Imperial College London

ProfessorDavidBrooks

Faculty of MedicineDepartment of Brain Sciences

Visiting Professor
 
 
 
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Contact

 

david.brooks

 
 
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Assistant

 

Ms Hyacinth Henry +44 (0)20 3313 3172

 
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Location

 

U106Block B Hammersmith HospitalHammersmith Campus

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Summary

 

Publications

Publication Type
Year
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834 results found

Venkataraman A, Mansur A, Lewis Y, Kocagoncu E, Lingford-Hughes A, Huiban M, Passchier J, Rowe J, Tsukada H, Brooks D, Gunn R, Matthews P, Rabiner E, MINDMAPS Consortiumet al., Evaluation of mitochondrial and synaptic function in Alzheimer’s disease (AD): a [18F]BCPP-EF, [11C]SA4503 and [11C]UCB-J PET study, Journal of Cerebral Blood Flow and Metabolism, Vol: 39, Pages: 121-122, ISSN: 1559-7016

ObjectivesMitochondrial deficits leading to synaptic dysfunction have been hypothesised in the pathophysiology of neurodegenerative disease, with Aβ/tau impairing mitochondrial function in AD. To date a combined evaluation of human mitochondrial and synaptic function has not been performed directly in vivo. We describe the pilot results of MINDMAPS-AD, a study within the MINDMAPS1 programme aiming to evaluate mitochondrial and synaptic function in the brain of patients with MCI/AD. MINDMAPS-AD uses the novel radioligands [18F]BCPP-EF, [11C]SA4503 and [11C]UCB-J, to compare the regional density of mitochondrial complex I (MC1), the sigma 1 receptor (s1R) and synaptic vesicular protein 2A (SV2A) respectively.MethodsSix participants with a range of AD related pathologies, EMCI (n = 2), LMCI (n = 2), and AD (n = 2), were enrolled into the study. Participants fulfilled NIA-AA criteria and were amyloid-beta +ve confirmed by [18F]Florbetaben PET. All participants underwent three PET scans with [18F]BCPP-EF, [11C]SA4503 and [11C]UCB-J. Arterial blood samples were collected and a metabolite corrected arterial plasma input function was estimated to derive regional volumes of distribution (VT). These data were compared to six age/sex matched cognitively normal (CN) healthy subjects recruited for ongoing studies within the MINDMAPS programme. Regions of interest (ROIs) were defined on individual subject MR images using an anatomical atlas and included: frontal cortex, hippocampus, amygdala, anterior cingulate, posterior cingulate, thalamus, temporal cortex, parietal cortex, caudate, putamen, and occipital lobe. Regional target density was evaluated using the VT, as well as VT corrected for the plasma free fraction of the radioligand (fP; VT/fp), and the regional VT ratio versus the VT in the centrum semiovale, a white matter region expected to have low levels of the targets evaluated (DVR). Comparison of regional target density and

Journal article

Venkataraman AV, Mansur A, Huiban M, Passchier J, Rowe JB, Tsukada H, Brooks D, Gunn RN, Matthews PM, Rabiner EAet al., 2019, Evaluation of mitochondrial and synaptic function in Alzheimer's disease (AD): a [F-18]BCPP-EF, [C-11]SA4503 and [C-11]UCB-J PET study, 29th International Symposium on Cerebral Blood Flow, Metabolism and Function / 14th International Conference on Quantification of Brain Function with PET (BRAIN and BRAIN Pet), Publisher: SAGE PUBLICATIONS INC, Pages: 121-122, ISSN: 0271-678X

Conference paper

Durcan R, Wiblin L, Lawson RA, Khoo TK, Yarnall AJ, Duncan GW, Brooks DJ, Pavese N, Burn DJet al., 2019, Prevalence and duration of non-motor symptoms in prodromal Parkinson's disease, EUROPEAN JOURNAL OF NEUROLOGY, Vol: 26, Pages: 979-985, ISSN: 1351-5101

Journal article

Nielsen RB, Parbo P, Ismail R, Dalby R, Tietze A, Braendgaard H, Gottrup H, Brooks DJ, Ostergaard L, Eskildsen SFet al., 2019, Impaired perfusion and capillary distribution of blood in mild cognitive impairment: Relation to oxygenation and amyloid load, 29th International Symposium on Cerebral Blood Flow, Metabolism and Function / 14th International Conference on Quantification of Brain Function with PET (BRAIN and BRAIN Pet), Publisher: SAGE PUBLICATIONS INC, Pages: 147-147, ISSN: 0271-678X

Conference paper

Paquini J, Durcan R, Wiblin L, Stokholm MG, Rochester L, Brooks DJ, Burn D, Pavese N, Pavese Net al., 2019, Clinical implications of early caudate dysfunction in Parkinson's disease, Journal of Neurology, Neurosurgery and Psychiatry, ISSN: 1468-330X

Objective Although not typical of Parkinson’s disease (PD), caudate dopaminergic dysfunction can occur in early stages of the disease. However, its frequency and longitudinal implications in large cohorts of recently diagnosed patients remain to be established. We investigated the occurrence of caudate dopaminergic dysfunction in the very early phases of PD (<2 years from diagnosis) using 123I-FP-CIT single photon emission CT and determined whether it was associated with the presence or subsequent development of cognitive impairment, depression, sleep and gait problems.Methods Patients with PD and healthy controls were identified from the Parkinson’s Progression Markers Initiative (PPMI) database. We defined a clinically significant caudate dysfunction as 123I-FP-CIT binding <–2 SDs compared with the controls’ mean and categorised three groups accordingly (no reduction, unilateral reduction, bilateral reduction). All statistical analyses were adjusted for mean putamen binding.Results At baseline, 51.6% of 397 patients had normal caudate dopamine transporter binding, 26.0% had unilateral caudate involvement, 22.4% had bilaterally impaired caudate.Compared with those with a baseline normal caudate function, at the4-year follow-up patients with a baseline bilateral caudate involvement showed a higher frequency of cognitive impairment (p<0.001) and depression (p<0.001), and worse cognitive (p<0.001), depression (<0.05) and gait (<0.001) ratings. Significant caudate involvement was observed in 83.9% of the population after 4 years (unilateral 22.5%, bilateral 61.4%).Conclusions Early significant caudate dopaminergic denervation was found in half of the cases in the PPMI series. Baseline bilateral caudate involvement was associated with increased risk of developing cognitive impairment, depression and gait problems over the next 4 years.

Journal article

Ismail R, Parbo P, Hansen KV, Schaldemose JL, Dalby RB, Tietze A, Kjeldsen PL, la Cour SH, Qvist P, Gottrup H, Eskildsen SF, Brooks DJet al., 2019, Abnormal amyloid load in mild cognitive impairment: the effect of reducing the PiB-PET threshold, Journal of Neuroimaging, ISSN: 1051-2284

BACKGROUND AND PURPOSE: In vivo detection of β-amyloid (Aβ) plaques in Alzheimer's disease (AD) is now possible with 11 C-PiB positron emission tomography (PET). Conventionally, a cortical:cerebellar PiB uptake ratio threshold of 1.4-1.5 has been used to categorize at-risk subjects as "amyloid-positive" and "amyloid-negative." It has been suggested that this threshold is too conservative and may miss early amyloid pathology. We investigated the relationship between conventional and lower baseline 11 C-PiB PET thresholds for raised amyloid load and the subsequent clinical and radiological progression of mild cognitive impairment (MCI) cases longitudinally. METHODS: We serially determined the cortical amyloid load with 11 C-PiB PET of 44 MCI subjects over 2 years and compared findings with those for 12 healthy controls (HC) and 5 AD cases. RESULTS: Twenty-four subjects were classified as normal at baseline with mean cortical PiB standard uptake value ratios (SUVR) between 1.2 and 1.5. Their cognitive status remained stable over time. Three of these cases increased their amyloid load above a threshold of 1.5 over 2 years. Twenty-seven "raised amyloid" MCI cases with baseline cortical SUVRs above 1.5, showed deteriorating cognition. Note that 50% of these cases converted clinically to AD during the follow-up period. CONCLUSION: Use of a PiB SUVR threshold of >1.5 for raised amyloid missed 14.3% of MCI cases who likely had Thal stage 1 or 2 pathology and showed a progressive amyloid increase over 2 years. Lowering the threshold for abnormality to 1.3 abolished all false negatives but resulted in 75% of HCs being falsely diagnosed as raised amyloid subjects.

Journal article

Pasquini J, Ceravolo R, Brooks DJ, Bonuccelli U, Pavese Net al., 2019, Progressive loss of raphe nuclei serotonin transporter in early Parkinson's disease: A longitudinal 123I-FP-CIT SPECT study., Parkinsonism Relat Disord

BACKGROUND: Serotonergic raphe nuclei dysfunction has been documented in Parkinson's disease, both in pathological and neuroimaging studies, and has been associated with scores of tremor and non-motor symptoms. However, no in vivo longitudinal investigations have been conducted to assess the rate of decline of raphe serotonin transporter availability in the early stages of the disease. OBJECTIVE: To measure the rate of decline of raphe serotonin transporter availability over a two-year interval in patients with recently diagnosed disease and its association with non-motor symptoms over time. METHODS: Baseline and two-year follow-up 123ioflupane-fluoropropyl-carbomethoxy-3-beta-4-iodo-phenyltropane (123I-FP-CIT) SPECT scans of 173 early Parkinson's disease patients enrolled in the Parkinson's Progressive Markers Initiative were analysed and non-motor symptoms scores recorded. RESULTS: A 16.6 ± 20.9% (mean ± SD) reduction in raphe serotonin transporter availability was found from baseline to two-year follow-up in the entire cohort. No differences in progression were found between tremor dominant and postural instability/gait difficulty phenotypes. At follow-up 34.1% of patients showed a moderate-to-severe reduction of raphe serotonin transporter availability with respect to the controls' mean. We did not find any significant correlation between raphe serotonin transporter availability and scores of depression, excessive daytime sleepiness and REM sleep behaviour disorder. CONCLUSION: 123I-FP-CIT SPECT was able to measure longitudinal reductions in raphe serotonin transporter availability in the early phases of Parkinson's disease. About four years after diagnosis, raphe serotonin transporter availability was significantly reduced in more than one third of the population, but does not appear to be correlated to non-motor symptoms at this stage.

Journal article

Femminella GD, Frangou E, Love SB, Busza G, Holmes C, Ritchie C, Lawrence R, McFarlane B, Tadros G, Ridha BH, Bannister C, Walker Z, Archer H, Coulthard E, Underwood BR, Prasanna A, Koranteng P, Karim S, Junaid K, McGuinness B, Nilforooshan R, Macharouthu A, Donaldson A, Thacker S, Russell G, Malik N, Mate V, Knight L, Kshemendran S, Harrison J, Brooks DJ, Passmore AP, Ballard C, Edison Pet al., 2019, Evaluating the effects of the novel GLP-1 analogue liraglutide in Alzheimer's disease: study protocol for a randomised controlled trial (ELAD study), Trials, Vol: 20, ISSN: 1745-6215

BACKGROUND: Liraglutide is a glucagon-like peptide-1 (GLP-1) analogue currently approved for type 2 diabetes and obesity. Preclinical evidence in transgenic models of Alzheimer's disease suggests that liraglutide exerts neuroprotective effects by reducing amyloid oligomers, normalising synaptic plasticity and cerebral glucose uptake, and increasing the proliferation of neuronal progenitor cells. The primary objective of the study is to evaluate the change in cerebral glucose metabolic rate after 12 months of treatment with liraglutide in participants with Alzheimer's disease compared to those who are receiving placebo. METHODS/DESIGN: ELAD is a 12-month, multi-centre, randomised, double-blind, placebo-controlled, phase IIb trial of liraglutide in participants with mild Alzheimer's dementia. A total of 206 participants will be randomised to receive either liraglutide or placebo as a daily injection for a year. The primary outcome will be the change in cerebral glucose metabolic rate in the cortical regions (hippocampus, medial temporal lobe, and posterior cingulate) from baseline to follow-up in the treatment group compared with the placebo group. The key secondary outcomes are the change from baseline to 12 months in z scores for clinical and cognitive measures (Alzheimer's Disease Assessment Scale-Cognitive Subscale and Executive domain scores of the Neuropsychological Test Battery, Clinical Dementia Rating Sum of Boxes, and Alzheimer's Disease Cooperative Study-Activities of Daily Living) and the incidence and severity of treatment-emergent adverse events or clinically important changes in safety assessments. Other secondary outcomes are 12-month change in magnetic resonance imaging volume, diffusion tensor imaging parameters, reduction in microglial activation in a subgroup of participants, reduction in tau formation and change in amyloid levels in a subgroup of participants measured by tau and amyloid imaging, and changes in composite scores u

Journal article

Kübler D, Wächter T, Cabanel N, Su Z, Turkheimer FE, Dodel R, Brooks DJ, Oertel WH, Gerhard Aet al., 2019, Widespread microglial activation in multiple system atrophy, Movement Disorders, Vol: 34, Pages: 564-568, ISSN: 0885-3185

BackgroundThe pattern and role of microglial activation in multiple system atrophy is largely unclear. The objective of this study was to use [11C](R)‐PK11195 PET to determine the extent and correlation of activated microglia with clinical parameters in MSA patients.MethodsFourteen patients with the parkinsonian phenotype of MSA (MSA‐P) with a mean disease duration of 2.9 years (range 2‐5 years) were examined with [11C](R)‐PK11195 PET and compared with 10 healthy controls.ResultsPatients with the parkinsonian phenotype of MSA showed a significant (P ≤ 0.01) mean increase in binding potentials compared with healthy controls in the caudate nucleus, putamen, pallidum, precentral gyrus, orbitofrontal cortex, presubgenual anterior cingulate cortex, and the superior parietal gyrus. No correlations between binding potentials and clinical parameters were found.ConclusionsIn early clinical stages of the parkinsonian phenotype of MSA, there is widespread microglial activation as a marker of neuroinflammatory changes without correlation to clinical parameters in our patient population. © 2019 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

Journal article

Schubert JJ, Veronese M, Marchitelli L, Bodini B, Tonietto M, Stankoff B, Brooks DJ, Bertoldo A, Edison P, Turkheimer Fet al., 2019, Dynamic 11C-PiB PET shows cerebrospinal fluid flow alterations in Alzheimer's disease and multiple sclerosis, Journal of Nuclear Medicine, ISSN: 1535-5667

Cerebrospinal fluid (CSF) plays an important role in the clearance of solutes and maintenance of brain homeostasis. 11C-PiB PET was recently proposed as a tool for detection of CSF clearance alterations in Alzheimer's disease. The current study seeks to investigate the magnitude of 11C-PiB PET signal in the lateral ventricles of an independent group of Alzheimer's and mild cognitive impairment subjects. We have also evaluated multiple sclerosis as a model of disease with CSF clearance alterations without amyloid-beta tissue accumulation. Methods: A set of Alzheimer's and mild cognitive impairment subjects and a set of multiple sclerosis subjects with matched healthy controls underwent MRI and dynamic 11C-PiB PET. Manual lateral ventricle regions of interest were generated from MRI data. PET data was analysed using a simplified reference tissue model with cerebellum or a supervised reference region, for the Alzheimer's and multiple sclerosis datasets, respectively. Magnitude of 11C-PiB signal in the lateral ventricles was calculated as area under curve from 35 to 80 minutes and standard uptake value ratio (SUVR) from 50 to 70 minutes. Compartmental modelling analysis was performed on a separate dataset containing Alzheimer's and matched healthy control data with an arterial input function to further understand the kinetics of the lateral ventricular 11C-PiB signal. Results: Analysis of variance revealed significant group differences in lateral ventricular SUVR across the Alzheimer's, mild cognitive impairment, and healthy control groups (P = 0.004). Additional pairwise comparisons revealed significantly lower lateral ventricular SUVR in Alzheimer's compared to healthy controls (p<0.001) and mild cognitive impairment (P = 0.029). Lateral ventricular SUVR was also significantly lower in multiple sclerosis compared to healthy controls (P = 0.008). Compartmental modelling analysis revealed significantly lower uptake rates of 11C-PiB signal from blood (P = 0.005) and b

Journal article

Dafsari HS, Martinez-Martin P, Rizos A, Trost M, dos Santos Ghilardi MG, Reddy P, Sauerbier A, Petry-Schmelzer JN, Kramberger M, Borgemeester RWK, Barbe MT, Ashkan K, Silverdale M, Evans J, Odin P, Fonoff ET, Fink GR, Henriksen T, Ebersbach G, Pirtosek Z, Visser-Vandewalle V, Antonini A, Timmermann L, Chaudhuri KR, Schrag A, Weintraub D, Barone P, Brooks DJ, Brown RG, Jenner P, Jeon B, Lyons K, Pavese N, Politis M, Postuma RB, Schapira A, Stocchi F, Tsuboi Yet al., 2019, EuroInf 2: Subthalamic stimulation, apomorphine, and levodopa infusion in Parkinson's disease, MOVEMENT DISORDERS, Vol: 34, Pages: 353-365, ISSN: 0885-3185

Journal article

Moller A, Thomsen KR, Brooks DJ, Mouridsen K, Blicher JU, Hansen K, Lou HCet al., 2019, Attenuation of dopamine-induced GABA release in problem gamblers, BRAIN AND BEHAVIOR, Vol: 9, ISSN: 2162-3279

Journal article

Femminella G, Dani M, Wood M, Fan Z, Calsolaro V, Atkinson R, Edginton T, Hinz R, Brooks D, Edison Pet al., 2019, Microglial activation in early Alzheimer trajectory is associated with higher grey matter volume, Neurology, Vol: 92, Pages: e1331-e1343, ISSN: 1526-632X

Objective: To investigate the influence of microglial activation in the early stages of Alzheimer’s disease trajectory, we assessed the relationship between microglial activation and grey matter volume and hippocampal volume in MCI patients.Methods: In this study, fifty-five participants (37 early stages MCI and 18 controls) underwent [11C]PBR28 PET, a marker of microglial activation; volumetric MRI to evaluate grey matter and hippocampal volumes as well as clinical and neuropsychometric evaluation. [11C]PBR28 VT(volume of distribution) was calculated using arterial input function and Logan Graphical analysis. Grey matter volume and hippocampal volumes were calculated from MRI for each subject. Statistical parametric mapping software was used to perform voxel-wise correlations and biological parametric mapping analysis. Amyloid status was assessed using [18F]Flutemetamol PET.Results: Higher [11C]PBR28 VT in different cortical areas correlated with higher grey matter volume in both amyloid positive and negative MCI. Additionally, higher hippocampal volume correlated with higher cortical [11C]PBR28 Logan VT.Conclusions: In this in vivo study, we have demonstrated that microglial activation quantified using [11C]PBR28 PET was associated with higher grey matter volume and higher hippocampal volume in MCI patients. This may suggest that microglial activation may not always be associatedwith neuronal damage, and indeed it may have beneficial effect in early stages of Alzheimer’s trajectory. While further longitudinal studies are necessary, these findings have significant implications on therapeutic strategies targeting microglial activation.

Journal article

Sridharan S, Raffel J, Nandoskar A, Record C, Brooks DJ, Owen D, Sharp D, Muraro PA, Gunn R, Nicholas Ret al., Confirmation of specific binding of the 18 kDa translocator protein (TSPO) radioligand [18F]GE-180: a blocking study using XBD173 in multiple sclerosis normal appearing white and grey matter, Molecular Imaging and Biology, ISSN: 1536-1632

Purpose: Positron emission tomography (PET) ligands exhibit different levels of non-displaceable binding in vivo. In the case of ligands for the 18 kDa translocator protein (TSPO), the component of non-displaceable binding for the most widely used radiotracer, [11C]-(R)-PK11195, is relatively high compared to that for newer TSPO ligands. Non-displaceable binding is not often quantified in humans in vivo, partially due to a lack of available ligands that are known to be safe with which to displace binding to the target receptor. Recently, however, a technique has been developed to quantify the non-displaceable binding of TSPO tracers in vivo, by blocking the receptor with the TSPO ligand XBD173 and comparing the total volume of distribution ( ) pre and post-blockade. Here, we used an occupancy plot to quantify the non-displaceable binding ( ) of the TSPO PET tracers [18F]GE-180 and [11C]PBR28 in cohorts of people with multiple sclerosis (MS). We also compared plots of subjects carrying both high and mixed binding affinity polymorphisms of TSPO to estimate while potentially avoiding the need for receptor blockade.Procedures: Twelve people with multiple sclerosis (MS) and high (HAB) or mixed (MAB) affinity binding for TSPO underwent baseline MRI and 90-minute dynamic [18F]GE-180 PET (n=6; 3 HAB and 3 MAB) or [11C]PBR28 PET (n=6; 3 HAB, 3 MAB). Either one week later ([18F]GE-180) or the same afternoon ([11C]PBR28), participants had repeat PET following a 90mg dose of XBD173. PET images were co-registered with T1 MR volumetric images and regions of interest (ROIs) were defined using the 83-region Hammers atlas. Arterial blood sampling was used to generate plasma input functions for the two-tissue compartment model to quantify . The non-displaceable fraction of the total volume of distribution ( ) was calculated using two independent methods: the occupancy plot (by modelling the differences in signal post XBD173), and the polymorphism plot (by modelling the differences in

Journal article

Dani M, Wood M, Mizoguchi R, Fan Z, Edginton T, Hinz R, Win Z, Brooks DJ, Edison Pet al., 2019, Tau Aggregation Correlates with Amyloid Deposition in Both Mild Cognitive Impairment and Alzheimer's Disease Subjects, JOURNAL OF ALZHEIMERS DISEASE, Vol: 70, Pages: 453-463, ISSN: 1387-2877

Journal article

McGinnity CJ, Arstad E, Beck K, Brooks DJ, Coles JP, Duncan JS, Galovic M, Hinz R, Hirani E, Howes OD, Jones PA, Koepp MJ, Luo F, Barros DAR, Singh N, Trigg W, Hammers Aet al., 2019, Comment on "In Vivo [F-18]GE-179 Brain Signal Does Not Show NMDA-Specific Modulation with Drug Challenges in Rodents and Nonhuman Primates", ACS CHEMICAL NEUROSCIENCE, Vol: 10, Pages: 768-772, ISSN: 1948-7193

Journal article

Lillethorup TP, Glud AN, Landeck N, Alstrup AKO, Jakobsen S, Vang K, Doudet DJ, Brooks DJ, Kirik D, Hinz R, Sorensen JC, Landau AMet al., 2018, In vivo quantification of glial activation in minipigs overexpressing human alpha-synuclein, SYNAPSE, Vol: 72, ISSN: 0887-4476

Journal article

Sridharan S, Raffel J, Nandoskar A, Record C, Brooks D, Owen D, Sharp D, Muraro P, Gunn R, Nicholas Ret al., 2018, Confirmation of specific binding of the 18 kDa translocator protein (TSPO) radioligand [F-18]GE-180: a blocking study using XDB173 in multiple sclerosis, 34th Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (ECTRIMS), Publisher: SAGE PUBLICATIONS LTD, Pages: 421-422, ISSN: 1352-4585

Conference paper

Parbo P, Ismail R, Sommerauer M, Stokholm MG, Hansen AK, Hansen KV, Amidi A, Schaldemose JL, Gottrup H, Braendgaard H, Eskildsen SF, Borghammer P, Hinz R, Aanerud J, Brooks DJet al., 2018, Does inflammation precede tau aggregation in early Alzheimer's disease? A PET study, NEUROBIOLOGY OF DISEASE, Vol: 117, Pages: 211-216, ISSN: 0969-9961

Journal article

Edison P, Dani M, wood M, Ruth M, Fan Z, Walker Z, Morgan R, Hinz R, Biju M, Kuruvilla T, Brooks D, Edison Pet al., Microglial activation correlates in vivo with both tau and amyloid in Alzheimer’s disease, Brain, ISSN: 1460-2156

Journal article

Femminella G, Fan Z, Frangou E, Love S, Calsolaro V, Holmes C, Ritchie C, Lawrence R, McFarlane B, Tadros G, Ridha B, Bannister C, Walker Z, Archer H, Coulthard E, Underwood B, Prasanna A, Korentang P, Karim S, Junaid K, McGuinness B, Passmore P, Nilforooshan R, Macharouthu A, Donaldson A, Thacker S, Russell G, Malik N, Mate V, Knight L, Kshemendran S, Harrison J, Ballard C, Brooks D, Edison Pet al., 2018, Peripheral insulin resistance does not correlate with cerebral glucose metabolic rate in non-diabetic Alzheimer’s patients, Alzheimer's and Dementia, Vol: 14, Pages: P1157-P1158, ISSN: 1552-5260

Journal article

Calsolaro V, Fan Z, Veronese M, Femminella G, Pasqualetti G, Trigg W, Buckley C, Turkheimer F, Gentleman S, Hinz R, Brooks D, Edison Pet al., 2018, Novel third generation microglial marker flutriciclamide ([18F]GE180) in Alzheimer’s disease and mild cognitive impairment, Alzheimer's and Dementia, Vol: 14, Pages: P506-P506, ISSN: 1552-5260

Journal article

Minett T, Su L, Mak E, Williams G, Firbank M, Lawson RA, Yarnall AJ, Duncan GW, Owen AM, Khoo TK, Brooks DJ, Rowe JB, Barker RA, Burn D, O'Brien JTet al., 2018, Longitudinal diffusion tensor imaging changes in early Parkinson's disease: ICICLE-PD study, JOURNAL OF NEUROLOGY, Vol: 265, Pages: 1528-1539, ISSN: 0340-5354

Journal article

Mattsson N, Groot C, Jansen WJ, Landau SM, Villemagne VL, Engelborghs S, Mintun MM, Lleo A, Molinuevo JL, Jagust WJ, Frisoni GB, Ivanoiu A, Chetelat G, de Oliveira CR, Rodrigue KM, Kornhuber J, Wallin A, Klimkowicz-Mrowiec A, Kandimalla R, Popp J, Aalten PP, Aarsland D, Alcolea D, Almdahl IS, Baldeiras I, van Buchem MA, Cavedo E, Chen K, Cohen AD, Foerster S, Fortea J, Frederiksen KS, Freund-Levi Y, Gill KD, Gkatzima O, Grimmer T, Hampel H, Herukka S-K, Johannsen P, van Laere K, de Leon MJ, Maier W, Marcusson J, Meulenbroek O, Mollergard HM, Morris JC, Mroczko B, Nordlund A, Prabhakar S, Peters O, Rami L, Rodriguez-Rodriguez E, Roe CM, Ruther E, Santana I, Schroder J, Seo SW, Soininen H, Spiru L, Stomrud E, Struyfs H, Teunissen CE, Verhey FRJ, Vos SJB, van Doorn LJCVW, Waldemar G, Wallin AK, Wiltfang J, Vandenberghe R, Brooks DJ, Fladby T, Rowe CC, Drzezga A, Verbeek MM, Sarazin M, Wolk DA, Fleisher AS, Klunk WE, Na DL, Sanchez-Juan P, Lee DY, Nordberg A, Tsolaki M, Camus V, Rinne JO, Fagan AM, Zetterberg H, Blennow K, Rabinovici GD, Hansson O, van Berckel BNM, van der Flier WM, Scheltens P, Visser PJ, Ossenkoppele Ret al., 2018, Prevalence of the apolipoprotein E epsilon 4 allele in amyloid beta positive subjects across the spectrum of Alzheimer's disease, ALZHEIMERS & DEMENTIA, Vol: 14, Pages: 913-924, ISSN: 1552-5260

Journal article

Fan Z, Dani M, Femminella GD, Wood M, Calsolaro V, Veronese M, Turkheimer F, Gentleman S, Brooks DJ, Hinz R, Edison Pet al., 2018, Parametric mapping using spectral analysis for11C-PBR28 PET reveals neuroinflammation in mild cognitive impairment subjects, European Journal of Nuclear Medicine and Molecular Imaging, Vol: 45, Pages: 1432-1441, ISSN: 1619-7070

PURPOSE: Neuroinflammation and microglial activation play an important role in amnestic mild cognitive impairment (MCI) and Alzheimer's disease. In this study, we investigated the spatial distribution of neuroinflammation in MCI subjects, using spectral analysis (SA) to generate parametric maps and quantify11C-PBR28 PET, and compared these with compartmental and other kinetic models of quantification. METHODS: Thirteen MCI and nine healthy controls were enrolled in this study. Subjects underwent11C-PBR28 PET scans with arterial cannulation. Spectral analysis with an arterial plasma input function was used to generate11C-PBR28 parametric maps. These maps were then compared with regional11C-PBR28 VT(volume of distribution) using a two-tissue compartment model and Logan graphic analysis. Amyloid load was also assessed with18F-Flutemetamol PET. RESULTS: With SA, three component peaks were identified in addition to blood volume. The11C-PBR28 impulse response function (IRF) at 90 min produced the lowest coefficient of variation. Single-subject analysis using this IRF demonstrated microglial activation in five out of seven amyloid-positive MCI subjects. IRF parametric maps of11C-PBR28 uptake revealed a group-wise significant increase in neuroinflammation in amyloid-positive MCI subjects versus HC in multiple cortical association areas, and particularly in the temporal lobe. Interestingly, compartmental analysis detected group-wise increase in11C-PBR28 binding in the thalamus of amyloid-positive MCI subjects, while Logan parametric maps did not perform well. CONCLUSIONS: This study demonstrates for the first time that spectral analysis can be used to generate parametric maps of11C-PBR28 uptake, and is able to detect microglial activation in amyloid-positive MCI subjects. IRF parametric maps of11C-PBR28 uptake allow voxel-wise single-subject analysis and could be used to evaluate microglial activation in individual subjects.

Journal article

Stokholm MG, Iranzo A, Ostergaard K, Serradell M, Otto M, Svendsen KB, Garrido A, Vilas D, Parbo P, Borghammer P, Santamaria J, Moller A, Gaig C, Brooks DJ, Tolosa E, Pavese Net al., 2018, Extrastriatal monoaminergic dysfunction and enhanced microglial activation in idiopathic rapid eye movement sleep behaviour disorder, NEUROBIOLOGY OF DISEASE, Vol: 115, Pages: 9-16, ISSN: 0969-9961

Journal article

Knudsen K, Fedorova TD, Hansen AK, Sommerauer M, Otto M, Svendsen KB, Nahimi A, Stokholm MG, Pavese N, Beier CP, Brooks DJ, Borghammer Pet al., 2018, In-vivo staging of pathology in REM sleep behaviour disorder: a multimodality imaging case-control study, LANCET NEUROLOGY, Vol: 17, Pages: 618-628, ISSN: 1474-4422

Journal article

Edison P, Brooks D, Edison P, Brooks Det al., 2018, Role of neuroinflammation in Alzheimer’s trajectory and in vivo quantification using PET, Journal of Alzheimers Disease, Vol: 64, Pages: S339-S351, ISSN: 1387-2877

Recent evidence suggests that neuroinflammation and immunity play a significant role in Alzheimer’s disease and other neurodegenerative diseases. It has also been observed that, independent of the presence of aggregated proteins, neuroinflammation could be present in different neurodegenerative diseases. It has also been suggested that neuroinflammation could occur well ahead of amyloid deposition in AD. Recent genetic studies and other preclinical studies specifically point to a role of neuroinflammation and, in this review, we evaluate the evidence of neuroinflammation in the Alzheimer’s disease trajectory and the different imaging modalities by which we could monitor neuroinflammation in vivo in humans.

Journal article

McGinnity CJ, Riaño Barros DA, Trigg W, Brooks DJ, Hinz R, Duncan JS, Koepp MJ, Hammers Aet al., 2018, Simplifying [18F]GE-179 PET: are both arterial blood sampling and 90-min acquisitions essential?, EJNMMI Research, Vol: 8, ISSN: 2191-219X

INTRODUCTION: The NMDA receptor radiotracer [18F]GE-179 has been used with 90-min scans and arterial plasma input functions. We explored whether (1) arterial blood sampling is avoidable and (2) shorter scans are feasible. METHODS: For 20 existing [18F]GE-179 datasets, we generated (1) standardised uptake values (SUVs) over eight intervals; (2) volume of distribution (VT) images using population-based input functions (PBIFs), scaled using one parent plasma sample; and (3) VT images using three shortened datasets, using the original parent plasma input functions (ppIFs). RESULTS: Correlations with the original ppIF-derived 90-min VTs increased for later interval SUVs (maximal ρ = 0.78; 80-90 min). They were strong for PBIF-derived VTs (ρ = 0.90), but between-subject coefficient of variation increased. Correlations were very strong for the 60/70/80-min original ppIF-derived VTs (ρ = 0.97-1.00), which suffered regionally variant negative bias. CONCLUSIONS: Where arterial blood sampling is available, reduction of scan duration to 60 min is feasible, but with negative bias. The performance of SUVs was more consistent across participants than PBIF-derived VTs.

Journal article

Sommerauer M, Hansen AK, Parbo P, Fedorova TD, Knudsen K, Frederiksen Y, Nahimi A, Barbe MT, Brooks DJ, Borghammer Pet al., 2018, Decreased noradrenaline transporter density in the motor cortex of Parkinson's disease patients, Movement Disorders, Vol: 33, Pages: 1006-1010, ISSN: 0885-3185

Reduced noradrenaline levels have been reported to occur in the motor cortices of PD patients postmortem. Imaging techniques have recently become available to specifically study noradrenergic terminal function in vivo using PET. The objective of this study was to evaluate cortical 11 C-MeNER binding in PD patients. Thirty PD patients and 12 healthy control subjects comparable in age, sex, and cognitive performance underwent PET imaging with 11 C-MeNER, a specific ligand of the noradrenaline transporter. Cortical noradrenaline transporter binding was compared at a voxel level using Statistical Parametric Mapping, whereas cortical thickness was assessed using FreeSurfer software with MRI. PD patients showed reduced 11 C-MeNER binding in the primary motor cortex unrelated to cortical thickness; other cortical regions did not differ between groups. In a subgroup analysis, patients with higher Hoehn & Yahr stage exhibited more pronounced 11 C-MeNER binding reductions. Loss of cortical noradrenergic projections to the primary motor cortex occurs in PD associated with disease stage. © 2018 International Parkinson and Movement Disorder Society.

Journal article

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