Dementia with Lewy Bodies

Abstract

).Dementia with Lewy bodies (DLB) is an atypical parkinsonian disorder characterized as a synucleinopathy based on the cardinal pathologic finding, the Lewy body, a neuronal inclusion comprised of aggregated α-synuclein. Lewy bodies are found in brainstem nuclei in both Parkinson disease (PD) as well as in DLB, though in DLB there is a concomitant presence of Lewy bodies in the cortex and subcortical white matter. The cortical Lewy bodies may not demonstrate the classic structure of an eosinophilic core with surrounding halo; however, they contain α-synuclein. Clinically, DLB manifests with fluctuating alertness, visual hallucinations, and parkinsonian motor symptoms, and has features of both a cortical and a subcortical dementia. EpidemiologyDementia with Lewy bodies is the second most common pathologic diagnosis of dementia, next to Alzheimer disease (AD) and accounts for 25% of all dementias. 1 The prevalence of DLB is estimated to be 0.7% of the population over 65 years of age. 2 Given the challenge of clinical diagnostic accuracy in dementia, there is a wide variation in estimates of the prevalence among dementia patients, ranging from 3 to 26.3% in those over the age of 65 years. 3,4 The incidence of DLB is 3.5 per 100,000 person years and this increases with age. 5 There is a slightly greater male predominance of 1.9:1. 6 Risk factors of DLB include advanced age, hypertension, hyperlipidemia, and carriers of one or more APOE ε4 alleles. 7-9 As in PD, there is overrepresentation of the CYP2D6B allele, and a greater heterozygous frequency of glucocerebrosidase 1 (GBA1) estimated at 3.5% versus 2.9% in Parkinson disease dementia (PDD) and 0.4% in the general population. 10 A separate study also found a significant association between GBA1 mutation carrier status and DLB with an odds ratio of 8.28 versus 6.48 in PDD. 11 PathophysiologyDementia with Lewy bodies is considered a synucleinopathy, along with PD and multiple system atrophy (MSA). It is distinguished pathologically by the presence of Lewy bodies, which are intracellular inclusions with an eosinophilic core Keywords ► dementia with Lewy bodies ► Lewy body ► synucleinopathy ► dementia ► parkinsonism AbstractDementia with Lewy bodies (DLB) is the second most common diagnosis of dementia after Alzheimer disease (AD). The essential pathologic feature is the Lewy body, a neuronal inclusion containing α-synuclein, found in brainstem nuclei and the neocortex. Clinical features include early fluctuations in attention, hallucinations, and parkinsonism, with progression to a combined cortical and subcortical dementia. To distinguish it from Parkinson disease dementia, a time course of one year from cognitive changes to motor feature onset has been established. There is more severe impairment of verbal fluency, executive function, and visuospatial abilities in DLB patients. Both rapid eye movement sleep behavior disorder and neuroleptic sensitivity are notable in this patient group. Treatment is aimed at symptom management. Cholinesterase inhibitors can be bene...

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

“…Dementia with Lewy bodies (DLB) is the second most common neurodegenerative dementia in the elderly, clinically manifested by fluctuating cognition with pronounced variation in attention and alertness, recurrent visual hallucinations which are typically well formed and detailed, and spontaneous motor features of parkinsonism; repeated falls, syncope, transient loss of consciousness, systematized delusions, hallucinations in other modalities, and neuroleptic sensitivity are not uncommon (1–4). 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).…”

Disease-modifying therapeutic directions for Lewy-Body dementias

“…Though DBS targeting fornix has attracted much attention in the field of AD treatment, NBM DBS currently holds the most promise for DLB patients. Unlike AD, which usually presents with memory deficits, DLB usually presents with fluctuating cognition and visuospatial deficits with relative sparing of memory in earlier stages (Mayo and Bordelon, 2014 ). While waiting for the results of ongoing clinical trials, it is worth noting that no DBS studies have been performed on animal models of dementia associated with synucleinopathy.…”

“…Dementia with Lewy bodies (DLB) is the second most common pathologic diagnosis of dementia, following Alzheimer's disease (AD), comprising 25% of all dementias (Heidebrink, 2002 ; Mayo and Bordelon, 2014 ). Yet, DLB is underdiagnosed (Galvin and Balasubramaniam, 2013 ).…”

Übergreifende Konzepte der Neurodegeneration

“…So zeigen Patienten mit Lewy-Körperchen Demenz regelhaft neben den typischen α-Synuklein-Ablagerungen auch Alzheimer-typische Veränderungen wie Amyloid-Plaques und Tau-Ablagerungen (▶Abb. 1) [4].…”