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Morphological characteristics differentiate dementia with Lewy bodies from Parkinson disease with and without dementia

  • Neurology and Preclinical Neurological Studies - Original Article
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Abstract

Dementia with Lewy bodies (DLB) and Parkinson disease (PD) with and without dementia are entities of a spectrum of Lewy body diseases. About 26.3% of all PD patients develop dementia increasing up to 83%. Parkinson disease-dementia (PDD) and DLB share many clinical and morphological features that separate them from non-demented PD (PDND). Clinically distinguished by the temporal sequence of motor and cognitive symptoms, the pathology of PDD and DLB includes variable combinations of Lewy body (LB) and Alzheimer (AD) lesions, both being more severe in DLB, but much less frequent and less severe in PDND. The objective of this study was to investigate the morphological differences between these three groups. 290 patients with pathologically confirmed PD were reviewed. 190 of them had clinical dementia; 110 met the neuropathological criteria of PDD and 80 of DLB. The major demographic and clinical data were obtained from medical records. Neuropathology included semiquantitative assessment of LB and AD pathologies including cerebral amyloid angiopathy (CAA). PDD patients were significantly older than PDND and DLB ones (83.9 vs 77.9 years, p < 0.05); the age of DLB patients was between them (80.0 years), while the disease duration was shortest in DLB. Brain weight was lowest in DLB, which showed higher Braak LB scores (mean 5.2 vs 4.2) and highest Braak tau stages (mean 5.2 vs 4.4 and 2.3, respectively). Thal Aβ phases were also highest in DLB (mean 4.1 vs 3.0 and 1.8, respectively). Major findings were frequency and degree of CAA, being highest in DLB (95% vs 50% and 24%, with scores 2.9 vs 0.7 and 0.3, respectively), whereas other small vessel lesions showed no significant differences. Striatal Aβ deposits also differentiated DLB from the other groups. This and other studies of larger cohorts of PD patients indicate that the association of CAA and cortical tau—but less—LB pathologies are associated with more severe cognitive decline and worse prognosis that distinguish DLB from PDD and PDND. The particular impact of both CAA and tau pathology supports the concept of a pathogenic continuum ranging from PDND to DLB + AD within the spectrum of age-related synucleinopathies.

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Data availability

The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

Abbreviations

αSyn:

α-Synuclein

AD:

Alzheimer disease

ADNC:

Alzheimer disease-related neuropathological changes

CAA:

Cerebral amyloid angiopathy

CI:

Cognitive impairment

DLB:

Dementia with Lewy bodies

LB:

Lewy body

LBD:

Lewy body disorder

LBP:

Lewy body pathology

LC:

Locus ceruleus

LN:

Lewy neurite

MMSE:

Mini Mental State Examination

NFT:

Neurofibrillary tangle

p-tau:

Phosphorylated tau

PD:

Parkinson disease

PDD:

Parkinson disease-dementia

PDND:

Non-demented Parkinson disease

SN:

Substantia nigra

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Acknowledgements

The author thanks Mr. E. Mitter-Ferstl, PhD, 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. Morphological characteristics differentiate dementia with Lewy bodies from Parkinson disease with and without dementia. J Neural Transm 130, 891–904 (2023). https://doi.org/10.1007/s00702-023-02660-3

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