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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852 results found

Morbelli S, Esposito G, Arbizu J, Barthel H, Boellaard R, Bohnen NI, Brooks DJ, Darcourt J, Dickson JC, Douglas D, Drzezga A, Dubroff J, Ekmekcioglu O, Garibotto V, Herscovitch P, Kuo P, Lammertsma A, Pappata S, Peñuelas I, Seibyl J, Semah F, Tossici-Bolt L, Van de Giessen E, Van Laere K, Varrone A, Wanner M, Zubal G, Law Iet al., 2020, EANM practice guideline/SNMMI procedure standard for dopaminergic imaging in Parkinsonian syndromes 1.0., Eur J Nucl Med Mol Imaging

PURPOSE: This joint practice guideline or procedure standard was developed collaboratively by the European Association of Nuclear Medicine (EANM) and the Society of Nuclear Medicine and Molecular Imaging (SNMMI). The goal of this guideline is to assist nuclear medicine practitioners in recommending, performing, interpreting, and reporting the results of dopaminergic imaging in parkinsonian syndromes. METHODS: Currently nuclear medicine investigations can assess both presynaptic and postsynaptic function of dopaminergic synapses. To date both EANM and SNMMI have published procedural guidelines for dopamine transporter imaging with single photon emission computed tomography (SPECT) (in 2009 and 2011, respectively). An EANM guideline for D2 SPECT imaging is also available (2009). Since the publication of these previous guidelines, new lines of evidence have been made available on semiquantification, harmonization, comparison with normal datasets, and longitudinal analyses of dopamine transporter imaging with SPECT. Similarly, details on acquisition protocols and simplified quantification methods are now available for dopamine transporter imaging with PET, including recently developed fluorinated tracers. Finally, [18F]fluorodopa PET is now used in some centers for the differential diagnosis of parkinsonism, although procedural guidelines aiming to define standard procedures for [18F]fluorodopa imaging in this setting are still lacking. CONCLUSION: All these emerging issues are addressed in the present procedural guidelines for dopaminergic imaging in parkinsonian syndromes.

Journal article

Nicholas R, Brooks D, Owen D, 2020, 18F-GE180, a radioligand for the TSPO protein: not ready for clinical trials in multiple sclerosis, EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING, ISSN: 1619-7070

Journal article

Ismail R, Parbo P, Madsen LS, Hansen AK, Hansen KV, Schaldemose JL, Kjeldsen PL, Stokholm MG, Gottrup H, Eskildsen SF, Brooks DJet al., 2020, The relationships between neuroinflammation, beta-amyloid and tau deposition in Alzheimer's disease: a longitudinal PET study., J Neuroinflammation, Vol: 17

BACKGROUND: The aim of this longitudinal study was to assess with positron emission tomography (PET) the relationship between levels of inflammation and the loads of aggregated β-amyloid and tau at baseline and again after 2 years in prodromal Alzheimer's disease. METHODS: Forty-three subjects with mild cognitive impairment (MCI) had serial 11C-PK11195 PET over 2 years to measure inflammation changes, and 11C-PiB PET to determine β-amyloid fibril load; 22 also had serial 18F-Flortaucipir PET to determine tau tangle load. Cortical surface statistical mapping was used to localise areas showing significant changes in tracer binding over time and to interrogate correlations between tracer binding of the tracers at baseline and after 2 years. RESULTS: Those MCI subjects with high 11C-PiB uptake at baseline (classified as prodromal Alzheimer's disease) had raised inflammation levels which significantly declined across cortical regions over 2 years although their β-amyloid levels continued to rise. Those MCI cases who had low/normal 11C-PiB uptake at baseline but their levels then rose over 2 years were classified as prodromal AD with low Thal phase 1-2 amyloid deposition at baseline. They showed levels of cortical inflammation which correlated with their rising β-amyloid load. Those MCI cases with baseline low 11C-PiB uptake that remained stable were classified as non-AD, and they showed no correlated inflammation levels. Finally, MCI cases which showed both high 11C-PiB and 18F-Flortaucipir uptake at baseline (MCI due to AD) showed a further rise in their tau tangle load over 2 years with a correlated rise in levels of inflammation. CONCLUSIONS: Our baseline and 2-year imaging findings are compatible with a biphasic trajectory of inflammation in Alzheimer's disease: MCI cases with low baseline but subsequently rising β-amyloid load show correlated levels of microglial activation which then later decline when the β-amyloid load approaches AD

Journal article

Stokholm MG, Garrido A, Tolosa E, Serradell M, Iranzo A, Ostergaard K, Borghammer P, Moller A, Parbo P, Staer K, Brooks DJ, Jose Marti M, Pavese Net al., 2020, Imaging dopamine function and microglia in asymptomatic LRRK2 mutation carriers, JOURNAL OF NEUROLOGY, ISSN: 0340-5354

Journal article

Rodda J, Okello A, Edison P, Dannhauser T, Brooks DJ, Walker Zet al., 2010, (11)C-PIB PET in subjective cognitive impairment., Eur Psychiatry.

Journal article

Vibholm AK, Landau AM, Alstrup AKO, Jacobsen J, Vang K, Munk OL, Dietz MJ, Orlowski D, Sørensen JCH, Brooks DJet al., 2020, Activation of NMDA receptor ion channels by deep brain stimulation in the pig visualised with [18F]GE-179 PET., Brain Stimul, Vol: 13, Pages: 1071-1078

BACKGROUND: No PET radioligand has yet demonstrated the capacity to map glutamate N-methyl-d-aspartate receptor ion channel (NMDAR-IC) function. [18F]GE-179 binds to the phencyclidine (PCP) site in open NMDAR-ICs and potentially provides a use-dependent PET biomarker of these ion channels. OBJECTIVE: To show [18F]GE-179 PET can detect increased NMDAR-IC activation during electrical deep brain stimulation (DBS) of pig hippocampus. METHODS: Six minipigs had an electrode implanted into their right hippocampus. They then had a baseline [18F]GE-179 PET scan with DBS turned off followed by a second scan with DBS turned on. Brain [18F]GE-179 uptake at baseline and then during DBS was measured with PET. Cerebral blood flow (CBF) was measured with [15O]H2O PET at baseline and during DBS and parametric CBF images were generated to evaluate DBS induced CBF changes. Functional effects of injecting the PCP blocker MK-801 were also evaluated. Electrode positions were later histologically verified. RESULTS: DBS induced a 47.75% global increase in brain [18F]GE-179 uptake (p = 0.048) compared to baseline. Global CBF was unchanged by hippocampal DBS. [18F]GE-179 PET detected a 5% higher uptake in the implanted compared with the non-implanted temporo-parietal cortex at baseline (p = 0.012) and during stimulation (p = 0.022). Administration of MK-801 before DBS failed to block [18F]GE-179 uptake during stimulation. CONCLUSION: PET detected an increase in global brain [18F]GE-179 uptake during unilateral hippocampal DBS while CBF remained unchanged. These findings support that [18F]GE-179 PET provides a use-dependent marker of abnormal NMDAR-IC activation.

Journal article

Hansen AK, Parbo P, Ismail R, Østergaard K, Brooks DJ, Borghammer Pet al., 2020, Tau tangles in Parkinson's disease: A 2-year follow-up flortaucipir PET study., Journal of Parkinsons Disease, Vol: 10, Pages: 161-171, ISSN: 1877-718X

BACKGROUND: Flortaucipir PET, a marker of tau tangles, has shown lower than expected cortical uptake in Parkinson's disease (PD), than would be predicted from neuropathologic estimates of Alzheimer's disease co-pathology. Instead, the most characteristic finding of flortaucipir imaging in PD is decreased uptake in the substantia nigra, reflecting reduction in its "off-target" binding to neuromelanin. We have previously reported these observations in cross-sectional studies. OBJECTIVE: Here, we present two-year follow-up data of cortical and nigral flortaucipir uptake in PD patients. METHODS: Seventeen PD patients received repeat flortaucipir PET two years after baseline. We interrogated vertex-based group-wise cortical tracer binding (SUVRs) with a cerebellar reference using the general linear model while mean substantia nigra SUVRs were compared with volumes of interest group comparisons and voxel-wise group analyses using ANOVA. Finally, we performed linear regressions of tau load with changes in MoCA and UPDRS motor scores. RESULTS: We found no significant changes in substantia nigra or cortex flortaucipir uptake in Parkinson's disease patients over two years and no association with changes in cognitive symptoms. Signal reduction in the medial substantia nigra trended towards an association with worsening of motor symptoms. CONCLUSION: No significant increase in tau tangles occurred after a two-year follow-up of Parkinson's disease patients using flortaucipir PET.

Journal article

Parbo P, Madsen LS, Ismail R, Zetterberg H, Blennow K, Eskildsen SF, Vorup-Jensen T, Brooks DJet al., 2020, Low plasma neurofilament light levels associated with raised cortical microglial activation suggest inflammation acts to protect prodromal Alzheimer's disease, ALZHEIMERS RESEARCH & THERAPY, Vol: 12

Journal article

Mansur A, Rabiner EA, Comley RA, Lewis Y, Middleton LT, Huiban M, Passchier J, Tsukada H, Gunn RNet al., 2020, Characterization of 3 PET tracers for Quantification of Mitochondrial and Synaptic function in Healthy Human Brain: 18F-BCPP-EF, 11C-SA-4503, 11C-UCB-J, Journal of Nuclear Medicine, Vol: 61, Pages: 96-103, ISSN: 1535-5667

Mitochondrial complex 1 (MC1) is involved in maintaining brain bioenergetics, the sigma 1 receptor (σ1R) responds to neuronal stress and synaptic vesicle protein 2A (SV2A) reflects synaptic integrity. Expression of each of these proteins is altered in neurodegenerative diseases. Here we characterise the kinetic behaviour of three positron emission tomography (PET) radioligands 18F-BCPP-EF, 11C-SA-4503 and 11CUCB- J, for the measurement of MC1, σ1R and SV2A, respectively, and determine appropriate analysis workflows for their application in future studies of the in vivo molecular pathology of these diseases. Methods: Twelve human subjects underwent dynamic PET scans including associated arterial blood sampling with each radioligand. A range of kinetic models were investigated to identify an optimal kinetic analysis method for each radioligand and a suitable acquisition duration. Results: All three radioligands readily entered the brain and yielded heterogeneous uptake consistent with the known distribution of the targets. The optimal models determined for the regional estimates of volume of distribution (VT) were multilinear analysis 1 (MA1) and the 2-tissue compartment (2TC) model for 18F-BCPP-EF, MA1 for 11C-SA- 4503, and both MA1 and the 1-tissue compartment (1TC) model for 11C-UCB-J. Acquisition times of 70, 80 and 60 minutes for 18F-BCPP-EF, 11C-SA-4503, 11C-UCB-J, respectively, provided good estimates of regional VT values. An effect of age was observed on 18F-BCPP-EF and 11C-UCB-J signal in the caudate. Conclusion: These ligands can be assessed for their potential to stratify patients or monitor the progression of molecular neuropathology in neurodegenerative diseases.

Journal article

Stokholm MG, Iranzo A, Ostergaard K, Serradell M, Otto M, Svendsen KB, Garrido A, Vilas D, Fedorova TD, Santamaria J, Moller A, Gaig C, Hiraoka K, Brooks DJ, Okamura N, Borghammer P, Tolosa E, Pavese Net al., 2019, Cholinergic denervation in patients with idiopathic rapid eye movement sleep behaviour disorder, EUROPEAN JOURNAL OF NEUROLOGY, Vol: 27, Pages: 644-652, ISSN: 1351-5101

Journal article

Metaxas A, Thygesen C, Kempf SJ, Anzalone M, Vaitheeswaran R, Petersen S, Landau AM, Audrain H, Teeling JL, Darvesh S, Brooks DJ, Larsen MR, Finsen Bet al., 2019, Ageing and amyloidosis underlie the molecular and pathological alterations of tau in a mouse model of familial Alzheimer's disease, SCIENTIFIC REPORTS, Vol: 9, ISSN: 2045-2322

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, Vol: 60, Pages: 1452-1460, 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

Sridharan S, Raffel J, Nandoskar A, Record C, Brooks DJ, Owen D, Sharp D, Muraro PA, Gunn R, Nicholas Ret al., 2019, 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, Vol: 21, Pages: 935-944, 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

Paquini J, Durcan R, Wiblin L, Stokholm MG, Rochester L, Brooks DJ, Burn D, Pavese Net al., 2019, Clinical implications of early caudate dysfunction in Parkinson's disease, Journal of Neurology, Neurosurgery and Psychiatry, Vol: 90, Pages: 1098-1104, 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

Stuart S, Lawson RA, Yarnall AJ, Nell J, Alcock L, Duncan GW, Khoo TK, Barker RA, Rochester L, Burn DJ, O'Brien JT, Brooks DJ, Wesnes KA, Robbins TW, Chinnery PF, Johnston F, McDonald C, Sleeman I, Rowe JB, Williams-Gray C, Breen D, Cummins GA, Evans Jet al., 2019, Pro-Saccades Predict Cognitive Decline in Parkinson's Disease: ICICLE-PD, MOVEMENT DISORDERS, Vol: 34, Pages: 1690-1698, ISSN: 0885-3185

Journal article

Perani D, Iaccarino L, Lammertsma AA, Windhorst AD, Edison P, Boellaard R, Hansson O, Nordberg A, Jacobs AH, Bottlaender M, Brooks D, Carroll MA, Chalon S, Edison P, Gee A, Gerhard A, Halldin C, Hansson O, Herholz K, Herth MM, Hinz R, Jacobs AH, Knudsen GM, Kuhnast B, Lammertsma AA, Lopez-Picon F, Moresco RM, Nordberg A, Pappata S, Perani D, Rinne JO, Rodriguez-Vieitez E, Santiago-Ribeiro MJ, Turkheimer FE, Van Laere K, Varrone A, Vercouillie J, Windhorst AD, Winkeler Aet al., 2019, A new perspective for advanced positron emission tomography-based molecular imaging in neurodegenerative proteinopathies, ALZHEIMERS & DEMENTIA, Vol: 15, Pages: 1081-1103, ISSN: 1552-5260

Journal article

Mollenhauer B, Caspell-Garcia CJ, Coffey CS, Taylor P, Singleton A, Shaw LM, Trojanowski JQ, Frasier M, Simuni T, Iranzo A, Oertel W, Siderowf A, Weintraub D, Seibyl J, Toga AW, Tanner CM, Kieburtz K, Chahine LM, Marek K, Galasko D, Jennings D, Lasch S, Siderowf A, Tanner C, Simuni T, Coffey C, Kieburtz K, Flagg E, Chowdhury S, Poewe W, Mollenhauer B, Sherer T, Frasier M, Meunier C, Rudolph A, Casaceli C, Seibyl J, Mendick S, Schuff N, Zhang Y, Toga A, Ansbach A, De Blasio P-Q, Piovella M, Trojanowski J, Shaw LM, Singleton A, Hawkins K, Eberling J, Russell D, Leary L, Factor S, Sommerfeld B, Pighetti E, Williams K, Standaert D, Guthrie S, Hauser R, Delgado H, Jankovic J, Hunter C, Stern M, Tran B, Leverenz J, Baca M, Frank S, Thomas C-A, Richard I, Deeley C, Rees L, Sprenger F, Oertel W, Lang E, Shill H, Obradov S, Fernandez H, Winters A, Berg D, Gauss K, Galasko D, Fontaine D, Mari Z, Gerstenhaber M, Brooks D, Malloy S, Barone P, Longo K, Comery T, Ravina B, Grachev I, Gallagher K, Collins M, Widnell KL, Ostrowizki S, Fontoura P, La-Roche FH, Ho T, Luthman J, van der Brug M, Reith AD, Taylor Pet al., 2019, Longitudinal analyses of cerebrospinal fluid alpha-Synuclein in prodromal and early Parkinson's disease, MOVEMENT DISORDERS, Vol: 34, Pages: 1354-1364, ISSN: 0885-3185

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

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

Cerri D, Albaugh D, Katz B, Lee S, Walton L, Zhang W, Etkin A, Cui G, Stuber G, Shih YYet al., 2019, Poster Viewing Sessions PA00-A01 to PA00-A49, JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, Vol: 39, Pages: 1-2, ISSN: 0271-678X

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

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

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

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, Vol: 29, Pages: 499-505, 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

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

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