Twinning 22.-23.10.2003

Neuropsychology in neurotoxicologyNeuropsychology in neurotoxicology

Ritva Akila, Ritva Akila, neuropsychologistneuropsychologist

Finnish Institute of Finnish Institute of Occupational Health Occupational Health

Helsinki, FinlandHelsinki, Finland

ritva. akila@ttl.firitva. akila@ttl.fi

Twinning 22.-23.10.2003

Clinical neuropsychologyClinical neuropsychology

Clinical neuropsychology studies human behaviour as it relates to normal and abnormal functioning of the central nervous system A neuropsychologist: a psychologist specialized in neuropsychology In Finland: four-year theoretical and clinical training programme after master's degree in psychology:

specialization studies (3200 hours) supervised working experience licenciate research -> degree of licenciate in psychology ~ 150 psychologists specialized in neuropsychology http://www.neuro.fi/npsy.htm (also in English)

Twinning 22.-23.10.2003

Chronic solvent encephalopathy (CSE)Chronic solvent encephalopathy (CSE)

Subjective symptoms Interview of a patient with

memory problems

Twinning 22.-23.10.2003

Symptoms of workers with CSESymptoms of workers with CSE

Acute symptomsAcute symptoms: dizziness, headache, nausea, feelings of intoxication

Common chronic symptoms:Common chronic symptoms:• forgetfullness• memory does not tolerate intervening factors • difficulties in learning new things• irritability, depressive mood, mood swings• feeling tired, problems in maintaining wakefulness• sleep problems• difficulties getting things started, difficulties in planning• slowness• withdrawal from social relations• headache, impotence

Twinning 22.-23.10.2003

Memory problems - interview IMemory problems - interview I

When did the memory problems begin?

How did the memory problems begin? Suddenly or gradually

What kind of memory difficulties the patient has ? Remembering old things? Learning new material? Problems with attention or concentration ? Tolerance to intervening factors?

How much problems does poor memory cause? At work, at home, in hobbies?

Twinning 22.-23.10.2003

Memory problems - interview II Memory problems - interview II

How much does the person worry about the memory ?

Other cognitive symptoms? Speaking, finding words Finding familiar places, routes Reading, writing, arithmetics Practical skills Speed of performance

Psychosocial stressors?Evaluation of depression is essential

Observation, interview, ratings, questionnaires

Twinning 22.-23.10.2003

Affective disorder in CSE ?Affective disorder in CSE ?

a) Psychological reaction to stressful events exposure health effects impairment in cognitive and social functioning

b) Abnormal brain function (metabolism) in neural systems dealing with emotions

limbic structures frontotemporal areas CSE patients often complain about problems in

initiation, decision making, withdrawal

c) Depression as a psychiatric disorder caused by other reasons

Twinning 22.-23.10.2003

Memory problems - interview IIIMemory problems - interview III

Central nervous system diseases, head injuries? Alcohol consumption, drugs?

Medication affecting central nervous system?

Sleep disorders, daytime sleepiness?

Chronic pain?

Education?

Work history? Exposure to neurotoxicants

(past/present)?

Social functioning?

Family history of memory disturbances?

Twinning 22.-23.10.2003

Toxic encephalopathyToxic encephalopathy

Neuropsychological assessment Differential diagnosis

Twinning 22.-23.10.2003

Neuropsychological assessment:Neuropsychological assessment:Sources of informationSources of information

Interview

Questionnaires

Observation

Standardized tests

Neuropsychological tasks

Twinning 22.-23.10.2003

Neurocognitive domains assessedNeurocognitive domains assessed

Attention, concentration

Learning and memory

Intelligence, Reasoning ability

Visual functions: visuospatial and constructive

Verbal functions: speech and language

Eye-hand co-ordination

Psychomotor functions

Reading, Writing, Arithmetics

Twinning 22.-23.10.2003

How to interpret the results?How to interpret the results?

Psychometric interpretation, "numbers"

Qualitative aspect of cognitive functioning

planning

monitoring

type of errors made

speed of information processing & performance

motivation, effort

Questionnaires, personality assessment

Twinning 22.-23.10.2003

Neuropsychological findings in CSENeuropsychological findings in CSE

What is impaired? Attention (shifting, dividing) Ability to learn new material (visual, verbal) Retrieval process (slow and uneffective) Information processing speed Performance speed (speech, eye and hand co-

ordination, visuomotor functions)

What is intact? Basic verbal or visual functions Academic skills (if not developmental handicap!) No more forgetting than normally Recognition memory

Twinning 22.-23.10.2003

Memory in depressionMemory in depression

Patients underestimate their memory capacity Memory complaints are frequentWhat is unimpaired in the memory tests?

Short term memory Autobiographical memory Semantic memory Recognition memory

What is impaired? Visual memory Effortful reasoning Information processing speed

prefrontal dysfunction hypothesis

Twinning 22.-23.10.2003

Alcohol & drugsAlcohol & drugs

Alcoholism: about half of patients have cognitive changes, 10% of chronic alcoholics are demented (usually vitamin B1 deficiency)

neurocognitive deficits: memory, learning, visuospatial functions, problem solving

memory disturbances are reversible, if abstinence > 5 years Cannabis: attention, learning, psychomotor functions

Stimulants (amphetamine, ecstasy, cocaine): attention, concentration, memory

Opiates (heroine, opium, morphine, codeine,): memory, reaction time

Medication with CNS effect analgesic drugs: see CNS effects of opiates diazepam: memory and psychomotor functions tricyclic antidepressants: reaction time, speed of information

processing, memory

Twinning 22.-23.10.2003

Degenerative brain diseasesDegenerative brain diseases

Dementia is quite rare in working population

Estimation of number of demented persons under

65 years in Finland: 7000 (MS ~ 5000) About 10-15 % of them has fronto-temporal

degeneration Inherited types of dementia: onset may be

already at the age of 35-45 years

Twinning 22.-23.10.2003

Mild cognitive impairment - MCIMild cognitive impairment - MCI

Diagnostic criteria of Mayo Clinic, USA (Petersen ym 1985):

Cognition: Subjective memory impairment, "memory

complaint" Objective memory impairment: impairment of 1.5

S.D. in memory testing compared to persons of same age and education level

MMSE normal to age

Functional capacity: Normal ADL Clinical Dementia Rating 0.5 (IADL may be

slightly impaired)

Twinning 22.-23.10.2003

MCI - risk of dementia ?MCI - risk of dementia ?

Neurocognitive impairment: Deficit in learning new material (word lists, logical

stories), repetition and hints does not help much, increased forgetting

Some patients are slow, some have problems with executive functions -- different diseases?

Follow up studies: MCI (with memory impairment) is associated with an

increased risk of developing Alzheimer's disease at a rate of 10-15% per year (healthy controls 1-2%).

Frequent follow-up of MCI-patients (every 6 months) is important

Twinning 22.-23.10.2003

Neuropsychological findings: Neuropsychological findings: differential diagnosticsdifferential diagnostics

+ no impairment (normal test performance) – impairment (poor test performance )

Depression MildCognitive

Impairment

Alcoholism Chronicsolvent

encephalo-pathy

Learning ― ― ― ― ―

Forgetting + ― ― ― +

Executivefunctioning

― +/― ― +/―

Visuospatialfunctions

+ +/― ― +

Reasoning + +/― + +

Speed ― +/― ― ― ―

Insight ++ ― ― +

Twinning 22.-23.10.2003

Future in differential diagnostics of CSE: Future in differential diagnostics of CSE: neuropsychological perspectiveneuropsychological perspective

Early detection, mild & subtle cognitive changes To characterise the nature of memory dysfunction

of patients with solvent encephalopathy (CSE) To study the role of attention problems in

neuropsychological findings To study the nature of slowness in performance

("input, output or both")

new tools: e.g. computerised test battery CANTAB a sensitive method for detecting early cognitive effects in

various neurodegenerative disorders (neuropathology of temporal structures vs. fronto-striatal circuitry)

Twinning 22.-23.10.2003

Neurocognitive effects of occupational Neurocognitive effects of occupational exposure to ...exposure to ...

Aluminium: subtle changes in working memory tasks, subjective symptoms, -- welders at the highest risk?

Mercury: in studies with high exposure: memory, psychomotor speed, motor functions, hand tremor

Manganese: tremor, motor functions, reaction time

Pesticides: only in cases with acute poisoning: attention, memory, flexibility in thinking, simple motor skills

Lead: attention, memory, psychomotor, reaction time

levels of exposure vary, in recent studies usually low-level neurobehavioural methods used vary: difficult to compare changes are often subtle: "statistically but not clinically

significant" symptoms vs. normal performance - ? "absence of evidence

is not evidence of absence" - do we have methods sensitive enough?

Twinning 22.-23.10.2003

Screening methods to detect neurotoxic Screening methods to detect neurotoxic adversive effectsadversive effects

Q16, Q18, Finnish questionnaire EuroQuest

Twinning 22.-23.10.2003

Some questionnaires for neurotoxic symptoms

Q16 (Örebro) and German Q18 -questionnaires: memory, headache, irritation, mood, fatigue. Yes/no alternatives for answering Exposed have excess symptoms (Lundberg 1997, Ihrig

2001)

Previously in Finland: Symptom questionnaire with 31 items (sleep, tiredness, memory, somatic complaints, mood, sensoric-motor symptoms, Hänninen 1988) and Profile of Mood Scales (POMS, McNair) were used in CSE screening. Three altenatives for the frequency og symptoms Exposed have elevated frequency of memory complaints,

subjective tiredness, and sleeping problems

Twinning 22.-23.10.2003

EuroQuest - questionnaire for neurotoxic symptoms

European consensus (1992) to detect symptoms relevant for CSE (Chouaniere et al 1997)

Self-administered questionnaire 83 questions in 10 dimensions:

chronic: neurological, psychosomatic, mood, memory and concentration, fatigue, sleep disturbances

acute irritation/intoxication, individual sensitivity, anxiety, and health perception

Frequency of symptoms: never or seldom, sometimes, often, very often

Previous studies: "Memory and concentration dimension sufficient" (Carter 2002) and "memory suggested to be the first symptom" (Chouaniere 2002)

Twinning 22.-23.10.2003

EUROQUESTEUROQUESTFinFin- Validation- Validation

Finnish asymptomatic painters vs. construction workers

(Ari Kaukianen/FIOH): Memory and concentration and mood lability correlated

to the amount of exposure information on general health and health behaviour

useful

We studied the EQ profile in 60 CSE cases (mean age 56y) at the time of receiving dg of an occupational disease or its follow-up

control group 230 aviation workers, of which a subgroup (N=63; >45y, mean 53y)

Twinning 22.-23.10.2003

EUROQUESTEUROQUESTFinFin-Results-Results

Almost in all questions (53/59) significantly more symptoms in CSE: especially in neurological and memory & concentration domains

The most often reported symptoms: 9/10 memory & concentration symptoms objects fall from hands, powerless hands/feet,

difficulties to control hand movements, hand tremor dizziness, balance difficulties to begin to work, slowness in daily activities irritability, impatiency, lack of enthusiasm

Euroquest is useful in the screening of CSE

Twinning 22.-23.10.2003

Mini-Mental State examination (MMSE) CERAD: Short neuropsychological battery

Screening methods of cognitive declineScreening methods of cognitive decline

Twinning 22.-23.10.2003

Mini-Mental State Examination - MMSEMini-Mental State Examination - MMSE

Widely used screen of cognitive functions orientation language concentration constructional praxis memory

Weaknesses: very coarse estimation of cognitive functions does not really measure memory (=learning, remembering) not sensitive: detects dementia, but not MCI

Twinning 22.-23.10.2003

CERAD - CERAD - short neuropsychological batteryshort neuropsychological battery

CERAD (The Consortium to Establish a Registry for Alzheimer's Disease)

Neuropsychological test battery, developed to reveal cognitive impairment of very early Alzheimer’s disease

Relatively brief (20-30 min) Easy to administrate

promising tool for occupational health care units

to screen patients with memory problems

Twinning 22.-23.10.2003

CERADCERADfinfin - - short neuropsychological batteryshort neuropsychological battery

Verbal fluency test Naming test MMSE Word-list memory Line drawing copy Delayed word-list recall Word-list recognition Finnish additions to improve the detection of dementia

syndromes other than AD (eg. frontotemporal dementia): Delayed recall of line drawings Draw-a-clock test

http://www.neuro.fi/cerad.htm (about CERAD in Finnish)

Twinning 22.-23.10.2003

CERADCERADfinfin study study

22 CSE patients Mean age 57.2 ±2.8 years, range 53 – 63y Mean years of education 8.4 y. All retired due to the CSE CERAD was administered during the more

comprehensive neuropsychological assessment Cut-off score for impaired performance is at the 10.

percentile. Normative US (50-89 years) and Finnish data (60-76 years) are available

Twinning 22.-23.10.2003

CERADCERADfinfin study: Results study: Results

On the group level, none of the results fall below the critical cut-off point.

N.B. the cut-off points are set for elderly (> 65), thus 'a normal' result for a younger patient does not exclude a possible problem

Naming (-1SD of US norms): usually mild semantic naming errors (rhino - hippo)

Delayed recall usually slow and troublesome: Word list recall: eight patients had a result < 80%

(range 56-78%). Recall of drawings: seven patients (different than

those poor in the delayed verbal task) performed at < 60 %

Twinning 22.-23.10.2003

CERADCERADfinfin study: Results study: Results

MMSE included in CERAD (-1 SD of US norms): Poorer performance in the memory task [subject

repeats three words, then performs the subtraction task 100-7 (93-86-79-92-65]

CSE patients subtract with difficulties, erroneously, and performance is slow. Recall of words is troublesome: 12/17 cases forget the third word

This implicates that cognitive performance requiring working memory is not intact

Twinning 22.-23.10.2003

CERADCERADfinfin study: Conclusions study: Conclusions

The memory impairment seen in the CSE is qualitatively different (attention & working memory processing) than memory problem in MCI/AD (word list learning),

thus CERAD is not sensitive for CSE CERAD gives a lot of valuable information about the

cognitive performance BUT when impaired performance is detected, it

suggests etiology other than CSE