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Pathomechanisms of cognitive and behavioral impairment in corticobasal degeneration

  • Neurology and Preclinical Neurological Studies - Review Article
  • Published:
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Abstract

Corticobasal degeneration (CBD) is a rare, sporadic, late-onset progressive neurodegenerative disorder of unknown etiology, clinically characterized by an akinetic–rigid syndrome, behavior and personality disorders, language problems (aphasias), apraxia, executive and cognitive abnormalities and limb dystonia. The syndrome is not specific, as clinical features of pathologically proven CBD include several phenotypes. This 4-repeat (4R) tauopathy is morphologically featured by often asymmetric frontoparietal atrophy, ballooned/achromatic neurons containing filamentous 4R-tau aggregates in cortex and striatum, thread-like processes that are more widespread than in progressive supranuclear palsy (PSP), pathognomonic "astroglial plaques", and numerous inclusions in both astrocytes and oligodendroglia ("coiled bodies") in the white matter. Cognitive deficits in CBD are frequent initial presentations before onset of motor symptoms, depending on the phenotypic variant. They predominantly include executive and visuospatial dysfunction, sleep disorders and language deficits with usually preserved memory domains. Neuroimaging studies showed heterogenous locations of brain atrophy, particularly contralateral to the dominant symptoms, with disruption of striatal connections to prefrontal cortex and basal ganglia circuitry. Asymmetric hypometabolism, mainly involving frontal and parietal regions, is associated with brain cholinergic deficits, and dopaminergic nigrostriatal degeneration. Widespread alteration of cortical and subcortical structures causing heterogenous changes in various brain functional networks support the concept that CBD, similar to PSP, is a brain network disruption disorder. Putative pathogenic factors are hyperphosphorylated tau-pathology, neuroinflammation and oxidative injury, but the basic mechanisms of cognitive impairment in CBD, as in other degenerative movement disorders, are complex and deserve further elucidation as a basis for early diagnosis and adequate treatment of this fatal disorder.

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Notes

  1. Alien hand syndrome is a phenomenon in which one hand is not under control of the mind. The person loses control of the hand, and it acts as if it has a mind of its own.

Abbreviations

4R:

4-Repeat

AD:

Alzheimer disease

APs:

Astroglial plaques

Aβ:

β-Amyloid

bvFTD:

Behavioral variant of frontotemporal dementia

CBD:

Corticobasal degeneration

CBD-RS:

PSP-like Richardson's syndrome

CBS:

Corticobasal syndrome

CI:

Cognitive impairment

FBS:

Frontal behavioral-spatial syndrome

FDG:

[18F]fluorodeoxyglucose

FTLD:

Frontotemporal lobe degeneration

GM:

Gray matter

nfvPPA:

Non-fluent/agrammatic variant of primary progressive aphasia

PNFA:

Progressive nonfluent aphasia

PSP:

Progressive supranuclear palsy

RBD:

REM sleep behavior disorder

RS:

Richardson's syndrome

WM:

White matter

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Acknowledgements

The author thanks Mr. E. Mitter-Ferstl for secretarial and editorial work.

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The study was funded by the Society for the Promotion of Research in Experimental Neurology, Vienna, Austria.

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    Kurt A. Jellinger

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Jellinger, K.A. Pathomechanisms of cognitive and behavioral impairment in corticobasal degeneration. J Neural Transm 130, 1509–1522 (2023). https://doi.org/10.1007/s00702-023-02691-w

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