Dementia with Lewy bodies and Parkinson's disease with dementia: Are they different?

Abstract

The relationship of dementia with Lewy bodies (DLB) and Parkinson's disease with dementia (PDD) is debated. In DLB, dementia antedates Parkinsonism; in PDD, Parkinsonism antedates dementia. Other than presenting features, diagnostic measures fail to distinguish DLB from PDD. There are few or no pathologic differences between DLB and PDD. In most cases cortical Lewy bodies (LBs) are widespread and there is coexistent Alzheimer type pathology, insufficient to diagnose Alzheimer's disease. Given the predominance of Parkinsonism in PDD, neuronal loss in the substantia nigra is more severe in PDD than DLB. Further clinicopathologic studies are needed to define other pathologic differences between DLB and PDD and to explore the role of neuritic, basal forebrain and striatal pathology in these clinical syndromes.

Introduction

Parkinson's disease (PD) is the most common, age-associated neurodegenerative movement disorder and is characterized by bradykinesia, rigidity, tremor, postural instability, autonomic dysfunction and bradyphrenia [1]. PD is sub-classified based upon the predominant clinical feature into akinetic-rigid and tremor-predominant types. Tremor-predominant PD may have a relatively more benign clinical course. Dementia develops in some cases of PD, particularly late in the disease course, and it appears to be more common in akinetic-rigid PD [1]. The neuropathologic substrate of PD with dementia (PDD) has been the subject of many studies [2], [3], and several recent studies have suggested that cortical Lewy body (LB) pathology may be the most common pathologic substrate of PDD [4], [5]. Alzheimer type pathology is present in most cases [6], but it is not sufficient to diagnose Alzheimer's disease (AD) with current neuropathologic criteria for AD [7].

Neurocognitive presentations of Lewy body disease (LBD) are increasingly recognized and recent studies suggest that a constellation of signs and symptoms correlate with a clinicopathologic disorder referred to as dementia with Lewy bodies (DLB) [8]. The relationship of DLB to PDD is unresolved and the topic of current research efforts. The predominant presenting clinical feature—dementia in DLB and Parkinsonism in PDD—is the major distinction between DLB and PDD. Several studies have now shown that with most diagnostic measures, there are few significant differences between DLB and PDD [9], [10]. Neuropsychiatric symptoms, especially well-formed, non-threatening visual hallucinations are one of the major clinical features of DLB [8], but hallucinations are also frequent in PD, especially after treatment with l-DOPA [11]. Delusions and violent or aggressive behavior and increased sensitivity to neuroleptic medications are additional common clinical characteristics of DLB [8]. Fluctuation, which is another major clinical feature of DLB, has proven difficult to operationalize, but has diagnostic utility in differentiating DLB from AD [12], but it is less clear if it has any differential diagnostic validity for PDD.

Most evidence would suggest that there are few differences in pathologic findings between DLB and PDD [13], but there have been few comparative studies. The purpose of this report is to compare neuropathologic features patients with antemortem clinical features consistent with DLB and PDD.