LECTURE 1
Neurology —> diagnosis and treatment of disease
Neuropsychology —> study of the psychological consequences
In a historical perspective, neuropsychology was part of neurology, however there’s still a strong
connection between the two.
Symptoms ≠ signs, the second ones are objectively noted by the neurologist during clinical checks,
the rst are noted by patients or relatives.
Experimental neuropsy is about using experimental paradigm in non-brain-damaged subjects, the
clinical neuropsy’s aim is assessment and diagnosis and design of rehab programs, cognitive
neuropsy investigates the effects of brain injury in order to decipher normal cognitive functioning.
When neuropsychology was born? 1861 Broca noticed changed in speech on a patient (patient tan)
combined with expressive gestures (he was able to communicate). Then it was noticed a damage in
the left hemisphere, on the inferior frontal gyrus.
Talking about a speci c syndrome, we expect a series of symptoms to occur, +/- together.
Double dissociation is useful to exclude cases in which patients do good in a task just because it’s
easier for them, dissociate 2 different paths. Dissociations can be weak or strong
Memory, attention, language and social cognition.
Mesial structures underlie phylogenetically primitive
functions, while lateral structures are subtending most complex
cognitive and executive activities.
Anterior regions deputed to intentional motor
activities and control functions
Posterior regions include primary somatosensory,
auditory, visual cortex.
Information is organized according to a gradient from
the most basic and rigidly organized to the most complex
Ventral regions deputed to visual processing towards a correct
perception and recognition of visual stimuli
Dorsal regions deputed to visual processing towards a correct action-based
interaction with the environment.
LECTURE 2
What to ask to a patient?
Basic anamnesis, clinical anamnesis, impact of the disease, neurological exam + instrumental
investigation in neurology. The timeline of symptoms in case of cerebrovascular or TBI (traumatic
brain injury) is completely different from that of neurodegenerative.
In an AD there’s a linear progression of the symptoms severity, in cerebrovascular dementia the
progression depends on the new vascular
damages that create time by time.
fi fi
, FDG PET
Technique that measures the glucose metabolism, useful to distinguish between different
neurodegenerative disorders
- Atypical parkinsonism vs PD -> no speci c pattern of hypometabolism in earlier stages
(In later stages, could be in basal ganglia); in atypical Parkinsonism the hypometabolism in present.
- LBD vs AD -> in AD the hypometabolism is more prominent in temporal and parietal lobes,
while in LBD is more pronounced in the occipital regions.
- FTD vs AD
1. Frontotemporal Dementia (FTD):
◦ Key Features: Hypometabolism is predominantly observed in the frontal and
anterior temporal lobes, often asymmetrically.
◦ Behavioral variant FTD (bvFTD): Hypometabolism primarily affects the
orbitofrontal, dorsolateral prefrontal cortex, and anterior cingulate cortex.
◦ Semantic variant primary progressive aphasia (svPPA): Hypometabolism is
focused in the anterior temporal lobes, more pronounced on the left side.
◦ Non- uent/agrammatic variant PPA: Hypometabolism is localized to the left
posterior frontoinsular region.
2. Alzheimer’s Disease (AD):
◦ Key Features: Hypometabolism mainly involves the posterior cingulate cortex,
precuneus, and parietotemporal regions, typically bilaterally. The frontal lobes are
relatively preserved in the early stages.
◦ Occipital lobe involvement is also rare in AD, which helps differentiate it from other
conditions like Dementia with Lewy Bodies (DLB).
The aim of neurocognitive rehabilitation is make the patient adequate, functional and capable of
performing certain activities again, to regain autonomy and to respond to real-life dif culties
Neuropsy evaluation -> an important aim is diagnostic, have an overall picture of of patient’s status.
There’s an actual debate about biomarkers -> they allow us to detect in vivo a dementia, Americans
think that they are enough to detect dementias like AD but there are people that result positive for
biomarkers but don’t show any kind of symptoms. The American perspective would change
de nitely all of the diagnostic plan.
When the caregiver asks for the neuropsy, it’s likely that the patient is not aware of their dif culties.
Other aims of the N.E.:
- Prognostic -> make predictions about the level of cognitive de cits a person might develop
- Planning of assistential interventions
- Cognitive rehabilitation
- Monitor of intervention ef cacy/impact
- Legal
The second neuro assessment is about the domain that resulted impaired during the rst one. This
follow-up helps to con rm the initial ndings, track changes over time, and assess whether the
impairment is stable, worsening, or improving, which is crucial for diagnostic and treatment
planning.
In a lot of cases long term memory is misinterpreted as short term memory, also patients (esp. old
age) tend to focus a lot about memory impairments (sometimes is an attentional i.).
fi fl fi fi fi fi fi fifi fi
, To test the language in the initial interview, you ask to the patient about random stuff (ex. Describe
me your day).
All the domains should be assessed, the neuropsychological tests are:
- all standardized -> speci c rules for their administration and scoring
- all representative -> they’re actually able to evaluate the cognitive function we want to evaluate
(Low score -> speci c de cit). The ecological value refers to the capacity of the test to really
represent the impairments showed by the patient.
It is important to have normative data from a population that is comparable to the subjects being
tested. The mastery approach is applied when it is expected that the entire population should be able
to perform a speci c task (e.g., copying a simple drawing). However, a patient with spatial attention
de cits, such as those caused by neglect, may fail to perform the task correctly, possibly omitting or
neglecting part of the drawing."
The Z-score -> able to tell me the % of population above and below the subject. There’s some
problems:
- not taking in consideration the effect of some variables (education, age, etc)
- Z scores require a normal distribution of x
- Usually computed based on values from a small sample of healthy controls
It is used the method of the equivalent score, able to adjust the score of the subject using multiple
regression analysis, considering demographic variables -> you use correction grids.
Equivalent scores -> rank position of the subject according to the reference population.
Using equivalent scores in a longitudinal way is not enough, in addition normative datas need to be
sometimes updated but it’s not always possible.
Psychological status is also involved in tests performance, e.g. a patient with anxiety does often a
bad performance in tests like the Digit span.
Instrumental investigation in neurology -> biomarkers are so useful but the most important thing is
to adopt a rational approach to diagnostic testing. This means f.e. that we can’t administer all
biomarkers analysis to all the patients we have just for the plot.
Brain biopsy: direct examination of a brain tissue piece, it’s a very invasive test used if a. We know
that the condition is treatable b. I have an atypical pattern that I cannot explain in other ways.
Autopsy: less rare than brain biopsy.
NB The diagnose is always a probable, if the patient is alive is impossible to really see the
pathology (the tissue), the exception is patients with genetic mutations (in this case the diagnose is
certain).
Sensitivity - speci city - accuracy: the rst two tell us the ability of a test to detect true positives
and true negatives (but we will discuss them better later).
CT scan -> fundamental to look for: 1. Symmetry 2. Density (changes in the color) 3. Location of
the lesion. In neurodegenerative conditions it is used also as an exclusion criteria -> the patient
reports dif culties in f.e. memory, then is put in the CT scan and some lesion is found -> we
exclude the possibility of a neurodegenerative condition.
Clinical MRI, can be used in ≠ ways:
- T1 really useful to see the anatomical structures
- T2 and air allows us to detect vascular de cits (the only difference is that in the air the signal
of cerebrospinal uid is suppressed, so it helps radiologist to distinguish lesions adjacent to the
ventricles or within the brain tissue more clearly without interference from the bright signal of
CSF, making it especially useful for identifying subtle lesions, such as those seen in multiple
sclerosis or small ischemic strokes).
1. Compare the single image with a control group
2. Visual Retin Scale (VRS)*, but it must be read within the clinical picture
*scale often used in neuropsychology and neurology to assess the degree of atrophy, or shrinkage,
in the medial temporal lobe of the brain, speci cally focusing on areas affected by conditions like
fi fl fi flfifi fi fifi fi fi fi fl
, Alzheimer’s Disease. This scale is especially useful for evaluating neurodegenerative diseases that
impact memory and cognitive function.
In VRS, MRI or CT brain scans are used to visually rate the extent of atrophy in regions like the
hippocampus. Scores typically range from 0 to 4, with:
• 0 indicating no atrophy
• 1-2 indicating mild to moderate atrophy
• 3-4 indicating severe atrophy
The VRS is a valuable tool for early diagnosis, disease progression monitoring, and differential
diagnosis between Alzheimer’s Disease and other types of dementia, as it speci cally focuses on
regions associated with memory and learning.
Structural alteration are evaluated with f.e. the are image of the brain, for the functional alteration
an ef cient method is PET, it allows us to use a large variety of radiotracers in order to the
biomarkers we want to detect.
SPECT allows in vivo imaging of dopamine transporter (DAT) availability by using radiotracers
that bind speci cally to DAT sites in the brain.
Cerebrospinal uid if performed in an AD patient to detect amyloid or tau, you obtain a certain
pro le:
a. amyloid-b (Ab) deposition into extracellular Ab plaques( LOW CSF Ab1-42)
b. intracellular neuro brillary tangles (NFT) formation (HIGH CSF p-tau)
c. neuronal loss (HIGH CSF t-tau)
Riassunto dei cambiamenti nei biomarcatori del CSF per l'Alzheimer
Biomarcatore Cambiamento Cosa indica?
Aβ1-42 ↓ Basso Deposizione di β-amiloide nelle placche
p-tau ↑ Alto Formazione di grovigli neuro brillari
t-tau ↑ Alto Perdita neuronale e neurodegenerazione
LECTURE 3
Lab - administration of screening Tests
Mini-Mental State Examination
The Mini-Mental State Examination (MMSE) is a widely used cognitive
screening tool designed to assess global cognitive functioning. It provides a
quick measure of mental state and is often used to detect cognitive impairments,
monitor changes over time, or evaluate the severity of conditions such as
dementia.
The MMSE is structured as a 30-point questionnaire, with questions grouped into
ve cognitive domains:
1. Orientation: Assessing awareness of time, date, and location.
2. Registration and Recall: Testing short-term memory by asking patients to
remember and later recall three objects.
3. Attention and Calculation: Measuring concentration and mental
arithmetic, such as counting backward from 100 by 7s.
fi fi fi
fi
fl fi fi fl fi
Neurology —> diagnosis and treatment of disease
Neuropsychology —> study of the psychological consequences
In a historical perspective, neuropsychology was part of neurology, however there’s still a strong
connection between the two.
Symptoms ≠ signs, the second ones are objectively noted by the neurologist during clinical checks,
the rst are noted by patients or relatives.
Experimental neuropsy is about using experimental paradigm in non-brain-damaged subjects, the
clinical neuropsy’s aim is assessment and diagnosis and design of rehab programs, cognitive
neuropsy investigates the effects of brain injury in order to decipher normal cognitive functioning.
When neuropsychology was born? 1861 Broca noticed changed in speech on a patient (patient tan)
combined with expressive gestures (he was able to communicate). Then it was noticed a damage in
the left hemisphere, on the inferior frontal gyrus.
Talking about a speci c syndrome, we expect a series of symptoms to occur, +/- together.
Double dissociation is useful to exclude cases in which patients do good in a task just because it’s
easier for them, dissociate 2 different paths. Dissociations can be weak or strong
Memory, attention, language and social cognition.
Mesial structures underlie phylogenetically primitive
functions, while lateral structures are subtending most complex
cognitive and executive activities.
Anterior regions deputed to intentional motor
activities and control functions
Posterior regions include primary somatosensory,
auditory, visual cortex.
Information is organized according to a gradient from
the most basic and rigidly organized to the most complex
Ventral regions deputed to visual processing towards a correct
perception and recognition of visual stimuli
Dorsal regions deputed to visual processing towards a correct action-based
interaction with the environment.
LECTURE 2
What to ask to a patient?
Basic anamnesis, clinical anamnesis, impact of the disease, neurological exam + instrumental
investigation in neurology. The timeline of symptoms in case of cerebrovascular or TBI (traumatic
brain injury) is completely different from that of neurodegenerative.
In an AD there’s a linear progression of the symptoms severity, in cerebrovascular dementia the
progression depends on the new vascular
damages that create time by time.
fi fi
, FDG PET
Technique that measures the glucose metabolism, useful to distinguish between different
neurodegenerative disorders
- Atypical parkinsonism vs PD -> no speci c pattern of hypometabolism in earlier stages
(In later stages, could be in basal ganglia); in atypical Parkinsonism the hypometabolism in present.
- LBD vs AD -> in AD the hypometabolism is more prominent in temporal and parietal lobes,
while in LBD is more pronounced in the occipital regions.
- FTD vs AD
1. Frontotemporal Dementia (FTD):
◦ Key Features: Hypometabolism is predominantly observed in the frontal and
anterior temporal lobes, often asymmetrically.
◦ Behavioral variant FTD (bvFTD): Hypometabolism primarily affects the
orbitofrontal, dorsolateral prefrontal cortex, and anterior cingulate cortex.
◦ Semantic variant primary progressive aphasia (svPPA): Hypometabolism is
focused in the anterior temporal lobes, more pronounced on the left side.
◦ Non- uent/agrammatic variant PPA: Hypometabolism is localized to the left
posterior frontoinsular region.
2. Alzheimer’s Disease (AD):
◦ Key Features: Hypometabolism mainly involves the posterior cingulate cortex,
precuneus, and parietotemporal regions, typically bilaterally. The frontal lobes are
relatively preserved in the early stages.
◦ Occipital lobe involvement is also rare in AD, which helps differentiate it from other
conditions like Dementia with Lewy Bodies (DLB).
The aim of neurocognitive rehabilitation is make the patient adequate, functional and capable of
performing certain activities again, to regain autonomy and to respond to real-life dif culties
Neuropsy evaluation -> an important aim is diagnostic, have an overall picture of of patient’s status.
There’s an actual debate about biomarkers -> they allow us to detect in vivo a dementia, Americans
think that they are enough to detect dementias like AD but there are people that result positive for
biomarkers but don’t show any kind of symptoms. The American perspective would change
de nitely all of the diagnostic plan.
When the caregiver asks for the neuropsy, it’s likely that the patient is not aware of their dif culties.
Other aims of the N.E.:
- Prognostic -> make predictions about the level of cognitive de cits a person might develop
- Planning of assistential interventions
- Cognitive rehabilitation
- Monitor of intervention ef cacy/impact
- Legal
The second neuro assessment is about the domain that resulted impaired during the rst one. This
follow-up helps to con rm the initial ndings, track changes over time, and assess whether the
impairment is stable, worsening, or improving, which is crucial for diagnostic and treatment
planning.
In a lot of cases long term memory is misinterpreted as short term memory, also patients (esp. old
age) tend to focus a lot about memory impairments (sometimes is an attentional i.).
fi fl fi fi fi fi fi fifi fi
, To test the language in the initial interview, you ask to the patient about random stuff (ex. Describe
me your day).
All the domains should be assessed, the neuropsychological tests are:
- all standardized -> speci c rules for their administration and scoring
- all representative -> they’re actually able to evaluate the cognitive function we want to evaluate
(Low score -> speci c de cit). The ecological value refers to the capacity of the test to really
represent the impairments showed by the patient.
It is important to have normative data from a population that is comparable to the subjects being
tested. The mastery approach is applied when it is expected that the entire population should be able
to perform a speci c task (e.g., copying a simple drawing). However, a patient with spatial attention
de cits, such as those caused by neglect, may fail to perform the task correctly, possibly omitting or
neglecting part of the drawing."
The Z-score -> able to tell me the % of population above and below the subject. There’s some
problems:
- not taking in consideration the effect of some variables (education, age, etc)
- Z scores require a normal distribution of x
- Usually computed based on values from a small sample of healthy controls
It is used the method of the equivalent score, able to adjust the score of the subject using multiple
regression analysis, considering demographic variables -> you use correction grids.
Equivalent scores -> rank position of the subject according to the reference population.
Using equivalent scores in a longitudinal way is not enough, in addition normative datas need to be
sometimes updated but it’s not always possible.
Psychological status is also involved in tests performance, e.g. a patient with anxiety does often a
bad performance in tests like the Digit span.
Instrumental investigation in neurology -> biomarkers are so useful but the most important thing is
to adopt a rational approach to diagnostic testing. This means f.e. that we can’t administer all
biomarkers analysis to all the patients we have just for the plot.
Brain biopsy: direct examination of a brain tissue piece, it’s a very invasive test used if a. We know
that the condition is treatable b. I have an atypical pattern that I cannot explain in other ways.
Autopsy: less rare than brain biopsy.
NB The diagnose is always a probable, if the patient is alive is impossible to really see the
pathology (the tissue), the exception is patients with genetic mutations (in this case the diagnose is
certain).
Sensitivity - speci city - accuracy: the rst two tell us the ability of a test to detect true positives
and true negatives (but we will discuss them better later).
CT scan -> fundamental to look for: 1. Symmetry 2. Density (changes in the color) 3. Location of
the lesion. In neurodegenerative conditions it is used also as an exclusion criteria -> the patient
reports dif culties in f.e. memory, then is put in the CT scan and some lesion is found -> we
exclude the possibility of a neurodegenerative condition.
Clinical MRI, can be used in ≠ ways:
- T1 really useful to see the anatomical structures
- T2 and air allows us to detect vascular de cits (the only difference is that in the air the signal
of cerebrospinal uid is suppressed, so it helps radiologist to distinguish lesions adjacent to the
ventricles or within the brain tissue more clearly without interference from the bright signal of
CSF, making it especially useful for identifying subtle lesions, such as those seen in multiple
sclerosis or small ischemic strokes).
1. Compare the single image with a control group
2. Visual Retin Scale (VRS)*, but it must be read within the clinical picture
*scale often used in neuropsychology and neurology to assess the degree of atrophy, or shrinkage,
in the medial temporal lobe of the brain, speci cally focusing on areas affected by conditions like
fi fl fi flfifi fi fifi fi fi fi fl
, Alzheimer’s Disease. This scale is especially useful for evaluating neurodegenerative diseases that
impact memory and cognitive function.
In VRS, MRI or CT brain scans are used to visually rate the extent of atrophy in regions like the
hippocampus. Scores typically range from 0 to 4, with:
• 0 indicating no atrophy
• 1-2 indicating mild to moderate atrophy
• 3-4 indicating severe atrophy
The VRS is a valuable tool for early diagnosis, disease progression monitoring, and differential
diagnosis between Alzheimer’s Disease and other types of dementia, as it speci cally focuses on
regions associated with memory and learning.
Structural alteration are evaluated with f.e. the are image of the brain, for the functional alteration
an ef cient method is PET, it allows us to use a large variety of radiotracers in order to the
biomarkers we want to detect.
SPECT allows in vivo imaging of dopamine transporter (DAT) availability by using radiotracers
that bind speci cally to DAT sites in the brain.
Cerebrospinal uid if performed in an AD patient to detect amyloid or tau, you obtain a certain
pro le:
a. amyloid-b (Ab) deposition into extracellular Ab plaques( LOW CSF Ab1-42)
b. intracellular neuro brillary tangles (NFT) formation (HIGH CSF p-tau)
c. neuronal loss (HIGH CSF t-tau)
Riassunto dei cambiamenti nei biomarcatori del CSF per l'Alzheimer
Biomarcatore Cambiamento Cosa indica?
Aβ1-42 ↓ Basso Deposizione di β-amiloide nelle placche
p-tau ↑ Alto Formazione di grovigli neuro brillari
t-tau ↑ Alto Perdita neuronale e neurodegenerazione
LECTURE 3
Lab - administration of screening Tests
Mini-Mental State Examination
The Mini-Mental State Examination (MMSE) is a widely used cognitive
screening tool designed to assess global cognitive functioning. It provides a
quick measure of mental state and is often used to detect cognitive impairments,
monitor changes over time, or evaluate the severity of conditions such as
dementia.
The MMSE is structured as a 30-point questionnaire, with questions grouped into
ve cognitive domains:
1. Orientation: Assessing awareness of time, date, and location.
2. Registration and Recall: Testing short-term memory by asking patients to
remember and later recall three objects.
3. Attention and Calculation: Measuring concentration and mental
arithmetic, such as counting backward from 100 by 7s.
fi fi fi
fi
fl fi fi fl fi
