Lewy bodies comprise one of the most encountered nerve cell pathologies with an undefined biochemical composition (Spillantini et al., 1997). Aggregation of misfolded alpha-synuclein is a major contributor to the intraneuronal Lewy bodies (Coughlin et al., 2020). The accumulation of aggregated forms of alpha-synuclein in the cells of the brain causes synucleopathies, which are the second most common neurodegenerative disorders leading to dementia (Boström et al., 2007; Outeiro et al., 2019). DLB and Parkinson’s disease dementia are categorized as Lewy body dementia (Taylor et al., 2020). Dementia with Lewy bodies (DLB) is the most encountered neurodegenerative dementia, and people with DLB are older than 65 years old (Mueller et al., 2017). The pathological hallmark of DLB involves the cortical lewy bodies and neurites composed of alpha-synuclein (Spillantini et al., 1997). Aggregated and insoluble forms of alpha-synuclein tend to form fibrillary alpha-synuclein, which constitutes Lewy body pathology (Baba et al., 1998). Distinct pathological mechanisms are assumed for understanding the pathogenesis of DLB. Especially, increased mRNA expression of alpha-synuclein or the tendency of insoluble alpha-synuclein to form aggregates abnormally may be reasons for Lewy bodies formation (Rockenstein et al., 2001).
Cognitive, neuropsychiatric, sleep, motor, and autonomic symptoms have been encountered in patients with Lewy body dementia (Taylor et al., 2020). Particularly, cognitive impairments, visual hallucinations, and progressive executive dysfunctions are common in Lewy body dementia, with worsening the symptoms in patients with Parkinson’s disease dementia (Lippa et al., 2007). Parkinsonian motor signs in Parkinson’s disease dementia precede the cognitive abnormalities by more than one year, while the motor symptoms in DLB might coexist within the first year of motor symptoms existence (Goetz et al., 2008; McKeith et al., 2005). The life span of patients with Lewy body dementia is complex to detect due to the existence of comorbidities that increase the risk of mortality (Mueller et al., 2017). Even so, a meta-analysis revealed that the life expectancy of patients with dementia with Lewy bodies, as proved by neuropathological analysis, was 6.1 years after diagnosis (Cercy & Bylsma, 1997). Moreover, current studies indicate that defects in genes, that play important roles in PD pathology, such as alpha-synuclein (SNCA), leucine-rich repeat kinase 2 (LRRK2) , and glucocerebrosidase (GBA) have been related to DLB (Nalls et al., 2013; Ross et al., 2006; Vergouw et al., 2017; Yamaguchi et al., 2005; Zarranz et al., 2004).
Patients with different types of dementia commonly possess cognitive impairment (Mueller et al., 2017). Cognitive impairment, visual hallucinations, apathy, and rapid eye movement (REM) sleep behavior disorder, in which loss of muscular atonia and prominent motor behaviors during REM sleep occur (Gagnon et al., 2006). The clinical properties of DLB overlie those of Alzheimer’s disease and Parkinson’s Disease (Walker et al., 2015). It is assumed that the rate and pathogenesis causing the cognitive decline are different among dementias with Lewy bodies and Alzheimer’s disease. However, the discrepancy between the different dementias is not yet well-understood (Mueller et al., 2017).

The diagnosis of DLB is based on neuroimaging investigations in addition to clinical diagnosis (Barber et al., 2001). Dopaminergic SPECT84 images are used to detect dopamine transporter loss at the level of the striatum, which is a marker of nigrostriatal degeneration for clinical differential diagnosis (Barber et al., 2001). Current studies have revealed some genetic risk factors and investigated potential biomarkers to support the diagnosis of DLB.
Experiencing hallucinations and behavioral symptoms, patients with DLB have tended to be placed in a nursing home at an earlier stage of the disease than is expected in AD (Mueller et al., 2017). Application of acetylcholinesterase inhibitors has been shown to ameliorate cholinergic deficits in DLB (Mori et al., 2012; Rongve et al., 2014). Treatment of DLB involves a four-stage approach implied by “accurate diagnosis, identification of target symptoms, non-pharmacological interventions, and pharmacological interventions” (Barber et al., 2001). Identification of target symptoms is based on the presence of cognitive impairment, autonomic dysfunction, or neuropsychiatric features such as hallucinations (McKeith et al., 2004). Unfortunately, there is no exact treatment approach for DLB (McKeith et al., 2004). Application of the lowest acceptable dose of levodopa, an antiparkinsonian drug, is thought to be one approach for DLB treatment (McKeith et al., 2004). It is assumed that the presence of additional intrinsic striatal pathology and dysfunction in DLB pathology lessens the effectiveness of levodopa on motor symptoms of DLB (Duda et al., 2002).
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Inspector: Beril GÜREL