Search

BackgroundThis study aimed to have international experts converge on a harmonized definition of whole hippocampus boundaries and segmentation procedures, to define standard operating procedures for magnetic resonance (MR)-based manual hippocampal segmentation.MethodsThe panel received a questionnaire regarding whole hippocampus boundaries and segmentation procedures. Quantitative information was supplied to allow evidence-based answers. A recursive and anonymous Delphi procedure was used to achieve convergence. Significance of agreement among panelists was assessed by exact probability on Fisher's and binomial tests.ResultsAgreement was significant on the inclusion of alveus/fimbria (P = .021), whole hippocampal tail (P = .013), medial border of the body according to visible morphology (P = .0006), and on this combined set of features (P = .001). This definition captures 100% of hippocampal tissue, 100% of Alzheimer's disease-related atrophy, and demonstrated good reliability on preliminary intrarater (0.98) and inter-rater (0.94) estimates.DiscussionConsensus was achieved among international experts with respect to hippocampal segmentation using MR resulting in a harmonized segmentation protocol.

BackgroundAn international Delphi panel has defined a harmonized protocol (HarP) for the manual segmentation of the hippocampus on MR. The aim of this study is to study the concurrent validity of the HarP toward local protocols, and its major sources of variance.MethodsFourteen tracers segmented 10 Alzheimer's Disease Neuroimaging Initiative (ADNI) cases scanned at 1.5 T and 3T following local protocols, qualified for segmentation based on the HarP through a standard web-platform and resegmented following the HarP. The five most accurate tracers followed the HarP to segment 15 ADNI cases acquired at three time points on both 1.5 T and 3T.ResultsThe agreement among tracers was relatively low with the local protocols (absolute left/right ICC 0.44/0.43) and much higher with the HarP (absolute left/right ICC 0.88/0.89). On the larger set of 15 cases, the HarP agreement within (left/right ICC range: 0.94/0.95 to 0.99/0.99) and among tracers (left/right ICC range: 0.89/0.90) was very high. The volume variance due to different tracers was 0.9% of the total, comparing favorably to variance due to scanner manufacturer (1.2), atrophy rates (3.5), hemispheric asymmetry (3.7), field strength (4.4), and significantly smaller than the variance due to atrophy (33.5%, P < .001), and physiological variability (49.2%, P < .001).ConclusionsThe HarP has high measurement stability compared with local segmentation protocols, and good reproducibility within and among human tracers. Hippocampi segmented with the HarP can be used as a reference for the qualification of human tracers and automated segmentation algorithms.

Background: Blood biomarkers of Alzheimer's disease (AD) may allow for the early detection of AD pathology in mild cognitive impairment (MCI) due to AD (MCI-AD) and as a co-pathology in MCI with Lewy bodies (MCI-LB). However not all cases of MCI-LB will feature AD pathology. Disease-general biomarkers of neurodegeneration, such as glial fibrillary acidic protein (GFAP) or neurofilament light (NfL), may therefore provide a useful supplement to AD biomarkers. We aimed to compare the relative utility of plasma A β 42/40, p -tau181, GFAP and NfL in differentiating MCI-AD and MCI-LB from cognitively healthy older adults, and from one another. Methods: Plasma samples were analysed for 172 participants (31 healthy controls, 48 MCI-AD, 28 possible MCI-LB and 65 probable MCI-LB) at baseline, and a subset (n = 55) who provided repeated samples after ≥1 year. Samples were analysed with a Simoa 4-plex assay for A β 42, A β 40, GFAP and NfL, and incorporated previously-collected p -tau181 from this same cohort. Results: Probable MCI-LB had elevated GFAP (p < 0.001) and NfL (p = 0.012) relative to controls, but not significantly lower A β 42/40 (p = 0.06). GFAP and p -tau181 were higher in MCI-AD than MCI-LB. GFAP discriminated all MCI subgroups, from controls (AUC of 0.75), but no plasma-based marker effectively differentiated MCI-AD from MCI-LB. NfL correlated with disease severity and increased with MCI progression over time (p = 0.011). Conclusion: Markers of AD and astrocytosis/neurodegeneration are elevated in MCI-LB. GFAP offered similar utility to p -tau181 in distinguishing MCI overall, and its subgroups, from healthy controls. [ABSTRACT FROM AUTHOR]

Biomarker-based differential diagnosis of the most common forms of dementia is becoming increasingly important. Machine learning (ML) may be able to address this challenge. The aim of this study was to develop and interpret a ML algorithm capable of differentiating Alzheimer's dementia, frontotemporal dementia, dementia with Lewy bodies and cognitively normal control subjects based on sociodemographic, clinical, and magnetic resonance imaging (MRI) variables. 506 subjects from 5 databases were included. MRI images were processed with FreeSurfer, LPA, and TRACULA to obtain brain volumes and thicknesses, white matter lesions and diffusion metrics. MRI metrics were used in conjunction with clinical and demographic data to perform differential diagnosis based on a Support Vector Machine model called MUQUBIA (Multimodal Quantification of Brain whIte matter biomArkers). Age, gender, Clinical Dementia Rating (CDR) Dementia Staging Instrument, and 19 imaging features formed the best set of discriminative features. The predictive model performed with an overall Area Under the Curve of 98%, high overall precision (88%), recall (88%), and F1 scores (88%) in the test group, and good Label Ranking Average Precision score (0.95) in a subset of neuropathologically assessed patients. The results of MUQUBIA were explained by the SHapley Additive exPlanations (SHAP) method. The MUQUBIA algorithm successfully classified various dementias with good performance using cost-effective clinical and MRI information, and with independent validation, has the potential to assist physicians in their clinical diagnosis. [ABSTRACT FROM AUTHOR]

Background and purpose: Mild cognitive impairment with Lewy bodies (MCI‐LB) is associated with a range of cognitive, motor, neuropsychiatric, sleep, autonomic, and visual symptoms. We investigated the cumulative frequency of symptoms in a longitudinal cohort of MCI‐LB compared with MCI due to Alzheimer disease (MCI‐AD) and analysed the ability of a previously described 10‐point symptom scale to differentiate MCI‐LB and MCI‐AD, in an independent cohort. Methods: Participants with probable MCI‐LB (n = 70), MCI‐AD (n = 51), and controls (n = 34) had a detailed clinical assessment and annual follow‐up (mean duration = 1.7 years). The presence of a range of symptoms was ascertained using a modified version of the Lewy Body Disease Association Comprehensive LBD Symptom Checklist at baseline assessment and then annually. Results: MCI‐LB participants experienced a greater mean number of symptoms (24.2, SD = 7.6) compared with MCI‐AD (11.3, SD = 7.4) and controls (4.2, SD = 3.1; p < 0.001 for all comparisons). A range of cognitive, parkinsonian, neuropsychiatric, sleep, and autonomic symptoms were significantly more common in MCI‐LB than MCI‐AD, although when present, the time of onset was similar between the two groups. A previously defined 10‐point symptom scale demonstrated very good discrimination between MCI‐LB and MCI‐AD (area under the receiver operating characteristic curve = 0.91, 95% confidence interval = 0.84–0.98), replicating our previous finding in a new cohort. Conclusions: MCI‐LB is associated with the frequent presence of a particular profile of symptoms compared to MCI‐AD. Clinicians should look for evidence of these symptoms in MCI and be aware of the potential for treatment. The presence of these symptoms may help to discriminate MCI‐LB from MCI‐AD. [ABSTRACT FROM AUTHOR]

Introduction: Amyloid-β (Aβ) deposition is common in dementia with Lewy bodies (DLB) and has been associated with more rapid disease progression. An effective biomarker that identified the presence of significant brain Aβ in people with DLB may be useful to identify and stratify participants for research studies and to inform prognosis in clinical practice. Plasma biomarkers are emerging as candidates to fulfil this role.Methods: Thirty-two participants with DLB had brain amyloid (18F-florbetapir) PET, of whom 27 also had an MRI to enable the calculation of 18F-florbetapir SUVR. Plasma Aβ42/40, phosphorylated tau (p-tau181), glial fibrillary acidic protein (GFAP) and neurofilament light (NfL) were measured using single molecule array (Simoa). The plasma biomarkers were investigated for correlation with 18F-florbetapir SUVR, discriminant ability to identify Aβ-positive cases based on a predefined SUVR threshold of 1.10 and correlation with subsequent cognitive decline over one year.Results: All four plasma markers significantly correlated with 18F-florbetapir SUVR (|β| = 0.40-0.49; p < .05). NfL had the greatest area under the receiver operating characteristic curve to identify Aβ-positive cases (AUROC 0.84 (95% CI 0.66, 1); β = 0.46, p = .001), whereas Aβ42/40 had the smallest (AUROC 0.73 (95% CI 0.52, 0.95); β = -0.47, p = .01). Accuracy was highest when combining all four biomarkers (AUROC 0.92 (95% CI 0.80, 1)). Lower plasma Aβ42/40 was significantly associated with more rapid decline in cognition (β = 0.53, p < .01).Conclusions: Plasma biomarkers have the potential to identify Aβ deposition in DLB. Further work in other cohorts is required to determine and validate optimal cut-offs for these biomarkers. [ABSTRACT FROM AUTHOR]

Visual hallucinations are a common feature of Lewy body dementia. Previous studies have shown that visual hallucinations are highly specific in differentiating Lewy body dementia from Alzheimer's disease dementia and Alzheimer-Lewy body mixed pathology cases. Computational models propose that impairment of visual and attentional networks is aetiologically key to the manifestation of visual hallucinations symptomatology. However, there is still a lack of experimental evidence on functional and structural brain network abnormalities associated with visual hallucinations in Lewy body dementia. We used EEG source localization and network based statistics to assess differential topographical patterns in Lewy body dementia between 25 participants with visual hallucinations and 17 participants without hallucinations. Diffusion tensor imaging was used to assess structural connectivity between thalamus, basal forebrain and cortical regions belonging to the functionally affected network component in the hallucinating group, as assessed with network based statistics. The number of white matter streamlines within the cortex and between subcortical and cortical regions was compared between hallucinating and not hallucinating groups and correlated with average EEG source connectivity of the affected subnetwork. Moreover, modular organization of the EEG source network was obtained, compared between groups and tested for correlation with structural connectivity. Network analysis showed that compared to non-hallucinating patients, those with hallucinations feature consistent weakened connectivity within the visual ventral network, and between this network and default mode and ventral attentional networks, but not between or within attentional networks. The occipital lobe was the most functionally disconnected region. Structural analysis yielded significantly affected white matter streamlines connecting the cortical regions to the nucleus basalis of Meynert and the thalamus in hallucinating compared to not hallucinating patients. The number of streamlines in the tract between the basal forebrain and the cortex correlated with cortical functional connectivity in non-hallucinating patients, while a correlation emerged for the white matter streamlines connecting the functionally affected cortical regions in the hallucinating group. This study proposes, for the first time, differential functional networks between hallucinating and not hallucinating Lewy body dementia patients, and provides empirical evidence for existing models of visual hallucinations. Specifically, the outcome of the present study shows that the hallucinating condition is associated with functional network segregation in Lewy body dementia and supports the involvement of the cholinergic system as proposed in the current literature. [ABSTRACT FROM AUTHOR]

Objectives: Impaired olfaction may be a biomarker for early Lewy body disease, but its value in mild cognitive impairment with Lewy bodies (MCI-LB) is unknown. We compared olfaction in MCI-LB with MCI due to Alzheimer's disease (MCI-AD) and healthy older adults. We hypothesized that olfactory function would be worse in probable MCI-LB than in both MCI-AD and healthy comparison subjects (HC). Design: Cross-sectional study assessing olfaction using Sniffin' Sticks 16 (SS-16) in MCI-LB, MCI-AD, and HC with longitudinal follow-up. Differences were adjusted for age, and receiver operating characteristic (ROC) curves were used for discriminating MCI-LB from MCI-AD and HC. Setting: Participants were recruited from Memory Services in the North East of England. Participants: Thirty-eight probable MCI-LB, 33 MCI-AD, 19 possible MCI-LB, and 32HC. Measurements: Olfaction was assessed using SS-16 and a questionnaire. Results: Participants with probable MCI-LB had worse olfaction than both MCI-AD (age-adjusted mean difference (B) = 2.05, 95% CI: 0.62–3.49, p = 0.005) and HC (B = 3.96, 95% CI: 2.51–5.40, p < 0.001). The previously identified cutoff score for the SS-16 of ≤ 10 had 84% sensitivity for probable MCI-LB (95% CI: 69–94%), but 30% specificity versus MCI-AD. ROC analysis found a lower cutoff of ≤ 7 was better (63% sensitivity for MCI-LB, with 73% specificity vs MCI-AD and 97% vs HC). Asking about olfactory impairments was not useful in identifying them. Conclusions: MCI-LB had worse olfaction than MCI-AD and normal aging. A lower cutoff score of ≤ 7 is required when using SS-16 in such patients. Olfactory testing may have value in identifying early LB disease in memory services. [ABSTRACT FROM AUTHOR]

Objectives: Orthostatic hypotension is a common feature of normal ageing, and age-related neurodegenerative diseases, in particular the synucleinopathies including dementia with Lewy bodies. Orthostatic hypotension and other abnormal cardiovascular responses may be early markers of Lewy body disease. We aimed to assess whether abnormal blood pressure and heart rate responses to orthostatic challenge and Valsalva manoeuvre would be more common in mild cognitive impairment with Lewy bodies (MCI-LB) than MCI due to Alzheimer's disease (MCI-AD).Methods: MCI patients (n = 89) underwent longitudinal clinical assessment with differential classification of probable MCI-LB, possible MCI-LB, or MCI-AD, with objective autonomic function testing at baseline. Blood pressure and heart rate responses to active stand and Valsalva manoeuvre were calculated from beat-to-beat cardiovascular data, with abnormalities defined by current criteria, and age-adjusted group differences estimated with logistic models.Results: Orthostatic hypotension and abnormal heart rate response to orthostatic challenge were not more common in probable MCI-LB than MCI-AD. Heart rate abnormalities were likewise not more common in response to Valsalva manoeuvre in probable MCI-LB. An abnormal blood pressure response to Valsalva (delayed return to baseline/absence of overshoot after release of strain) was more common in probable MCI-LB than MCI-AD. In secondary analyses, magnitude of blood pressure drop after active stand and 10-s after release of Valsalva strain were weakly correlated with cardiac sympathetic denervation.Conclusions: Probable MCI-LB may feature abnormal blood pressure response to Valsalva, but orthostatic hypotension is not a clear distinguishing feature from MCI-AD. [ABSTRACT FROM AUTHOR]

Patients who have dementia with Lewy bodies and Alzheimer's disease show early degeneration of the cholinergic nucleus basalis of Meynert. However, how white matter projections between the nucleus basalis of Meynert and the cortex are altered in neurodegenerative disease is unknown. Tractography of white matter pathways originating from the nucleus basalis of Meynert was performed using diffusion-weighted imaging in 46 patients with Alzheimer's disease dementia, 48 with dementia with Lewy bodies, 35 with mild cognitive impairment with Alzheimer's disease, 38 with mild cognitive impairment with Lewy bodies and 71 control participants. Mean diffusivity of the resulting pathways was compared between groups and related to cognition, attention, functional EEG changes and dementia conversion in the mild cognitive impairment groups. We successfully tracked a medial and a lateral pathway from the nucleus basalis of Meynert. Mean diffusivity of the lateral pathway was higher in both dementia and mild cognitive impairment groups than controls (all P < 0.03). In the patient groups, increased mean diffusivity of this pathway was related to more impaired global cognition (β = -0.22, P = 0.06) and worse performance on an attention task (β = 0.30, P = 0.03). In patients with mild cognitive impairment, loss of integrity of both nucleus basalis of Meynert pathways was associated with increased risk of dementia progression [hazard ratio (95% confidence interval), medial pathway: 2.51 (1.24-5.09); lateral pathway: 2.54 (1.24-5.19)]. Nucleus basalis of Meynert volume was reduced in all clinical groups compared to controls (all P < 0.001), but contributed less strongly to cognitive impairment and was not associated with attention or dementia conversion. EEG slowing in the patient groups as assessed by a decrease in dominant frequency was associated with smaller nucleus basalis of Meynert volumes (β = 0.22, P = 0.02) and increased mean diffusivity of the lateral pathway (β = -0.47, P = 0.003). We show that degeneration of the cholinergic nucleus basalis of Meynert in Alzheimer's disease and dementia with Lewy bodies is accompanied by an early reduction in integrity of white matter projections that originate from this structure. This is more strongly associated with cognition and attention than the volume of the nucleus basalis of Meynert itself and might be an early indicator of increased risk of dementia conversion in people with mild cognitive impairment. [ABSTRACT FROM AUTHOR]

Background: Recently published diagnostic criteria for mild cognitive impairment with Lewy bodies (MCI-LB) include five neuropsychiatric supportive features (non-visual hallucinations, systematised delusions, apathy, anxiety and depression). We have previously demonstrated that the presence of two or more of these symptoms differentiates MCI-LB from MCI due to Alzheimer's disease (MCI-AD) with a likelihood ratio >4. The aim of this study was to replicate the findings in an independent cohort. Methods: Participants ⩾60 years old with MCI were recruited. Each participant had a detailed clinical, cognitive and imaging assessment including FP-CIT SPECT and cardiac MIBG. The presence of neuropsychiatric supportive symptoms was determined using the Neuropsychiatric Inventory (NPI). Participants were classified as MCI-AD, possible MCI-LB and probable MCI-LB based on current diagnostic criteria. Participants with possible MCI-LB were excluded from further analysis. Results: Probable MCI-LB (n = 28) had higher NPI total and distress scores than MCI-AD (n = 30). In total, 59% of MCI-LB had two or more neuropsychiatric supportive symptoms compared with 9% of MCI-AD (likelihood ratio 6.5, p < 0.001). MCI-LB participants also had a significantly greater delayed recall and a lower Trails A:Trails B ratio than MCI-AD. Conclusions: MCI-LB is associated with significantly greater neuropsychiatric symptoms than MCI-AD. The presence of two or more neuropsychiatric supportive symptoms as defined by MCI-LB diagnostic criteria is highly specific and moderately sensitive for a diagnosis of MCI-LB. The cognitive profile of MCI-LB differs from MCI-AD, with greater executive and lesser memory impairment, but these differences are not sufficient to differentiate MCI-LB from MCI-AD. [ABSTRACT FROM AUTHOR]

Objectives: Autonomic symptoms are a common feature of the synucleinopathies, and may be a distinguishing feature of prodromal Lewy body disease. We aimed to assess whether the cognitive prodrome of dementia with Lewy bodies, mild cognitive impairment (MCI) with Lewy bodies (MCI-LB), would have more severe reported autonomic symptoms than cognitively healthy older adults, with MCI due to Alzheimer's disease (MCI-AD) also included for comparison. We also aimed to assess the utility of an autonomic symptom scale in differentiating MCI-LB from MCI-AD.Methods: Ninety-three individuals with MCI and 33 healthy controls were assessed with the Composite Autonomic Symptom Score 31-item scale (COMPASS). Mild cognitive impairment patients also underwent detailed clinical assessment and differential classification of MCI-AD or MCI-LB according to current consensus criteria. Differences in overall COMPASS score and individual symptom sub-scales were assessed, controlling for age.Results: Age-adjusted severity of overall autonomic symptomatology was greater in MCI-LB (Ratio = 2.01, 95% CI: 1.37-2.96), with higher orthostatic intolerance and urinary symptom severity than controls, and greater risk of gastrointestinal and secretomotor symptoms. MCI-AD did not have significantly higher autonomic symptom severity than controls overall. A cut-off of 4/5 on the COMPASS was sensitive to MCI-LB (92%) but not specific to this (42% specificity vs. MCI-AD and 52% vs. healthy controls).Conclusions: Mild cognitive impairment with Lewy bodies had greater autonomic symptom severity than normal ageing and MCI-AD, but such autonomic symptoms are not a specific finding. The COMPASS-31 may therefore have value as a sensitive screening test for early-stage Lewy body disease. [ABSTRACT FROM AUTHOR]

Objectives: Previous research has identified that dementia with Lewy bodies (DLB) has abnormal pareidolic responses which are associated with severity of visual hallucinations (VH), and the pareidolia test accurately classifies DLB with VH. We aimed to assess whether these findings would also be evident at the earlier stage of mild cognitive impairment (MCI) with Lewy bodies (MCI‐LB) in comparison to MCI due to AD (MCI‐AD) and cognitively healthy comparators. Methods: One‐hundred and thirty‐seven subjects were assessed prospectively in a longitudinal study with a mean follow‐up of 1.2 years (max = 3.7): 63 MCI‐LB (22% with VH) and 40 MCI‐AD according to current research diagnostic criteria, and 34 healthy comparators. The pareidolia test was administered annually as a repeated measure. Results: Probable MCI‐LB had an estimated pareidolia rate 1.2–6.7 times higher than MCI‐AD. Pareidolia rates were not associated with concurrent VH, but had a weak association with total score on the North East Visual Hallucinations Inventory. The pareidolia test was not an accurate classifier of either MCI‐LB (Area under curve (AUC) = 0.61), or VH (AUC = 0.56). There was poor sensitivity when differentiating MCI‐LB from controls (41%) or MCI‐AD (27%), though specificity was better (91% and 89%, respectively). Conclusions: Whilst pareidolic responses are specifically more frequent in MCI‐LB than MCI‐AD, sensitivity of the pareidolia test is poorer than in DLB, with fewer patients manifesting VH at the earlier MCI stage. However, the high specificity and ease of use may make it useful in specialist clinics where imaging biomarkers are not available. Key Points: Pareidolia responses to ambiguous visual stimuli may be a surrogate for visual hallucinationsPareidolias are more common in dementia with Lewy bodies than in Alzheimer's disease (AD)We found an increased rate of pareidolias in mild cognitive impairment (MCI) with Lewy bodies than in AD or healthy comparatorsMisperceptions in the pareidolia test are reasonably specific to MCI with Lewy bodies, but these may lack sensitivity at early stages [ABSTRACT FROM AUTHOR]

Background: Dopaminergic imaging is an established biomarker for dementia with Lewy bodies, but its diagnostic accuracy at the mild cognitive impairment (MCI) stage remains uncertain.Aims: To provide robust prospective evidence of the diagnostic accuracy of dopaminergic imaging at the MCI stage to either support or refute its inclusion as a biomarker for the diagnosis of MCI with Lewy bodies.Method: We conducted a prospective diagnostic accuracy study of baseline dopaminergic imaging with [123I]N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropane single-photon emission computerised tomography (123I-FP-CIT SPECT) in 144 patients with MCI. Images were rated as normal or abnormal by a panel of experts with access to striatal binding ratio results. Follow-up consensus diagnosis based on the presence of core features of Lewy body disease was used as the reference standard.Results: At latest assessment (mean 2 years) 61 patients had probable MCI with Lewy bodies, 26 possible MCI with Lewy bodies and 57 MCI due to Alzheimer's disease. The sensitivity of baseline FP-CIT visual rating for probable MCI with Lewy bodies was 66% (95% CI 52-77%), specificity 88% (76-95%) and accuracy 76% (68-84%), with positive likelihood ratio 5.3.Conclusions: It is over five times as likely for an abnormal scan to be found in probable MCI with Lewy bodies than MCI due to Alzheimer's disease. Dopaminergic imaging appears to be useful at the MCI stage in cases where Lewy body disease is suspected clinically. [ABSTRACT FROM AUTHOR]

Background: Lewy body dementia (LBD), which includes dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD), is characterised by marked deficits within the cholinergic system which are more severe than in Alzheimer's disease (AD) and are mainly caused by degeneration of the nucleus basalis of Meynert (NBM) whose widespread cholinergic projections provide the main source of cortical cholinergic innervation. EEG alpha reactivity, which refers to the reduction in alpha power over occipital electrodes upon opening the eyes, has been suggested as a potential marker of cholinergic system integrity. Methods: Eyes-open and eyes-closed resting state EEG data were recorded from 41 LBD patients (including 24 patients with DLB and 17 with PDD), 21 patients with AD, and 40 age-matched healthy controls. Alpha reactivity was calculated as the relative reduction in alpha power over occipital electrodes when opening the eyes. Structural MRI data were used to assess volumetric changes within the NBM using a probabilistic anatomical map. Results: Alpha reactivity was reduced in AD and LBD patients compared to controls with a significantly greater reduction in LBD compared to AD. Reduced alpha reactivity was associated with smaller volumes of the NBM across all groups (ρ = 0.42, pFDR = 0.0001) and in the PDD group specifically (ρ = 0.66, pFDR = 0.01). Conclusions: We demonstrate that LBD patients show an impairment in alpha reactivity upon opening the eyes which distinguishes this form of dementia from AD. Furthermore, our results suggest that reduced alpha reactivity might be related to a loss of cholinergic drive from the NBM, specifically in PDD. [ABSTRACT FROM AUTHOR]

We performed a clinicopathological study to assess the burden of small vessel disease (SVD) type of pathological changes in elderly demented subjects, who had clinical evidence of autonomic dysfunction, either carotid sinus hypersensitivity or orthostatic hypotension or both or had exhibited unexpected repeated falls. Clinical and neuropathological diagnoses in 112 demented subjects comprised dementia with Lewy bodies (DLB), Parkinson's disease with dementia (PDD), Alzheimer's disease (AD), Mixed dementia (mostly AD‐DLB) and vascular dementia (VaD). Of these, 12 DLB subjects had no recorded unexpected falls in life and therefore no evidence of concomitant autonomic dysfunction. A further 17 subjects were assessed as aging controls without significant pathology or signs of autonomic dysfunction. We quantified brain vascular pathological changes and determined severities of neurodegenerative lesions including α‐synuclein pathology. We found moderate‐severe vascular changes and high‐vascular pathology scores (P < 0.01) in all neurodegenerative dementias and as expected in VaD compared to similar age controls. Arteriolosclerosis, perivascular spacing and microinfarcts were frequent in the basal ganglia and frontal white matter (WM) across all dementias, whereas small infarcts (<5 mm) were restricted to VaD. In a sub‐set of demented subjects, we found that vascular pathology scores were correlated with WM hyperintensity volumes determined by MRI in life (P < 0.02). Sclerotic index values were increased by ~50% in both the WM and neocortex in all dementias compared to similar age controls. We found no evidence for increased α‐synuclein deposition in subjects with autonomic dysfunction. Our findings suggest greater SVD pathological changes occur in the elderly diagnosed with neurodegenerative dementias including DLB and who develop autonomic dysfunction. SVD changes may not necessarily manifest in clinically overt symptoms but they likely confound motor or cognitive dysfunction. We propose dysautonomia promotes chronic cerebral hypoperfusion to impact upon aging‐related neurodegenerative disorders and characterize their end‐stage clinical syndromes. [ABSTRACT FROM AUTHOR]

Background: Lewy body dementia (LBD) and Alzheimer's disease (AD) are common forms of degenerative dementia. While they are characterized by different clinical profiles, attentional deficits are a common feature. The objective of this study was to investigate how attentional problems in LBD and AD differentially affect different aspects of reaction time performance and to identify possible structural neural correlates. Methods: We studied reaction time data from an attention task comparing 39 LBD patients, 28 AD patients, and 22 age-matched healthy controls. Data were fitted to an ex-Gaussian model to characterize different facets of the reaction time distribution (mean reaction time, reaction time variability, and the subset of extremely slow responses). Correlations between ex-Gaussian parameters and grey and white matter volume were assessed by voxel-based morphometry. Results: Both dementia groups showed an increase in extremely slow responses. While there was no difference between AD and controls with respect to mean reaction time and variability, both were significantly increased in LBD patients compared to controls and AD. There were widespread correlations between mean reaction time and variability and grey matter loss in AD, but not in LBD. Conclusions: This study shows that different aspects of reaction time performance are differentially affected by AD and LBD, with a difference in structural neural correlates underlying the observed behavioural deficits. While impaired attentional performance is linked to brain atrophy in AD, in LBD it might be related to functional or microstructural rather than macrostructural changes. [ABSTRACT FROM AUTHOR]

Lewy body dementia includes dementia with Lewy bodies and Parkinson's disease dementia and is characterized by transient clinical symptoms such as fluctuating cognition, which might be driven by dysfunction of the intrinsic dynamic properties of the brain. In this context we investigated whole-brain dynamics on a subsecond timescale in 42 Lewy body dementia compared to 27 Alzheimer's disease patients and 18 healthy controls using an EEG microstate analysis in a cross-sectional design. Microstates are transiently stable brain topographies whose temporal characteristics provide insight into the brain's dynamic repertoire. Our additional aim was to explore what processes in the brain drive microstate dynamics. We therefore studied associations between microstate dynamics and temporal aspects of large-scale cortical-basal ganglia-thalamic interactions using dynamic functional MRI measures given the putative role of these subcortical areas in modulating widespread cortical function and their known vulnerability to Lewy body pathology. Microstate duration was increased in Lewy body dementia for all microstate classes compared to Alzheimer's disease (P < 0.001) and healthy controls (P < 0.001), while microstate dynamics in Alzheimer's disease were largely comparable to healthy control levels, albeit with altered microstate topographies. Correspondingly, the number of distinct microstates per second was reduced in Lewy body dementia compared to healthy controls (P < 0.001) and Alzheimer's disease (P < 0.001). In the dementia with Lewy bodies group, mean microstate duration was related to the severity of cognitive fluctuations (ρ = 0.56, PFDR = 0.038). Additionally, mean microstate duration was negatively correlated with dynamic functional connectivity between the basal ganglia (r = - 0.53, P = 0.003) and thalamic networks (r = - 0.38, P = 0.04) and large-scale cortical networks such as visual and motor networks in Lewy body dementia. The results indicate a slowing of microstate dynamics and disturbances to the precise timing of microstate sequences in Lewy body dementia, which might lead to a breakdown of the intricate dynamic properties of the brain, thereby causing loss of flexibility and adaptability that is crucial for healthy brain functioning. When contrasted with the largely intact microstate dynamics in Alzheimer's disease, the alterations in dynamic properties in Lewy body dementia indicate a brain state that is less responsive to environmental demands and might give rise to the apparent slowing in thinking and intermittent confusion which typify Lewy body dementia. By using Lewy body dementia as a probe pathology we demonstrate a potential link between dynamic functional MRI fluctuations and microstate dynamics, suggesting that dynamic interactions within the cortical-basal ganglia-thalamic loop might play a role in the modulation of EEG dynamics. [ABSTRACT FROM AUTHOR]

Background: Alzheimer's disease (AD) is associated with atrophy in entorhinal cortex (ERC), the hippocampus, and its subfields Cornu Ammonis 1 (CA1) and subiculum, which predict conversion from mild cognitive impairment (MCI) to clinical AD. The stratum radiatum, lacunosum, and moleculare (SRLM) are also important gateways involving ERC and CA1, which are affected by early AD pathology.Objective: To assess whether the SRLM is affected in MCI and AD.Methods: In this proof-of-concept study, 27 controls, 13 subjects with AD, and 22 with MCI underwent 3T MRI. T1 maps were used for whole-hippocampal volumetry, T2 maps were segmented for hippocampal subfield areas, entorhinal cortex and subiculum thickness, and evaluated for SRLM integrity.Results: Significant CA1 atrophy and subiculum thinning were found in both AD and MCI compared to similarly aged controls. However, SRLM integrity was only significantly reduced in AD but not in MCI compared to controls. There were no significant differences in other hippocampal subfields (CA2, CA3/dentate gyrus) or ERC thickness between the groups. Finally, CA1 and CA3/DG areas and SRLM clarity were correlated with clinical and cognitive measurements of disease severity.Conclusion: Although this study was cross sectional, it suggests a progression of specific subfield changes from MCI to established AD that is associated with the reduced integrity of SRLM, which may reflect more widespread hippocampal involvement as the disease progresses and the relative preservation of SRLM in MCI. These results provide new MRI biomarkers for disease staging and understanding of the neurobiology in AD. [ABSTRACT FROM AUTHOR]

Aims Complex visual hallucinations occur in 70% of dementia with Lewy bodies ( DLB) cases and significantly affect patient well-being. Visuo-cortical and retinal abnormalities have been recorded in DLB and may play a role in visual hallucinations. The present study aimed to investigate the lateral geniculate nucleus ( LGN), a visual relay centre between the retina and visual cortex, to see if changes to this structure underlie visual hallucinations in DLB. Methods Fifty-one [17 probable DLB, 19 control and 15 probable Alzheimer's disease ( AD)] cases were recruited for a functional magnetic resonance imaging study, in which patients' response to a flashing checkerboard stimulus was detected and measured in the LGN, before comparison across experimental groups. Additionally, post mortem LGN tissue was acquired for a cross-sectional study using 20 (six DLB, seven control and seven AD) cases and analysed using stereology. α-Synuclein, phosphorylated tau and amyloid-β pathology was also assessed in all cases. Results DLB cases did not significantly differ from controls on neuroimaging, morphometry or pathology. However, a significant increase in amyloid-β pathology, a reduction in number of parvocellular neurones and magnocellular gliosis was found in AD cases compared with control and DLB cases. Conclusions These findings suggest that the early visual system is relatively spared in DLB, which implies that upstream visual structures may be largely responsible for the generation of hallucinatory percepts. The significance of the degeneration of the LGN in AD cases is uncertain. [ABSTRACT FROM AUTHOR]

Background: Imaging biomarkers for Alzheimer's disease include medial temporal lobe atrophy (MTLA) depicted on computed tomography (CT) or magnetic resonance imaging (MRI) and patterns of reduced metabolism on fluorodeoxyglucose positron emission tomography (FDG-PET).Aims: To investigate whether MTLA on head CT predicts the diagnostic usefulness of an additional FDG-PET scan.Method: Participants had a clinical diagnosis of Alzheimer's disease (n = 37) or dementia with Lewy bodies (DLB; n = 30) or were similarly aged controls (n = 30). We visually rated MTLA on coronally reconstructed CT scans and, separately and blind to CT ratings, abnormal appearances on FDG-PET scans.Results: Using a pre-defined cut-off of MTLA ⩾5 on the Scheltens (0-8) scale, 0/30 controls, 6/30 DLB and 23/30 Alzheimer's disease had marked MTLA. FDG-PET performed well for diagnosing Alzheimer's disease v DLB in the low-MTLA group (sensitivity/specificity of 71%/79%), but in the high-MTLA group diagnostic performance of FDG-PET was not better than chance.Conclusions: In the presence of a high degree of MTLA, the most likely diagnosis is Alzheimer's disease, and an FDG-PET scan will probably not provide significant diagnostic information. However, in cases without MTLA, if the diagnosis is unclear, an FDG-PET scan may provide additional clinically useful diagnostic information. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Positron emission tomography (PET) and single photon emission computed tomography (SPECT) brain imaging are widely used as diagnostic tools for suspected dementia but no studies have directly compared participant views of the two procedures. We used a range of methods to explore preferences for PET and SPECT.Methods: Patients and controls (and accompanying carers) completed questionnaires immediately after undergoing PET and SPECT brain scans. Pulse rate data were collected during each scan. Scan attributes were prioritized using a card sorting exercise; carers and controls additionally answered willingness to pay (WTP) questions.Results: Few differences were found either between the scans or groups of participants, although carers marginally preferred SPECT. Diagnostic accuracy was prioritized over other scan characteristics. Mean heart rate during both scans was lower than baseline heart rate measured at home (p < 0.001).Conclusion: Most participants viewed PET and SPECT scans as roughly equivalent and did not have a preference for either scan. Carer preference for SPECT is likely to reflect their desire to be with the patient (routine practice for SPECT but not for PET), suggesting that they should be able to accompany vulnerable patients throughout imaging procedures wherever possible. Pulse rate data indicated that brain imaging was no more stressful than a home visit (HV) from a researcher. The data do not support the anecdotal view that PET is a more burdensome procedure and the use of PET or SPECT scans in dementia should be based on diagnostic accuracy of the technique. [ABSTRACT FROM AUTHOR]

Introduction: Cerebral white matter lesions (WML), visualized as white matter hyperintensities (WMH) on T2-weighted MRI, encompass structural damage and loss of integrity of the cerebral white matter (WM) and are commonly assumed to be associated with small vessel disease (SVD). However, it has been suggested that WM damage may also be the result of degenerative axonal loss that is secondary to cortical Alzheimer's disease (AD) pathologies i.e., hyperphosphorylated tau (HPτ) and amyloid-beta (Aβ). Here we investigate the influence of HPτ, Aβ and SVD on WMH severity. Results: 36 human post-mortem right fixed cerebral hemispheres (mean age 84.4 ± 7.7 years; male: 16, female: 20) containing varying amounts of AD-pathology (AD: 23, controls: 13) underwent T2- weighted MRI with WMH assessed according to the age related white matter change scale (ARWMC). After dissection, using tissue samples from the frontal, temporal, parietal and occipital regions from the right hemisphere, we quantitatively assessed cortical HPτ and Aβ pathology burden by measuring the percentage area covered by AT8 immunoreactivity (HPτ-IR) and 4G8 immunoreactivity (Aβ-IR), and assessed the severity of WM SVD by calculating the sclerotic index (SI) of WMarteries/arterioles.HPτ-IR, Aβ-IR, and SI were compared with ARWMC scores. HPτ-IR, Aβ-IR and WM ARWMC scores were all significantly higher in AD cases compared to controls, while SI values were similar between groups. ARWMC scores correlated with HPτ-IR, Aβ-IR and SI in various regions, however, linear regression revealed that only HPτ-IR was a significant independent predictor of ARWMC scores. Conclusions: Here we have shown that increasing cortical HPτ burden independently predicted the severity of WMH indicating its potentially important role in the pathogenesis of WM damage. Moreover, our findings suggest that in AD patients the presence of WMH may indicate cortical AD-associated pathology rather than SVD. Further studies are warranted to elucidate the pathological processes that lead to WM damage and to clarify if WMH may serve as a general biomarker for cortical AD-associated pathology. [ABSTRACT FROM AUTHOR]

Background: Resting-state functional magnetic resonance imaging (fMRI) can be used to measure correlations in spontaneous low-frequency fluctuations in the blood oxygen level-dependent (BOLD) signal which represent functional connectivity between key brain areas.Aims: To investigate functional connectivity with regions hypothesised to be differentially affected in dementia with Lewy bodies (DLB) compared with Alzheimer's disease and controls.Method: Fifteen participants with probable DLB, 16 with probable Alzheimer's disease and 16 controls were scanned in the resting-state using a 3T scanner. The BOLD signal time-series of fluctuations in seed regions were correlated with all other voxels to measure functional connectivity.Results: Participants with DLB and Alzheimer's disease showed greater caudate and thalamic connectivity compared with controls. Those with DLB showed greater putamen connectivity compared with those with Alzheimer's disease and the controls. No regions showed less connectivity in DLB or Alzheimer's disease v. controls, or in DLB v. Alzheimer's disease.Conclusions: Altered connectivity in DLB and Alzheimer's disease provides new insights into the neurobiology of these disorders and may aid in earlier diagnosis. [ABSTRACT FROM AUTHOR]

Objectives Visuo-perceptual abnormalities are a prominent feature in dementia with Lewy bodies (DLB) and also occur in Alzheimer's disease (AD) to a lesser extent. We studied the progression of visuo-perceptual abnormalities over a 12-month period in DLB and AD by using a novel computerised test battery. Methods Following our previous work using the Newcastle Visual Perception (NEVIP) battery, we re-assessed 16 AD, 12 DLB and 28 similar-aged comparison participants 12 months after initial baseline assessment. Results DLB visual perception at follow-up showed worse performance than AD ( U = 43, p = 0.027); however, there were no significant changes in visuo-perceptual scores between baseline assessment and 12-month assessment within groups. A poor baseline score on the NEVIP predicted subsequent deterioration on the Bristol Activities of Daily Living Scale ( rs = −0.725, p = 0.014) in DLB participants but not in the AD group. Conclusions The NEVIP is a reliable test of visuo-perception, relatively independent of cognitive decline, with predictive value in identifying DLB participants at risk of functional decline. Visuo-perceptual dysfunction is a core feature of the disorder for some DLB patients and was stable over the 12-month period examined here. Copyright © 2012 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background Stroke is a risk factor for subsequent death and dementia. Being able to identify subjects at particular risk would be beneficial to inform treatment and patient management. Methods Subjects aged over 75 years with incident stroke were recruited. Subjects had a cognitive assessment at 3 months post stroke to exclude dementia, and had an MRI scan (n¼106) at that time. Subjects were then follo Results Independent neuroimaging predictors of survival to dementia were medial temporal atrophy (MTA; p¼0.013) and the presence of thalamic infarcts (p¼0.002). After inclusion of cognitive score in the model, the significance of MTA (p¼0.049) and thalamic infarcts (p¼0.04) was reduced, with survival being best predicted by baseline cognitive score (p¼0.004). The only independent significant predictor of survival to death was MTA. Apart from thalamic infarcts, the NINDS/ AIREN neuroimaging criteria did not independently predict survival to death or dementia. Conclusions MTA was associated with shorter time to dementia, suggesting a role for Alzheimer pathology in the development of post stroke dementia. [ABSTRACT FROM AUTHOR]

Using resting-state functional magnetic resonance imaging, spontaneous low-frequency fluctuations in the blood oxygenation level-dependent signal were measured to investigate connectivity between key brain regions hypothesized to be differentially affected in dementia with Lewy bodies compared with Alzheimer's disease and healthy controls. These included connections of the hippocampus, because of its role in learning, and parietal and occipital areas involved in memory, attention and visual processing. Connectivity was investigated in 47 subjects aged 60 years and over: 15 subjects with dementia with Lewy bodies, 16 subjects with Alzheimer's disease and 16 control subjects. Subjects were scanned using a 3 Tesla magnetic resonance imaging system. The mean blood oxygenation level-dependent signal time series was extracted from seed regions in the hippocampus, posterior cingulate cortex, precuneus and primary visual cortex and correlated with all other brain voxels to determine functional connectivity. Both subjects with dementia with Lewy bodies and Alzheimer's disease showed greater connectivity than control subjects. Compared with controls, the dementia with Lewy bodies group had greater connectivity between the right posterior cingulate cortex and other brain areas. In dementia with Lewy bodies, there were no significant differences in hippocampal connectivity compared with controls, but in Alzheimer's disease left hippocampal connectivity was greater compared with controls. There were no significant differences between groups for precuneus or primary visual cortex connectivity. No seed regions showed significantly less connectivity in subjects with dementia with Lewy bodies or Alzheimer's disease compared with controls. We found greater connectivity with the posterior cingulate in dementia with Lewy bodies and with the hippocampus in Alzheimer's disease. Consistent with the known relative preservation of memory in dementia with Lewy bodies compared with Alzheimer's disease, hippocampal connectivity was not found to be greater in dementia with Lewy bodies. Importantly, while metabolic imaging shows functional change in primary visual cortex in dementia with Lewy bodies, which is hypothesized to account for visual hallucinations, we found connectivity with this region to be unaffected. This implicates areas beyond visual sensory input level in the visual symptoms and visual–perceptual dysfunction seen in dementia with Lewy bodies. [ABSTRACT FROM PUBLISHER]

Greater understanding of the risk factors and mechanisms of incident dementia in stroke survivors is needed for prevention and management. There is limited information on the long-term consequences and forms of incident dementia in older stroke survivors. We recruited 355 patients aged >75 years from hospital-based stroke registers into a longitudinal study 3 months after stroke. At baseline none of the patients had dementia. Patients were genotyped for apolipoprotein E and assessed annually for cognition and development of incident dementia over up to 8 years of follow-up. The effect of baseline vascular risk factors upon incidence of dementia and mortality were estimated by Cox proportional regression analyses adjusted for age and gender. Standard neuropathological examination was performed to diagnose the first 50 cases that came to autopsy. We found that the median survival from the date of the index stroke was 6.72 years (95% confidence intervals: 6.38–7.05). During the follow-up of a mean time of 3.79 years, 23.9% of subjects were known to have developed dementia and 76.1% remained alive without dementia or died without dementia. The incidence of delayed dementia was calculated to be 6.32 cases per 100 person years whereas that for death or dementia was 8.62. Univariate and multivariate regression analyses showed that the most robust predictors of dementia included low (1.5 standard deviations below age-matched control group) baseline Cambridge Cognitive Examination executive function and memory scores, Geriatric Depression Scale score and three or more cardiovascular risk factors. Autopsy findings suggested that remarkably &geq;75% of the demented stroke survivors met the current criteria for vascular dementia. Demented subjects tended to exhibit marginally greater neurofibrillary pathology including tauopathy and Lewy bodies and microinfarcts than non-demented survivors. Despite initial improvements in cognition following stroke in older stroke survivors, risk of progression to delayed dementia after stroke is substantial, but is related to the presence of vascular risk factors. Careful monitoring and treatment of modifiable vascular risk factors may be of benefit in preventing post-stroke dementia in the general population. [ABSTRACT FROM PUBLISHER]

We used high resolution (0.3 mm in-plane) coronal 3T magnetic resonance (MR) imaging of the medial temporal lobe in 16 subjects with Alzheimer's disease (AD), 16 with dementia with Lewy bodies (DLB), and 16 similarly aged healthy subjects. On the anterior section of the hippocampus body, regions of interest were manually drawn blind to diagnosis on the CA1, CA2, and CA3/4 subregions, and the width of the subiculum and entorhinal cortex was measured. Controlling for intracranial volume, age, and years of education, we found the subiculum thickness was significantly reduced in AD (2.03 ± 0.29 mm) compared to both control (2.37 ± 0.28 mm, p = 0.008) and DLB (2.35 ± 0.24 mm, p = 0.001) subjects. The area of CA1 was likewise reduced in AD compared to controls and DLB. In the hippocampus images, a hypointense line is visible between CA1 and CA3/4. This line was significantly less distinct in AD, suggesting disease related changes to this region. Future studies should investigate whether subiculum thickness or the hypointense line could be a diagnostic feature to help discriminate AD from DLB. [ABSTRACT FROM AUTHOR]

99mTc-exametazime single photon emission computed tomography (SPECT) scans of 36 patients with Alzheimer's disease (AD) and 30 with dementia with Lewy bodies (DLB) underwent region of interest (ROI) and principal component analysis (PCA). Principal component analysis was performed on the entire ROI data set. Principal components (PCs) were obtained, representing common intercorrelated regions in AD and DLB. Topographic expression that signified the extent to which a participant expressed the topographic covariance pattern was derived and used as a discriminatory variable. Principal components were identified, accounting for 77% of total data variance. Significant (PC × group) interaction was observed (P < .001). Topographic expression was significantly higher in DLB than AD (F1,64 = 21.6, P < .001), and differentiated DLB from AD with sensitivity 73% specificity 72%. Calculating the topographic expression in an independent data set of 48 patients with AD and 23 with DLB gave sensitivity = 70%, specificity = 67%. Principal component analysis captures additional sources of variance and if perfusion SPECT is the only scan available, this procedure may offer extra information. [ABSTRACT FROM AUTHOR]

Abstract: Stroke is an important risk factor for dementia, but the exact mechanisms involved in cognitive decline remain unclear. In this study, we related baseline MRI brain measures with later cognitive decline. Seventy-nine stroke survivors aged 75+ years without dementia were recruited 3-month post-stroke. They underwent yearly neuropsychological assessments and had an MRI at baseline and 2 years. Medial temporal lobe atrophy (MTA) was scored and volume of white matter hyperintensities (WMH) was measured at baseline. The rate of ventricular enlargement was measured by comparing the baseline and repeat images. Linear regression indicated that memory loss was related to both baseline memory and MTA (p =0.001; standardized regression coefficient β =−0.35) but not WMH volume. The only independent predictor of ventricular enlargement was MTA (p =0.003; β =0.47). However, no baseline MRI variable differed between those who did (18%) and did not (82%) develop dementia. The association of MTA but not WMH with subsequent cognitive decline and increasing brain atrophy suggests a greater role for Alzheimer type than vascular pathology in delayed cognitive impairment after stroke. [Copyright &y& Elsevier]

Abstract: Dementia with Lewy bodies (DLB) is a common form of dementia, with fewer memory deficits, and more visuo-perceptual problems than Alzheimer''s disease (AD). We hypothesized that there would be disease specific alterations revealed by diffusion tensor imaging with AD showing temporal lobe and DLB more parietal changes. We recruited 15 people with AD, 16 with DLB, and 15 healthy control subjects of similar age. They were scanned on a 1.5 T MRI system with diffusion tensor FLAIR imaging. Apparent diffusion coefficient (ADC) and fractional anisotropy (FA) maps were calculated, and data were analysed using pre-defined regions of interest (ROI) and also with SPM. We found a significant decrease in the FA map in a ROI in the parietal lobe (precuneus) of the DLB group. Using SPM we found increased ADC in the left temporal lobe of AD subjects compared to controls. There were no other significant differences between groups. We conclude that there are subtle changes visible with diffusion imaging in DLB and AD which may reflect disrupted connectivity and underlie observed perfusion changes in these disorders. [Copyright &y& Elsevier]

Background: Dementia with Lewy bodies (DLB) is a common form of late-life dementia that can be difficult to differentiate from other disorders, especially Alzheimer disease (AD), during life. At autopsy the striatal dopaminergic transporter is reduced. Objectives: To examine the extent and pattern of dopamine transporter loss using iodine I 123-radiolabeled 2β-carbomethoxy-3β-(4-iodophenyl)-N-(3fluoropropyl) nortropane (FP-CIT) with single-photon emission computed tomography (SPECT) in DLBs compared with other dementias and to assess its potential to enhance a differential diagnosis. Design: Cohort study comparing FP-CIT with criterion standard of consensus clinical diagnosis. Setting: General hospital. Participants: One hundred sixty-four older subjects (33 healthy older control subjects, 34 with NINCDS/ADRDA [National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association]-confirmed AD, 23 with consensus guideline-confirmed DLB, 38 with United Kingdom's Parkinson Disease Society Brain Bank-confirmed Parkinson disease [PD], and 36 with PD and dementia). Interventions: Injection of 123I-2β-carbomethoxy-3β- (4-iodophenyl)-N-(3-fluoropropyl) nortropane with SPECT scan performed at 4 hours. Main Outcome Measures: Visual ratings of scans and region of interest analysis. Results: Significant reductions (P <. 001) in FP-CIT binding occurred in the caudate and anterior and posterior putamens in subjects with DLB compared with subjects with AD and controls. Transporter loss in DLBs was of similar magnitude to that seen in PD, but with a flatter rostrocaudal (caudate-putamen) gradient (P=.001), while the greatest loss in all 3 areas was seen in those who had PD and dementia. Both region of interest analysis and visual ratings provided good separation between DLBs and AD (region of interest: sensitivity, 78%; specificity, 94%; positive predictive value, 90%) but not among subjects with DLB, PD, and PD with dementia. Conclusions: Dopamine transporter loss can be detected in vivo using FP-CIT SPECT in DLB. Further studies, especially of subjects with DLB without PD, are required to fully establish use in clinical practice. [ABSTRACT FROM AUTHOR]

• In the differential diagnosis of dementia with Lewy body and Alzhiemer's disease, spatial covariance analysis of FDG-PET significantly outperforms that of HMPAO-SPECT. • With a relatively small derivation group, spatial covariance analysis of FDG-PET performed similarly to visual interpretation and a univariate quantification method. • Unlike the univariate method, there was little concordance between spatial covariance analysis and visual interpretation of FDG-PET scans, implying that spatial covariance analysis and visual interpretation rely on different sources of variance to separate disease subgroups. We investigated diagnostic characteristics of spatial covariance analysis (SCA) of FDG-PET and HMPAO-SPECT scans in the differential diagnosis of dementia with Lewy bodies (DLB) and Alzheimer's disease (AD), in comparison with visual ratings and region of interest (ROI) analysis. Sixty-seven patients (DLB 29, AD 38) had both HMPAO-SPECT and FDG-PET scans. Spatial covariance patterns were used to separate AD and DLB in an initial derivation group (DLB n=15, AD n=19), before being forward applied to an independent group (DLB n=14, AD n=19). Visual ratings were by consensus, with ROI analysis utilising medial occipital/medial temporal uptake ratios. SCA of HMPAO-SPECT performed poorly (AUC 0.59±0.10), whilst SCA of FDG-PET (AUC 0.83±0.07) was significantly better. For FDG-PET, SCA showed similar diagnostic performance to ROI analysis (AUC 0.84±0.08) and visual rating (AUC 0.82±0.08). In contrast to ROI analysis, there was little concordance between SCA and visual ratings of FDG-PET scans. We conclude that SCA of FDG-PET outperforms that of HMPAO-SPECT. SCA of FDG-PET also performed similarly to the other analytical approaches, despite the limitations of a relatively small SCA derivation group. Compared to visual rating, SCA of FDG-PET relies on different sources of group variance to separate DLB from AD. [ABSTRACT FROM AUTHOR]

Dementia is caused by neurodegenerative conditions and characterized by cognitive decline. Diagnostic accuracy for dementia subtypes, such as Alzheimer's Disease (AD), Dementia with Lewy Bodies (DLB) and Parkinson's Disease with dementia (PDD), remains challenging. Here, different methods of quantitative electroencephalography (qEEG) analyses were employed to assess their effectiveness in distinguishing dementia subtypes from healthy controls under eyes closed (EC) and eyes open (EO) conditions. Classic Fast-Fourier Transform (FFT) and autoregressive (AR) power analyses differentiated between all conditions for the 4–8 Hz theta range. Only individuals with dementia with Lewy Bodies (DLB) differed from healthy subjects for the wider 4–15 Hz frequency range, encompassing the actual dominant frequency of all individuals. FFT results for this range yielded wider significant discriminators vs AR, also detecting differences between AD and DLB. Analyses of the inclusive dominant / peak frequency range (4–15 Hz) indicated slowing and reduced variability, also discriminating between synucleinopathies vs controls and AD. Dissociation of periodic oscillations and aperiodic components of AR spectra using Fitting-Oscillations-&-One-Over-F (FOOOF) modelling delivered a reliable and subtype-specific slowing of brain oscillatory peaks during EC and EO for all groups. Distinct and robust differences were particularly strong for aperiodic parameters, suggesting their potential diagnostic power in detecting specific changes resulting from age and cognitive status. Our findings indicate that qEEG methods can reliably detect dementia subtypes. Spectral analyses comprising an integrated, multi-parameter EEG approach discriminating between periodic and aperiodic components under EC and EO conditions may enhance diagnostic accuracy in the future. • FFT spectra discriminated between synucleinopathies and controls. • Autoregressive spectra identified fewer differences between cohorts. • Slowing (dominant frequency) differentiated between synucleinopathies vs. controls. • Combining AR & FOOOF yielded robust differences between all conditions. • Aperiodic parameters achieved superior discrimination for all conditions. [ABSTRACT FROM AUTHOR]

Clinical parkinsonism is a core diagnostic feature for mild cognitive impairment with Lewy bodies (MCI-LB) but can be challenging to identify. A five-item scale derived from the Unified Parkinson's Disease Rating Scale (UPDRS) has been recommended for the assessment of parkinsonism in dementia. This study aimed to determine whether the five-item scale is effective to identify parkinsonism in MCI. Participants with MCI from two cohorts (n = 146) had a physical examination including the UPDRS and [123I]-FP-CIT SPECT striatal dopaminergic imaging. Participants were classified as having clinical parkinsonism (P+) or no parkinsonism (P-), and with abnormal striatal dopaminergic imaging (D+) or normal imaging (D-). The five-item scale was the sum of UPDRS tremor at rest, bradykinesia, action tremor, facial expression, and rigidity scores. The ability of the scale to differentiate P+D+ and P-D- participants was examined. The five-item scale had an AUROC of 0.92 in Cohort 1, but the 7/8 cut-off defined for dementia had low sensitivity to identify P+D+ participants (sensitivity 25%, specificity 100%). Optimal sensitivity and specificity was obtained at a 3/4 cut-off (sensitivity 83%, specificity 88%). In Cohort 2, the five-item scale had an AUROC of 0.97, and the 3/4 cut-off derived from Cohort 1 showed sensitivity of 100% and a specificity of 82% to differentiate P+D+ from P-D- participants. The five-item scale was not effective in differentiating D+ from D- participants. The five-item scale is effective to identify parkinsonism in MCI, but a lower threshold must be used in MCI compared with dementia. • A five-item scale derived from the UPDRS can help identify parkinsonism in dementia. • The scale was tested in mild cognitive impairment (MCI). • It accurately identified MCI with parkinsonism and abnormal dopaminergic imaging. • A lower threshold is required in MCI compared with dementia. • The scale may help identify parkinsonism in clinical and research settings. [ABSTRACT FROM AUTHOR]