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Significance of cerebral amyloid angiopathy and other co-morbidities in Lewy body diseases

  • Neurology and Preclinical Neurological Studies - Original Article
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Abstract

Lewy body dementia (LBD) and Parkinson's disease-dementia (PDD) are two major neurocognitive disorders with Lewy bodies (LB) of unknown etiology. There is considerable clinical and pathological overlap between these two conditions that are clinically distinguished based on the duration of Parkinsonism prior to development of dementia. Their morphology is characterized by a variable combination of LB and Alzheimer's disease (AD) pathologies. Cerebral amyloid angiopathy (CAA), very common in aged persons and particularly in AD, is increasingly recognized for its association with both pathologies and dementia. To investigate neuropathological differences between LB diseases with and without dementia, 110 PDD and 60 LBD cases were compared with 60 Parkinson's disease (PD) cases without dementia (PDND). The major demographic and neuropathological data were assessed retrospectively. PDD patients were significantly older than PDND ones (83.9 vs 77.8 years; p < 0.05); the age of LB patients was in between both groups (mean 80.2 years), while the duration of disease was LBD < PDD < PDND (mean 6.7 vs 12.5 and 14.3 years). LBD patients had higher neuritic Braak stages (mean 5.1 vs 4.5 and 4.0, respectively), LB scores (mean 5.3 vs 4.2 and 4.0, respectively), and Thal amyloid phases (mean 4.1 vs 3.0 and 2.3, respectively) than the two other groups. CAA was more common in LBD than in the PDD and PDND groups (93 vs 50 and 21.7%, respectively). Its severity was significantly greater in LBD than in PDD and PDND (p < 0.01), involving mainly the occipital lobes. Moreover, striatal Aβ deposition highly differentiated LBD brains from PDD. Braak neurofibrillary tangle (NFT) stages, CAA, and less Thal Aβ phases were positively correlated with LB pathology (p < 0.05), which was significantly higher in LBD than in PDD < PDND. Survival analysis showed worse prognosis in LBD than in PDD (and PDND), which was linked to both increased Braak tau stages and more severe CAA. These and other recent studies imply the association of CAA—and both tau and LB pathologies—with cognitive decline and more rapid disease progression that distinguishes LBD from PDD (and PDND).

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Data availability

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

Abbreviations

Aβ:

β-Amyloid

CAA:

Cerebral amyloid angiopathy

LB:

Lewy body

LBD:

Lewy body dementia

MMSE:

Mini Mental State Examination

PD:

Parkinson's disease

PDD:

Parkinson's disease-dementia

PDND:

Parkinson's disease without dementia

rCBF:

Regional cerebral blood flow

αSyn:

α-Synuclein

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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. Significance of cerebral amyloid angiopathy and other co-morbidities in Lewy body diseases. J Neural Transm 128, 687–699 (2021). https://doi.org/10.1007/s00702-021-02345-9

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