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Mild cognitive impairment in dementia with Lewy bodies: an update and outlook

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

Dementia with Lewy bodies (DLB), the second most common degenerative neurocognitive disorder after Alzheimer disease (AD), is frequently preceded by a period of mild cognitive impairment (MCI), in which cognitive decline is associated with impairment of executive functions/attention, visuospatial deficits, or other cognitive domains and a variety of noncognitive and neuropsychiatric symptoms, many of which are similar but less severe than in prodromal AD. While 36–38% remain in the MCI state, at least the same will convert to dementia. Biomarkers are slowing of the EEG rhythms, atrophy of hippocampus and nucleus basalis of Meynert, temporoparietal hypoperfusion, signs of degeneration of the nigrostriatal dopaminergic, cholinergic and other neurotransmitter systems, and inflammation. Functional neuroimaging studies revealed disturbed connectivity of frontal and limbic networks associated with attention and cognitive controls, dopaminergic and cholinergic circuits manifested prior to overt brain atrophy. Sparse neuropathological data showed varying Lewy body and AD-related stages associated with atrophy of entorhinal, hippocampal, and mediotemporal cortices. Putative pathomechanisms of MCI are degeneration of limbic, dopaminergic, and cholinergic systems with Lewy pathology affecting specific neuroanatomical pathways associated with progressing AD-related lesions, but many pathobiological mechanisms involved in the development of MCI in LBD remain to be elucidated as a basis for early diagnosis and future adequate treatment modalities to prevent progression of this debilitating disorder.

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Abbreviations

AD:

Alzheimer disease

ADNC:

Alzheimer disease pathology

Aβ:

β-Amyloid

αSyn:

α-Synuclein

CI:

Cognitive impairment

CSF:

Cerebrospinal fluid

DLB:

Dementia with Lewy bodies

DMN:

Default mode network

EF:

Executive function

GFAP:

Glial fibrillar acidic protein

GM:

Gray matter

LB:

Lewy body

LBP:

Lewy body pathology

MCI:

Mild cognitive impairment

MCI-AD:

Mild cognitive impairment developing to Alzheimer disease

MCI-LB:

Mild cognitive impairment stage of dementia with Lewy bodies

NAA:

N-acetylaspartate

NBM:

Nucleus basalis of Meynert

NfL:

Neurofilament light-chain protein

PDD:

Parkinson disease dementia

PD-MCI:

Mild cognitive impairment in Parkinson disease

RBD:

Rapid eye movement sleep behavior disorder

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. Mild cognitive impairment in dementia with Lewy bodies: an update and outlook. J Neural Transm 130, 1491–1508 (2023). https://doi.org/10.1007/s00702-023-02670-1

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