Executive function impairment

● Differential diagnoses, including distinctive history and examination findings

▪ Vascular cognitive impairment, including vascular dementia

Patients may initially present with slowed cognition, impaired attention, and executive dysfunction. A stepwise or fluctuating course, or a history of vascular risk factors or previous strokes, may also support a vascular contribution. Neurocognitive testing typically demonstrates impaired executive function and slowed processing speed, with other cognitive domains variably affected. On general physical examination, there may be signs of vascular or cardiovascular disease. On neurological examination, there may be upper motor neuron signs, including weakness in a pyramidal distribution (predominantly affecting the extensor muscles of the upper limbs and flexor muscles of the lower limbs), hyperreflexia, and/or a Babinski sign. Gait may be normal or may be slow, with reduced stride length or a hemiparetic pattern.

▪ Behavioural variant frontotemporal dementia

Patients typically present with progressive behavioural or personality changes, which may include apathy, disinhibition, loss of empathy, stereotyped or compulsive behaviours, or changes in eating behaviour. Cognitive impairment may initially be subtle, with executive function and other cognitive domains preserved when clinical manifestations are predominantly behavioural. Neurocognitive testing may therefore be relatively preserved early in the disorder, although executive dysfunction and other cognitive impairments may emerge as the disorder progresses, depending on the clinical phenotype. On neurological examination, findings may initially be normal, but some patients develop motor neuron disease, with upper and/or lower motor neuron signs such as hyperreflexia, pathological reflexes, weakness, or muscle wasting.

▪ Dementia with Lewy bodies and Parkinson disease dementia

Patients may initially present with executive dysfunction, visuospatial impairment, and/or slowed cognition, and may be accompanied by characteristic cognitive fluctuations. When dementia precedes or occurs within approximately one year of the onset of parkinsonism, the syndrome is classified as dementia with Lewy bodies; when dementia develops in the setting of established Parkinson disease, it is classified as Parkinson disease dementia. Neurocognitive testing typically supports the predominant cognitive deficit and may reveal additional executive, visuospatial, or other cognitive dysfunction. On neurological examination, there is typically parkinsonism, with rigidity and bradykinesia, with or without resting tremor. Gait may be slow and shuffling, with reduced stride length and other features of parkinsonian gait. Other distinctive clinical features may include recurrent visual hallucinations and REM sleep behaviour disorder.

▪ Corticobasal syndrome

Patients may initially present with language dysfunction, executive dysfunction, apraxia, visuospatial impairment, and/or slowed cognition, which may be accompanied by asymmetric motor or cortical features. Neurocognitive testing typically supports the predominant cognitive deficit and may reveal additional executive, language, visuospatial, or other cognitive dysfunction. On neurological examination, there is typically markedly asymmetric rigidity and parkinsonism, often accompanied by limb apraxia, cortical sensory abnormalities, alien-limb phenomena, dystonia, or myoclonus. Hyperreflexia or other upper motor neuron features may also occur, and gait may show a combination of parkinsonian and hemiparetic features. CBS may result from corticobasal degeneration or other underlying neurodegenerative pathologies, including Alzheimer disease and progressive supranuclear palsy.

▪ Progressive supranuclear palsy

Patients may initially present with slowed cognition, executive dysfunction, or language dysfunction, often accompanied by early falls or postural instability. PSP can present with several clinical phenotypes, including a frontal-predominant phenotype (PSP-F) with prominent executive and behavioural dysfunction, a speech/language-predominant phenotype (PSP-SL), and phenotypes characterised predominantly by parkinsonism, gait freezing, or postural instability. Neurocognitive testing typically demonstrates executive dysfunction and slowed processing, with other cognitive domains variably affected. On cranial nerve examination, there may be slowing of vertical saccades or a supranuclear limitation of vertical gaze (limited range of voluntary gaze with relative preservation of range on the vestibulo-ocular reflex [doll’s-eye manoeuvre]), particularly affecting downgaze. There is typically axial-predominant rigidity, and gait may be stiff and shuffling, with reduced stride length, freezing, early postural instability, retropulsion, and falls.