Prodromal Dementia With Lewy Bodies: Clinical Characterization and Predictors of Progression.

OBJECTIVE: The objective of this study was to examine clinical characteristics, cognitive decline, and predictors for time to dementia in prodromal dementia with Lewy bodies with mild cognitive impairment (MCI-LB) compared with prodromal Alzheimer's disease (MCI-AD). METHODS: We included 73 MCI-LB patients (12% female; 68 ± 6 years; Mini Mental State Examination, 27 ± 2) and 124 MCI-AD patients (48% female; 68 ± 7 years; Mini Mental State Examination, 27 ± 2) from the Amsterdam Dementia Cohort. Follow-up was available for 61 MCI-LB patients and all MCI-AD patients (3 ± 2 years). We evaluated dementia with Lewy bodies core features, neuropsychiatric symptoms, caregiver burden (Zarit caregiver burden interview), MRI, apolipoprotein genotype, and cerebrospinal fluid biomarkers (tau/Aß1-42 ratio). Longitudinal outcome measures included cognitive slopes (memory, attention, executive functions, and language and visuospatial functions) and time to dementia. RESULTS: Parkinsonism was the most frequently present core feature in MCI-LB (69%). MCI-LB patients more often had neuropsychiatric symptoms and scored higher on ZARIT when compared with the MCI-AD patients. Linear mixed models showed that at baseline, MCI-LB patients performed worse on nonmemory cognitive domains, whereas memory performance was worse in MCI-AD patients. Over time, MCI-LB patients declined faster on attention, whereas MCI-AD patients declined faster on the Mini Mental State Examination and memory. Cox proportional hazards regressions showed that in the MCI-LB patients, lower attention (hazard ratio [HR] = 1.6; 95% confidence interval [CI], 1.1-2.3) and more posterior cortical atrophy (HR = 3.0; 95% CI, 1.5-5.8) predicted shorter time to dementia. In the MCI-AD patients, worse performance on memory (HR = 1.1; 95% CI, 1.0-1.2) and executive functions (HR = 1.3; 95% CI, 1.0-1.6) were independently associated with time to Alzheimer's dementia. CONCLUSION: MCI-LB patients have distinct neuropsychiatric and cognitive profiles with prominent decline in attention when compared with MCI-AD patients. Our results highlight the importance of early diagnosis because symptoms already have an impact in the prodromal stages. © 2020 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

Striatal DAT and extrastriatal SERT binding in early-stage Parkinson's disease and dementia with Lewy bodies, compared with healthy controls: An 123I-FP-CIT SPECT study.

Parkinson's disease (PD) and dementia with Lewy bodies (DLB) are thought to be part of a spectrum: both have a clinical profile including symptoms associated with dopaminergic and serotonergic loss, yet few imaging studies have focused on serotonergic neurodegeneration in both disorders. We aimed to study degeneration of terminals with dopamine and serotonin transporter (DAT and SERT, respectively) in patients with early-stage PD and DLB relative to healthy controls, using 123I-N-ω-fluoropropyl-2ß-carbomethoxy-3ß-(4-iodophenyl)nortropane (123I-FP-CIT) single photon emission computed tomography (SPECT). We conducted region of interest (ROI) and voxel-based analyses on 123I-FP-CIT SPECT scans. Using the cerebellum as a reference region, we determined binding ratios (BRs) for bilateral ROIs in the DAT-rich striatum (head of the caudate nucleus and posterior putamen) and SERT-rich extrastriatal brain regions (thalamus, hypothalamus and hippocampus). We compared BRs in PD and DLB patients with BRs in healthy controls (all groups: n = 16). Both PD and DLB patients had lower striatal 123I-FP-CIT BRs than healthy controls for the bilateral caudate head (PD-left: F(1,29) = 28.778, P < .001, ω2 = 0.35; right: F(1,29) = 35.338, P < .001, ω2 = 0.42; DLB-left: F(1,29) = 28.241, P < .001, ω2 = 0.31; right: F(1,29) = 18.811, P < .001, ω2 = 0.26) and bilateral posterior putamen (PD-left: F(1,29) = 107.531, P < .001, ω2 = 0.77; right: F(1,29) = 87.525, P < .001, ω2 = 0.72; DLB-left: F(1,29) = 39.910, P < .001, ω2 = 0.48; right: F(1,29) = 26.882, P < .001, ω2 = 0.38). DLB patients had lower hypothalamic 123I-FP-CIT BRs than healthy controls (F(1,29) = 6.059, P = .020, ω2 = 0.12). In the voxel-based analysis, PD and DLB patients had significantly lower striatal binding than healthy controls. Both PD patients in the early disease stages and DLB patients have reduced availability of striatal DAT, and DLB patients lower hypothalamic SERT compared with healthy controls. These observations add to the growing body of evidence that PD and DLB are not merely dopaminergic diseases, thereby providing additional clinicopathological insights.

EEG Characteristics of Dementia With Lewy Bodies, Alzheimer's Disease and Mixed Pathology.

Introduction: Previous studies on electroencephalography (EEG) to discriminate between dementia with Lewy bodies (DLB) and Alzheimer's disease (AD) have been promising. These studies did not consider the pathological overlap of the two diseases. DLB-patients with concomitant AD pathology (DLB/AD+) have a more severe disease manifestation. The EEG may also be influenced by a synergistic effect of the two pathologies. We aimed to compare EEG characteristics between DLB/AD+, "pure" DLB (DLB/AD-) and AD. Methods: We selected probable DLB patients who had an EEG and cerebrospinal fluid (CSF) available, from the Amsterdam Dementia Cohort (ADC). Concomitant AD-pathology was defined as a CSF tau/Aß-42 ratio > 0.52. Forty-one DLB/AD+ cases were matched for age (mean 70 (range 53-85)) and sex (85% male) 1:1 to DLB/AD- and AD-patients. EEGs were assessed visually, with Fast Fourier Transform (FFT), network- and connectivity measures. Results: EEG visual severity score (range 1-5) did not differ between DLB/AD- and DLB/AD+ (2.7 in both groups) and was higher compared to AD (1.9, p < 0.01). Both DLB groups had a lower peak frequency (7.0 Hz and 6.9 Hz in DLB vs. 8.2 in AD, p < 0.05), more slow-wave activity and more prominent disruptions of connectivity and networks, compared to AD. No significant differences were found between DLB/AD+ and DLB/AD-. Discussion: EEG abnormalities are more pronounced in DLB, regardless of AD co-pathology. This emphasizes the valuable role of EEG in discriminating between DLB and AD. It suggests that EEG slowing in DLB is influenced more by the α-synucleinopathy, or the associated cholinergic deficit, than by amyloid and tau pathology.

Gray matter atrophy in dementia with Lewy bodies with and without concomitant Alzheimer's disease pathology.

We aimed to study if patients with dementia with Lewy bodies (DLB) who have concomitant Alzheimer's disease (AD) pathology (detected antemortem by cerebrospinal fluid [CSF] biomarkers) have additional loss of gray matter volume. Ninety-eight DLB patients were divided into a "pure DLB" (DLB/AD-, n = 62) and a "mixed DLB" group (DLB/AD+, n = 36) and matched for age and symptom duration to 84 AD patients and 75 controls. We compared visual atrophy ratings, and in a subset, we analyzed cortical thickness and subcortical gray matter volumes. DLB/AD+ patients had more pronounced medial temporal lobe atrophy (MTA) compared to DLB/AD- (mean [total] MTA score 2.5 vs. 1.3, p = 0.02). Global and parietal atrophy scores were comparable between the 3 dementia groups and differed from controls. MTA score was associated with CSF Aß-42, while posterior cortical and global atrophy scores were associated with CSF tau. Cortical thinning was found in DLB/AD-, DLB/AD+, and AD compared to controls. Concomitant AD pathology seems to cause additional (hippocampal) atrophy in DLB, and this may contribute to a more devastating disease course in DLB/AD+ patients.

Lower 123I-FP-CIT binding to the striatal dopamine transporter, but not to the extrastriatal serotonin transporter, in Parkinson's disease compared with dementia with Lewy bodies.

In this retrospective cross-sectional study we compared 123I­N­ω­fluoropropyl­2ß­carbomethoxy­3ß­(4­iodophenyl)nortropane (123I-FP-CIT) binding to the striatal dopamine and the extrastriatal serotonin transporter (DAT and SERT, respectively) between Parkinson's disease (PD) and dementia with Lewy bodies (DLB) to gain more insight in the pathophysiology of the two diseases. We compared 123I-FP-CIT single photon emission computed tomography scans of, age-, gender matched patients with cognitive decline in same range of severity with PD (n = 53) or DLB (n = 53) using a regions of interest (ROIs) approach. We derived ROIs anatomically from individual magnetic resonance imaging brain scans. To corroborate the ROI findings, we performed additional whole-brain voxel-based analyses. In both ROI and voxel-based analyses, 123I-FP-CIT binding in PD patients was significantly lower in the bilateral posterior putamen than in DLB patients (left: F(1,103) = 18.363, P < 0.001, ω2  = 0.14; right: F(1,103) = 20.434, P < 0.001, ω2  = 0.15) (Pcorr  < 0.033). Caudate/putamen ratios were also significantly lower in DLB than in PD (U(105) = 724.0, P < 0.001). Extrastriatal SERT binding showed no difference between PD and DLB. These results suggest similar involvement of serotonergic structures in the degenerative process in PD and DLB.

Random forest to differentiate dementia with Lewy bodies from Alzheimer's disease.

INTRODUCTION: The aim of this study was to build a random forest classifier to improve the diagnostic accuracy in differentiating dementia with Lewy bodies (DLB) from Alzheimer's disease (AD) and to quantify the relevance of multimodal diagnostic measures, with a focus on electroencephalography (EEG). METHODS: A total of 66 DLB, 66 AD patients, and 66 controls were selected from the Amsterdam Dementia Cohort. Quantitative EEG (qEEG) measures were combined with clinical, neuropsychological, visual EEG, neuroimaging, and cerebrospinal fluid data. Variable importance scores were calculated per diagnostic variable. RESULTS: For discrimination between DLB and AD, the diagnostic accuracy of the classifier was 87%. Beta power was identified as the single-most important discriminating variable. qEEG increased the accuracy of the other multimodal diagnostic data with almost 10%. DISCUSSION: Quantitative EEG has a higher discriminating value than the combination of the other multimodal variables in the differentiation between DLB and AD.