Advanced Clinical Neuropsychology – Summary Lectures
Topic 1 – General Introduction and Cost Effectiveness
Definition of a clinical neuropsychologist (National Academy of Neuropsychology, 2001):
Dimensions of a clinical neuropsychological examination:
▪ Processing speed
▪ Attention
▪ Memory and learning
▪ Executive functions
▪ Visuospatial skills
▪ Speech and language functions
▪ Perceptual skills (auditory, visual and tactual)
▪ Psychomotor speed and coordination of simple motor responses
▪ Emotional and motivational characteristics
▪ Social functioning and social cognition
▪ Self-awareness of level of functioning and judgements regarding psychosocial implications
Administration of neuropsychological tests, scoring, interpretation and reporting of tests results is time consuming -> “Brief”
assessments take around 2 hours, extensive assessments 8 to 10 hours (without scoring, interpretation and reporting).
➢ Consequently -> Neuropsychological examinations are expensive.
➢ Thus -> Neuropsychological examinations might need justification (in particular in times of financial crisis).
Clinical neuropsychological examinations from an economic perspective:
▪ The costs are more (720,000 a year) than the income (420,000 per year).
▪ So why examinations? -> Because of markers of values.
Marker of value:
▪ Refers to money equivalent (e.g. cost saving) of the service received.
▪ Comparison between costs of assessment and treatment, with money saved by avoiding other health care costs and by
returning an individual to work and social responsibility.
Objective markers:
▪ Reduce costs and liability -> Examples:
– Savings associated with identification of malingerers (unnecessary medical costs, trial costs).
– Savings associated with differential diagnosis on basis of neuropsychological assessments, e.g. between dementia
and depression.
» Psychiatric treatment available for depression -> Which might result in productive lifestyle of patients.
» If neuropsychological findings are indicative of early dementia -> Patients and families can plan for the
patients’ early significant decline in cognitive and behavioral functioning.
▪ Improve QoL -> By revealing cognitive deficits that would have otherwise gone undetected and might have impacted QoL
negatively (e.g. undetected impaired executive functioning led to bankruptcy of man’s furniture shop).
▪ Assess the effectiveness of treatment.
, ▪ Guide treatment procedures -> E.g. neuropsychological findings contribute significantly to decision whether patients undergo
epilepsy surgery.
▪ Provide a continuum of care for patients -> E.g. clinical neuropsychologists consult with patients and their families about the
patients’ deficits, and prepares them to deal with intermediate and long-term consequences of patients’ brain dysfunctions.
▪ Improve physician education and decision making -> E.g. patients and their families may suffer from pain, stress and economic
burden when patients return prematurely to work.
Subjective markers:
▪ Reduce patients’ sense of psychological aloneness with daily problems -> E.g. relief of a patient with brain tumour (“I am not
mad”) when describing an association between deficits and tumour location to her.
▪ Reduce patients’ expectations, confusion and frustration about the nature of their disturbances -> Patients and families
often have unrealistic expectations or wrong understandings about deficits and their development.
▪ Help family members feel less guilty in making decisions regarding brain-dysfunctional adults and children.
→ Many families struggle with the issue of placing a loved-one in a residential/nursing home.
→ In children -> Often considerable relief when parents learn that problems (e.g. ADHD) are not the consequence of
“poor” parenting or psychodynamic processes.
→ Example -> Feelings of guilt and self-reproach of father who slapped daughter in the face and who got a brain tumour
diagnosed 10 days later.
Topic 2 – Fatigue
Significant proportion of general population affected by excessive fatigue -> One of the most common complaints reported to primary
care physicians.
➢ Frequent and prolonged tiredness interfering with everyday life in about 27% of patients in primary care settings.
Pathological fatigue is characterized by (compared to non-pathological):
▪ Greater intensity;
▪ Longer duration;
▪ More disabling effects on functional activities;
▪ Remains after rest as a severe condition.
Fatigue is viewed as both symptom and disease.
Fatigue as a symptom:
▪ Often reported as the most disabling symptom in many diseases by affecting the patient’s physical, psychological and social
well-being.
▪ Non-specific symptom, because it can be indicative of many causes or conditions:
– Neurological conditions (e.g. TBI, MS, stroke, Parkinson’s);
– Psychiatric diseases (e.g. depression, somatoform disorders);
– Medical conditions (e.g. infections, cancer, coronary heart disease, thyroid abnormalities);
– Medications (e.g. anti-histamines, chemo);
– Unhealthy lifestyles (e.g. sleep deprivation);
Fatigue as a disease:
▪ Often part of a group of ‘unexplained’ illnesses (e.g. chronic fatigue syndrome, CFS), with little understanding of its causes.
▪ CFS = Persistent debilitating fatigue for at least 6 months not due to ongoing exertion, not substantially relieved by rest, and
not caused by other medical conditions.
▪ Chronic fatigue = Estimated to occur in 4% to 5% in the general population.
Defining fatigue:
▪ No general consensus on a universal definition of the term fatigue.
▪ This remains a major obstacle to understanding the clinical manifestations of fatigue.
Fatigue van be conceptualized as:
▪ A subjective feeling -> Example for a definition emphasizing subjective experience: “A subjective lack of physical and/or mental
energy that is perceived by the individual or caregiver to interfere with usual or desired activities”.
, ▪ A performance decrement -> Example for a definition emphasizing changes in objective performance: “Any exercise-induced
reduction in the maximal capacity to generate force or power output”.
➢ Clinical definitions of fatigue focus primarily on patients’ subjective feelings of fatigue!
Problem -> Poor correlation between subjective and behavioural (or objective, performance-based) fatigue.
➢ Lack of correlation between objective measurement and subjective experience hinders better understanding of the enigma
of fatigue.
Another categorization:
▪ Peripheral fatigue -> Defined as failure to sustain force or power output because of neuromuscular dysfunction outside of the
CNS.
▪ Central fatigue -> Defined as resulting from failure to achieve and maintain the recruitment of high-threshold motor units,
implicating dysfunction in the CNS.
➢ However, again different definitions by different articles.
➢ Categorization is difficult -> Even motor fatigue can result from muscle fatigue (peripheral), or from brain control over the
muscle (central).
➢ Different illnesses vary in the relative contributions of peripheral and central fatigue to the overall experience of fatigue.
➢ Contribution of both peripheral and central fatigue, to overall subjective reports of fatigue is not well understood.
Fatigue is a multidimensional construct, it compromises at least four components:
▪ Behavior (effects on performance);
▪ Feeling (subjective experience);
▪ Mechanism (physiological and psychological);
▪ Context (e.g. environment).
Neurobiological correlates -> Fatigue has been suggested as a general indicator of brain
damage, but study of neural mechanisms is still in its infancy.
➢ Primary mechanisms of fatigue include:
→ Basal ganglia;
→ Frontal lobes;
→ Hypothalamic-pituitary-adrenal (HPA) axis;
→ Proinflammatory cytokines affecting neural metabolism.
Limbic encephalitis -> Inflammation of the brain affecting the limbic system. Disease however seldom limited to the limbic system.
Myotonic dystrophy -> Inherited disorder of muscle function which can also affect other body systems.
Chiari malformation -> Downward displacement of cerebellum (cerebellar tonsils) through foramen magnum.
Little doubt that the experience of fatigue is a manifestation of dysfunctional brain activity, however, research supports the involvement
of multiple dimensions, with biological, psychological, and psychosocial factors contributing to the experience of fatigue.
Primary fatigue -> Caused by its primary neural mechanisms (e.g. changes in basal ganglia activation during fatigue-producing activity).
Secondary fatigue -> Includes factors perpetuating or exacerbating its effects (e.g. deconditioning, sleep habits, medication).
➢ Example:
– MS may cause the initial symptoms of fatigue through specific biological mechanisms (e.g. basal ganglia, HPA,
cytokines, demyelination).
– Fatigue symptom may be exacerbated by secondary factors such as deconditioning, sleep disturbance, depression
and pain.
Although 42% of patients with PD complain of fatigue, only 25% (!) of doctors recognize the symptom -> This difference is much less for
e.g. depression, anxiety and sleep problems.
➢ Indicating that clinicians may not pay sufficient attention to fatigue as a symptom of the disorder.
➢ Emphasizing the importance of assessment of fatigue in neurological and psychiatric disorders.
Assessment -> Reflects the two conceptualizations of fatigue:
1. Self-report / questionnaires (subjective feeling):
– A number of questionnaires available for use in a variety of clinical populations (e.g. cancer, MS, CFS) as well as
healthy individuals.
, * Fatigue Severity Scale (FSS) – subject needs to rate their level of fatigue and its effects on daily functioning.
* Fatigue Descriptive Scale (FDS) – looks at severity, frequency and quality of fatigue caused by MS.
* Modified Fatigue Impact Scale (MFIS) – self-report, can be used to generate scores for physical, cognitive,
and psychosocial functioning over the last four weeks.
* Neurological Fatigue Index (NFI-MS) – specific to MS.
* Visual Analogue Scale for Fatigue (VAS-F) – individual can mark on a horizontal 10 cm scale how much
fatigue has an influence over completion of a named task.
– Characteristics of questionnaires:
A. Number of items -> Questionnaires range in length (from single item scales to longer, multidimensional
assessments).
Authors of focused scales argue: Pure measures of fatigue are more homogenous (measuring
only the core feelings of fatigue and excluding other aspects which might be better assessed by
separate instruments).
Authors of multidimensional scales argue: Including many factors is necessary to assess the
complexity of fatigue.
B. Item content -> Most scales include items to assess both (I) feelings of fatigue and (II) the perceived impact
of fatigue on the lives of patients (e.g. physical or mental activities).
To measure the core feelings of fatigue, questionnaires generally ask about the degree to which
respondents feel tired, fatigued or worn out.
Content varies to some extent with the targeted audience -> E.g. questions regarding particular
vulnerability of patients with MS to heat-related fatigue.
C. Duration of fatigue -> Important issue! -> However, many questionnaires fail to ask subjects how long they
have experienced fatigue symptoms.
Unfortunate because longer-lasting fatigue can signal greater pathology.
D. Time frame -> Many scales fail to specify the time frame on which respondents should focus when
answering items (e.g. right now, over the past week(s), in general).
Appropriate time frame depends in part on the clinical or research objective at hand (e.g. for
examining pathological fatigue associated with a neurological disorder a longer duration may be
appropriate).
A specified time frame can be helpful in monitoring changes in fatigue associated with disease
course or treatment approach.
Another temporal aspect of fatigue is its diurnal pattern, involving assessment of whether
symptoms are worse at particular times of the day.
– Advantages:
* Inexpensive;
* Readily available;
* Quickly administered;
* Require little staff training;
* Place few demands on seriously ill patients.
2. Direct observation of behaviour (objective performance decrement):
– Different approaches for the objective measurement of cognitive fatigue (see article 1.2):
* Cognitive fatigue over an extended time;
* Cognitive fatigue during sustained mental effort;
* Cognitive fatigue after challenging mental exertion;
* Cognitive fatigue after challenging physical exertion.
– Advantage -> Provides objectively verifiable data.
➢ The lack of correlation between direct measurement of performance decline and subject reporting of fatigue is a concern ->
BUT, it is not proof of the superiority of objective performance-based measures.
➢ Self-reported measures may reflect a greater effort required to maintain a given level of performance.
Fatigue and neuropsychology -> Reasonable evidence that cognitive fatigue is related to reduced cognitive performance in healthy
individuals.
➢ Assumption -> Detrimental influence of fatigue on neuropsychological performance.
➢ Recommendations to minimize the effect of fatigue on neuropsychological performance during assessment:
– Shortening test sessions;
– Giving difficult tests early in a session;
Topic 1 – General Introduction and Cost Effectiveness
Definition of a clinical neuropsychologist (National Academy of Neuropsychology, 2001):
Dimensions of a clinical neuropsychological examination:
▪ Processing speed
▪ Attention
▪ Memory and learning
▪ Executive functions
▪ Visuospatial skills
▪ Speech and language functions
▪ Perceptual skills (auditory, visual and tactual)
▪ Psychomotor speed and coordination of simple motor responses
▪ Emotional and motivational characteristics
▪ Social functioning and social cognition
▪ Self-awareness of level of functioning and judgements regarding psychosocial implications
Administration of neuropsychological tests, scoring, interpretation and reporting of tests results is time consuming -> “Brief”
assessments take around 2 hours, extensive assessments 8 to 10 hours (without scoring, interpretation and reporting).
➢ Consequently -> Neuropsychological examinations are expensive.
➢ Thus -> Neuropsychological examinations might need justification (in particular in times of financial crisis).
Clinical neuropsychological examinations from an economic perspective:
▪ The costs are more (720,000 a year) than the income (420,000 per year).
▪ So why examinations? -> Because of markers of values.
Marker of value:
▪ Refers to money equivalent (e.g. cost saving) of the service received.
▪ Comparison between costs of assessment and treatment, with money saved by avoiding other health care costs and by
returning an individual to work and social responsibility.
Objective markers:
▪ Reduce costs and liability -> Examples:
– Savings associated with identification of malingerers (unnecessary medical costs, trial costs).
– Savings associated with differential diagnosis on basis of neuropsychological assessments, e.g. between dementia
and depression.
» Psychiatric treatment available for depression -> Which might result in productive lifestyle of patients.
» If neuropsychological findings are indicative of early dementia -> Patients and families can plan for the
patients’ early significant decline in cognitive and behavioral functioning.
▪ Improve QoL -> By revealing cognitive deficits that would have otherwise gone undetected and might have impacted QoL
negatively (e.g. undetected impaired executive functioning led to bankruptcy of man’s furniture shop).
▪ Assess the effectiveness of treatment.
, ▪ Guide treatment procedures -> E.g. neuropsychological findings contribute significantly to decision whether patients undergo
epilepsy surgery.
▪ Provide a continuum of care for patients -> E.g. clinical neuropsychologists consult with patients and their families about the
patients’ deficits, and prepares them to deal with intermediate and long-term consequences of patients’ brain dysfunctions.
▪ Improve physician education and decision making -> E.g. patients and their families may suffer from pain, stress and economic
burden when patients return prematurely to work.
Subjective markers:
▪ Reduce patients’ sense of psychological aloneness with daily problems -> E.g. relief of a patient with brain tumour (“I am not
mad”) when describing an association between deficits and tumour location to her.
▪ Reduce patients’ expectations, confusion and frustration about the nature of their disturbances -> Patients and families
often have unrealistic expectations or wrong understandings about deficits and their development.
▪ Help family members feel less guilty in making decisions regarding brain-dysfunctional adults and children.
→ Many families struggle with the issue of placing a loved-one in a residential/nursing home.
→ In children -> Often considerable relief when parents learn that problems (e.g. ADHD) are not the consequence of
“poor” parenting or psychodynamic processes.
→ Example -> Feelings of guilt and self-reproach of father who slapped daughter in the face and who got a brain tumour
diagnosed 10 days later.
Topic 2 – Fatigue
Significant proportion of general population affected by excessive fatigue -> One of the most common complaints reported to primary
care physicians.
➢ Frequent and prolonged tiredness interfering with everyday life in about 27% of patients in primary care settings.
Pathological fatigue is characterized by (compared to non-pathological):
▪ Greater intensity;
▪ Longer duration;
▪ More disabling effects on functional activities;
▪ Remains after rest as a severe condition.
Fatigue is viewed as both symptom and disease.
Fatigue as a symptom:
▪ Often reported as the most disabling symptom in many diseases by affecting the patient’s physical, psychological and social
well-being.
▪ Non-specific symptom, because it can be indicative of many causes or conditions:
– Neurological conditions (e.g. TBI, MS, stroke, Parkinson’s);
– Psychiatric diseases (e.g. depression, somatoform disorders);
– Medical conditions (e.g. infections, cancer, coronary heart disease, thyroid abnormalities);
– Medications (e.g. anti-histamines, chemo);
– Unhealthy lifestyles (e.g. sleep deprivation);
Fatigue as a disease:
▪ Often part of a group of ‘unexplained’ illnesses (e.g. chronic fatigue syndrome, CFS), with little understanding of its causes.
▪ CFS = Persistent debilitating fatigue for at least 6 months not due to ongoing exertion, not substantially relieved by rest, and
not caused by other medical conditions.
▪ Chronic fatigue = Estimated to occur in 4% to 5% in the general population.
Defining fatigue:
▪ No general consensus on a universal definition of the term fatigue.
▪ This remains a major obstacle to understanding the clinical manifestations of fatigue.
Fatigue van be conceptualized as:
▪ A subjective feeling -> Example for a definition emphasizing subjective experience: “A subjective lack of physical and/or mental
energy that is perceived by the individual or caregiver to interfere with usual or desired activities”.
, ▪ A performance decrement -> Example for a definition emphasizing changes in objective performance: “Any exercise-induced
reduction in the maximal capacity to generate force or power output”.
➢ Clinical definitions of fatigue focus primarily on patients’ subjective feelings of fatigue!
Problem -> Poor correlation between subjective and behavioural (or objective, performance-based) fatigue.
➢ Lack of correlation between objective measurement and subjective experience hinders better understanding of the enigma
of fatigue.
Another categorization:
▪ Peripheral fatigue -> Defined as failure to sustain force or power output because of neuromuscular dysfunction outside of the
CNS.
▪ Central fatigue -> Defined as resulting from failure to achieve and maintain the recruitment of high-threshold motor units,
implicating dysfunction in the CNS.
➢ However, again different definitions by different articles.
➢ Categorization is difficult -> Even motor fatigue can result from muscle fatigue (peripheral), or from brain control over the
muscle (central).
➢ Different illnesses vary in the relative contributions of peripheral and central fatigue to the overall experience of fatigue.
➢ Contribution of both peripheral and central fatigue, to overall subjective reports of fatigue is not well understood.
Fatigue is a multidimensional construct, it compromises at least four components:
▪ Behavior (effects on performance);
▪ Feeling (subjective experience);
▪ Mechanism (physiological and psychological);
▪ Context (e.g. environment).
Neurobiological correlates -> Fatigue has been suggested as a general indicator of brain
damage, but study of neural mechanisms is still in its infancy.
➢ Primary mechanisms of fatigue include:
→ Basal ganglia;
→ Frontal lobes;
→ Hypothalamic-pituitary-adrenal (HPA) axis;
→ Proinflammatory cytokines affecting neural metabolism.
Limbic encephalitis -> Inflammation of the brain affecting the limbic system. Disease however seldom limited to the limbic system.
Myotonic dystrophy -> Inherited disorder of muscle function which can also affect other body systems.
Chiari malformation -> Downward displacement of cerebellum (cerebellar tonsils) through foramen magnum.
Little doubt that the experience of fatigue is a manifestation of dysfunctional brain activity, however, research supports the involvement
of multiple dimensions, with biological, psychological, and psychosocial factors contributing to the experience of fatigue.
Primary fatigue -> Caused by its primary neural mechanisms (e.g. changes in basal ganglia activation during fatigue-producing activity).
Secondary fatigue -> Includes factors perpetuating or exacerbating its effects (e.g. deconditioning, sleep habits, medication).
➢ Example:
– MS may cause the initial symptoms of fatigue through specific biological mechanisms (e.g. basal ganglia, HPA,
cytokines, demyelination).
– Fatigue symptom may be exacerbated by secondary factors such as deconditioning, sleep disturbance, depression
and pain.
Although 42% of patients with PD complain of fatigue, only 25% (!) of doctors recognize the symptom -> This difference is much less for
e.g. depression, anxiety and sleep problems.
➢ Indicating that clinicians may not pay sufficient attention to fatigue as a symptom of the disorder.
➢ Emphasizing the importance of assessment of fatigue in neurological and psychiatric disorders.
Assessment -> Reflects the two conceptualizations of fatigue:
1. Self-report / questionnaires (subjective feeling):
– A number of questionnaires available for use in a variety of clinical populations (e.g. cancer, MS, CFS) as well as
healthy individuals.
, * Fatigue Severity Scale (FSS) – subject needs to rate their level of fatigue and its effects on daily functioning.
* Fatigue Descriptive Scale (FDS) – looks at severity, frequency and quality of fatigue caused by MS.
* Modified Fatigue Impact Scale (MFIS) – self-report, can be used to generate scores for physical, cognitive,
and psychosocial functioning over the last four weeks.
* Neurological Fatigue Index (NFI-MS) – specific to MS.
* Visual Analogue Scale for Fatigue (VAS-F) – individual can mark on a horizontal 10 cm scale how much
fatigue has an influence over completion of a named task.
– Characteristics of questionnaires:
A. Number of items -> Questionnaires range in length (from single item scales to longer, multidimensional
assessments).
Authors of focused scales argue: Pure measures of fatigue are more homogenous (measuring
only the core feelings of fatigue and excluding other aspects which might be better assessed by
separate instruments).
Authors of multidimensional scales argue: Including many factors is necessary to assess the
complexity of fatigue.
B. Item content -> Most scales include items to assess both (I) feelings of fatigue and (II) the perceived impact
of fatigue on the lives of patients (e.g. physical or mental activities).
To measure the core feelings of fatigue, questionnaires generally ask about the degree to which
respondents feel tired, fatigued or worn out.
Content varies to some extent with the targeted audience -> E.g. questions regarding particular
vulnerability of patients with MS to heat-related fatigue.
C. Duration of fatigue -> Important issue! -> However, many questionnaires fail to ask subjects how long they
have experienced fatigue symptoms.
Unfortunate because longer-lasting fatigue can signal greater pathology.
D. Time frame -> Many scales fail to specify the time frame on which respondents should focus when
answering items (e.g. right now, over the past week(s), in general).
Appropriate time frame depends in part on the clinical or research objective at hand (e.g. for
examining pathological fatigue associated with a neurological disorder a longer duration may be
appropriate).
A specified time frame can be helpful in monitoring changes in fatigue associated with disease
course or treatment approach.
Another temporal aspect of fatigue is its diurnal pattern, involving assessment of whether
symptoms are worse at particular times of the day.
– Advantages:
* Inexpensive;
* Readily available;
* Quickly administered;
* Require little staff training;
* Place few demands on seriously ill patients.
2. Direct observation of behaviour (objective performance decrement):
– Different approaches for the objective measurement of cognitive fatigue (see article 1.2):
* Cognitive fatigue over an extended time;
* Cognitive fatigue during sustained mental effort;
* Cognitive fatigue after challenging mental exertion;
* Cognitive fatigue after challenging physical exertion.
– Advantage -> Provides objectively verifiable data.
➢ The lack of correlation between direct measurement of performance decline and subject reporting of fatigue is a concern ->
BUT, it is not proof of the superiority of objective performance-based measures.
➢ Self-reported measures may reflect a greater effort required to maintain a given level of performance.
Fatigue and neuropsychology -> Reasonable evidence that cognitive fatigue is related to reduced cognitive performance in healthy
individuals.
➢ Assumption -> Detrimental influence of fatigue on neuropsychological performance.
➢ Recommendations to minimize the effect of fatigue on neuropsychological performance during assessment:
– Shortening test sessions;
– Giving difficult tests early in a session;
