Diagnosis and management of dementia with Lewy bodies: Fourth consensus report of the DLB Consortium

Abstract

The Dementia with Lewy Bodies (DLB) Consortium has refined its recommendations about the clinical and pathologic diagnosis of DLB, updating the previous report, which has been in widespread use for the last decade. The revised DLB consensus criteria now distinguish clearly between clinical features and diagnostic biomarkers, and give guidance about optimal methods to establish and interpret these. Substantial new information has been incorporated about previously reported aspects of DLB, with increased diagnostic weighting given to REM sleep behavior disorder and ¹²³iodine-metaiodobenzylguanidine (MIBG) myocardial scintigraphy. The diagnostic role of other neuroimaging, electrophysiologic, and laboratory investigations is also described. Minor modifications to pathologic methods and criteria are recommended to take account of Alzheimer disease neuropathologic change, to add previously omitted Lewy-related pathology categories, and to include assessments for substantia nigra neuronal loss. Recommendations about clinical management are largely based upon expert opinion since randomized controlled trials in DLB are few. Substantial progress has been made since the previous report in the detection and recognition of DLB as a common and important clinical disorder. During that period it has been incorporated into DSM-5, as major neurocognitive disorder with Lewy bodies. There remains a pressing need to understand the underlying neurobiology and pathophysiology of DLB, to develop and deliver clinical trials with both symptomatic and disease-modifying agents, and to help patients and carers worldwide to inform themselves about the disease, its prognosis, best available treatments, ongoing research, and how to get adequate support.

Figure 1. Coronal T1-weighted MRI and ¹²³iodine FP-CIT SPECT images in Alzheimer disease (AD), dementia with Lewy bodies (DLB), and normal controls (NC)

(A) On the MRI, note the relative preservation of medial temporal lobe volume (rectangles) in DLB, which is similar to NC, whereas atrophy is obvious in AD. (B) On the FP-CIT SPECT images, note the minimal uptake in DLB, which is restricted to the caudate (period or full-stop appearance) compared to the robust uptake in the caudate and putamen in AD and NC (comma appearance). Reproduced with permission from Dr. Val Lowe, Mayo Clinic, Rochester, MN.

Figure 2. ¹²³Iodine-metaiodobenzylguanidine myocardial imaging in patients with Alzheimer disease (AD), dementia with Lewy bodies (DLB), and age-matched normal controls (NC)

Images taken 3 hours after injection are shown in 2 color scales, and typical regions of interest are shown on the heart (dotted circle) and upper mediastinum (rectangle). Heart-to-mediastinum (H/M) ratios are standardized to the values comparable to a medium-energy general-purpose collimator condition.^e12 Reproduced with permission from Dr. Kenichi Nakajima, Department of Nuclear Medicine, Kanazawa University.

Figure 3. Polysomnographic (PSG) recordings

PSG recordings of normal REM sleep (A) and REM sleep without atonia, typical of REM sleep behavior disorder (B).REM are reflected by the high-amplitude, abrupt deviations from baseline in the electro-oculogram (EOG) leads during a 30-second epoch. In (A), note the absence of EMG activity in the submental, leg, and arm leads (green arrows), whereas increased EMG tone is present in the same leads (red arrows) in B, particularly in the middle (arm lead), in this patient.

Figure 4. ¹⁸F-FDG-PET images in Alzheimer disease (AD), dementia with Lewy bodies (DLB), and normal controls (NC)

(A) Right lateral metabolic surface map projection. (B) Standard axial view transecting the posterior cingulate region. Occipital lobe metabolism is preserved in AD and NC but reduced (blue arrows) in DLB. Hypometabolism in AD is predominantly in the temporal, parietal, and frontal regions. There is normal metabolism as reflected by the normal ¹⁸F-FDG uptake (lighter shade of gray) in the posterior cingulate region (yellow arrowhead) surrounded by reduced ¹⁸F-FDG uptake (darker gray) in the adjacent occipital cortex in DLB, representing the cingulate island sign. This contrasts with the relatively reduced ¹⁸F-FDG uptake in the posterior cingulate and relatively preserved ¹⁸F-FDG uptake in the occipital cortex regions in AD. In the control, there is normal ¹⁸F-FDG uptake in the posterior cingulate, occipital, and other neocortical regions. Color and grayscale sidebars show increasing degrees of deviation from normal as the signal trends lower in the sidebars (red is normal while black is maximally abnormal in color images; white is normal while black is maximally abnormal in grayscale images). Reproduced with permission from Dr. Val Lowe, Mayo Clinic, Rochester, MN.