Imperial College London

DrPareshMalhotra

Faculty of MedicineDepartment of Brain Sciences

Reader in Cognitive & Behavioural Neurology
 
 
 
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Contact

 

+44 (0)20 3313 5525p.malhotra

 
 
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Location

 

Lab BlockCharing Cross Campus

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Summary

 

Publications

Publication Type
Year
to

87 results found

Loreto F, Gunning S, Golemme M, Watt H, Patel N, Win Z, Carswell C, Perry R, Malhotra Pet al., 2021, COGNITIVE PERFORMANCE AND AFFECTIVE SYMPTOMS IN PATIENTS UNDERGOING CLINICAL AMYLOID PET IMAGING, British Neuropsychiatry Annual Meeting, Publisher: BMJ PUBLISHING GROUP, ISSN: 0022-3050

Conference paper

Fitzgerald A, Loreto F, Golemme M, Win Z, Patel N, Carswell C, Perry R, Malhotra Pet al., 2021, HIGH PREVALENCE OF LIFETIME DEPRESSIVE SYMPTOMS IN PATIENTS REFERRED FOR CLINICAL AMYLOID-PET: A RETROSPECTIVE STUDY, British Neuropsychiatry Annual Meeting, Publisher: BMJ PUBLISHING GROUP, ISSN: 0022-3050

Conference paper

Mallon DH, Malhotra P, Naik M, Edison P, Perry R, Carswell C, Win Zet al., 2021, The role of amyloid PET in patient selection for extra-ventricular shunt insertion for the treatment of idiopathic normal pressure hydrocephalus: A pooled analysis., J Clin Neurosci, Vol: 90, Pages: 325-331

BACKGROUND: Idiopathic Normal Pressure Hydrocephalus (iNPH) can be effectively treated through shunt insertion. However, most shunted patients experience little or no clinical benefit, which suggests suboptimal patient selection. While contentious, multiple studies have reported poorer shunt outcomes associated with concomitant Alzheimer's disease. Prompted by this observation, multiple studies have assessed the role of amyloid PET, a specific test for Alzheimer's disease, in patient selection for shunting. METHODS: A comprehensive literature search was performed to identify studies that assessed the association between amyloid PET result and the clinical response to shunting in patients with suspected iNPH. Pooled diagnostic statistics were calculated. RESULTS: Across three relevant studies, a total of 38 patients with suspected iNPH underwent amyloid PET imaging and shunt insertion. Twenty-three patients had a positive clinical response to shunting. 18/28 (64.3%) of patients with a negative amyloid PET and 5/10 (50%) with a positive amyloid PET had a positive response to shunting. The pooled sensitivity, specificity and accuracy was 33.3%, 76.2% and 58.3%. None of these statistics reached statistical significance. CONCLUSION: The results of this pooled analysis do not support the selection of patients with suspected iNPH for shunting on the basis of amyloid PET alone. However, due to small cohort sizes and weakness in study design, further high-quality studies are required to properly determine the role of amyloid PET in assessing this complex patient group.

Journal article

Kapsetaki ME, Militaru IE, Sanguino I, Boccanera M, Zaara N, Zaman A, Loreto F, Malhotra PA, Russell Cet al., 2021, Type of encoded material and age modulate the relationship between episodic recall of visual perspective and autobiographical memory, Journal of Cognitive Psychology, Pages: 1-18, ISSN: 2044-5911

Episodic memory enables us to form a bank of autobiographical memories across our lifespan. The relationship between autobiographical memory and laboratory-measures of episodic memory is complicated and these processes might be differentially affected by ageing (e.g. Diamond et al., [2020]. Different patterns of recollection for matched real-world and laboratory-based episodes in younger and older adults. Cognition, 202, 104309.). Here, we examine whether the ability to recall one’s own visual perspective relates to richness of autobiographical recall, and how this relationship is affected by age. Memory of perspective at encoding, was assessed in younger (18–35 years) and older adults (65–85 years). Participants, wearing head cameras, viewed arrays of objects. Later they were asked which images represented earlier scenes, and if the image was taken from their perspective (i.e. from their camera). Performance was compared with autobiographical memory. Accuracy in identifying their own perspective correlated with autobiographical scores. Age-group was a moderating factor in this relationship. Subsequently, new participants encoded photographs of objects and were later asked whether they recognised the images. Visual perspective was manipulated in these photographs. In this task there was no relationship between performance and autobiographical memory. In younger adults only 3-D encoding of scenes relates directly to autobiographical memory but ability to complete these two tasks appears to operate independently in the older group.

Journal article

Loreto F, Gunning S, Golemme M, Watt H, Patel N, Win Z, Carswell C, Perry R, Malhotra Pet al., 2021, Evaluating cognitive profiles of patients undergoing clinical Amyloid-PET Imaging, Brain Communications, Vol: 3, Pages: 1-12, ISSN: 2632-1297

Episodic memory impairment and brain amyloid-beta (Aβ) are two of the main hallmarks of Alzheimer’s Disease (AD). In patients with suspected AD, these are often evaluated through neuropsychological testing and amyloid PET imaging (API), respectively. Crucially, the use of amyloid PET in clinical practice is only indicated in patients with substantial diagnostic uncertainty due to atypical clinical presentation, multiple comorbidities and/or early age of onset. The relationship between Aβ and cognition has been previously investigated, but no study has examined how neuropsychological features relate to the presence of amyloid pathology in the clinical population meeting the appropriate use criteria for API.In this study, we evaluated a clinical cohort of patients (n=107) who presented at the Imperial Memory Clinic and were referred for clinical API and neuropsychological assessment as part of their diagnostic workup. We compared the cognitive performance of amyloid-positive patients (Aβ-pos, n=47) with that of stable amyloid-negative (stableAβ-neg, n=26) and progressive amyloid-negative (progAβ-neg, n=34) patients.The Aβ-pos group performed significantly worse than both the amyloid- negative groups in the visuospatial and working memory domains. Episodic memory performance, instead, effectively differentiated the Aβ-pos group from the stableAβ-neg but not the progAβ-neg group. On affective questionnaires, the stableAβ-neg group reported significantly higher levels of depression than the Aβ-pos group.In our clinical cohort, visuospatial dysfunction and working memory impairment were better indicators of amyloid positivity than episodic memory dysfunction. These findings highlight the limited value of isolated cognitive scores in patients with atypical clinical presentation, comorbidities and/or early age of onset.

Journal article

Kolanko M, Loreto F, Win Z, Patel N, Perry R, Carswell C, Gontsarova A, Malhotra Pet al., 2020, Amyloid PET imaging in clinical practice, Practical Neurology, Vol: 20, Pages: 451-462, ISSN: 1474-7766

The introduction of Amyloid PET imaging enables in vivo detection of brain beta-amyloid deposition, one of the neuropathological hallmarks of Alzheimer disease. There is increasing evidence in support of the clinical utility of Amyloid PET with major studies demonstrating that Amyloid PET improves diagnostic accuracy, increases diagnostic certainty, and results in therapeutic changes. Appropriate use criteria have been developed by the Amyloid Imaging Taskforce (AIT), to guide clinicians by predefining certain scenarios in which amyloid PET would be justified.In this review we aim to provide a practical guide on how and when to use Amyloid PET based on the available research and our own experience. We discuss three main appropriate indications for Amyloid PET and illustrate with them with clinical cases. We stress the importance of a multidisciplinary approach when deciding which patients would benefit from Amyloid PET imaging. Finally, we highlight some practical points and common pitfalls in interpretation.

Journal article

Frost E, Porat T, Malhotra P, Picinali Let al., 2020, Collaborative design of a gamified application for auditory-cognitive training, JMIR Human Factors, Vol: 7, ISSN: 2292-9495

Background:Multiple gaming applications under the dementia umbrella for skills such as navigation exist, but there has yet to be an application designed specifically to investigate the role hearing loss may have in the process of cognitive decline. There is a demonstrable gap in utilising serious games to further the knowledge of the potential relationship between hearing loss and dementia.Objective:The aim of this study was to identify the needs, facilitators and barriers in designing a novel auditory-cognitive training gaming application.Methods:A participatory design approach was used to engage key stakeholders across audiology and cognitive disorders specialisms. Two rounds, including paired semi-structured interviews and focus groups were completed and thematically analysed.Results:18 stakeholders participated in total and 6 themes were identified to inform the next stage of the application’s development.Conclusions:The findings can now be implemented into the development of the beta-version of the application. The application will be evaluated against outcome measures of speech listening in noise, cognitive and attentional tasks, quality of life and usability.

Journal article

Olgiati E, Malhotra P, 2020, Using non-invasive transcranial Direct Current Stimulation for Neglect and Associated Attentional Deficits following Stroke, Neuropsychological Rehabilitation, ISSN: 0960-2011

Journal article

Patel NH, Perry L, Lilja J, Golemme M, McMeekin H, Alves L, Nijran KS, Malhotra P, Perry RJ, Win Zet al., 2020, Quantification of 18F-Florbetaben amyloid PET images in patients with Alzheimer's disease, 33rd Annual Congress of the European-Association-of-Nuclear-Medicine (EANM), Publisher: SPRINGER, Pages: S166-S166, ISSN: 1619-7070

Conference paper

Kolanko M, Win Z, Patel N, Malik O, Carswell C, Gontsarova A, Nicholas R, Perry R, Malhotra Pet al., 2020, Using Amyloid PET imaging to diagnose Alzheimer’s disease in patients with Multiple Sclerosis, Journal of Neurology, Vol: 267, Pages: 3268-3273, ISSN: 0340-5354

BackgroundCognitive dysfunction affects 40–60% of individuals with multiple sclerosis (MS). The neuropsychological profile commonly consists of a subcortical pattern of deficits, although a proportion of patients have a severe progressive cortical dementia. However, patients with MS can be affected by other neurodegenerative diseases, such as Alzheimer’s disease (AD). Little is known about the co-existence of these two conditions but distinguishing dementia due to MS alone from a coexisting neurodegenerative disease is challenging. Amyloid PET imaging has allowed improved AD diagnosis, especially in patients with atypical presentations or multiple possible causes of cognitive impairment. Amyloid PET demonstrates increased cortical signal in AD, whereas reductions in subcortical uptake are associated with demyelination. To the authors knowledge, there are no reports of clinical Amyloid PET use in MS patients with dementia.MethodsHere, three MS patients presenting to the Cognitive Neurology Clinic with progressive cognitive impairment are described. Due to lack of diagnostic clarity from standard investigations, they underwent Amyloid PET Imaging with 18F-florbetapir according to established appropriate use criteria and after review by a multidisciplinary team.ResultsTwo patients were diagnosed with AD based on positive Amyloid PET imaging and were subsequently started on cholinesterase inhibitor treatment. The other patient had a negative scan, leading to further investigations and identification of another potential cause of worsening cognitive impairment.ConclusionsThe experience from this case series suggests that Amyloid PET Imaging may be of diagnostic value in selected patients with MS and dementia. In these individuals, it may provide diagnostic clarity and assist with therapeutic decisions.

Journal article

Li K, Bentley P, Nair A, Halse O, Barker G, Russell C, Soto D, Malhotra PAet al., 2020, Reward sensitivity predicts dopaminergic response in spatial neglect, Cortex, Vol: 122, Pages: 213-224, ISSN: 0010-9452

It has recently been revealed that spatial neglect can be modulated by motivational factors including anticipated monetary reward. A number of dopaminergic agents have been evaluated as treatments for neglect, but the results have been mixed, with no clear anatomical or cognitive predictors of dopaminergic responsiveness. Given that the effects of incentive motivation are mediated by dopaminergic pathways that are variably damaged in stroke, we tested the hypothesis that the modulatory influences of reward and dopaminergic drugs on neglect are themselves related.We employed a single-dose, double-blind, crossover design to compare the effects of Co-careldopa and placebo on a modified visual cancellation task in patients with neglect secondary to right hemisphere stroke. Whilst confirming that reward improved visual search in this group, we showed that dopaminergic stimulation only enhances visual search in the absence of reward. When patients were divided into REWARD-RESPONDERs and REWARD-NON-RESPONDERs, we found an interaction, such that only REWARD-NON-RESPONDERs showed a positive response to reward after receiving Co-careldopa, whereas REWARD-RESPONDERs were not influenced by drug. At a neuroanatomical level, responsiveness to incentive motivation was most associated with intact dorsal striatum.These findings suggest that dopaminergic modulation of neglect follows an ‘inverted U’ function, is dependent on integrity of the reward system, and can be measured as a behavioural response to anticipated reward.

Journal article

Malhotra P, 2019, Impairments of attention in Alzheimer’s disease, Current Opinion in Psychology, Vol: 29, Pages: 41-48, ISSN: 2352-250X

Alzheimer’s Disease (AD) is characteristically perceived as primarily being a disorder of episodic memory, with prominent attentional impairments more typically being associated with other neurodegenerative conditions, such as Dementia with Lewy Bodies. However, attention is also affected early on in Alzheimer’s, particularly in individuals with young onset and atypical syndromes. In addition, some initial symptoms that are apparently due to episodic memory loss may be secondary to failures of attentional processes.This review describes the various attentional impairments that can be observed in patients with AD, and addresses them through the conceptual framework of attention proposed by Posner and Petersen. It also explains how current knowledge of the development of AD has influenced our understanding of how these deficits arise. Finally, there is a brief summary of the effects of current AD treatments on attentional deficits, and how future pharmacological approaches might better target these deficits.

Journal article

Dumba M, Khan S, Patel N, Perry L, Malhotra P, Perry R, Nijran K, Barwick T, Wallitt K, Win Zet al., 2019, Clinical 18F-FDG and amyloid brain positron emission tomography/CT in the investigation of cognitive impairment: where are we now?, British Journal of Radiology, Vol: 92, ISSN: 0007-1285

The number of people living with dementia is increasing, but as yet there remains no cure or disease-modifying treatment. This review aims to help readers understand the role of 18F-FDG PET/CT imaging in the investigation of cognitive impairment and how the advent of amyloid PET/CT imaging may hold the key to radically changing management of the most common form of dementia - Alzheimer's disease. The indications for 18F-FDG PET/CT and amyloid PET/CT imaging in cognitive impairment are outlined. Additionally, the mechanisms of action, technique, patient preparation and acquisition parameters for both are detailed. We conclude by providing a framework for interpreting 18F-FDG PET/CT and amyloid PET/CT imaging in the more common conditions that lead to cognitive impairment conditions with tips on avoiding pitfalls in interpretation.

Journal article

Fakhry-Darian D, Patel NH, Khan S, Barwick T, Svensson W, Khan S, Perry RJ, Malhotra P, Carswell CJ, Nijran KS, Win Zet al., 2019, Optimisation and usefulness of quantitative analysis of 18F-florbetapir PET, British Journal of Radiology, Vol: 92, ISSN: 0007-1285

OBJECTIVES: This study investigates the usefulness of quantitative SUVR thresholds on sub types of typical (type A) and atypical (non-type A) positive (Aβ+) and negative (Aβ-) 18F-florbetapir scans and aims to optimise the thresholds. METHODS: Clinical 18F-florbetapir scans (n = 100) were categorised by sub type and visual reads were performed independently by three trained readers. Inter-reader agreement and reader-to-reference agreement were measured. Optimal SUVR thresholds were derived by ROC analysis and were compared with thresholds derived from a healthy control group and values from published literature. RESULTS: Sub type division of 18F-florbetapir PET scans improves accuracy and agreement of visual reads for type A: accuracy 90%, 96% and 70% and agreement κ > 0.7, κ ≥ 0.85 and -0.1 < κ < 0.9 for all data, type A and non-type A respectively. Sub type division also improves quantitative classification accuracy of type A: optimum mcSUVR thresholds were found to be 1.32, 1.18 and 1.48 with accuracy 86%, 92% and 76% for all data, type A and non-type A respectively. CONCLUSIONS: Aβ+/Aβ- mcSUVR threshold of 1.18 is suitable for classification of type A studies (sensitivity = 97%, specificity = 88%). Region-wise SUVR thresholds may improve classification accuracy in non-type A studies. Amyloid PET scans should be divided by sub type before quantification. ADVANCES IN KNOWLEDGE: We have derived and validated mcSUVR thresholds for Aβ+/Aβ- 18F-florbetapir studies. This work demonstrates that division into sub types improves reader accuracy and agreement and quantification accuracy in scans with typical presentation and highlights the atypical presentations not suited to global SUVR quantification.

Journal article

Curry S, Patel N, Fakhry-Darian D, Khan S, Perry RJ, Malhotra PA, Nijran KS, Win Zet al., 2019, Quantitative evaluation of beta-amyloid brain PET imaging in dementia: a comparison between two commercial software packages and the clinical report, British Journal of Radiology, Vol: 92, ISSN: 0007-1285

OBJECTIVE: To compare commercially available image analysis tools Hermes BRASS and Siemens Syngo.VIA with clinical assessment in 18F-Florbetapir PET scans. METHODS: 225 scans were reported by clinicians and quantified using two software packages. Scans were classified into Type A (typical features) or non-Type A (atypical features) for both positive and negative scans. For BRASS, scans with z-score ≥ 2 in 2 ≥ region of interest were classed positive. For Syngo.VIA a positive scan was indicated when mean cortical standardized uptake value ratio (mcSUVR) ≥ 1.17. RESULTS: 81% scans were Type A, and 19% scans were non-Type A. The sensitivity of BRASS and Syngo.VIA for Type A scans was 98.8 and 96.3%, specificity was 73 and 92%, respectively. Sensitivity for non-Type A scans was 95.8 and 79.2%, specificity was 36.8 and 57.9%, respectively. A third threshold of identifiable levels of plaque (1.08 ≤ mcSUVR ≤ 1.17) was recommended for Syngo.VIA to increase detection of false negative scans. The false positive rate of BRASS significantly decreased when an alternative positive threshold value of mcSUVR ≥ 1.18. Introduction of alternative criteria did not improve prediction outcome for non-Type A scans. More complex solutions are recommended. CONCLUSION: Hermes criteria for a positive scan leads to a high sensitivity but a low specificity. Siemens Syngo.VIA criteria gives a high sensitivity and specificity and agrees better with the clinical report. Alternative thresholds and classifications may help to improve agreement with the clinical report. ADVANCES IN KNOWLEDGE: Software packages may assist with clinical reporting of more difficult to interpret cases that require a more experienced read.

Journal article

Koychev I, Lawson J, Chessell T, Mackay C, Gunn R, Sahakian B, Rowe JB, Thomas AJ, Rochester L, Chan D, Tom B, Malhotra P, Ballard C, Chessell I, Ritchie CW, Raymont V, Leroi I, Lengyel I, Murray M, Thomas DL, Gallacher J, Lovestone Set al., 2019, Deep and frequent phenotyping study protocol: an observational study in prodromal Alzheimer's disease., BMJ Open, Vol: 9, ISSN: 2044-6055

INTRODUCTION: Recent failures of potential novel therapeutics for Alzheimer's disease (AD) have prompted a drive towards clinical studies in prodromal or preclinical states. However, carrying out clinical trials in early disease stages is extremely challenging-a key reason being the unfeasibility of using classical outcome measures of dementia trials (eg, conversion to dementia) and the lack of validated surrogate measures so early in the disease process. The Deep and Frequent Phenotyping (DFP) study aims to resolve this issue by identifying a set of markers acting as indicators of disease progression in the prodromal phase of disease that could be used as indicative outcome measures in proof-of-concept trials. METHODS AND ANALYSIS: The DFP study is a repeated measures observational study where participants will be recruited through existing parent cohorts, research interested lists/databases, advertisements and memory clinics. Repeated measures of both established (cognition, positron emission tomography (PET) imaging or cerebrospinal fluid (CSF) markers of pathology, structural MRI markers of neurodegeneration) and experimental modalities (functional MRI, magnetoencephalography and/or electroencephalography, gait measurement, ophthalmological and continuous smartphone-based cognitive and other assessments together with experimental CSF, blood, tear and saliva biomarkers) will be performed. We will be recruiting male and female participants aged >60 years with prodromal AD, defined as absence of dementia but with evidence of cognitive impairment together with AD pathology as assessed using PET imaging or CSF biomarkers. Control participants without evidence of AD pathology will be included at a 1:4 ratio. ETHICS AND DISSEMINATION: The study gained favourable ethical opinion from the South Central-Oxford B NHS Research Ethics Committee (REC reference 17/SC/0315; approved on 18 August 2017; amendment 13 February 2018). Data will be shared with the scientific commu

Journal article

Dahdaleh S, Malhotra P, 2019, Treatment of central nervous system complications of renal dialysis and transplantation, Current Treatment Options in Neurology, Vol: 21, ISSN: 1092-8480

Purpose of reviewMost clinical neurologists will have come across individuals receiving renal replacement therapy who have developed a neurological complication, and neurologists working in, or close to, hospitals with a Renal Unit will be very aware of the range of central nervous system (CNS) complications that may develop in these patients. These can often be difficult to differentiate from disorders relating to renal failure or systemic conditions leading to kidney disease and can in fact arise from the interaction between underlying disease and the side effects of treatment. Patients with renal disease frequently have multiple comorbidities, and it is necessary to take a generally inclusive approach to diagnosis and treatment.Recent findingsUnfortunately, there is a lack of specific high-quality evidence for a number of CNS complications of renal replacement therapy. Here, we review the major CNS complications of dialysis and transplantation, discussing evidence for treatments where available and detailing standard management approaches where evidence is scarce.SummaryGiven the lack of specific evidence for interventions in the treatment of CNS complications of renal replacement therapy, it is often necessary to take an individualised approach based on comorbidities and applying findings from the general population. In these complex patients, we must stress the importance of collaborative working between neurologists and renal physicians when treating this complex patient group.

Journal article

Russell C, Davies S, Li K, Musil A-S, Malhotra PA, Williams ALet al., 2019, Self-perspective in episodic memory after parietal damage and in healthy ageing, Neuropsychologia, Vol: 124, Pages: 171-181, ISSN: 0028-3932

Although there is strong support from functional imaging studies for lateral parietal lobe involvement in episodic memory, patients with damage to these regions do not appear to suffer from severe deficits in this cognitive domain. As such there has been no definitive explanation of this area's precise involvement. Here, we hypothesised that parietal regions play a crucial role in episodic memory - specifically in recollecting details from an egocentric perspective. In order to test this hypothesis systematically, we designed a novel experimental task utilising a head-mounted camera to record images from the participant's perspective, enabling us to evaluate the integrity of memory from the individual's own point of view. In the first study we examined patients with parietal damage and in a second study, using fMRI, we examined young and older healthy participants. Right-hemisphere patients with parietal damage were able to recall information accurately when recollecting what items had been present and where these items had been. However, patients were significantly impaired when attempting to judge from which perspective they had viewed the scenes. Critically, the patient group showed no evidence of impairment on standard tests of episodic and working memory. Examination of healthy participants in the second study utilised multi-voxel pattern analysis on neural activity during the recognition phase of a similar task. This revealed sensitivity to be highest around the angular gyrus of the lateral parietal cortex for our critical comparison - that is, when viewing stimuli that were the same as their egocentric view during encoding versus the identical scene but presented from an alternative angle. Our results provide important evidence that parietal cortex is directly involved in egocentric spatial perspective aspects of episodic memory and demonstrate for the first time a specific deficit in episodic memory in patients with right parietal damage.

Journal article

Koychev I, Galna B, Zetterberg H, Lawson J, Zamboni G, Ridha BH, Rowe JB, Thomas A, Howard R, Malhotra P, Ritchie C, Lovestone S, Rochester Let al., 2019, A beta 42/A beta 40 and A beta 42/A beta 38 Ratios Are Associated with Measures of Gait Variability and Activities of Daily Living in Mild Alzheimer's Disease: A Pilot Study (vol 65, pg 1377, 2018), JOURNAL OF ALZHEIMERS DISEASE, Vol: 72, Pages: 359-359, ISSN: 1387-2877

Journal article

Venkataraman A, Perry R, Malhotra P, 2018, Young Onset Dementia

Book chapter

Carswell C, Malhotra P, 2018, Rapidly Progressive Dementia, Reference Module in Neuroscience and Biobehavioral Psychology, Editors: Husain

Rapidly Progressive Dementia describes those patients with a Major Neurocognitive Disorder (DSM V) which progresses over a period of weeks or months and occasionally over days. In addition to the diseases which cause more insidious cognitive impairment, a number of pathological processes can lead to much more rapid decline. As a number of these conditions are potentially treatable, rapid and accurate diagnosis is critical. There have been a number of recent diagnostic advances in the field, especially in relation to prion disease and autoimmune encephalitis. Brain biopsy may still need to be considered in some cases, particularly where there is cerebrospinal fluid pleocytosis.

Book chapter

Kolanko MA, Malhotra PA, 2018, Exploring Alzheimer's disease subtypes at the prodromal stage, Brain, Vol: 141, Pages: 3285-3287, ISSN: 1460-2156

This scientific commentary refers to ‘Atrophy subtypes in prodromal Alzheimer’s disease are associated with cognitive decline', by ten Kate et al. (doi:10.1093/brain/awy264).

Journal article

Koychev I, Galna B, Zetterberg H, Lawson J, Zamboni G, Ridha BH, Rowe JB, Thomas A, Howard R, Malhotra P, Ritchie C, Lovestone S, Rochester Let al., 2018, A beta(42)/A beta(40) and A beta(42)/A beta(38 ) ratios are associated with measures of gait variability and activities of daily living in mild Alzheimer's disease: a pilot study, Journal of Alzheimer's Disease, Vol: 65, Pages: 1377-1383, ISSN: 1387-2877

Gait disturbances are some of the earliest changes in dementia and their monitoring presents an opportunity for early diagnosis. The exact relationship between gait and well-established biomarkers of Alzheimer’s disease (AD) remains to be clarified. In this study we compared gait-related measures with cerebrospinal fluid (CSF) markers of AD pathology. We recruited seventeen participants with mild AD in a multi-site study and performed gait assessment as well as lumbar punctures to obtain CSF. CSF Aβ42/Aβ40 and Aβ42/Aβ38 correlated positively with measures of variability (step time and step length) in the clinic-based assessments. This was driven by a negative relationship between gait variability and Aβ40 and Aβ38 but not Aβ42.The amyloid ratios and gait variability measures were also associated with more severe functional impairment. We interpret these data as an indication that increasing amyloid production (i.e., increasing Aβ40 and Aβ38) is associated with diminishing cognitive-motor control of gait. These preliminary results suggest that the two amyloid ratios may be a marker of the earliest disturbances in the interplay between cognitive and motor control which characterize dementia.

Journal article

Carswell CJ, Win Z, Muckle K, Kennedy A, Waldman A, Dawe G, Barwick TD, Khan S, Malhotra PA, Perry RJet al., 2018, Clinical utility of amyloid PET imaging with (18)F-florbetapir: a retrospective study of 100 patients., J Neurol Neurosurg Psychiatry, Vol: 89, Pages: 294-299

BACKGROUND AND OBJECTIVE: Amyloid-positron emission tomography (PET) imaging (API) detects amyloid-beta pathology early in the course of Alzheimer's disease (AD) with high sensitivity and specificity. (18)F-florbetapir (Amyvid) is an amyloid-binding PET ligand with a half-life suitable for clinical use outside of the research setting. How API affects patient investigation and management in the 'real-world' arena is unknown. To address this, we retrospectively documented the effect of API in patients in the memory clinic. METHODS: We reviewed the presenting clinical features, the pre-API and post-API investigations, diagnosis and outcomes for the first 100 patients who had API as part of their routine work-up at the Imperial Memory Centre, a tertiary referral clinic in the UK National Health Service. RESULTS: API was primarily used to investigate patients with atypical clinical features (56 cases) or those that were young at onset (42 cases). MRI features of AD did not always predict positive API (67%), and 6 of 23 patients with MRIs reported as normal were amyloid-PET positive. There were significantly more cases categorised as non-AD dementia post-API (from 11 to 23). Patients investigated when API was initially available had fewer overall investigations and all patients had significantly fewer investigations in total post-API. CONCLUSIONS: API has a clear impact on the investigation of young-onset or complex dementia while reducing the overall burden of investigations. It was most useful in younger patients, atypical presentations or individuals with multiple possible causes of cognitive impairment.

Journal article

Dalmaijer E, Li K, Gorgoraptis N, Leff A, Parton A, Cohen D, Husain M, Malhotra PAet al., 2018, A randomised double-blind, placebo-controlled crossover study of single-dose guanfacine in unilateral neglect following stroke, Journal of Neurology, Neurosurgery and Psychiatry, Vol: 89, Pages: 593-598, ISSN: 1468-330X

ObjectiveUnilateral neglect is a post-stroke disorder that impacts negatively on functional outcome and lacks established, effective treatment. This multi-component syndrome is characterised by a directional bias of attention away from contralesional space, together with impairments in several cognitive domains, including sustained attention and spatial working memory. This study aims to test the effects of guanfacine, a noradrenergic alpha-2A agonist, on ameliorating aspects of neglect.MethodsThirteen right hemisphere stroke patients with leftward neglect were included in a randomised double-blind, placebo-controlled proof-of-concept crossover study that examined the effects of a single dose ofguanfacine. Patients were tested on a computerised, time-limited cancellation paradigm, as well as tasks that independently assessed sustained attention and spatial working memory.ResultsOn guanfacine, there was a statistically significant improvement in the total number of targets found onthe cancellation task when compared to placebo (mean improvement of 5, out of a possible 64). However, there was no evidence of a change in neglect patients' directional attention bias. Furthermore,Bayesian statistical analysis revealed reliable evidence against any effects of guanfacine on search organisation and performance on our sustained attention and spatial working memory tasks. ConclusionsGuanfacine improves search in neglect by boosting the number of targets found, but had no effects on directional bias, or search organisation; nor did it improve sustained attention or working memory on independent tasks. Further work is necessary to determine whether longer-term treatment with guanfacine may be effective for some neglect patients, and whether it affects functional outcome measures.

Journal article

Rinne P, Hassan M, Fernandes C, Han E, Hennessy E, Waldman A, Sharma P, Soto D, Leech R, Malhotra P, Bentley Pet al., 2018, Motor dexterity and strength depend upon integrity of the attention-control system, Proceedings of the National Academy of Sciences, Vol: 115, Pages: E536-E545, ISSN: 0027-8424

Attention control (or executive control) is a higher cognitive function involved in response selection and inhibition, through close interactions with the motor system. Here, we tested whether influences of attention control are also seen on lower level motor functions of dexterity and strength—by examining relationships between attention control and motor performance in healthy-aged and hemiparetic-stroke subjects (n = 93 and 167, respectively). Subjects undertook simple-tracking, precision-hold, and maximum force-generation tasks, with each hand. Performance across all tasks correlated strongly with attention control (measured as distractor resistance), independently of factors such as baseline performance, hand use, lesion size, mood, fatigue, or whether distraction was tested during motor or nonmotor cognitive tasks. Critically, asymmetric dissociations occurred in all tasks, in that severe motor impairment coexisted with normal (or impaired) attention control whereas normal motor performance was never associated with impaired attention control (below a task-dependent threshold). This implies that dexterity and force generation require intact attention control. Subsequently, we examined how motor and attention-control performance mapped to lesion location and cerebral functional connectivity. One component of motor performance (common to both arms), as well as attention control, correlated with the anatomical and functional integrity of a cingulo-opercular “salience” network. Independently of this, motor performance difference between arms correlated negatively with the integrity of the primary sensorimotor network and corticospinal tract. These results suggest that the salience network, and its attention-control function, are necessary for virtually all volitional motor acts while its damage contributes significantly to the cardinal motor deficits of stroke.

Journal article

Karunaratne K, Taube D, Khalil N, Perry R, Malhotra PAet al., 2017, Neurological complications of renal dialysis and transplantation, Practical Neurology, Vol: 18, Pages: 115-125, ISSN: 1474-7766

Neurological complications from renal replacement therapy contribute significantly to morbidity and mortality in patients with renal failure. Such complications can affect either the central or peripheral nervous systems. Most neurological disturbances associated with the uraemic state do not respond fully to renal replacement therapy. There are also complications specifically associated with dialysis and transplantation. A multidisciplinary approach, involving both nephrologists and neurologists, is critical for the diagnosis and effective management of these disorders.

Journal article

Arshad Q, Nigmatullina Y, Siddiqui S, Franka M, Mediratta S, Ramachandaran S, Lobo R, Malhotra PA, Roberts RE, Bronstein AMet al., 2017, Influence of biases in numerical magnitude allocation on human prosocial decision making, JOURNAL OF NEUROPHYSIOLOGY, Vol: 118, Pages: 3007-3013, ISSN: 0022-3077

Journal article

Carswell C, Muckle K, Waldman A, Win Z, Malhotra P, Perry Ret al., 2016, FLORBETAPIR IMAGING IN CLINICAL PRACTICE: A RETROSPECTIVE STUDY OF 100 PATIENTS, Annual Meeting of the Association-of-British-Neurologists (ABN), Publisher: BMJ PUBLISHING GROUP, ISSN: 0022-3050

Conference paper

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