Characterization of symptoms and determinants of disease burden in dementia with Lewy bodies: DEvELOP design and baseline results.

BACKGROUND: The DEmEntia with LEwy bOdies Project (DEvELOP) aims to phenotype patients with dementia with Lewy bodies (DLB) and study the symptoms and biomarkers over time. Here, we describe the design and baseline results of DEvELOP. We investigated the associations between core and suggestive DLB symptoms and different aspects of disease burden, i.e., instrumental activities of daily living (IADL) functioning, quality of life (QoL), and caregiver burden. METHODS: We included 100 DLB patients (69 ± 6 years, 10%F, MMSE 25 ± 3) in the prospective DEvELOP cohort. Patients underwent extensive assessment including MRI, EEG/MEG, 123FP-CIT SPECT, and CSF and blood collection, with annual follow-up. Core (hallucinations, parkinsonism, fluctuations, RBD) and suggestive (autonomous dysfunction, neuropsychiatric symptoms) symptoms were assessed using standardized questionnaires. We used multivariate regression analyses, adjusted for age, sex, and MMSE, to evaluate how symptoms related to the Functional Activities Questionnaire, QoL-AD questionnaire, and Zarit Caregiver Burden Interview. RESULTS: In our cohort, RBD was the most frequently reported core feature (75%), while visual hallucinations were least frequently reported (39%) and caused minimal distress. Suggestive clinical features were commonly present, of which orthostatic hypotension was most frequently reported (64%). Ninety-five percent of patients showed EEG/MEG abnormalities, 88% of 123FP-CIT SPECT scans were abnormal, and 53% had a CSF Alzheimer's disease profile. Presence of fluctuations, lower MMSE, parkinsonism, and apathy were associated with higher IADL dependency. Depression, constipation, and lower IADL were associated with lower QoL-AD. Apathy and higher IADL dependency predisposed for higher caregiver burden. CONCLUSION: Baseline data of our prospective DLB cohort show clinically relevant associations between symptomatology and disease burden. Cognitive and motor symptoms are related to IADL functioning, while negative neuropsychiatric symptoms and functional dependency are important determinants of QoL and caregiver burden. Follow-up is currently ongoing to address specific gaps in DLB research.

Serotonergic deficits in dementia with Lewy bodies with concomitant Alzheimer's disease pathology: An 123I-FP-CIT SPECT study.

PURPOSE: To study the influence of concomitant Alzheimer's disease (AD) pathology in dementia with Lewy bodies (DLB) on dopamine transporter (DAT) and serotonin transporter (SERT) availability, using 123I-N-ω-fluoropropyl-2ß-carbomethoxy-3ß-(4-iodophenyl) nortropane (123I-FP-CIT) single photon emission computed tomography (SPECT). METHODS: Based on their cerebrospinal fluid biomarker profile, fifty-two patients with probable DLB were divided in a group with (DLB/AD+, N = 15) and without concomitant AD-pathology (DLB/AD-, N = 37). We conducted atrophy-corrected region of interest (ROI) analyses comparing binding ratios (BRs) in the DAT-rich striatal and SERT-rich extrastriatal brain areas (amygdala, hippocampus, thalamus, midbrain and pons). RESULTS: DLB/AD+ patients had significantly lower 123I-FP-CIT BRs in the left amygdala, and a trend was seen in the right hippocampus. Groups did not differ significantly in striatal 123I-FP-CIT BRs, neuropsychiatric or motor symptoms. Motor symptoms correlated negatively with striatal DAT BRs. CONCLUSIONS: DLB/AD+ patients may have lower SERT binding in limbic brain regions than DLB/AD- patients, possibly indicating faster neurodegeneration in mixed pathology.

[(123)]FP-CIT SPECT scans initially rated as normal became abnormal over time in patients with probable dementia with Lewy bodies.

PURPOSE: Decreased 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+). METHODS: DLB patients who underwent DAT imaging ([(123)I]FP-CIT SPECT) were selected from the Amsterdam Dementia Cohort. All [(123)I]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. RESULTS: Of 67 [(123)I]FP-CIT SPECT scans, 7 (10.4 %) were rated as normal. In five DLB/S- patients, a second [(123)I]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. CONCLUSION: This study was the first to investigate DLB patients with the initial [(123)I]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 [(123)I]FP-CIT SPECT should be considered.

CT angiography for differentiation between intracerebral and intra-sylvian hematoma in patients with ruptured middle cerebral artery aneurysms.

BACKGROUND AND PURPOSE: ISHs and ICHs from ruptured MCA aneurysms can be difficult to distinguish on NCE-CT but may have a different impact on admission status and outcome. The presence of IHCEV on CTA may differentiate ISHs and ICHs. MATERIALS AND METHODS: Two observers independently reviewed non-contrast-enhanced CT scans and CTAs of 71 patients with MCA aneurysm hematomas for the site of the hematoma, according to predefined characteristics, and for the presence of IHCEV. We compared CTAs with NCE-CT scans in which both observers were confident about hematoma localization. We calculated κ statistics for interobserver agreement, and RRs for poor clinical condition and poor outcome. RESULTS: Agreement for IHCEV was almost perfect (κ, 0.87; 95% CI, 0.74-0.99). After consensus reading, 30 of 71 patients had IHCEV. In 28 of the 71 NCE-CT scans, both observers were confident as to the the site of the hematoma (κ, 0.55; 95% CI, 37%-73%). IHCEV were present in 10 of these 28 patients, of whom 9 had an ISH based on NCE-CT (positive predictive value, 90%; 95% CI, 55%-100%). In all 18 of 28 patients without IHCEV, the hematoma was not intra-Sylvian (negative predictive value, 100%; 95% CI, 82%-100%). Poor admission status occurred in 50% of patients with IHCEV and in 60% without IHCEV (RR, 1.2; 95% CI, 0.8-1.9). Poor outcome occurred in 63% of patients with IHCEV and in 65% without IHCEV (RR, 1.0; 95% CI, 0.7-1.5). CONCLUSIONS: Although CTA could reliably and accurately differentiate the hematoma types, admission status and outcome were similar for both groups.