Diagnosis and management of dementia with Lewy bodies

Abstract

The dementia with Lewy bodies (DLB) Consortium has revised criteria for the clinical and pathologic diagnosis of DLB incorporating new information about the core clinical features and suggesting improved methods to assess them. REM sleep behavior disorder, severe neuroleptic sensitivity, and reduced striatal dopamine transporter activity on functional neuroimaging are given greater diagnostic weighting as features suggestive of a DLB diagnosis. The 1-year rule distinguishing between DLB and Parkinson disease with dementia may be difficult to apply in clinical settings and in such cases the term most appropriate to each individual patient should be used. Generic terms such as Lewy body (LB) disease are often helpful. The authors propose a new scheme for the pathologic assessment of LBs and Lewy neurites (LN) using alpha-synuclein immunohistochemistry and semiquantitative grading of lesion density, with the pattern of regional involvement being more important than total LB count. The new criteria take into account both Lewy-related and Alzheimer disease (AD)-type pathology to allocate a probability that these are associated with the clinical DLB syndrome. Finally, the authors suggest patient management guidelines including the need for accurate diagnosis, a target symptom approach, and use of appropriate outcome measures. There is limited evidence about specific interventions but available data suggest only a partial response of motor symptoms to levodopa: severe sensitivity to typical and atypical antipsychotics in approximately 50%, and improvements in attention, visual hallucinations, and sleep disorders with cholinesterase inhibitors.

Network dysfunction in α‐synuclein transgenic mice and human Lewy body dementia

“…To further assess whether aberrant network excitability may contribute to SYN‐related dementia, we reviewed the charts of patients who were seen at the UCSF Memory and Aging Center between 2007 and 2012 and who met research criteria for DLB1 (Table 3). We searched the charts for myoclonus and seizure disorders, both of which are thought to result from aberrant network excitability 39, 43, 44…”

“…Based on McKeith criteria,1 there was a high likelihood that Lewy body pathology accounted for dementia in six cases and an intermediate likelihood for the remaining five cases, which had high levels of concomitant AD pathology. Four DLB patients with myoclonus that came to autopsy all had neocortical Lewy bodies; two of them also had numerous plaques and tangles, one had a high level of plaques without tangles, and one had no appreciable AD pathology.…”

“…We searched the electronic database of the UCSF Memory and Aging Center for patients who were seen between 2007 and 2012, met McKeith criteria1 for DLB on their latest evaluation during that period, and had a clinical diagnosis of DLB ( n = 178) (Fig. 1).…”

“…While much is known about the motor impairments in PD, very little is known about the mechanisms of cognitive impairment and cortical network dysfunction in DLB and PDD. DLB and PDD patients have dementia with visual hallucinations, attentional fluctuations, and parkinsonism 1. These symptoms are associated with a prominent slowing of cortical oscillations on electroencephalography (EEG), resulting in a shift in spectral power from higher (alpha, beta, gamma) to lower (delta, theta) frequency bands 2, 3.…”

Structural grey matter changes in the substantia innominata in Alzheimer's disease and dementia with Lewy bodies: a DARTEL‐VBM study

“…A total of 127 participants ( M age  = 78.26 years; SD age  = 7.33 years), including 47 with probable AD (McKhann et al ., 1984), 41 with probable DLB (McKeith et al ., 2005) and 39 similarly‐aged healthy controls, were recruited from a community‐dwelling population of patients referred to local Old Age Psychiatry, Geriatric Medicine or Neurology Services. Control participants were recruited from friends and spouses of patients and from a bank of volunteer participants held by the university and local clinical research network.…”