Nisha Rani

Johns Hopkins Medicine

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Baljinder Singh

Post Graduate Institute of Medical Education and Research

Puja Panwar Hazari

Institute of Nuclear Medicine & Allied Sciences

Anil K. Mishra

Institute of Nuclear Medicine & Allied Sciences

Narendra Kumar

Post Graduate Institute of Medical Education and Research

Paramjeet Singh

Post Graduate Institute of Medical Education and Research

Hsiao‐Ying Wey

Harvard University

Richard C. Mohs

Global Alzheimer's Platform Foundation

Bishan Das Radotra

Post Graduate Institute of Medical Education and Research

Sunil Gupta

All India Institute of Medical Sciences

Anish Bhattacharya

Post Graduate Institute of Medical Education and Research

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Post Graduate Institute of Medical Education and Research

Harvard University

Massachusetts General Hospital

Govind Ballabh Pant University of Agriculture and Technology

Indian Institute of Technology Roorkee

Institute of Nuclear Medicine & Allied Sciences

All India Institute of Medical Sciences

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Athinoula A. Martinos Center for Biomedical Imaging

Johns Hopkins Medicine

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The HOPE4MCI study: AGB101 treatment slows progression of entorhinal cortex atrophy in APOE ε4 non‐carriers with mild cognitive impairment due to Alzheimer's disease

Alzheimer s & Dementia Translational Research & Clinical Interventions (2024)

Arnold Bakker Nisha Rani Richard C. Mohs Michela Gallagher

Abstract Introduction Hippocampal hyperactivity is a hallmark of prodromal Alzheimer's disease (AD) that predicts progression in patients with amnestic mild cognitive impairment (aMCI). AGB101 is an extended‐release formulation of levetiracetam in the dose range previously demonstrated to normalize hippocampal activity and improve cognitive performance in aMCI. The HOPE4MCI study was a 78‐week trial to assess the progression of MCI due to AD. As reported in Mohs et al., the decline in the Clinical Dementia Rating Sum of Boxes score (CDR‐SB) was reduced by 40% in apolipoprotein E ( APOE ) ε4 non‐carriers over the 78‐week duration of the study with a negligible effect in carriers. Here we report an exploratory analysis of the effects of AGB101 on neuroimaging and biomarker measures in the 44 APOE ε4 non‐carriers who completed the 78‐week protocol. Methods Structural magnetic resonance imaging scans obtained at baseline and after 78 weeks were analyzed using the Automated Segmentation of Hippocampal Subfields software providing volume measures of key structures of the medial temporal lobe relevant to AD progression. Blood samples collected at 78 weeks in the study were analyzed for plasma biomarkers. Results Treatment with AGB101 significantly reduced atrophy of the left entorhinal cortex (ERC) compared to placebo. This reduction in atrophy was correlated with less decline in the CDR‐SB score over 78 weeks and with lower neurofilament light chain (NfL), a marker of neurodegeneration. Discussion The HOPE4MCI study showed that APOE ε4 non‐carriers treated with AGB101 demonstrated a substantially more favorable treatment effect compared to carriers. Here we report that treatment with AGB101 in non‐carriers of APOE ε4 significantly reduced atrophy of the left ERC over 78 weeks. That reduction in atrophy was closely coupled with the change in CDR‐SB and with plasma NfL indicative of neurodegeneration in the brain. These exploratory analyses are consistent with a reduction in neurodegeneration in APOE ε4 non‐carriers treated with AGB101 before a clinical diagnosis of dementia. Highlights AGB101 slows entorhinal cortex (ERC) atrophy in apolipoprotein E ( APOE ) ε4 non‐carriers with mild cognitive impairment (MCI) due to Alzheimer's disease (AD). Slowing ERC atrophy by AGB101 is associated with less Clinical Dementia Rating Sum of Boxes decline. Slowing ERC atrophy by AGB101 is associated with lower neurofilament light chain. AGB101 treatment reduces neurodegeneration in APOE ε4 non‐carriers with MCI due to AD.

Entorhinal cortex

Apolipoprotein E

Clinical Dementia Rating

10.1002/trc2.70004

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Tau PET burden in Brodmann areas 35 and 36 is associated with individual differences in cognition in non-demented older adults

Frontiers in Aging Neuroscience (2023)

Nisha Rani Kylie H. Alm Caitlin A. Corona-Long Caroline L. Speck Anja Soldan

Introduction The accumulation of neurofibrillary tau tangles, a neuropathological hallmark of Alzheimer’s disease (AD), occurs in medial temporal lobe (MTL) regions early in the disease process, with some of the earliest deposits localized to subregions of the entorhinal cortex. Although functional specialization of entorhinal cortex subregions has been reported, few studies have considered functional associations with localized tau accumulation. Methods In this study, stepwise linear regressions were used to examine the contributions of regional tau burden in specific MTL subregions, as measured by 18 F-MK6240 PET, to individual variability in cognition. Dependent measures of interest included the Clinical Dementia Rating Sum of Boxes (CDR-SB), Mini Mental State Examination (MMSE), and composite scores of delayed episodic memory and language. Other model variables included age, sex, education, APOE4 status, and global amyloid burden, indexed by 11 C-PiB. Results Tau burden in right Brodmann area 35 (BA35), left and right Brodmann area 36 (BA36), and age each uniquely contributed to the proportion of explained variance in CDR-SB scores, while right BA36 and age were also significant predictors of MMSE scores, and right BA36 was significantly associated with delayed episodic memory performance. Tau burden in both left and right BA36, along with education, uniquely contributed to the proportion of explained variance in language composite scores. Importantly, the addition of more inclusive ROIs, encompassing less granular segmentation of the entorhinal cortex, did not significantly contribute to explained variance in cognition across any of the models. Discussion These findings suggest that the ability to quantify tau burden in more refined MTL subregions may better account for individual differences in cognition, which may improve the identification of non-demented older adults who are on a trajectory of decline due to AD.

Cognitive Decline

Healthy aging

Brain Aging

Cognitive aging

10.3389/fnagi.2023.1272946

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Investigation of neurovascular coupling to cannabinoid 1 receptor occupancy: a simultaneous PET/fMRI study on non-human primates

Proceedings on CD-ROM - International Society for Magnetic Resonance in Medicine. Scientific Meeting and Exhibition/Proceedings of the International Society for Magnetic Resonance in Medicine, Scientific Meeting and Exhibition (2023)

Chi-Hyeon Yoo Nisha Rani Frederick A. Bagdasarian Sarah Reid Changning Wang

The goal of this study was to investigate relationship between hemodynamic responses and underlying neurochemistry targeting cannabinoid receptor 1 (CB1R) in response to the injection of rimonabant in non-human primates using simultaneous positron emission tomography (PET) and function magnetic resonance imaging (fMRI). Following the rimonabant injection, fast and slow hemodynamic responses were identified throughout the brain. The CB1R occupancy estimates suggested that the radiotracer binding to CB1R was blocked by rimonabant highly in cerebellum and several brain regions. Future PET/fMRI studies with other CB1R-agonists/antagonists and more accurate occupancy estimates will provide further understanding about neurovascular coupling to CB1R.

Rimonabant

Neurochemistry

Neurovascular bundle

Occupancy

Human brain

10.58530/2022/4422

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Investigating neuroepigenetic alterations in chronic low back pain with positron emission tomography

Pain (2024)

Chi-Hyeon Yoo Nisha Rani Shiqian Shen Marco L. Loggia Kate Gaynor

Epigenetics has gained considerable interest as potential mediators of molecular alterations that could underlie the prolonged sensitization of nociceptors, neurons, and glia in response to various environmental stimuli. Histone acetylation and deacetylation, key processes in modulating chromatin, influence gene expression; elevated histone acetylation enhances transcriptional activity, whereas decreased acetylation leads to DNA condensation and gene repression. Altered levels of histone deacetylase (HDAC) have been detected in various animal pain models, and HDAC inhibitors have demonstrated analgesic effects in these models, indicating HDACs' involvement in chronic pain pathways. However, animal studies have predominantly examined epigenetic modulation within the spinal cord after pain induction, which may not fully reflect the complexity of chronic pain in humans. Moreover, methodological limitations have previously impeded an in-depth study of epigenetic changes in the human brain. In this study, we employed [ 11 C]Martinostat, an HDAC-selective radiotracer, positron emission tomography to assess HDAC availability in the brains of 23 patients with chronic low back pain (cLBP) and 11 age-matched and sex-matched controls. Our data revealed a significant reduction of [ 11 C]Martinostat binding in several brain regions associated with pain processing in patients with cLBP relative to controls, highlighting the promising potential of targeting HDAC modulation as a therapeutic strategy for cLBP.

10.1097/j.pain.0000000000003272

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Stroke recurrence risk modelling in symptomatic carotid stenosis patients: Preliminary study

Journal of the Neurological Sciences (2017)

Mukesh Kumar Dheeraj Khurana Chirag Ahuja Niranjan Khandelwal Baljinder Singh

Stroke

Carotid stenting

Medical Therapy

10.1016/j.jns.2017.08.2465

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A focus on melorheostosis disease: a literature review and case report of femoral-acetabular impingement due to melorheostosis treated with surgical hip osteoplasty

Reumatismo (2024)

Marco Ruggiero Andrea Conforti Antonio Culcasi Cinzia Mazzanti G. Sibahi

Objective. Melorheostosis is a rare, non-hereditary, benign bone disease characterized by abnormal bone growth. Generally, melorheostosis develops during childhood or adolescence and progresses gradually over time. This disease represents a true challenge to the physician because of its variability due to location, extension of the affected bone, and involvement of associated soft tissue. Pain management, physical therapy, and surgery may be recommended, depending on the individual case. This review aims to get an overview of the latest evidence relating to epidemiology, clinical and radiographic characteristics, diagnosis, and possible therapeutic strategies for melorheostosis and describe our experience through a clinical case. Methods. We designed a comprehensive literature search on melorheostosis in MEDLINE (via Pubmed) up to April 2023 and reviewed reports published in international journals. Results. The purpose is to highlight the importance of a multidisciplinary approach in the management of a rare disease such as melorheostosis. We discuss the role of different physicians, including genetists, rheumatologists, physiatrists, physical therapists, and orthopedic surgeons, in providing accurate diagnoses and effective treatments. We conducted a comprehensive review of the literature on the treatment of melorheostosis to support these findings. In addition, the article presents a case study of a patient suffering from melorheostosis, focusing on difficulties in reaching a correct diagnosis and attempts towards conservative and surgical interventions. The patient underwent hip arthroplasty, and the final result was an improvement in function and a reduction in pain. Conclusions. Managing melorheostosis can be challenging, and there is no standardized treatment for this condition at the moment.

Osteoplasty

10.4081/reumatismo.2024.1621

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Glutamate level in anterior cingulate predicts anxiety in healthy humans: A magnetic resonance spectroscopy study

Psychiatry Research Neuroimaging (2014)

Shilpi Modi Poonam Rana Prabhjot Kaur Nisha Rani Subash Khushu

Neurochemical

Cingulate cortex

Neurochemistry

10.1016/j.pscychresns.2014.03.001

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REVERSAL OF HYPERMETHYLATION AND REACTIVATION OF TUMOR SUPPRESSOR GENES DUE TO NATURAL COMPOUNDS IN BREAST CANCER CELLS

International Journal of Biological Innovations (2020)

Debasray Saha Neeraj Vaishnav Zubiya Ahsan Nisha Rani Runjhun Mathur

Breast oncogenesis is a multistage process that involves epigenetic and genetic changes.Epigenetics is outlined as reversible changes in gene expression, with no alteration in gene sequence.DNA methylation, histone modification, and nucleosome transformation are the foremost epigenetic changes that may get dysregulated in breast cancer.Epigenetic silencing of tumor suppressor genes (TSGs) is reversed by varied molecules as well as natural compounds like polyphenols which will act as a hypermethylation agent.Nowadays, much of the research is going in the direction of natural and dietary compounds and attempting to search out novel and extra effective medical aid for the breast cancer patients.In this literature, few vital natural chemical compounds effective against the breast oncogenesis with their mode of actions are discussed.Such chemicals act as an analytical and prognostic tool in breast cancer due to their role in epigenetic regulation.

10.46505/ijbi.2020.2109

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99mTc-MDM Brain SPECT for the Detection of Recurrent/Remnant Glioma—Comparison With ceMRI and 18F-FLT PET Imaging

Clinical Nuclear Medicine (2015)

Baljinder Singh Narendra Kumar Sarika Sharma Ankit Watts Puja Panwar Hazari

To evaluate the diagnostic use of an indigenously developed single vial ready to label (with Tc) kit preparation of bis-methionine-DTPA (Tc-MDM) for the detection of recurrent/residual glioma.We prospectively studied 32 patients (21 male and 11 female subjects aged 43.0±16.0 years) with clinical suspicion of postoperative recurrent/residual glioma. After radical radiotherapy (54.0-60.0 Gy) with or without concurrent temozolomide as indicated, Tc-MDM SPECT and ceMRI of the brain was performed in all the patients and F-FLT-PET imaging in 16 of 32 patients.MDM SPECT and ceMRI findings were concordant in 28 patients (15 positive and 13 negative). The findings were discordant in the remaining 5 patients, with positive ceMRI and negative MDM-SPECT in 2 patients and negative ceMRI and positive MDM-SPECT in 3 patients. Tc-MDM-SPECT, F-FLT PET, and ceMRI scan findings were positive in 9 of 16 and negative in 5 of 16 patients. In the remaining 2 of 16 patients, both F-FLT-PET and Tc-MDM-SPECT were positive, but ceMRI was negative. Sensitivity, specificity, PPV, NPV, and DA of Tc-MDM-SPECT for diagnosing recurrent/residual glioma were 88.24%, 81.25%, 83.3%, 86.7%, and 84.8%, respectively.The diagnostic accuracy of Tc-bis-methionine (MDM)-SPECT imaging was comparable with that of ceMRI and F-FLT-PET and may be useful in the management of glioma patients in the postsurgical follow-up period. This imaging technique may be of special interest in peripheral hospitals/developing countries lacking access to expensive PET/cyclotron technology. However, comparison with the existing "gold standard" PET tracers, especially with C-11-methionine-PET imaging and histopathological correlation, is warranted in a large cohort of glioma patients through multicentric studies.

Spect imaging

PET Imaging

10.1097/rlu.0000000000000881

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Citations (11)

Tau PET accumulation in Brodmann areas 35 and 36 is associated with individual differences in cognition in non‐demented older adults

Alzheimer s & Dementia (2023)

Nisha Rani Kylie H. Alm Caroline L. Speck Anja Soldan Corinne Pettigrew

Abstract Background Mounting evidence indicates that tau accumulation in the entorhinal cortex (EC) occurs early in the course of Alzheimer’s disease (AD). Recent advances in automated segmentation methods allow for the investigation of smaller regions of the medial temporal lobes (MTL), including subregions of the EC. This study examined tau deposition in relation to individual differences in cognition among older adults, assessing whether MTL subregions explained a greater proportion of variance in cognition, when compared to standard labeling methods. Method Analyses included 91 BIOCARD study participants who were cognitively unimpaired (CU; n = 82) or had mild cognitive impairment (MCI; n = 9). Stepwise linear regressions were used to examine the contributions of regional tau burden to individual differences in the CDR sum of boxes (CDR‐SB), MMSE, and composite scores of global cognition and memory. Other model variables included amyloid burden, APOE4 status, sex, and education. Amyloid burden was assessed by 11C‐PiB and regional tau was assessed by 18F‐MK‐6240 PET. SUVR values representing tau accumulation were extracted using two MRI segmentation methods: (1) the FreeSurfer‐derived EC label, and (2) Automatic Segmentation of Hippocampal Subfields (ASHS)‐derived MTL subregions, including the EC and Brodmann areas 35 and 36 (Br35, Br36) defined in 1mm‐MNI space. Partial volume correction was applied to the motion‐corrected PET data. Result Tau burden in the right Br35, right Br36, and age were significant predictors of CDR‐SB scores, with the greatest proportion of variance explained when all three were included. The FreeSurfer‐labeled EC and other variables did not significantly contribute to the model. Right Br36 and age were significant predictors of MMSE while right Br36 and APOE4 status were significant predictors of the global cognition composite score, and right Br36 was a significant predictor of the memory composite score. Follow‐up analyses showed that addition of the FreeSurfer EC region did not significantly contribute to any of the models. Conclusion Quantifying tau burden in Br35 and Br36 better accounted for individual variability in cognition, when compared to standard EC labeling approaches. This suggests tau burden in these subregions may help identify CU and MCI individuals who are on a trajectory of decline due to AD.

Entorhinal cortex

Cognitive Decline

10.1002/alz.083095

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