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Depression in dementia with Lewy bodies: a critical update

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

Depression with an estimated prevalence of 35% is a frequent manifestation of dementia with Lewy bodies (DLB), having negative effects on cognitive performance and life expectancy, yet the underlying neurobiology is poorly understood and most likely heterogeneous. Depressive symptoms in DLB can occur during the clinical course and, together with apathy, is a common prodromal neuropsychiatric symptom of this neurocognitive disorder in the group of Lewy body synucleinopathies. There are no essential differences in the frequency of depression in DLB and Parkinson disease-dementia (PDD), while its severity is up to twice as high as in Alzheimer disease (AD). Depression in DLB that is frequently underdiagnosed and undertreated, has been related to a variety of pathogenic mechanisms associated with the basic neurodegenerative process, in particular dysfunctions of neurotransmitter systems (decreased monoaminergic/serotonergic, noradrenergic and dopaminergic metabolism), α-synuclein pathology, synaptic zinc dysregulation, proteasome inhibition, gray matter volume loss in prefrontal and temporal areas as well as dysfunction of neuronal circuits with decreased functional connectivity of specific brain networks. Pharmacotherapy should avoid tricyclic antidepressants (anticholinergic adverse effects), second-generation antidepressants being a better choice, while modified electroconvulsive therapy, transcranial magnetic stimulation therapy and deep brain stimulation may be effective for pharmacotherapy-resistant cases. Since compared to depression in other dementias like Alzheimer disease and other parkinsonian syndromes, our knowledge of its molecular basis is limited, and further studies to elucidate the heterogeneous pathogenesis of depression in DLB are warranted.

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Abbreviations

AD:

Alzheimer disease

ADNC:

Alzheimer disease neuropathological changes

αSyn:

α-Synuclein

CBD:

Corticobasal degeneration

CI:

Cognitive impairment

DLB:

Dementia with Lewy bodies

DRN:

Dorsal raphe nucleus

GDS:

Geriatric Depression Scale

LB:

Lewy body

LBP:

Lewy body pathology

LC:

Locus ceruleus

MSA:

Multiple system atrophy

PDD:

Parkinson disease-dementia

PSP:

Progressive supranuclear palsy

RBD:

REM sleep behavior disorder

SNc:

Substantia nigra compacta

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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. Depression in dementia with Lewy bodies: a critical update. J Neural Transm 130, 1207–1218 (2023). https://doi.org/10.1007/s00702-023-02669-8

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