Cognitive impairment is a core feature of progressive supranuclear palsy (PSP), often emerging early in the disease course and contributing significantly to functional disability. Unlike Alzheimer's disease, PSP cognitive deficits are characterized by prominent frontal executive dysfunction, slowed information processing, and behavioral changes rather than prominent memory impairment.
Cognitive dysfunction in PSP affects multiple domains, with frontal executive abilities being most prominently affected. Studies indicate that cognitive impairment is present in the majority of patients at diagnosis and progresses alongside motor symptoms. The pattern of cognitive deficits helps distinguish PSP from other parkinsonian disorders and contributes to the diagnostic criteria[1].
Frontal executive dysfunction represents the most characteristic cognitive profile in PSP. Patients demonstrate:
Executive dysfunction in PSP correlates with neurodegeneration in:
The disruption of frontal-subcortical circuits, particularly the dorsolateral prefrontal circuit, underlies these deficits. Tau pathology affects these regions early in the disease course[6].
Patients with PSP demonstrate significant attentional deficits:
Marked slowing of information processing is a hallmark of PSP cognitive impairment:
Unlike Alzheimer's disease, memory impairment in PSP is typically mild and reflects:
The memory profile suggests primarily frontal-subcortical dysfunction rather than medial temporal lobe involvement. However, some patients develop co-pathology (e.g., Alzheimer's disease comorbidity) leading to more significant memory impairment[9].
Apathy is the most common behavioral change in PSP, present in up to 70% of patients:
Gender differences have been noted, with male patients presenting with more severe apathy as demonstrated in a recent study[11].
Standardized assessment includes:
| Test | Domain Assessed |
|---|---|
| Trail Making Test A/B | Processing speed, set-shifting |
| Wisconsin Card Sorting Test | Executive function |
| Stroop Test | Inhibition, processing speed |
| Digit Span (WAIS) | Working memory |
| Rey Auditory Verbal Learning Test | Memory |
| Boston Naming Test | Language |
| Frontal Assessment Battery | Frontal function |
Cognitive assessment helps differentiate PSP from:
Cognitive impairment progresses with disease stage:
The rate of progression correlates with motor phenotype, with some variants (e.g., PSP-Parkinsonism) showing slower cognitive decline[13].
Cognitive and behavioral changes in PSP significantly impact caregivers:
Current clinical trials target:
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Gagliardi M, Procopio R, Felicetti A, et al. MAPT Subhaplotypes in Different Progressive Supranuclear Palsy Phenotypes. 2025. ↩︎
Santangelo G, Vitale C, Picillo M, et al. Apathy in PSP: A multicentric study. 2019. ↩︎
Ye L, Greten S, Wilkens I, et al. Tackling gender in progressive supranuclear palsy: Male patients present more apathy. 2025. ↩︎
Clark HM, Stierwalt JA, Meade G, et al. Tongue strength in progressive supranuclear palsy. 2025. ↩︎
Olfati N, Akhoundi FH, Litvan I. Atypical Parkinsonian Disorders. 2025. ↩︎