Patterns of tau, amyloid and synuclein pathology in ageing, Alzheimer's disease and synucleinopathies.

Alzheimer's disease (AD) is neuropathologically defined by deposits of misfolded hyperphosphorylated tau (HP-tau) and β-amyloid. Lewy body (LB) dementia, which includes dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD), is characterised pathologically by α-synuclein aggregates. HP-tau and β-amyloid can also occur as copathologies in LB dementia, and a diagnosis mixedAD/DLB can be made if present in sufficient quantities.

Gait-Related Metabolic Covariance Networks at Rest in Parkinson's Disease.

Background: Gait impairments are characteristic motor manifestations and significant predictors of poor quality of life in Parkinson's disease (PD). Neuroimaging biomarkers for gait impairments in PD could facilitate effective interventions to improve these symptoms and are highly warranted.

Objective: The aim of this study was to identify neural networks of discrete gait impairments in PD.

Functional and structural brain network correlates of visual hallucinations in Lewy body dementia.

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.

Spatial covariance analysis of FDG-PET and HMPAO-SPECT for the differential diagnosis of dementia with Lewy bodies and Alzheimer's disease.

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).

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.

Frontal white matter lesions in Alzheimer's disease are associated with both small vessel disease and AD-associated cortical pathology.

Cerebral white matter lesions (WML) encompass axonal loss and demyelination and are assumed to be associated with small vessel disease (SVD)-related ischaemia. However, our previous study in the parietal lobe white matter revealed that WML in Alzheimer's disease (AD) are linked with degenerative axonal loss secondary to the deposition of cortical AD pathology. Furthermore, neuroimaging data suggest that pathomechanisms for the development of WML differ between anterior and posterior lobes with AD-associated degenerative mechanism driving posterior white matter disruption, and both AD-associated degenerative and vascular mechanisms contributed to anterior matter disruption.

Spatial Covariance of Cholinergic Muscarinic M /M Receptors in Parkinson's Disease.

Background: Parkinson's disease (PD) is associated with cholinergic dysfunction, although the role of M1 and M4 receptors remains unclear.

Objective: To investigate spatial covariance patterns of cholinergic muscarinic M /M receptors in PD and their relationship with cognition and motor symptoms.

Methods: Some 19 PD and 24 older adult controls underwent I-iodo-quinuclidinyl-benzilate (QNB) (M /M receptor) and Tc-exametazime (perfusion) single-photon emission computed tomography (SPECT) scanning.

Accuracy of Cardiac Innervation Scintigraphy for Mild Cognitive Impairment With Lewy Bodies.

Objective: To provide evidence that cardiac I-123-metaiodobenzylguanidine sympathetic innervation imaging (MIBG) scintigraphy differentiates probable mild cognitive impairment with Lewy bodies (MCI-LB) from mild cognitive impairment due to Alzheimer disease (MCI-AD), we scanned patients with MCI and obtained consensus clinical diagnoses of their MCI subtype. We also performed baseline FP-CIT scans to compare the accuracy of MIBG and FP-CIT.

Methods: We conducted a prospective cohort study into the accuracy of cardiac MIBG scintigraphy in the diagnosis of MCI-LB.

Concomitant neurodegenerative pathologies contribute to the transition from mild cognitive impairment to dementia.

Introduction: The aged brain frequently exhibits multiple pathologies, rather than a single hallmark pathology (pure pathology [PurP]), ranging from low/intermediate levels of additional pathology (LowP) to mixed severe pathology (mixed SevP). We investigated the frequency of PurP, LowP, and mixed SevP, and the impact of additional LowP on cognition.

Methods: Data came from 670 cases from the Brains for Dementia research program.

Accuracy of dopaminergic imaging as a biomarker for mild cognitive impairment with Lewy bodies.

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.

Cholinergic muscarinic M/M receptor networks in dementia with Lewy bodies.

Cholinergic dysfunction is central in dementia with Lewy bodies, possibly contributing to the cognitive and psychiatric phenotypes of this condition. We investigated baseline muscarinic M/M receptor spatial covariance patterns in dementia with Lewy bodies and their association with changes in cognition and neuropsychiatric symptoms after 12 weeks of treatment with the cholinesterase inhibitor donepezil. Thirty-eight participants (14 cholinesterase inhibitor naive patients, 24 healthy older individuals) underwent I-iodo-quinuclidinyl-benzilate (M/M receptor assessment) and Tc-exametazime (perfusion) single-photon emission computed tomography scanning.

Cortical thinning in dementia with Lewy bodies and Parkinson disease dementia.

Background: We investigated the structural changes associated with Alzheimer's disease, dementia with Lewy bodies and Parkinson disease dementia by means of cortical thickness analysis.

Methods: Two hundred and forty-five participants: 76 Alzheimer's disease, 65 dementia with Lewy bodies, 29 Parkinson disease dementia and 76 cognitively normal controls underwent 3-T T1-weighted magnetic resonance imaging and clinical and cognitive assessments. We implemented FreeSurfer to obtain cortical thickness estimates to contrast patterns of cortical thinning across groups and their clinical correlates.

Neuropathological Changes in Dementia With Lewy Bodies and the Cingulate Island Sign.

The cingulate island sign (CIS) refers to the relative sparing of metabolism in the posterior cingulate cortex (PCC) and represents an important biomarker in distinguishing dementia with Lewy bodies (DLB) from Alzheimer disease (AD). The underlying basis of the CIS is unknown; therefore, our aim was to investigate which neurodegenerative changes underpin the formation of CIS. Using quantitative neuropathology, α-synuclein, phosphorylated Tau, and amyloid-β pathology was assessed in 12 DLB, 9 AD and 6 age-matched control patients in the anterior cingulate (ACC), midcingulate, PCC, precuneus/cuneus and parahippocampal gyrus.

Consecutive sessions of transcranial direct current stimulation do not remediate visual hallucinations in Lewy body dementia: a randomised controlled trial.

Background: Complex visual hallucinations are common in Lewy body dementia (LBD) and can cause significant patient and caregiver distress. Current treatments are primarily pharmacological in nature and have limited efficacy and associated side effects. The objective of this study was to assess the effects of consecutive sessions of transcranial direct current stimulation (tDCS) on visual hallucination frequency and severity in LBD, at short-term and long-term follow-up stages.

A new visual rating scale for Ioflupane imaging in Lewy body disease.

Background: Dopaminergic loss on I-Ioflupane brain imaging is a recognised biomarker for dementia with Lewy bodies. It is usually assessed using a visual rating scale developed for Parkinson's disease, which may not be optimal for dementia with Lewy bodies, as patterns of dopaminergic loss can be different.

Objectives: We aimed to develop a new visual rating scale for I-Ioflupane brain images in Lewy body disease that encompasses appearances seen in dementia with Lewy bodies, and validate this against autopsy diagnosis.

Diagnostic accuracy of dopaminergic imaging in prodromal dementia with Lewy bodies.

Background: Dopaminergic imaging has high diagnostic accuracy for dementia with Lewy bodies (DLB) at the dementia stage. We report the first investigation of dopaminergic imaging at the prodromal stage.

Methods: We recruited 75 patients over 60 with mild cognitive impairment (MCI), 33 with probable MCI with Lewy body disease (MCI-LB), 15 with possible MCI-LB and 27 with MCI with Alzheimer's disease.

Neuropsychiatric symptoms and cognitive profile in mild cognitive impairment with Lewy bodies.

Background: The accurate clinical characterisation of mild cognitive impairment (MCI) is becoming increasingly important. The aim of this study was to compare the neuropsychiatric symptoms and cognitive profile of MCI with Lewy bodies (MCI-LB) with Alzheimer's disease MCI (MCI-AD).

Methods: Participants were ⩾60 years old with MCI.

Does attentional dysfunction and thalamic atrophy predict decline in dementia with Lewy bodies?

Introduction: To evaluate the clinical characteristics of DLB subjects who died within 1 year of assessment compared to those who survived and investigate their patterns of in vivo regional thalamic atrophy using structural MRI.

Methods: Seventy subjects (35 DLB, 35 aged controls) underwent 3 T T1-weighted MR scanning as well as clinical and cognitive assessments, including a computerised assessment of attention. All subjects were contacted after 12 months for reassessment.

Parietal white matter lesions in Alzheimer's disease are associated with cortical neurodegenerative pathology, but not with small vessel disease.

Cerebral white matter lesions (WML) encompass axonal loss and demyelination, and the pathogenesis is assumed to be small vessel disease (SVD)-related ischemia. However, WML may also result from the activation of Wallerian degeneration as a consequence of cortical Alzheimer's disease (AD) pathology, i.e.

The influence of hippocampal atrophy on the cognitive phenotype of dementia with Lewy bodies.

Objective: The level of hippocampal atrophy in dementia with Lewy bodies (DLB) is typically less than that observed in Alzheimer's disease (AD). However, it is not known how the cognitive phenotype of DLB is influenced by hippocampal atrophy or the atrophy of adjacent medial temporal lobe structures.

Methods: Dementia with Lewy bodies (n = 65), AD (n = 76) and control (n = 63) participants underwent 3T magnetic resonance imaging and cognitive Cambridge Cognitive Examination and Mini-Mental State Examination (CAMCOG and MMSE) assessments.

Autopsy validation of 123I-FP-CIT dopaminergic neuroimaging for the diagnosis of DLB.

Objective: To conduct a validation study of I-N-fluoropropyl-2b-carbomethoxy-3b-(4-iodophenyl) nortropane (I-FP-CIT) SPECT dopaminergic imaging in the clinical diagnosis of dementia with Lewy bodies (DLB) with autopsy as the gold standard.

Methods: Patients >60 years of age with dementia who had undergone I-FP-CIT imaging in research studies and who had donated their brain tissue to the Newcastle Brain Tissue Resource were included. All had structured clinical research assessments, and clinical diagnoses were applied by consensus panels using international diagnostic criteria.

A spatial covariance I-5IA-85380 SPECT study of α4β2 nicotinic receptors in Alzheimer's disease.

Alzheimer's disease (AD) is characterized by widespread degeneration of cholinergic neurons, particularly in the basal forebrain. However, the pattern of these deficits and relationship with known brain networks is unknown. In this study, we sought to clarify this and used I-5-iodo-3-[2(S)-2-azetidinylmethoxy] pyridine (5IA-85380) single photon emission computed tomography to investigate spatial covariance of α4β2 nicotinic acetylcholine receptors in AD and healthy controls.