Lewy body compared with Alzheimer dementia is associated with decreased functional connectivity in resting state networks.

Resting state functional magnetic resonance imaging (fMRI) was used to measure whole brain functional connectivity within specific networks hypothesised to be more affected in dementia with Lewy bodies (DLB) (a disease characterised by prominent attentional deficits, spontaneous motor features of parkinsonism and depression) than in Alzheimer׳s disease (AD) and controls. This study involved 68 subjects (15 DLB, 13 AD and 40 controls) who were scanned using resting state BOLD (blood-oxygen-level-dependent) fMRI on a 3T MRI scanner. Functional connectivity was measured using a model-free independent component analysis approach that consisted of temporally concatenating the resting state fMRI data of all study subjects and investigating group differences using a back-reconstruction procedure. Resting state functional connectivity was affected in the default mode, salience, executive and basal ganglia networks in DLB subjects compared with AD and controls. Functional connectivity was lower in DLB compared with AD and controls in these networks, except for the basal ganglia network, where connectivity was greater in DLB. No resting state networks showed less connectivity in AD compared with DLB or controls. Our results suggest that functional connectivity of resting state networks can identify differences between DLB and AD subjects that may help to explain why DLB subjects have more frequent attentional deficits, parkinsonian symptoms, and depression than those with AD.North East Dementia and Neurodegenerative Diseases Research Network (DeNDRoN)This is the author accepted manuscript. The final version is available from Elsevier via http://dx.doi.org/10.1016/j.pscychresns.2014.06.00

Advanced qEEG analyses discriminate between dementia subtypes

Acknowledgement This study is part of the academic postgraduate research of Masha Burelo, financed through the postgraduate fellowship program of the National Council of Science and Technology (CONACYT, by its Spanish acronym) of Mexico.Peer reviewe

The assessment of cognition in visually impaired older adults

Background: visual and cognitive impairments are common in later life. Yet there are very few cognitive screening tests for the visually impaired. Objective: to screen for cognitive impairment in the visually impaired. Methods: case-control study including 150 elderly participants with visual impairment (n=74) and a control group without visual impairment (n=76) using vision-independent cognitive tests and cognitive screening tests (MMSE and clock drawing tests (CDT)) which are in part vision dependent. Results: the scoring of the two groups did not differ in the vision-independent cognitive tests. Visually impaired patients performed poorer than controls in the vision-dependent items of the MMSE (T=7.3; df: 148; P<0.001) and in CDT (T=3.1; df: 145; P=0.003). No group difference was found when vision-independent items were added to MMSE and CDT. The test score gain by the use of vision-independent items correlated with the severity of visual impairment (P<0.002). Conclusion: visually impaired patients benefit from cognitive tests, which do not rely on vision. The more visually impaired the greater the benefi

Quantifying test–retest reliability of repeated objective attentional measures in Lewy body dementia

Objective cognitive impairment is a feature of Lewy body dementia (LBD), and computerised attentional tasks are commonly used as outcome measures in interventional trials. However, the reliability of these measures, in the absence of interventions, are unknown. This study examined the reliability of these attentional measures at short-term and longer-term follow-up stages. LBD patients (n = 36) completed computerised attentional tasks (Simple and Choice Reaction Time, and Digit Vigilance (SRT, CRT, DV)) at short-term (Day 0 – Day 5) and longer-term (4 and 12 weeks) follow-up. Intra-class correlations (ICCs) were calculated to assess test-retest reliability. At short-term, the reciprocal SRT, CRT and DV mean reaction time to correct answers, the reciprocal DV coefficient of variation, and reciprocal power of attention (PoA) all showed excellent levels of reliability (all ICCs > 0.90). The reciprocal PoA showed the highest level of reliability (ICC = 0.978). At longer-term follow-up, only the reciprocal PoA had excellent levels of reliability (ICC = 0.927). Reciprocal SRT, CRT and DV reaction time to correct answers, and the CRT coefficient of variation values, showed good levels of test-retest reliability (ICCs ≥ 0.85). Contrary to expectations, most attentional measures demonstrated high levels of test-retest reliability at both short-term and longer-term follow-up time points. The reciprocal PoA composite measure demonstrated excellent levels of test-retest reliability, both in the short-term and long-term. This indicates that objective attentional tasks are suitable outcome measures in LBD studies and that the composite PoA measure may offer the highest levels of reliability

Progressive cortical thinning and subcortical atrophy in dementia with Lewy bodies and Alzheimer's disease.

Patterns of progressive cortical thinning in dementia with Lewy bodies (DLB) remain poorly understood. We examined spatiotemporal patterns of cortical thinning and subcortical atrophy over 12 months in DLB (n = 13), compared with Alzheimer's disease (AD) (n = 23) and healthy control subjects (HC) (n = 33). Rates of temporal thinning in DLB were relatively preserved compared with AD. Volumetric analyses subcortical changes revealed that the AD group demonstrated significantly increased hippocampal atrophy (-5.8%) relative to the HC (-1.7%; p < 0.001) and DLB groups (-2.5%, p = 0.006). Significant lateral ventricular expansion was also observed in AD (8.9%) compared with HC (4.3%; p < 0.001) and DLB (4.7%; p = 0.008) at trend level. There was no significant difference in subcortical atrophy and ventricular expansion between DLB and HC. In the DLB group, increased rates of cortical thinning in the frontal and parietal regions were significantly correlated with decline in global cognition (Mini-Mental State Examination) and motor deterioration (Unified Parkinson's Disease Rating Scale 3), respectively. Overall, AD and DLB are characterized by different spatiotemporal patterns of cortical thinning over time. Our findings warrant further consideration of longitudinal cortical thinning as a potential imaging marker to differentiate DLB from AD.This work was supported by the Sir Jules Thorn Charitable Trust (Grant number 05/JTA), the NIHR Biomedical Research Unit in Dementia and the Biomedical Research Centre awarded to Cambridge University Hospitals NHS Foundation Trust and the University of Cambridge, and the NIHR Biomedical Research Unit in Dementia and the Biomedical Research Centre awarded to Newcastle upon Tyne Hospitals NHS Foundation Trust and the Newcastle University. Elijah Mak was in receipt of a Gates Cambridge PhD studentship. Elijah Mak formulated the research question, performed the statistical analyses, interpreted the results, and wrote the article. Li Su and Guy Williams assisted with the interpretation of the results and provided comments and additional suggestions for revisions of the draft. Rosie Watson recruited and assessed study participants, assisted with the interpretation of the results, and reviewed the article. Michael Firbank designed the imaging protocol, assisted with the interpretation of the results, and reviewed the article. Andrew Blamire obtained funding for the project, designed the imaging protocol, undertook routine quality assurance on the MR system, assisted with the interpretation of the results, and reviewed the article. John O’Brien obtained funding for the project, designed the imaging protocol, assisted with recruitment of study participants, assisted with the interpretation of the results, and reviewed the article. All authors approved the final article.This is the accepted manuscript for a paper published in Neurobiology of Aging Volume 36, Issue 4, April 2015, Pages 1743–1750, DOI: 10.1016/j.neurobiolaging.2014.12.03

Longitudinal diffusion tensor imaging in dementia with Lewy bodies and Alzheimer's disease.

OBJECTIVE: Changes in the white matter of dementia with Lewy bodies (DLB) and Alzheimer's disease (AD) have been reported using diffusion weighted MRI, though few longitudinal studies have been done. METHODS: We performed diffusion weighted MRI twice, a year apart on 23 AD, 14 DLB, and 32 healthy control subjects. Mean diffusivity (MD) and fractional anisotropy (FA) were calculated. RESULTS: In AD, there were widespread regions where the longitudinal MD increase was greater than in controls, and small areas in the parietal and temporal lobes where it was greater in AD than DLB. In AD, decrease in brain volume correlated with increased MD. There were no significant differences in progression between DLB and controls. CONCLUSIONS: In AD the white matter continues to degenerate during the disease process, whereas in DLB, changes in the white matter structure are a relatively early feature. Different mechanisms are likely to underpin changes in diffusivity.The study was supported by the NIHR Biomedical Research Unit in Dementia and the Biomedical Research Centre awarded to Cambridge University Hospitals NHS Foundation Trust and the University of Cambridge, and the NIHR Biomedical Research Unit in Dementia and the Biomedical Research Centre awarded to Newcastle upon Tyne Hospitals NHS Foundation Trust and Newcastle University. Elijah Mak was in receipt of a Gates Cambridge PhD studentship.This is the author accepted manuscript. The final version is available from Elsevier via http://dx.doi.org/10.1016/j.parkreldis.2016.01.00

Electroencephalographic derived network differences in Lewy body dementia compared to Alzheimer's disease patients.

Dementia with Lewy bodies (DLB) and Alzheimer's disease (AD) require differential management despite presenting with symptomatic overlap. Currently, there is a need of inexpensive DLB biomarkers which can be fulfilled by electroencephalography (EEG). In this regard, an established electrophysiological difference in DLB is a decrease of dominant frequency (DF)-the frequency with the highest signal power between 4 and 15 Hz. Here, we investigated network connectivity in EEG signals acquired from DLB patients, and whether these networks were able to differentiate DLB from healthy controls (HCs) and associated dementias. We analysed EEG recordings from old adults: HCs, AD, DLB and Parkinson's disease dementia (PDD) patients. Brain networks were assessed with the minimum spanning tree (MST) within six EEG bands: delta, theta, high-theta, alpha, beta and DF. Patients showed lower alpha band connectivity and lower DF than HCs. DLB and PDD showed a randomised MST compared with HCs and AD in high-theta and alpha but not in DF. The MST randomisation in DLB and PDD reflects decreased brain efficiency as well as impaired neural synchronisation. However, the lack of network topology differences at the DF between all dementia groups and HCs may indicate a compensatory response of the brain to the neuropathology.The research was funded by The Newcastle upon Tyne Hospitals NHS Charity, and supported by the Northumberland Tyne & Wear National Health Service (NHS) Foundation Trust and the National Institute of Health Research (NIHR) Biomedical Research Centre (BRC) at Newcastle University. S.G. was supported by the NIHR MedTech In vitro diagnostic Co-operatives scheme (ref MIC-2016-014). The study —participant recruitment and data collection— was funded by an intermediate clinical Wellcome Trust Fellowship (WT088441MA) to J-P.T

18F-FDG PET and perfusion SPECT in the diagnosis of Alzheimer and Lewy body dementias.

UNLABELLED: Brain imaging with glucose ((18)F-FDG) PET or blood flow (hexamethylpropyleneamine oxime) SPECT is widely used for the differential diagnosis of dementia, though direct comparisons to clearly establish superiority of one method have not been undertaken. METHODS: Subjects with Alzheimer disease (AD; n = 38) and dementia with Lewy bodies (DLB; n = 30) and controls (n = 30) underwent (18)F-FDG PET and SPECT in balanced order. The main outcome measure was area under the curve (AUC) of receiver-operating-characteristic analysis of visual scan rating. RESULTS: Consensus diagnosis with (18)F-FDG PET was superior to SPECT for both dementia vs. no-dementia (AUC = 0.93 vs. 0.72, P = 0.001) and AD vs. DLB (AUC = 0.80 vs. 0.58, P = 0.005) comparisons. The sensitivity and specificity for dementia/no-dementia was 85% and 90%, respectively, for (18)F-FDG PET and 71% and 70%, respectively, for SPECT. CONCLUSION: (18)F-FDG PET was significantly superior to blood flow SPECT. We recommend (18)F-FDG PET be performed instead of perfusion SPECT for the differential diagnosis of degenerative dementia if functional imaging is indicated.We thank the Dementia and Neurodegenerative Diseases Research Network (DeNDRoN) for valuable support with clinical recruitment. We also thank the National Institute for Health Research.This research was originally published in JNM. O’Brien JT, Firbank MJ, Davison C, Barnett N, Bamford C, Donaldson C, Olsen K, Herholz K, Williams D, Lloyd J. 18F-FDG PET and Perfusion SPECT in the Diagnosis of Alzheimer and Lewy Body Dementias. JNM. 2014;55:1959–1965. © by the Society of Nuclear Medicine and Molecular Imaging, Inc