Neuropsychological Testing in Corticobasal Syndrome and Progressive Supranuclear Palsy

Overview

Neuropsychological assessment is essential for the diagnosis, differential diagnosis, and monitoring of corticobasal syndrome (CBS) and progressive supranuclear palsy (PSP). These conditions exhibit distinct cognitive profiles that reflect the underlying pattern of cortical and subcortical neurodegeneration. Comprehensive neuropsychological testing helps differentiate CBS from PSP, distinguish them from other dementias (particularly Alzheimer’s disease and frontotemporal dementia), and provides baseline measures for tracking disease progression. [@neuropsychology]

The characteristic cognitive deficits in CBS and PSP arise from the specific brain regions affected: CBS typically involves asymmetric cortical involvement of the frontoparietal regions, basal ganglia, and corpus callosum, while PSP primarily affects subcortical structures including the basal ganglia, brainstem, and frontal lobe. These distinct patterns produce measurable differences in cognitive performance that neuropsychological testing can detect and quantify. [@cognitive]

Clinical Indications

Neuropsychological testing is indicated in the following scenarios:

Initial diagnostic workup: When patients present with parkinsonism plus cognitive or behavioral changes, neuropsychological testing helps establish the cognitive phenotype and guide differential diagnosis
Differential diagnosis: Distinguishing CBS from PSP, Alzheimer’s disease, frontotemporal dementia, and other parkinsonian syndromes
Characterizing cortical vs. subcortical patterns: Identifying whether cognitive deficits reflect primarily cortical or subcortical dysfunction
Baseline establishment: Creating baseline measures for tracking disease progression
Treatment planning: Identifying specific cognitive strengths and weaknesses to guide rehabilitation strategies
Capacity assessment: Evaluating decision-making capacity for medical and legal planning

Executive Function Assessment

Executive dysfunction is a hallmark of both CBS and PSP, reflecting the involvement of prefrontal cortical and subcortical structures. However, the specific pattern and severity differ between conditions.

Trail Making Test

The Trail Making Test is a widely used measure of visual attention, task switching, and executive function. It consists of two parts:

Part A (Line Drawing): Patients connect numbered circles in sequential order. This primarily assesses visual scanning and psychomotor speed.

Part B (Alternating): Patients alternate between numbers and letters in sequence (1-A-2-B-3-C…). This places greater demands on cognitive flexibility, task switching, and working memory.

flowchart TD
    A["Trail Making Test"]  -->  B["Part A"]
    A  -->  C["Part B"]
    B  -->  B1["Visual Scanning"]
    B  -->  B2["Psychomotor Speed"]
    C  -->  C1["Cognitive Flexibility"]
    C  -->  C2["Task Switching"]
    C  -->  C3["Working Memory"]

Interpretation in CBS/PSP:

CBS: Performance is typically markedly impaired on both parts, with Part B showing particular difficulty due to the need for cognitive flexibility. Errors are common, including sequencing mistakes and perseveration.
PSP: Both parts are significantly impaired, often with greater slowing on Part B. The impairment reflects subcortical (basal ganglia-frontocortical) dysfunction rather than primary cortical dysfunction. [@trail]
Cortical vs. subcortical distinction: In cortical patterns (more typical of CBS), patients make more errors and show learning effects across trials. In subcortical patterns (more typical of PSP), patients show marked slowing but may make fewer errors, reflecting a retrieval deficit rather than a planning deficit. [@subcortical]

Scoring norms: Results are compared to age- and education-matched normative data. Impairment is typically defined as performance more than 1.5 standard deviations below the mean.

Stroop Color and Word Test

The Stroop Test assesses the ability to inhibit automatic reading responses in favor of color naming. It consists of three conditions:

Word Reading: Reading color words (red, blue, green) printed in black ink
Color Naming: Naming colored patches
Interference: Naming the ink color of color words that spell different colors (the “Stroop effect”)

flowchart TD
    A["Stroop Test Conditions"]  -->  B["Word Reading"]
    A  -->  C["Color Naming"]
    A  -->  D["Interference Trial"]
    B  -->  B1["Baseline Reading Speed"]
    C  -->  C1["Basic Color Processing"]
    D  -->  D1["Response Inhibition"]
    D  -->  D2["Cognitive Control"]
    D  -->  D3["Processing Speed"]

Interpretation in CBS/PSP:

CBS: Marked impairment on the interference trial, reflecting frontostriatal dysfunction. Patients show significant slowing and increased errors. The effect size is often larger than in PSP.
PSP: Significant impairment on all conditions, with particular difficulty on the interference trial. The deficits reflect the prominent subcortical involvement affecting the caudate nucleus and prefrontal cortex. [@stroop]
Cortical vs. subcortical: Patients with cortical patterns (CBS) may show greater susceptibility to interference with preserved automaticity. Those with subcortical patterns (PSP) often show generalized slowing across all conditions.

Wisconsin Card Sorting Test (WCST)

The WCST assesses abstract reasoning, cognitive flexibility, and problem-solving. Patients sort cards based on varying principles (color, shape, number) and must discover and shift sorting rules based on feedback.

Interpretation in CBS/PSP:

CBS: Patients typically show marked impairment with high rates of perseverative errors, reflecting frontal lobe dysfunction. The pattern suggests difficulty with set-shifting and feedback utilization.
PSP: Significant impairment is common, with deficits in both abstract reasoning and flexibility. Performance correlates with frontal lobe hypometabolism on FDG-PET. [@wisconsin]

Additional Executive Function Measures

Letter Fluency (FAS/CFL): Patients generate as many words as possible beginning with a specific letter in 60 seconds. Sensitive to frontal lobe dysfunction.

Category Fluency (Animals/Vegetables): Patients generate as many exemplars from a semantic category. Tests both executive function and semantic memory.

Digit Span (WAIS): Forward and backward digit span assess attention and working memory. Backward span is particularly sensitive to executive dysfunction.

Apraxia Testing

Apraxia is a hallmark of CBS, reflecting the cortical involvement of the left hemisphere (for limb apraxia) and the frontoparietal networks. Testing helps distinguish cortical from subcortical patterns.

Ideomotor Apraxia

Definition: Inability to perform learned gestures on command or to imitate gestures, despite intact motor strength and coordination.

Testing Procedure:

Pantomime to command: Patient demonstrates how to use a tool (e.g., “show me how to use a hammer”)
Imitation: Patient imitates gestures performed by the examiner
Tool use: Patient uses actual tools appropriately

Scoring: Each gesture is scored based on accuracy, spatial organization, and temporal sequencing.

Interpretation:

CBS: Ideomotor apraxia is common and often severe, particularly in the dominant hand. The pattern is typically limb-specific, reflecting cortical (posterior frontal and parietal) involvement. Patients may show:
- Spatial errors (incorrect hand posture, orientation)
- Temporal errors (abnormal sequencing of movements)
- Conduction errors (correct hand position, wrong movement)
- Omission errors (complete failure to initiate)
PSP: Apraxia is less prominent than in CBS but may be present, particularly with disease progression. When present, it tends to reflect subcortical rather than cortical patterns. [@apraxia]

Ideational Apraxia

Definition: Inability to conceptualize or sequence a multi-step task.

Testing: Patient is asked to demonstrate a complex task (e.g., making coffee, writing a letter) or to sequence a series of pictures showing task steps.

Interpretation:

More common in CBS than PSP
Correlates with parietal lobe involvement
May impact activities of daily living significantly

Limb-Kinetic Apraxia

Definition: Loss of fine motor dexterity and the ability to make precise, coordinated movements.

Testing: Rapid alternating movements, finger tapping, complex finger sequences.

Interpretation:

Common in CBS, reflecting the cortical (precentral gyrus, premotor cortex) involvement
May be difficult to distinguish from bradykinesia in parkinsonian conditions

Orofacial Apraxia

Definition: Impaired ability to perform facial movements on command (e.g., “show me how to blow out a match,” “pucker your lips”).

Testing: Imitation and command tasks for facial, buccal, and lingual movements.

Interpretation:

More common in CBS than PSP
May affect speech and swallowing evaluation

Language Assessment

Language deficits in CBS and PSP have distinct profiles that reflect the underlying pathology.

Confrontation Naming

Boston Naming Test (BNT): Patients name line drawings of objects, with semantic and phonemic cues provided for failed items.

Interpretation:

CBS: Anomia is common, often reflecting a combination of lexical retrieval failure and possibly apraxia of speech. Semantic errors may occur. The pattern may differ from typical aphasia.
PSP: Naming deficits are usually milder than in CBS but may emerge with disease progression. Errors are more likely to be phonemic paraphasias.

Semantic Knowledge

Category Fluency vs. Letter Fluency: Comparison helps distinguish semantic from phonemic retrieval deficits.

Picture Matching and Semantic Association: Tests such as the Pyramids and Palm Trees Test assess semantic knowledge.

Interpretation:

CBS: May show semantic memory impairment if temporal lobe involvement is present
PSP: Typically shows relatively preserved semantic knowledge early in disease

Language Production

Spontaneous Speech Analysis:

CBS: May show reduced speech output, paraphasias, and apraxia of speech features. Speech is often sparse and may include phonemic errors.
PSP: Patients typically show reduced speech output with a “dysexecutive” pattern—speech is sparse but grammatically correct. Reduced verbal fluency is prominent.

Comprehension

Token Test: Assesses comprehension of complex, grammatically elaborate sentences.

Interpretation:

CBS: May show impaired comprehension, particularly for syntactically complex sentences
PSP: Generally better preserved than in CBS, though deficits emerge later

Behavioral Screening

Behavioral changes are prominent in both CBS and PSP and significantly impact quality of life.

Frontal Lobe Behavioral Assessment

Frontal Assessment Battery (FAB): A brief bedside test assessing:

Lexical fluency (S-words in 60 seconds)
Motor series (Luria’s task: fist-palm-side)
Conflicting instructions (“tap twice when I tap once”)
Go/No-Go response inhibition
Prehension behavior

Interpretation:

CBS: Typically significantly impaired, reflecting frontal cortical dysfunction
PSP: Also impaired but may show a different pattern reflecting subcortical-frontocortical disconnection

Neuropsychiatric Inventory (NPI)

The NPI assesses behavioral and psychological symptoms including:

Delusions
Hallucinations
Agitation/aggression
Depression/dysphoria
Anxiety
Euphoria/elation
Apathy/indifference
Disinhibition
Irritability/lability
Motor behavior (pacing, wandering)
Sleep and night-time behaviors
Appetite/eating changes

Interpretation in CBS/PSP:

CBS: Apathy, agitation, and irritability are common. May also see behavioral variant FTD-like features if co-pathology exists.
PSP: Apathy is particularly prominent and often severe. Depression is also common. May see disinhibition less frequently than in FTD. [@behavioral]

Specific Behavioral Features

Apathy vs. Depression: Both are common in CBS and PSP but require different management approaches. Apathy is characterized by loss of initiative, interest, and emotional range without the sadness and guilt of depression.

Disinhibition: More common in CBS with co-existing FTD pathology. May manifest as socially inappropriate behavior, loss of manners, or impulse control problems.

Obsessive-Compulsive Behaviors: Can occur in both conditions, possibly reflecting frontostriatal dysfunction.

Cortical vs. Subcortical Patterns

A key goal of neuropsychological assessment in CBS and PSP is distinguishing cortical from subcortical cognitive profiles.

flowchart TD
    A["Cognitive Profile Patterns"]  -->  B["Cortical Pattern"]
    A  -->  C["Subcortical Pattern"]
    B  -->  B1["Prominent aphasia"]
    B  -->  B2["Apraxia prominent"]
    B  -->  B3["Memory: Encoding/Retrieval"]
    B  -->  B4["Executive: Planning deficits"]
    B  -->  B5["Preserved processing speed early"]
    C  -->  C1["Minimal aphasia"]
    C  -->  C2["Minimal apraxia"]
    C  -->  C3["Memory: Retrieval only"]
    C  -->  C4["Executive: Slowing prominent"]
    C  -->  C5["Generalized slowing"]

Feature	Cortical (CBS)	Subcortical (PSP)
Memory	Encoding and retrieval deficits	Isolated retrieval deficit
Language	Anomia, aphasia features	Relatively preserved
Apraxia	Prominent	Minimal to mild
Executive	Set-shifting deficits	Generalized slowing
Processing speed	Preserved early	Impaired early
Attention	Variable	Fluctuating deficits

Implications for Diagnosis

Prominent apraxia, aphasia, and asymmetric deficits favor CBS
Early gait disturbance, vertical gaze palsy, and prominent slowing favor PSP
Mixed patterns may indicate comorbid pathologies
The pattern may evolve as disease progresses

Test Battery Recommendations

A comprehensive neuropsychological evaluation for CBS/PSP should include:

Core Battery

Intellectual functioning: WASI or WAIS-IV Full Scale IQ (abbreviated)
Attention/Working Memory: Digit Span, Letter-Number Sequencing
Executive Function: Trail Making Test (A and B), Stroop Test, Wisconsin Card Sorting Test, FAS/CFL fluency
Language: Boston Naming Test, Semantic fluency (animals), Token Test
Memory: Word List Learning (CVLT-II or RAVLT), Story Memory (Logical Memory or Craft Story)
Visuospatial: Judgment of Line Orientation, Block Design
Praxis: Apraxia screening (ideomotor, ideational)
Behavioral: Frontal Assessment Battery, NPI or frontal lobe checks

Supplementary Tests (Optional)

Detailed memory testing: Doors and People Test
Social cognition: Reading the Mind in the Eyes, Faux Pas recognition
Constructional ability: Rey-Osterrieth Complex Figure
Executive function: Delis-Kaplan Executive Function System (D-KEFS)

Interpretation and Reporting

Report Structure

A comprehensive neuropsychological report should include:

Referral question and background: Reason for evaluation, medical history, current medications
Behavioral observations: Test behavior, effort, cooperation, any confounding factors
Test results by domain: Organized by cognitive domain with specific scores and percentiles
Pattern analysis: Cortical vs. subcortical, focal vs. diffuse, asymmetric findings
Diagnostic impressions: Integration with clinical findings, differential diagnosis
Recommendations: Treatment, rehabilitation, safety considerations, follow-up

Integration with Neuroimaging

Neuropsychological findings should be integrated with neuroimaging results:

CBS: Asymmetric frontoparietal atrophy on MRI
PSP: Midbrain atrophy (“hummingbird sign”), PSP-specific patterns on MRI, hypometabolism on FDG-PET in frontal and brainstem regions

Differential Diagnosis Considerations

Neuropsychological testing helps distinguish CBS and PSP from:

Alzheimer’s disease: Prominent episodic memory deficits early, cortical patterns
Frontotemporal dementia: Behavioral variant FTD shows prominent disinhibition, loss of social conduct; semantic variant shows severe naming deficits
Parkinson’s disease with dementia: More prominent memory retrieval deficits, less apraxia
Lewy body dementia: Fluctuating cognition, visual hallucinations, relatively preserved language

References

Pathway Diagram

The following diagram shows the key molecular relationships involving Neuropsychological Testing in CBS and PSP discovered through SciDEX knowledge graph analysis:

graph TD
    ALZHEIMER["ALZHEIMER"] -->|"associated with"| PSP["PSP"]
    MOBP["MOBP"] -->|"regulates"| PSP["PSP"]
    TAU["TAU"] -->|"activates"| PSP["PSP"]
    SNCA["SNCA"] -->|"therapeutic target"| PSP["PSP"]
    TAU["TAU"] -->|"associated with"| PSP["PSP"]
    CDKN2A["CDKN2A"] -->|"associated with"| PSP["PSP"]
    UBIQUITIN["UBIQUITIN"] -->|"expressed in"| PSP["PSP"]
    TAU["TAU"] -->|"expressed in"| PSP["PSP"]
    P62["P62"] -->|"expressed in"| PSP["PSP"]
    AKT["AKT"] -->|"activates"| PSP["PSP"]
    PI3K["PI3K"] -->|"activates"| PSP["PSP"]
    MAPT["MAPT"] -->|"activates"| PSP["PSP"]
    NLGN1["NLGN1"] -.->|"inhibits"| PSP["PSP"]
    TUBULIN["TUBULIN"] -.->|"inhibits"| PSP["PSP"]
    PI3K["PI3K"] -->|"treats"| PSP["PSP"]
    style ALZHEIMER fill:#ce93d8,stroke:#333,color:#000
    style PSP fill:#ce93d8,stroke:#333,color:#000
    style MOBP fill:#ce93d8,stroke:#333,color:#000
    style TAU fill:#ce93d8,stroke:#333,color:#000
    style SNCA fill:#ce93d8,stroke:#333,color:#000
    style CDKN2A fill:#ce93d8,stroke:#333,color:#000
    style UBIQUITIN fill:#ce93d8,stroke:#333,color:#000
    style P62 fill:#ce93d8,stroke:#333,color:#000
    style AKT fill:#ce93d8,stroke:#333,color:#000
    style PI3K fill:#ce93d8,stroke:#333,color:#000
    style MAPT fill:#ce93d8,stroke:#333,color:#000
    style NLGN1 fill:#ce93d8,stroke:#333,color:#000
    style TUBULIN fill:#ce93d8,stroke:#333,color:#000

Neuropsychological Testing in Corticobasal Syndrome and Progressive Supranuclear Palsy

Overview

Clinical Indications

Executive Function Assessment

Trail Making Test

Stroop Color and Word Test

Wisconsin Card Sorting Test (WCST)

Additional Executive Function Measures

Apraxia Testing

Ideomotor Apraxia

Ideational Apraxia

Limb-Kinetic Apraxia

Orofacial Apraxia

Language Assessment

Confrontation Naming

Semantic Knowledge

Language Production

Comprehension

Behavioral Screening

Frontal Lobe Behavioral Assessment

Neuropsychiatric Inventory (NPI)

Specific Behavioral Features

Cortical vs. Subcortical Patterns

Implications for Diagnosis

Test Battery Recommendations

Core Battery

Supplementary Tests (Optional)

Interpretation and Reporting

Report Structure

Integration with Neuroimaging

Differential Diagnosis Considerations

Related Pages

References

Pathway Diagram