DLB and PDD boundary issues

Abstract

For more than a decade, researchers have refined criteria for the diagnosis of dementia with Lewy bodies (DLB) and at the same time have recognized that cognitive impairment and dementia occur commonly in patients with Parkinson disease (PD). This article addresses the relationship between DLB, PD, and PD with dementia (PDD). The authors agreed to endorse "Lewy body disorders" as the umbrella term for PD, PDD, and DLB, to promote the continued practical use of these three clinical terms, and to encourage efforts at drug discovery that target the mechanisms of neurodegeneration shared by these disorders of alpha-synuclein metabolism. We concluded that the differing temporal sequence of symptoms and clinical features of PDD and DLB justify distinguishing these disorders. However, a single Lewy body disorder model was deemed more useful for studying disease pathogenesis because abnormal neuronal alpha-synuclein inclusions are the defining pathologic process common to both PDD and DLB. There was consensus that improved understanding of the pathobiology of alpha-synuclein should be a major focus of efforts to develop new disease-modifying therapies for these disorders. The group agreed on four important priorities: 1) continued communication between experts who specialize in PDD or DLB; 2) initiation of prospective validation studies with autopsy confirmation of DLB and PDD; 3) development of practical biomarkers for alpha-synuclein pathologies; 4) accelerated efforts to find more effective treatments for these diseases.

Paired Studies Comparing Clinical Profiles of Lewy Body Dementia with Alzheimer’s and Parkinson’s Diseases

“…Identifying the onset of dementia is subjective and often suspect in its accuracy [12,[17][18][19][20]. Therefore, we decided to combine our DLB and PDD subjects into one group, called LBD.…”

“…It is therefore not surprising that the literature shows that the sensitivity of the clinical criteria is very low for the accurate clinical diagnosis of DLB conditions [16]. Additionally, distinctions between DLB and PDD, both forms of Lewy Body Dementia (LBD), are still being explored [12,[17][18][19][20]. Since the use of amyloid PET and other biomarkers for the diagnosis of AD, PD, and LBD are limited in clinical practice and since prognosis and management are distinct for each of these conditions, improved clinical methods in differentiating these groups to achieve accurate diagnoses are critically needed.…”

Target-Specific PET Probes for Neurodegenerative Disorders Related to Dementia

“…In a recent study, patients undergoing brain biopsy and showing high Ab aggregation in the frontal cortical biopsy specimen also revealed high cortical 11 C-PIB uptake with PET (109). Furthermore, a significant correlation has been reported between 11 C-PIB imaging in vivo and levels of Ab in postmortem brain tissue (110). The strong correlation between in vivo 11 C-PIB retention and region-matched quantitative analysis of Ab plaques at autopsy supports the validity of 11 C-PIB PET as a method for in vivo evaluation of Ab plaque burden (110).…”

“…Patients with DLB also show a decrease in cerebral acetylcholinesterase activity as measured by 11 C-MP4A (69).…”

“…In addition to manifesting cognitive impairment, PD patients can manifest personality and behavioral changes along with fluctuating confusion and visual hallucinosis. Although most clinical features of PDD overlap with DLB (11), recent guidelines defined the 1-y rule for distinction between them according to the onset of cognitive dysfunction in relation to extrapyramidal motor symptoms (7,12). Pathologically, PD is characterized by the presence of cortical Lewy bodies and degeneration of subcortical nuclei including the dopaminergic medial substantia nigra, the cholinergic nucleus basalis of Meynert, the noradrenergic locus ceruleus, and serotonergic median raphe, along with other brain stem nuclei.…”