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1.  Cholinesterase inhibitor use does not significantly influence the ability of 123I‐FP‐CIT imaging to distinguish Alzheimer's disease from dementia with Lewy bodies 
123I‐labelled 2β‐carbomethoxy‐3β‐(4‐iodophenyl)‐N‐(3‐fluoropropyl) nortropane (123I‐FP‐CIT) imaging is a diagnostic tool to help differentiate dementia with Lewy bodies (DLB) from Alzheimer's disease (AD). However, in animals, cholinesterase inhibitors (ChEi) have been reported to reduce radioligand binding to the striatal dopamine transporter. As ChEi are frequently used in people with dementia, it is important to determine whether their use affects 123I‐FP‐CIT uptake in the striatum.
To clarify whether chronic ChEi therapy modulates striatal dopamine transporter binding measured by 123I‐FP‐CIT in patients with AD, DLB and Parkinson's disease with dementia (PDD).
Cross sectional study in 99 patients with AD (nine on ChEi, 25 not on ChEi), DLB (nine on ChEi, 19 not on ChEi) and PDD (six on ChEi, 31 not on ChEi) comparing 123I‐FP‐CIT striatal binding (caudate, anterior and posterior putamen) in patients receiving compared with those not receiving ChEi, correcting for key clinical variables including diagnosis, age, sex, Mini‐Mental State Examination score, severity of parkinsonism and concurrent antidepressant use.
As previously described, 123I‐FP‐CIT striatal uptake was lower in DLB and PDD subjects compared with those with AD. Median duration of ChEi use was 180 days. 123I‐FP‐CIT uptake was not significantly reduced in subjects receiving ChEi compared those not receiving ChEi (mean percentage reduction: AD 4.3%; DLB 0.7%; PDD 6.1%; p = 0.40). ChEi use did not differentially affect striatal 123FP‐CIT uptake between patient groups (p = 0.83).
Use of ChEi does not significantly influence the ability of 123I‐FP‐CIT imaging to distinguish AD from DLB.
PMCID: PMC2117542  PMID: 17299017
2.  Multivariate spatial covariance analysis of 99mTc-exametazime SPECT images in dementia with Lewy bodies and Alzheimer's disease: utility in differential diagnosis 
We examined 99mTc-exametazime brain blood flow single-photon emission computed tomography (SPECT) images using a spatial covariance analysis (SCA) approach to assess its diagnostic value in distinguishing dementia with Lewy bodies (DLB) from Alzheimer's disease (AD). Voxel SCA was simultaneously applied to a set of preprocessed images (AD, n=40; DLB, n=26), generating a series of eigenimages representing common intercorrelated voxels in AD and DLB. Linear regression derived a spatial covariance pattern (SCP) that discriminated DLB from AD. To investigate the diagnostic value of the model SCP, the SCP was validated by applying it to a second, independent, AD and DLB cohort (AD, n=34; DLB, n=29). Mean SCP expressions differed between AD and DLB (F1,64=36.2, P<0.001) with good diagnostic accuracy (receiver operating characteristic (ROC) curve area 0.87, sensitivity 81%, specificity 88%). Forward application of the model SCP to the independent cohort revealed similar differences between groups (F1,61=38.4, P<0.001), also with good diagnostic accuracy (ROC 0.86, sensitivity 80%, specificity 80%). Multivariate analysis of blood flow SPECT data appears to be robust and shows good diagnostic accuracy in two independent cohorts for distinguishing DLB from AD.
PMCID: PMC3618400  PMID: 23361395
Alzheimer's disease; differential diagnosis; dementia with Lewy bodies; perfusion; spatial covariance; SPECT
3.  fMRI resting state networks and their association with cognitive fluctuations in dementia with Lewy bodies 
NeuroImage : Clinical  2014;4:558-565.
Cognitive fluctuations are a core symptom in dementia with Lewy bodies (DLB) and may relate to pathological alterations in distributed brain networks. To test this we analysed resting state fMRI changes in a cohort of fluctuating DLB patients (n = 16) compared with age matched controls (n = 17) with the aim of finding functional connectivity (FC) differences between these two groups and whether these associate with cognitive fluctuations in DLB. Resting state networks (RSNs) were estimated using independent component analysis and FC between the RSN maps and the entirety of the brain was assessed using dual regression. The default mode network (DMN) appeared unaffected in DLB compared to controls but significant cluster differences between DLB and controls were found for the left fronto-parietal, temporal, and sensory–motor networks. Desynchronization of a number of cortical and subcortical areas related to the left fronto-parietal network was associated with the severity and frequency of cognitive fluctuations. Our findings provide empirical evidence for the potential role of attention–executive networks in the aetiology of this core symptom in DLB.
•We report resting state network (RSN) alterations in dementia with Lewy bodies (DLB).•The default mode network was intact in DLB compared to healthy controls (HC).•Fronto-parietal, temporal, and sensory–motor RSNs showed differences (DLB < HC).•The left fronto-parietal network (FPN) correlated with cognitive fluctuations in DLB.•The FPN therefore may be a potential marker for cognitive fluctuations in DLB.
PMCID: PMC3984441  PMID: 24818081
Cognitive fluctuations; Visual hallucinations; Resting state network; Lewy bodies; Dementia
4.  Covariant perfusion patterns provide clues to the origin of cognitive fluctuations and attentional dysfunction in Dementia with Lewy bodies 
International Psychogeriatrics / Ipa  2013;25(12):1917-1928.
Fluctuating cognition (FC), particularly in attention, is a core and defining symptom in dementia with Lewy bodies (DLB) but is seen much less frequently in Alzheimer's dementia (AD). However, its neurobiological origin is poorly understood. The aim of our study was therefore to characterize perfusion patterns in DLB patients that are associated with the severity and frequency of FC as measured both clinically and using objective neuropsychological assessments.
Spatial covariance analyses were applied to data derived from single photon emission computed tomography (SPECT) HMPAO brain imaging in 19 DLB and 23 AD patients. Patients underwent clinical assessment of their FC and cognitive function as well as objective testing of their attention.
Covariant perfusion principal components (PCs) were not associated with either FC or cognitive or attentional measures in AD. However, in DLB patients, the second PC (defined as DLB-cognitive motor pattern, DLB-PCI2) which was characterized by bilateral relative increases in cerebellum, basal ganglia, and supplementary motor areas and widespread bilateral decreases in parietal regions, positively correlated with poorer cognitive function, increased FC and worse attentional function measured both clinically and neurophysiologically (p < 0.05) as well as with the severity of bradykinesia (p = 0.04).
FC in DLB appears distinct from those seen in AD, and likely to be driven by internal neurobiological perturbations in brain circuitry as evidenced using spatial covariance analyses of cerebral perfusion. FC and certain aspects of attentional dysfunction in DLB may, in part, depend upon both distributed motor and non-motor networks.
PMCID: PMC3819183  PMID: 24148774
attention; Alzheimer’s disease; single photon emission computed tomography; SPECT; imaging
5.  Characterizing dementia with Lewy bodies by means of diffusion tensor imaging 
Neurology  2012;79(9):906-914.
To investigate patterns of in vivo white matter tract change using diffusion tensor imaging (DTI), we conducted a cross-sectional study of dementia with Lewy bodies (DLB) in comparison with Alzheimer disease (AD) and normal aging.
The study included 106 subjects (35 with DLB, 36 with AD, and 35 elderly controls) who underwent clinical and neuropsychological assessment and diffusion tensor MRI. We used tract-based spatial statistics to investigate patterns of reduced fractional anisotropy (FA) and increased mean diffusivity (MD) across the entire white matter tract skeleton and also investigated correlations with clinical features.
Areas of reduced FA in subjects with DLB vs controls were found primarily in parieto-occipital white matter tracts; in AD, the changes were much more diffuse. DLB was also associated with reduced FA in the pons and left thalamus, in comparison with AD. The pattern of MD increase was diffuse in AD and DLB. We found an association between DTI parameters and impaired episodic memory, letter fluency, and severity of motor parkinsonism in DLB.
Despite a similar level of dementia severity, patterns of DTI changes in AD and DLB differed significantly. The selective involvement of the visual association areas and subcortical structures and the significant clinical correlations highlight the potential importance of white matter tract change in the pathogenesis of DLB. DTI may be a useful technique to investigate early and possible preclinical changes in DLB and warrants further investigation.
PMCID: PMC3425843  PMID: 22895591

Results 1-5 (5)