood (positive affect

scale: PA, negative affect scale: NA), assessment of

fatigue(general fatigue, physical fatigue, mental fatigue,

reduced motivation) reduced activity)

Marshall PS, et al. Psychosomatic Med 2002;64:684-91.

Asymptomatic group Final performance testing

n=107 n=94 n=62

n=413 n=302 n=234

Symptomatic group Final performance testing

Conducted during off-

season for AR symptom

Case control study in Adults Randomized parallel, case-control, blinded study

Comprehensive battery of computerized cognitive performance

tests

Wilken JA et al. Ann Allergy Asthma Immunol 2002;89:372-80.

AEU: six 90min allergen priming

session over a 7-day period

Kay Continuous Performance Test for Vigilance

But, No correlation between any of composite symptom scores and

decrements in cognitive performance (-0.11~0.15)

Throughput § : composite measure of efficacy (response time, accuracy)

Allergen challenge test on Cognition

and learning

• 26 healthy volunteers

• 25 patients with SAR to tree, grass or weed: age

between 18-26yr, positive medical history, anti-

allergic treatment during the previous season.

• Out of the allergy season.

• In Netherland.

Hartgerink-Lutgen et al. Clin Exp Allergy 2009;39:500-8.

Long cognitive performance test

(sustained attention test)

Planning.

Working-

memory.

Cognitive-

flexibility

Short

cognitive

test

3.4 8.0

Psychomotor:

reaction time

Subjective rating of mental efforts

Childhood and adolescence

Virtual vs Real world

Eighty-three persons (12-17yr old) with grass or

ragweed AR

Juniper EF, et al. J Allergy Clin Immunol 1994;93:413-23

Case control study in children

• 10-12 year old, winter to early spring

• N=52 with seasonal allergic rhinitis.

• 21 normal without history of allergy

• Dutch language intelligence test, ‘didactic

stimulation’: factual knowledge score, concept

knowledge score, application knowledge score,

composite learning score

Vuurman EF, et al. Ann Allergy 1993;71:121-6.

Group Male Female

N Age Cognitive

score

N Age Cognitive score

Normal 13 11.4 75(5.1) 8 11.1 74(6.6)

Loratadine 11 11.0 74(6.7) 8 11.4 76(6.1)

Placebo 12 11.1 79(5.5) 8 11.2 76(6.9)

Diphenhydramine 12 11.2 76(6.1) 8 11.2 78(7.3)

Enrollment

: case-control

Observation

for symptom

Training

day

Examination

day

Instruction for Sahel

desert & agriculture

2 weeks

Factual, Conceptual knowledge score, Knowledge application score

Mean composite learning score

Actual examination performance

• 15-17 year old

• General certificate of secondary

education(GCSE) examination in UK

• During a 6-week period (mid May to the end of

June)

• Mathematics, English, Science: drop 1 grade

Practice

Examination

Winter

Questionnaire

before pollen

season

Questionnaire on the day of each

relevant examination during pollen

season

Walker S, et al. J Allergy Clin Immunol 2007;120:381-8

Relationship between self-reported allergic rhinitis, allergic rhinitis

mediation, and asthma and case/control status

Walker et al. J Allergy Clin Immunol 2007;120:381-8

relationship

Hyperactivity, Attention- deficiency n=30, Psychiatrist diagnosed ADHD patients

Brawley et al. Ann Allergy Asthma Immunol 2004;92:663-7

• Neuro-immune system in allergy, depression and suicide. • Postolache TT, et al. Curr Treat Options Neurol 2008;10:363-76

What in CNS attributable to cognitive

function rather than mechanical explanation

in allergic rhinitis?

‘No correlation between any of composite symptom scores and

decrements in cognitive performance (-0.11~0.15)’ Wilken JA et al. Ann Allergy Asthma Immunol 2002;89:372-80.

‘Sickness behavior in allergic rhintis’.

Vuurman EF, et al. Ann Allergy 1993;71:121-6.

Allergic rhinitis in rodents:

Allergic inflammation and Anxiety

RI (Resident-intruder) test: unfamiliar intruder animal

EPM(elevated plus-maze) test: time and number of crossing between 2open room and

2closed room

OF(open field) test: ambulatory motor activity in 49x49cm room

Tonelli LH, et al. Brain, behavior, and Immunity 2009;23:784-93.

Mice

Rats

Activity in the open field test of mice and rats. Activity in the elevated plus-maze test of mid

and rats

Latency to initiate contact and duration of social

contact in Resident-intruder test

TH2 Cytokines in mice and rats, compared with control

Relative increasing in corticotropin releasing

factor after induction of allergic rhinitis

Anxiety-like behavior and reduced social interaction paralleled by increased TH2

cytokines and CRF in experimentally induced AR!

Rosenkranz MA, et al. PNAS 2005;101:13319-24

Asthma symptom exacerbation & Emotion:

inflammation and change of brain MRI

Allergen challenge test in human

r=0.92, P<0.01 r=0.99 P<0.001

r=0.98, P<0.001 r=-0.97 P<0.01

CNS activities predict

peripheral inflammatory potential and lung function

Conclusion

• Different tools by psychiatrists, not allergists.

• Allergic rhinitis impairs the cognitive function.

• Mechanism yet determined but in part, direct influence

on CNS.

• How to minimize the impairment of cognitive function.

• Further, the research about cognitive function in

perennial AR or persistent AR.

Thank you for attention!