Publications by authors named "Ajenthan Surendranathan"

Dementia with Lewy bodies (DLB) is the second most common neurodegenerative cause of dementia, behind Alzheimer's disease (AD). The profile of inflammation in AD has been extensively researched in recent years, with evidence that chronic peripheral inflammation in midlife increases the risk of late-onset AD, and data supporting inflammation being associated with disease progression. In contrast, our understanding of the role of inflammation in DLB is less developed.

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While [F]-AV-1451 was developed as a PET radiotracer with high affinity for hyperphosphorylated tau, it has been proposed that loss of 'off-target' [F]-AV-1451 binding to neuromelanin in the substantia nigra could be a surrogate marker of Lewy body diseases. [F]-AV-1451 binding was measured in the substantia nigra of patients with Parkinson's disease ( = 35), dementia with Lewy bodies ( = 10) and separate control groups ( = 37; = 14). Associations with motor symptoms, cognition and disease duration were evaluated using linear regression models.

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Objective: This study aimed to quantify the trajectory and magnitude of change of the key clinical features and corresponding symptom domains of dementia with Lewy bodies (DLB) and Parkinson disease dementia (PDD), including global cognition, parkinsonism, recurrent visual hallucinations, cognitive fluctuations, and sleep disturbance.

Methods: One hundred sixteen patients with Lewy body dementia (DLB = 72, PDD = 44) underwent assessment at baseline and 3 and 6 months as part of a prospective multicenter randomized controlled trial. Linear mixed models were constructed for core outcome measures using the Mini-Mental State Examination (MMSE), motor section of the Unified Parkinson's Disease Rating Scale (UPDRS-III), Dementia Cognitive Fluctuations Scale (DCFS), and Neuropsychiatric Inventory (NPI).

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Alzheimer's disease (AD) pathology is frequently observed as a comorbidity in people with dementia with Lewy bodies (DLB). Here, we evaluated the in vivo distribution of tau burden and its influence on the clinical phenotype of DLB. Tau deposition was quantified using [F]-AV1451 positron emission tomography in people with DLB (n = 10), AD (n = 27), and healthy controls (n = 14).

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The impairment of large-scale brain networks has been observed in dementia with Lewy bodies (DLB) using functional connectivity, but the potential for an analogous effect on structural covariance patterns has not been determined. Twenty-four probable DLB subjects (mean age 74.3 ± 6.

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Objectives: Dementia with Lewy bodies (DLB) is a major cause of degenerative dementia, yet the diagnosis is often missed or mistaken for Alzheimer's disease (AD). We assessed whether the revised Addenbrooke's Cognitive Examination (ACE-R), a brief test for dementia, differentiates DLB from AD.

Methods: We first compared baseline ACE-R performance in 76 individuals with DLB, 40 individuals with AD and 66 healthy controls.

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Background: Lewy body dementia, comprising both dementia with Lewy bodies and Parkinson's disease dementia, is challenging to manage because of a complex symptom profile and lack of clear evidence-based management guidelines.

Objectives: We assessed the feasibility of undertaking a cluster randomized study of the introduction of an evidence-based management toolkit for Lewy body dementia, assessing the outcomes for patients and carers as secondary measures.

Methods: We randomized 23 memory/dementia, movement disorder, or nonspecialist secondary care services to the management toolkit or usual care.

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Background: Lewy body dementia, consisting of both dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD), is considerably under-recognised clinically compared with its frequency in autopsy series.

Aims: This study investigated the clinical diagnostic pathways of patients with Lewy body dementia to assess if difficulties in diagnosis may be contributing to these differences.

Method: We reviewed the medical notes of 74 people with DLB and 72 with non-DLB dementia matched for age, gender and cognitive performance, together with 38 people with PDD and 35 with Parkinson's disease, matched for age and gender, from two geographically distinct UK regions.

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Dementia with Lewy bodies (DLB) is characterized by alpha-synuclein protein deposition with variable degree of concurrent Alzheimer's pathology. Neuroinflammation is also increasingly recognized as a significant contributor to degeneration. We aimed to examine the relationship between microglial activation as measured with [C]-PK11195 brain PET, MR diffusion tensor imaging (DTI) and grey matter atrophy in DLB.

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There is evidence of increased microglial activation in Parkinson's disease (PD) as shown by in vivo PET ligand such as C-PK11195. In addition, diffusion tensor imaging (DTI) imaging reveals widespread changes in PD, especially when the associated dementia develops. In the present case series, we studied five subjects with Parkinson's disease dementia (PDD).

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Introduction: The deposition of neurofibrillary tangles in neurodegenerative disorders is associated with neuronal loss on autopsy; however, their in vivo associations with atrophy across the continuum of Alzheimer's disease (AD) remain unclear.

Methods: We estimated cortical thickness, tau ([F]-AV-1451), and amyloid β (Aβ) status ([C]-PiB) in 47 subjects who were stratified into Aβ- (14 healthy controls and six mild cognitive impairment-Aβ-) and Aβ+ (14 mild cognitive impairment-Aβ+ and 13 AD) groups.

Results: Compared with the Aβ- group, tau was increased in widespread regions whereas cortical thinning was restricted to the temporal cortices.

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Inflammation is increasingly recognized as part of the pathology of neurodegenerative conditions such as Alzheimer's disease and Parkinson's disease, but its role in dementia with Lewy bodies remains unclear. Using multimodal imaging and peripheral cytokine analysis, we therefore investigated central and peripheral inflammation in this common form of dementia. Nineteen participants with probable dementia with Lewy bodies and 16 similarly aged controls underwent 3 T MRI and PET imaging with 11C-PK11195, a marker of microglial activation in vivo.

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Objective: We tested whether in vivo neuroinflammation relates to the distinctive distributions of pathology in Alzheimer disease (AD) and progressive supranuclear palsy (PSP).

Methods: Sixteen patients with symptomatic AD (including amnestic mild cognitive impairment with amyloid-positive PET scan), 16 patients with PSP-Richardson syndrome, and 13 age-, sex-, and education-matched healthy controls were included in this case-control study. Participants underwent [C]PK11195 PET scanning, which was used as an in vivo index of neuroinflammation.

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Dementia with Lewy bodies (DLB) is a common neurodegenerative dementia in older people; however, the clinical features, particularly cognitive fluctuations and rapid eye movement sleep disorder, are often hard to elicit, leading to difficulty in making the diagnosis clinically. Here we examine the literature for the evidence behind imaging modalities that could assist in making the diagnosis. Dopamine transporter (DAT) imaging remains the best modality for differentiation from dementia of Alzheimer's type with high sensitivity and specificity reported based on pathological diagnoses.

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Background: The prevalence of dementia with Lewy bodies (DLB) and dementia in Parkinson's disease (PDD) in routine clinical practice is unclear. Prevalence rates observed in clinical and population-based cohorts and neuropathological studies vary greatly. Small sample sizes and methodological factors in these studies limit generalisability to clinical practice.

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The ability to assess the distribution and extent of tau pathology in Alzheimer's disease and progressive supranuclear palsy in vivo would help to develop biomarkers for these tauopathies and clinical trials of disease-modifying therapies. New radioligands for positron emission tomography have generated considerable interest, and controversy, in their potential as tau biomarkers. We assessed the radiotracer 18F-AV-1451 with positron emission tomography imaging to compare the distribution and intensity of tau pathology in 15 patients with Alzheimer's pathology (including amyloid-positive mild cognitive impairment), 19 patients with progressive supranuclear palsy, and 13 age- and sex-matched controls.

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Background: Volumetric atrophy and microstructural alterations in diffusion tensor imaging (DTI) measures of the hippocampus have been reported in people with Alzheimer's disease (AD) and mild cognitive impairment (MCI). However, no study to date has jointly investigated concomitant microstructural and volumetric changes of the hippocampus in dementia with Lewy bodies (DLB).

Methods: A total of 84 subjects (23 MCI, 17 DLB, 14 AD, and 30 healthy controls) were recruited for a multi-modal imaging (3T MRI and DTI) study that included neuropsychological evaluation.

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Introduction: Inflammation of the central nervous system is increasingly regarded as having a role in cognitive disorders such as dementia and depression, but it is not clear how such inflammation relates to other aspects of neuropathology, structural and functional changes in the brain and symptoms (as assessed via clinical and neuropsychological assessment and MRI). This study will explore these pathophysiological mechanisms using positron emission tomography (PET) which allows in vivo imaging of inflammation, amyloid and τ deposition, together with neuropsychological profiling, MRI and peripheral biomarker analysis.

Methods And Analysis: Using PET imaging of the ligand [C]PK11195, we will test for increased neuroinflammation in vivo in patients with Alzheimer's disease, Lewy body dementia, frontotemporal dementia, progressive supranuclear palsy, late-onset depression and mild cognitive impairment, when compared to healthy controls.

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Neuroinflammation is increasingly recognized as a key factor in the pathogenesis of neurodegenerative conditions. However, it remains unclear whether it has a protective or damaging role. Studies of Alzheimer's disease and Parkinson's disease have provided much of the evidence for inflammatory pathology in neurodegeneration.

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