twinning 22.-23.10.2003 neuropsychology in neurotoxicology ritva akila, neuropsychologist finnish...
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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. [email protected]. [email protected]
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