Visual cortical excitability in dementia with Lewy bodies.

Alterations in the visual system may underlie visual hallucinations in dementia with Lewy bodies (DLB). However, cortical excitability as measured by transcranial magnetic stimulation (TMS) and functional magnetic resonance imaging (fMRI) activation of lower visual areas (V1-3) to visual stimuli appear normal in DLB. We explored the relationship between TMS-determined phosphene threshold and fMRI-related visual activation and found a positive relationship between the two in controls but a negative one in DLB. This double dissociation suggests a loss of inhibition in the visual system in DLB, which may predispose individuals to visual dysfunction and visual hallucinations.The research was funded by an Intermediate Clinical Fellowship to J.-P.T. (WT088441MA) and also supported by the National Institute for Health Research (NIHR) Newcastle Biomedical Research Unit based at Newcastle upon Tyne Hospitals NHS Foundation Trust and Newcastle University. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health.This is the final version of the article. It first appeared from the Royal College of Psychiatrists via http://dx.doi.org/10.1192/bjp.bp.114.15273

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

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

Longitudinal assessment of global and regional atrophy rates in Alzheimer's disease and dementia with Lewy bodies.

BACKGROUND & OBJECTIVE: Percent whole brain volume change (PBVC) measured from serial MRI scans is widely accepted as a sensitive marker of disease progression in Alzheimer's disease (AD). However, the utility of PBVC in the differential diagnosis of dementia remains to be established. We compared PBVC in AD and dementia with Lewy bodies (DLB), and investigated associations with clinical measures. METHODS: 72 participants (14 DLBs, 25 ADs, and 33 healthy controls (HCs)) underwent clinical assessment and 3 Tesla T1-weighted MRI at baseline and repeated at 12 months. We used FSL-SIENA to estimate PBVC for each subject. Voxelwise analyses and ANCOVA compared PBVC between DLB and AD, while correlational tests examined associations of PBVC with clinical measures. RESULTS: AD had significantly greater atrophy over 1 year (1.8%) compared to DLB (1.0%; p = 0.01) and HC (0.9%; p < 0.01) in widespread regions of the brain including periventricular areas. PBVC was not significantly different between DLB and HC (p = 0.95). There were no differences in cognitive decline between DLB and AD. In the combined dementia group (AD and DLB), younger age was associated with higher atrophy rates (r = 0.49, p < 0.01). CONCLUSIONS: AD showed a faster rate of global brain atrophy compared to DLB, which had similar rates of atrophy to HC. Among dementia subjects, younger age was associated with accelerated atrophy, reflecting more aggressive disease in younger people. PBVC could aid in differentiating between DLB and AD, however its utility as an outcome marker in DLB is limited.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.This is the final published version. It first appeared at http://www.sciencedirect.com/science/article/pii/S2213158215000182#

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

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