Prodromal dementia with Lewy bodies

Donaghy, Paul C.; O’Brien, John T.; Thomas, Alan

doi:10.1017/s0033291714000816

Cited by 53 publications

(45 citation statements)

References 51 publications

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“…In particular, RBD appears to be the most common and earliest‐developing diagnostic symptom in this phase (Ferman et al, ). Retrospective studies based on symptom questionnaires have replicated these findings, with visual hallucinations, gait problems, tremor/stiffness, falls and sleep symptoms including RBD reported as more common in early stages of disease in DLB than AD, in addition to other symptoms such as hyposmia and constipation (Auning et al, ; Chiba et al, ; Donaghy et al, ).…”

Section: Introductionmentioning

confidence: 99%

Symptoms associated with Lewy body disease in mild cognitive impairment

Donaghy

Barnett

Olsen

et al. 2017

Int J Geriat Psychiatry

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Section: Introductionmentioning

confidence: 99%

Symptoms associated with Lewy body disease in mild cognitive impairment

Donaghy

Barnett

Olsen

et al. 2017

Int J Geriat Psychiatry

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“…These symptoms are preceded by rapid eye movement sleep behavior disorder, psychiatric symptoms, loss of smell, and dysautonomia, together with occipital hypo-metabolism, hallucinations, and cognitive impairment (5, 6). …”

Section: Introductionmentioning

confidence: 99%

Dementia with Lewy Bodies: Molecular Pathology in the Frontal Cortex in Typical and Rapidly Progressive Forms

et al. 2017

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ObjectivesThe goal of this study was to assess mitochondrial function, energy, and purine metabolism, protein synthesis machinery from the nucleolus to the ribosome, inflammation, and expression of newly identified ectopic olfactory receptors (ORs) and taste receptors (TASRs) in the frontal cortex of typical cases of dementia with Lewy bodies (DLB) and cases with rapid clinical course (rpDLB: 2 years or less) compared with middle-aged non-affected individuals, in order to learn about the biochemical abnormalities underlying Lewy body pathology.MethodsReal-time quantitative PCR, mitochondrial enzymatic assays, and analysis of β-amyloid, tau, and synuclein species were used.ResultsThe main alterations in DLB and rpDLB, which are more marked in the rapidly progressive forms, include (i) deregulated expression of several mRNAs and proteins of mitochondrial subunits, and reduced activity of complexes I, II, III, and IV of the mitochondrial respiratory chain; (ii) reduced expression of selected molecules involved in energy metabolism and increased expression of enzymes involved in purine metabolism; (iii) abnormal expression of nucleolar proteins, rRNA18S, genes encoding ribosomal proteins, and initiation factors of the transcription at the ribosome; (iv) discrete inflammation; and (v) marked deregulation of brain ORs and TASRs, respectively. Severe mitochondrial dysfunction involving activity of four complexes, minimal inflammatory responses, and dramatic altered expression of ORs and TASRs discriminate DLB from Alzheimer’s disease. Altered solubility and aggregation of α-synuclein, increased β-amyloid bound to membranes, and absence of soluble tau oligomers are common in DLB and rpDLB. Low levels of soluble β-amyloid are found in DLB. However, increased soluble β-amyloid 1–40 and β-amyloid 1–42, and increased TNFα mRNA and protein expression, distinguish rpDLB.ConclusionMolecular alterations in frontal cortex in DLB involve key biochemical pathways such as mitochondria and energy metabolism, protein synthesis, purine metabolism, among others and are accompanied by discrete innate inflammatory response.

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“…The diagnosis of alpha-synucleinopathies is based on the presence of specific motor and cognitive symptoms, but some patients develop a variety of other symptoms over a period of years during which the neurodegenerative process has been theorized to have already begun(Tolosa and Pont-Sunyer 2011, Donaghy et al 2015, Iranzo et al 2016). For example, RBD patients with a 2.5–5 year risk of phenoconversion to an alpha-synucleinopathy have been found to display substantia nigra hyperechogenicity, a reduction in dopamine transporter uptake in the striatum, hyposmia, and dysfunction of color vision perception(Iranzo et al 2010, Postuma et al 2011, Iranzo et al 2016).…”

Section: Factors In Prediction Of Phenoconversion To Alpha-synucleinomentioning

confidence: 99%

Rapid eye movement sleep behavior disorder and the link to alpha-synucleinopathies

Barone

Henchcliffe

2018

Clinical Neurophysiology

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Rapid eye movement (REM) sleep behavior disorder (RBD) involves REM sleep without atonia in conjunction with a recurrent nocturnal dream enactment behavior, with vocalizations such as shouting and screaming, and motor behaviors such as punching and kicking. Secondary RBD is well described in association with neurological disorders including Parkinson's disease (PD), multiple system atrophy (MSA), and other conditions involving brainstem structures such as tumors. However, RBD alone is now considered to be a potential harbinger of later development of neurodegenerative disorders, in particular PD, MSA, dementia with Lewy bodies (DLB), and pure autonomic failure. These conditions are linked by their underpinning pathology of alpha-synuclein protein aggregation. In RBD, it is therefore important to recognize the potential risk for later development of an alpha-synucleinopathy, and to investigate for other potential causes such as medications. Other signs and symptoms have been described in RBD, such as orthostatic hypotension, or depression. While it is important to recognize these features to improve patient management, they may ultimately provide clinical clues that will lead to risk stratification for phenoconversion. A critical need is to improve our ability to counsel patients, particularly with regard to prognosis. The ability to identify who, of those with RBD, is at high risk for later neurodegenerative disorders will be paramount, and would in addition advance our understanding of the prodromal stages of the alpha-synucleinopathies. Moreover, recognition of at-risk individuals for neurodegenerative disorders may ultimately provide a platform for the testing of possible neuroprotective agents for these neurodegenerative disorders.

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Prodromal dementia with Lewy bodies

Abstract: The evidence available suggests that prodromal DLB may be differentiated from other dementia prodromes in most cases. Further research is needed to confirm this, and to assess the utility of biomarkers such as 123I-FP-CIT and 123I-MIBG imaging.

Cited by 53 publications

References 51 publications

Symptoms associated with Lewy body disease in mild cognitive impairment

Symptoms associated with Lewy body disease in mild cognitive impairment

Dementia with Lewy Bodies: Molecular Pathology in the Frontal Cortex in Typical and Rapidly Progressive Forms

Rapid eye movement sleep behavior disorder and the link to alpha-synucleinopathies

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