PurposeDecreased striatal dopamine transporter (DAT) binding on SPECT imaging is a strong biomarker for the diagnosis of dementia with Lewy bodies (DLB). There is still a lot of uncertainty about patients meeting the clinical criteria for probable DLB who have a normal DAT SPECT scan (DLB/S−). The aim of this study was to describe the clinical and imaging follow-up in these patients, and compare them to DLB patients with abnormal baseline scans (DLB/S+).MethodsDLB patients who underwent DAT imaging ([123I]FP-CIT SPECT) were selected from the Amsterdam Dementia Cohort. All [123I]FP-CIT SPECT scans were evaluated independently by two nuclear medicine physicians and in patients with normal scans follow-up imaging was obtained. We matched DLB/S-− patients for age and disease duration to DLB/S+ patients and compared their clinical characteristics.ResultsOf 67 [123I]FP-CIT SPECT scans, 7 (10.4 %) were rated as normal. In five DLB/S− patients, a second [123I]FP-CIT SPECT was performed (after on average 1.5 years) and these scans were all abnormal. No significant differences in clinical characteristics were found at baseline. DLB/S− patients could be expected to have a better MMSE score after 1 year.ConclusionThis study was the first to investigate DLB patients with the initial [123I]FP-CIT SPECT scan rated as normal and subsequent scans during disease progression rated as abnormal. We hypothesize that DLB/S− scans could represent a relatively rare DLB subtype with possibly a different severity or spread of alpha-synuclein pathology (“neocortical predominant subtype”). In clinical practice, if an alternative diagnosis is not imminent in a DLB/S− patient, repeating [123I]FP-CIT SPECT should be considered.

IntroductionThe 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).MethodsA 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.ResultsFor 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%.DiscussionQuantitative EEG has a higher discriminating value than the combination of the other multimodal variables in the differentiation between DLB and AD.

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/Aβ-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.

Objective:Early biomarkers for dementia with Lewy bodies (DLB) are still lacking. To determine whether electroencephalography (EEG) differentiates the prodromal phase of DLB from other causes of mild cognitive impairment (MCI) and whether EEG is predictive for time to conversion from MCI to DLB, we compared EEGs and clinical follow-up of patients with MCI due to DLB with MCI due to Alzheimer’s disease (MCI-AD).Methods:We compared 37 MCI-patients who developed DLB during follow-up and/or had an abnormal 123I-PF-CIT SPECT scan (MCI-DLB) with 67 age-matched MCI-AD-patients. EEGs were assessed visually with a score of increasing abnormality (range 1-5). We performed Fast Fourier Transform to analyze the power spectrum. With survival analyses, EEG characteristics were related to time to progression to dementia.Results:The visual EEG-score was higher in MCI-DLB (score>2 in 60%) compared to MCI-AD (score>2 in 8%, p<0.001). We found frontal intermittent delta activity in 22% of MCI-DLB, not in MCI-AD. MCI-DLB patients had a lower peak frequency (7.5 (6.0-9.9) Hz vs 8.8(6.8-10.2) in MCI-AD, p<0.001), and more slow-wave activity. Several individual EEG-measures showed good performance to discriminate MCI-DLB from MCI-AD (AUCs up to 0.94). In MCI-DLB low visual EEG-score, diffuse abnormalities, and low alpha2-power were related to time to progression to dementia (Hazard ratios 4.1, 9.9, 5.1 respectively).Conclusions:Profound EEG abnormalities are already present in the prodromal stage of DLB and have diagnostic and prognostic value.Classification of evidence:This study provides Class III evidence that EEG abnormalities are more common in MCI-DLB patients than MCI-AD patients.