Do patients with multiple system atrophy develop cognitive changes?

Do Patients with Multiple System Atrophy Develop Cognitive Changes?

Yes, patients with multiple system atrophy (MSA) do develop cognitive changes, with mild cognitive impairment (MCI) reported in 20-47% of cases, primarily affecting executive function, attention, language, memory, and processing speed. 1, 2, 3, 4

Cognitive Profile in MSA

The cognitive impairment in MSA is now recognized as an integral part of the disease rather than an exclusion criterion, as it was previously considered in older diagnostic criteria. The specific cognitive domains affected include:

• Executive function and attention (most commonly impaired)
• Language (including logopenia as the most common frontal behavioral change)
• Memory (both verbal and visual)
• Processing speed (mental and motor)
• Visuospatial function

1, 2, 5, 6

Differences Between MSA Subtypes

MSA-P (Parkinsonian variant) shows more impairment in:

• Motor and mental speed
• Working memory
• Executive functions
• Focused attention

MSA-C (Cerebellar variant) demonstrates greater deficits in:

• New learning
• Immediate recall
• Verbal fluency
• Sustained attention

However, these differences are often not statistically significant, and both subtypes experience substantial cognitive burden. 2

Neuroimaging Correlates

The cognitive impairment correlates with specific brain changes:

• Frontal and cerebellar metabolism reduction on FDG-PET imaging correlates with attention, executive function, and language deficits 5
• Gray matter atrophy in frontotemporal cortical areas, insula, caudate, thalamus, and cerebellum 2
• Hot-cross bun (HCB) sign on MRI is independently associated with cognitive impairment, particularly affecting language, visuospatial function, and processing speed 1
• Disrupted cerebello-cerebral networks and decreased functional connectivity in parietal lobe, cuneus, precuneus, and limbic structures 4

Pathological Basis

In cases with moderate to severe cognitive impairment, neuropathological studies reveal:

• 35.3% of MSA patients show mild-to-moderate cognitive impairment
• These patients are significantly older than those without cognitive changes
• Cortical Alzheimer pathology (Braak stages III-IV) and Lewy body co-pathologies are frequently present in those with cognitive symptoms
• However, 77.1% of MSA cases are free of Alzheimer-type lesions, suggesting MSA pathology itself contributes to cognitive dysfunction 3

Clinical Implications

Frontal behavioral changes are common and include:

1. Logopenia (most common)
2. Apathy
3. Inflexibility

These behavioral changes, along with disease severity and depression, are independent determinants of poor quality of life in MSA patients. 6

Important Caveats

• Severe dementia is rare in MSA (only occasional cases show fully developed Alzheimer disease) 3
• The cognitive impairment in MSA represents a brain network disorder rather than isolated cortical pathology 4
• Early cognitive screening should be performed in all MSA patients, as cognitive dysfunction affects quality of life independent of motor symptoms 6
• The presence of cognitive impairment should not exclude the diagnosis of MSA, as this represents an outdated diagnostic criterion 7, 4