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Neuropsychology in neurotoxicology

Neuropsychology in neurotoxicology. Ritva Akila, neuropsychologist Finnish Institute of Occupational Health Helsinki, Finland ritva. akila@ttl.fi. Clinical neuropsychology. Clinical neuropsychology studies human behaviour as it

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Neuropsychology in neurotoxicology

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  1. Neuropsychology in neurotoxicology Ritva Akila, neuropsychologist Finnish Institute of Occupational Health Helsinki, Finland ritva. akila@ttl.fi Twinning 22.-23.10.2003

  2. Clinical 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

  3. Chronic solvent encephalopathy (CSE) Subjective symptoms Interview of a patient with memory problems Twinning 22.-23.10.2003

  4. Symptoms of workers with CSE Acute symptoms:dizziness, headache, nausea, feelings of intoxication 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

  5. Memory 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

  6. 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

  7. 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

  8. Memory 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

  9. Toxic encephalopathy Neuropsychological assessment Differential diagnosis Twinning 22.-23.10.2003

  10. Neuropsychological assessment:Sources of information • Interview • Questionnaires • Observation • Standardized tests • Neuropsychological tasks Twinning 22.-23.10.2003

  11. Neurocognitive 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

  12. 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

  13. Neuropsychological 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

  14. Memory in depression Patients underestimate their memory capacity Memory complaints are frequent What 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

  15. Alcohol & 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

  16. Degenerative 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

  17. Mild 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

  18. 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

  19. Neuropsychological findings: differential diagnostics + no impairment (normal test performance) – impairment (poor test performance ) Twinning 22.-23.10.2003

  20. Future in differential diagnostics of CSE: neuropsychological 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

  21. Neurocognitive effects of occupational 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

  22. Screening methods to detect neurotoxic adversive effects Q16, Q18, Finnish questionnaire EuroQuest Twinning 22.-23.10.2003

  23. 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

  24. EuroQuest - questionnaire for neurotoxic symptoms • Europeanconsensus (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

  25. EUROQUESTFin- 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

  26. EUROQUESTFin-Results Almostin 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

  27. Screening methods of cognitive decline Mini-Mental State examination (MMSE) CERAD: Short neuropsychological battery Twinning 22.-23.10.2003

  28. Mini-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

  29. CERAD - short 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

  30. CERADfin - short 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

  31. CERADfin 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

  32. CERADfin 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

  33. CERADfin 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

  34. CERADfin 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 Twinning 22.-23.10.2003

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