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Morphological basis of Parkinson disease-associated cognitive impairment: an update

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

Cognitive impairment is one of the most salient non-motor symptoms of Parkinson disease (PD) that poses a significant burden on the patients and carers as well as being a risk factor for early mortality. People with PD show a wide spectrum of cognitive dysfunctions ranging from subjective cognitive decline and mild cognitive impairment (MCI) to frank dementia. The mean frequency of PD with MCI (PD-MCI) is 25.8% and the pooled dementia frequency is 26.3% increasing up to 83% 20 years after diagnosis. A better understanding of the underlying pathological processes will aid in directing disease-specific treatment. Modern neuroimaging studies revealed considerable changes in gray and white matter in PD patients with cognitive impairment, cortical atrophy, hypometabolism, dopamine/cholinergic or other neurotransmitter dysfunction and increased amyloid burden, but multiple mechanism are likely involved. Combined analysis of imaging and fluid markers is the most promising method for identifying PD-MCI and Parkinson disease dementia (PDD). Morphological substrates are a combination of Lewy- and Alzheimer-associated and other concomitant pathologies with aggregation of α-synuclein, amyloid, tau and other pathological proteins in cortical and subcortical regions causing destruction of essential neuronal networks. Significant pathological heterogeneity within PD-MCI reflects deficits in various cognitive domains. This review highlights the essential neuroimaging data and neuropathological changes in PD with cognitive impairment, the amount and topographical distribution of pathological protein aggregates and their pathophysiological relevance. Large-scale clinicopathological correlative studies are warranted to further elucidate the exact neuropathological correlates of cognitive impairment in PD and related synucleinopathies as a basis for early diagnosis and future disease-modifying therapies.

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Abbreviations

AD:

Alzheimer disease

ADNC:

Alzheimer disease-related neuropathological changes

aMCI:

Amnestic mild cognitive impairment

Aβ:

β-amyloid

αSyn:

α-synuclein

CA:

Cornu ammonis

CAA:

Cerebral amyloid angiopathy

CI:

Cognitive impairment

CMBs:

Cerebral microbleeds

DLB:

Dementia with lewy bodies

DMN:

Default mode network

FA:

Fractional anisotropy

FW:

Free water

GM:

Gray matter

GMV:

Gray matter volume

LB:

Lewy body

LBP:

Lewy body pathology

MCI:

Mild cognitive impairment

MMSE:

Mini mental state examination

MRI:

Magentic resonance imaging

naMCI:

Non-amnestic mild cognitive impairment

NBM:

Nucleus basalis of Meynert

NFT:

Neurofibrillary tangle

PD:

Parkinson disease

PDD:

Parkinson disease dementia

PD-MCI:

Parkinson disease with mild cognitive impairment

PD-NC:

Parkinson disease with normal cognition

PDND:

Parkinson disease-no dementia

PET:

Positron emission tomography

SAN:

Salience network

SCD:

Subjective cognitive decline

SN:

Substantia nigra

WM:

White matter

WMH:

White matter hyperintensity

WMV:

White matter volume

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Acknowledgements

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

Funding

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

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  1. Institute of Clinical Neurobiology, Alberichgasse 5/13, 1150, Vienna, Austria

    Kurt A. Jellinger

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Jellinger, K.A. Morphological basis of Parkinson disease-associated cognitive impairment: an update. J Neural Transm 129, 977–999 (2022). https://doi.org/10.1007/s00702-022-02522-4

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