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  1. Book: Dementia

    Dickerson, Bradford C. / Atri, Alireza

    comprehensive principles and practice

    2014  

    Author's details ed. by Bradford C. Dickerson and Alireza Atri
    Keywords Dementia
    Language English
    Size XX, 666 S., [8] Bl. : Ill., graph. Darst.
    Publisher Oxford Univ. Press
    Publishing place Oxford u.a.
    Publishing country Great Britain
    Document type Book
    Note Includes bibliographical references
    HBZ-ID HT018431214
    ISBN 978-0-19-992845-3 ; 0-19-992845-2
    Database Catalogue ZB MED Medicine, Health

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  2. Article ; Online: The role of cerebrospinal fluid and other biomarker modalities in the Alzheimer's disease diagnostic revolution.

    Schindler, Suzanne E / Atri, Alireza

    Nature aging

    2023  Volume 3, Issue 5, Page(s) 460–462

    MeSH term(s) Humans ; Alzheimer Disease/diagnosis ; Amyloid beta-Peptides/cerebrospinal fluid ; tau Proteins/cerebrospinal fluid ; Biomarkers/cerebrospinal fluid
    Chemical Substances Amyloid beta-Peptides ; tau Proteins ; Biomarkers
    Language English
    Publishing date 2023-05-17
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ISSN 2662-8465
    ISSN (online) 2662-8465
    DOI 10.1038/s43587-023-00400-6
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Current and Future Treatments in Alzheimer's Disease.

    Atri, Alireza

    Seminars in neurology

    2019  Volume 39, Issue 2, Page(s) 227–240

    Abstract: The foundation of current Alzheimer's disease (AD) treatment involves pharmacological and nonpharmacological management and care planning predicated on patient-centered psychoeducation, shared goal-setting, and decision-making forged by a strong triadic ... ...

    Abstract The foundation of current Alzheimer's disease (AD) treatment involves pharmacological and nonpharmacological management and care planning predicated on patient-centered psychoeducation, shared goal-setting, and decision-making forged by a strong triadic relationship between clinician and the patient-caregiver dyad. Food and Drug Administration (FDA) approved AD medications, cholinesterase-inhibitors (ChEIs), and the N-methyl-d-aspartate (NMDA) antagonist memantine, when utilized as part of a comprehensive care plan, while generally considered symptomatic medications, can provide modest "disease course-modifying" effects by enhancing cognition, and reducing loss of independence. When combined, pharmacologic and nonpharmacologic treatments can meaningfully mitigate symptoms and reduce clinical progression and care burden. AD pharmacotherapy first involves identification and elimination of potentially harmful medications and supplements. First line treatment for neuropsychiatric symptoms and problem behaviors is nonpharmacological and involves psychoeducation, trigger identification, and implementation, iterative evaluation, and adjustment of behavioral and environmental interventions. Intensive research efforts are underway to develop more accurate and practical AD diagnostic biomarkers and clinical tools and better therapeutics. Ongoing research studies for primary and secondary prevention of AD and clinical trials evaluating symptomatic and disease-modifying treatments in symptomatic AD are directed at diverse therapeutic targets including neurochemicals, amyloid and tau pathological processes, mitochondria, inflammatory pathways, neuroglia, and multimodal lifestyle interventions.
    MeSH term(s) Alzheimer Disease/drug therapy ; Alzheimer Disease/therapy ; Cholinesterase Inhibitors/pharmacology ; Excitatory Amino Acid Antagonists/pharmacology ; Humans ; Psychotherapy/methods
    Chemical Substances Cholinesterase Inhibitors ; Excitatory Amino Acid Antagonists
    Language English
    Publishing date 2019-03-29
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 603165-1
    ISSN 1098-9021 ; 0271-8235
    ISSN (online) 1098-9021
    ISSN 0271-8235
    DOI 10.1055/s-0039-1678581
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: The Alzheimer's Disease Clinical Spectrum: Diagnosis and Management.

    Atri, Alireza

    The Medical clinics of North America

    2018  Volume 103, Issue 2, Page(s) 263–293

    Abstract: Alzheimer's disease (AD) care requires timely diagnosis and multidisciplinary management. Evaluation involves structured patient and caregiver history and symptom-function reviews, examination, and testing (laboratory and neuroimaging) to delineate ... ...

    Abstract Alzheimer's disease (AD) care requires timely diagnosis and multidisciplinary management. Evaluation involves structured patient and caregiver history and symptom-function reviews, examination, and testing (laboratory and neuroimaging) to delineate impairment level, determine the cognitive-behavioral syndrome, and diagnose cause. Clinical biomarkers are available to aid high confidence in etiologic diagnosis. Management uses psychoeducation, shared goal setting, and patient-caregiver dyad decision making. When combined, pharmacologic and nonpharmacologic therapies mitigate symptoms and reduce clinical progression and care burden. AD biopathologic processes develop over decades before symptoms manifest; this period is increasingly targeted in research as an opportunity to best delay or prevent AD dementia.
    MeSH term(s) Alzheimer Disease/diagnosis ; Alzheimer Disease/therapy ; Biomarkers ; Diagnosis, Differential ; Disease Progression ; Humans ; Neuroimaging ; Parkinson Disease/diagnosis
    Chemical Substances Biomarkers
    Language English
    Publishing date 2018-12-03
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 215710-x
    ISSN 1557-9859 ; 0025-7125
    ISSN (online) 1557-9859
    ISSN 0025-7125
    DOI 10.1016/j.mcna.2018.10.009
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: Current and Future Treatments in Alzheimer's Disease

    Atri, Alireza

    Seminars in Neurology

    (Dementia)

    2019  Volume 39, Issue 02, Page(s) 227–240

    Abstract: The foundation of current Alzheimer's disease (AD) treatment involves pharmacological and nonpharmacological management and care planning predicated on patient-centered psychoeducation, shared goal-setting, and decision-making forged by a strong triadic ... ...

    Series title Dementia
    Abstract The foundation of current Alzheimer's disease (AD) treatment involves pharmacological and nonpharmacological management and care planning predicated on patient-centered psychoeducation, shared goal-setting, and decision-making forged by a strong triadic relationship between clinician and the patient-caregiver dyad. Food and Drug Administration (FDA) approved AD medications, cholinesterase-inhibitors (ChEIs), and the N-methyl-d-aspartate (NMDA) antagonist memantine, when utilized as part of a comprehensive care plan, while generally considered symptomatic medications, can provide modest “disease course-modifying” effects by enhancing cognition, and reducing loss of independence. When combined, pharmacologic and nonpharmacologic treatments can meaningfully mitigate symptoms and reduce clinical progression and care burden. AD pharmacotherapy first involves identification and elimination of potentially harmful medications and supplements. First line treatment for neuropsychiatric symptoms and problem behaviors is nonpharmacological and involves psychoeducation, trigger identification, and implementation, iterative evaluation, and adjustment of behavioral and environmental interventions. Intensive research efforts are underway to develop more accurate and practical AD diagnostic biomarkers and clinical tools and better therapeutics. Ongoing research studies for primary and secondary prevention of AD and clinical trials evaluating symptomatic and disease-modifying treatments in symptomatic AD are directed at diverse therapeutic targets including neurochemicals, amyloid and tau pathological processes, mitochondria, inflammatory pathways, neuroglia, and multimodal lifestyle interventions.
    Keywords cognitive impairment ; dementia ; cholinesterase-inhibitor
    Language English
    Publishing date 2019-03-29
    Publisher Thieme Medical Publishers
    Publishing place Stuttgart ; New York
    Document type Article
    ZDB-ID 603165-1
    ISSN 1098-9021 ; 0271-8235
    ISSN (online) 1098-9021
    ISSN 0271-8235
    DOI 10.1055/s-0039-1678581
    Database Thieme publisher's database

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  6. Article: Molecular Imaging Biomarkers in Dementia: Amyloid and tau PET imaging aids evaluation of patients suspected of having Alzheimer disease or other dementias.

    Dickerson, Brad / Atri, Alireza

    Practical neurology (Fort Washington, Pa.)

    2021  Volume 19, Issue 9, Page(s) 34–45

    Language English
    Publishing date 2021-08-30
    Publishing country United States
    Document type Journal Article
    ISSN 1540-1367
    ISSN 1540-1367
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article: Imaging of neurodegenerative cognitive and behavioral disorders: practical considerations for dementia clinical practice.

    Atri, Alireza

    Handbook of clinical neurology

    2016  Volume 136, Page(s) 971–984

    Abstract: This chapter reviews clinical applications and imaging findings useful in medical practice relating to neurodegenerative cognitive/dementing disorders. The preponderance of evidence and consensus guidelines support an essential role of multitiered ... ...

    Abstract This chapter reviews clinical applications and imaging findings useful in medical practice relating to neurodegenerative cognitive/dementing disorders. The preponderance of evidence and consensus guidelines support an essential role of multitiered neuroimaging in the evaluation and management of neurodegenerative cognitive/dementia syndrome that range in severity from mild impairments to frank dementia. Additionally, imaging features are incorporated in updated clinical and research diagnostic criteria for most dementias, including Alzheimer's disease (AD), Dementia with Lewy bodies (DLB), Frontotemporal Lobar Degenerations/Frontotemporal Dementia (FTD), and Vascular Cognitive Impairment (VCI). Best clinical practices dictate that structural imaging, preferably with magnetic resonance imaging (MRI) when possible and computed tomography when not, be obtained as a first-tier approach during the course of a thorough clinical evaluation to improve diagnostic confidence and assess for nonneurodegenerative treatable conditions that may cause or substantially contribute to cognitive/behavioral symptoms or which may dictate a substantial change in management. These conditions include less common structural (e.g., mass lesions such as tumors and hematomas; normal-pressure hydrocephalus), inflammatory, autoimmune and infectious conditions, and more common comorbid contributing conditions (e.g., vascular cerebral injury causing leukoaraiosis, infarcts, or microhemorrhages) that can produce a mixed dementia syndrome. When, after appropriate clinical, cognitive/neuropsychologic, and structural neuroimaging assessment, a dementia specialist remains in doubt regarding etiology and appropriate management, second-tier imaging with molecular methods, preferably with fluorodexoyglucose positron emission tomography (PET) (or single-photon emission computed tomography if PET is unavailable) can provide more diagnostic specificity (e.g., help differentiate between atypical AD and FTD as the etiology for a frontal/dysexecutive syndrome). The potential clinical utility of other promising methods, whether already approved for use (e.g., amyloid PET) or as yet only used in research (e.g., tau PET, functional MRI, diffusor tensor imaging), remains to be proven for widespread use in community practice. However, these constitute unreimbursed third-tier options that merit further study for clinical and cost-effective utility. In the future, combination use of imaging methods will likely improve diagnostic accuracy.
    MeSH term(s) Cognition Disorders/complications ; Cognition Disorders/diagnostic imaging ; Dementia/complications ; Dementia/diagnostic imaging ; Humans ; Image Processing, Computer-Assisted ; Mental Disorders/complications ; Mental Disorders/diagnostic imaging ; Neurodegenerative Diseases/complications ; Neurodegenerative Diseases/diagnostic imaging ; Neuroimaging
    Language English
    Publishing date 2016
    Publishing country Netherlands
    Document type Journal Article ; Review
    ISSN 0072-9752
    ISSN 0072-9752
    DOI 10.1016/B978-0-444-53486-6.00050-8
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Combining Blood-Based Biomarkers and Structural MRI Measurements to Distinguish Persons with and without Significant Amyloid Plaques.

    Chen, Yanxi / Su, Yi / Wu, Jianfeng / Chen, Kewei / Atri, Alireza / Caselli, Richard J / Reiman, Eric M / Wang, Yalin

    Journal of Alzheimer's disease : JAD

    2024  Volume 98, Issue 4, Page(s) 1415–1426

    Abstract: Background: Amyloid-β (Aβ) plaques play a pivotal role in Alzheimer's disease. The current positron emission tomography (PET) is expensive and limited in availability. In contrast, blood-based biomarkers (BBBMs) show potential for characterizing Aβ ... ...

    Abstract Background: Amyloid-β (Aβ) plaques play a pivotal role in Alzheimer's disease. The current positron emission tomography (PET) is expensive and limited in availability. In contrast, blood-based biomarkers (BBBMs) show potential for characterizing Aβ plaques more affordably. We have previously proposed an MRI-based hippocampal morphometry measure to be an indicator of Aβ plaques.
    Objective: To develop and validate an integrated model to predict brain amyloid PET positivity combining MRI feature and plasma Aβ42/40 ratio.
    Methods: We extracted hippocampal multivariate morphometry statistics from MR images and together with plasma Aβ42/40 trained a random forest classifier to perform a binary classification of participant brain amyloid PET positivity. We evaluated the model performance using two distinct cohorts, one from the Alzheimer's Disease Neuroimaging Initiative (ADNI) and the other from the Banner Alzheimer's Institute (BAI), including prediction accuracy, precision, recall rate, F1 score, and AUC score.
    Results: Results from ADNI (mean age 72.6, Aβ+ rate 49.5%) and BAI (mean age 66.2, Aβ+ rate 36.9%) datasets revealed the integrated multimodal (IMM) model's superior performance over unimodal models. The IMM model achieved prediction accuracies of 0.86 in ADNI and 0.92 in BAI, surpassing unimodal models based solely on structural MRI (0.81 and 0.87) or plasma Aβ42/40 (0.73 and 0.81) predictors.
    Conclusions: Our IMM model, combining MRI and BBBM data, offers a highly accurate approach to predict brain amyloid PET positivity. This innovative multiplex biomarker strategy presents an accessible and cost-effective avenue for advancing Alzheimer's disease diagnostics, leveraging diverse pathologic features related to Aβ plaques and structural MRI.
    MeSH term(s) Humans ; Aged ; Alzheimer Disease/diagnostic imaging ; Alzheimer Disease/pathology ; Plaque, Amyloid/diagnostic imaging ; Amyloid beta-Peptides ; Amyloid ; Positron-Emission Tomography ; Magnetic Resonance Imaging ; Biomarkers ; Cognitive Dysfunction/diagnostic imaging ; tau Proteins
    Chemical Substances Amyloid beta-Peptides ; Amyloid ; Biomarkers ; tau Proteins
    Language English
    Publishing date 2024-04-05
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 1440127-7
    ISSN 1875-8908 ; 1387-2877
    ISSN (online) 1875-8908
    ISSN 1387-2877
    DOI 10.3233/JAD-231162
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Amyloid-related imaging abnormalities (ARIA): radiological, biological and clinical characteristics.

    Hampel, Harald / Elhage, Aya / Cho, Min / Apostolova, Liana G / Nicoll, James A R / Atri, Alireza

    Brain : a journal of neurology

    2023  Volume 146, Issue 11, Page(s) 4414–4424

    Abstract: Excess accumulation and aggregation of toxic soluble and insoluble amyloid-β species in the brain are a major hallmark of Alzheimer's disease. Randomized clinical trials show reduced brain amyloid-β deposits using monoclonal antibodies that target ... ...

    Abstract Excess accumulation and aggregation of toxic soluble and insoluble amyloid-β species in the brain are a major hallmark of Alzheimer's disease. Randomized clinical trials show reduced brain amyloid-β deposits using monoclonal antibodies that target amyloid-β and have identified MRI signal abnormalities called amyloid-related imaging abnormalities (ARIA) as possible spontaneous or treatment-related adverse events. This review provides a comprehensive state-of-the-art conceptual review of radiological features, clinical detection and classification challenges, pathophysiology, underlying biological mechanism(s) and risk factors/predictors associated with ARIA. We summarize the existing literature and current lines of evidence with ARIA-oedema/effusion (ARIA-E) and ARIA-haemosiderosis/microhaemorrhages (ARIA-H) seen across anti-amyloid clinical trials and therapeutic development. Both forms of ARIA may occur, often early, during anti-amyloid-β monoclonal antibody treatment. Across randomized controlled trials, most ARIA cases were asymptomatic. Symptomatic ARIA-E cases often occurred at higher doses and resolved within 3-4 months or upon treatment cessation. Apolipoprotein E haplotype and treatment dosage are major risk factors for ARIA-E and ARIA-H. Presence of any microhaemorrhage on baseline MRI increases the risk of ARIA. ARIA shares many clinical, biological and pathophysiological features with Alzheimer's disease and cerebral amyloid angiopathy. There is a great need to conceptually link the evident synergistic interplay associated with such underlying conditions to allow clinicians and researchers to further understand, deliberate and investigate on the combined effects of these multiple pathophysiological processes. Moreover, this review article aims to better assist clinicians in detection (either observed via symptoms or visually on MRI), management based on appropriate use recommendations, and general preparedness and awareness when ARIA are observed as well as researchers in the fundamental understanding of the various antibodies in development and their associated risks of ARIA. To facilitate ARIA detection in clinical trials and clinical practice, we recommend the implementation of standardized MRI protocols and rigorous reporting standards. With the availability of approved amyloid-β therapies in the clinic, standardized and rigorous clinical and radiological monitoring and management protocols are required to effectively detect, monitor, and manage ARIA in real-world clinical settings.
    MeSH term(s) Humans ; Alzheimer Disease/complications ; Antibodies, Monoclonal, Humanized/therapeutic use ; Amyloid beta-Peptides/metabolism ; Brain/metabolism ; Amyloid ; Amyloidogenic Proteins
    Chemical Substances Antibodies, Monoclonal, Humanized ; Amyloid beta-Peptides ; Amyloid ; Amyloidogenic Proteins
    Language English
    Publishing date 2023-06-09
    Publishing country England
    Document type Review ; Journal Article
    ZDB-ID 80072-7
    ISSN 1460-2156 ; 0006-8950
    ISSN (online) 1460-2156
    ISSN 0006-8950
    DOI 10.1093/brain/awad188
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Effective pharmacological management of Alzheimer's disease.

    Atri, Alireza

    The American journal of managed care

    2011  Volume 17 Suppl 13, Page(s) S346–55

    Abstract: Alzheimer's dementia represents organ failure of the brain. It denotes a clinical milestone that is the result of a pathological process, Alzheimer's disease (AD), which over 1 or more decades has wrought insidious destruction, and finally overwhelmed ... ...

    Abstract Alzheimer's dementia represents organ failure of the brain. It denotes a clinical milestone that is the result of a pathological process, Alzheimer's disease (AD), which over 1 or more decades has wrought insidious destruction, and finally overwhelmed the brain's capacities to compensate. It is incurable, progressive, and follows an individual pace and course. AD is particularly demanding and devastating to family and caregivers, and patients, all of whom suffer psychologically and emotionally. The cholinesterase inhibitors (ChEIs) donepezil, galantamine, and rivastigmine and the N-methyl- D-aspartate receptor antagonist memantine are approved by the US Food and Drug Administration for AD; they are often used in combination once the disease reaches moderate stages. The relatively good safety profile of these medications, along with their efficacy in alleviating symptoms, is supported by several level-I evidence-grade, short-term, randomized, placebo-controlled trials (RCTs). However, these studies are of limited value in assessing the real-world clinical and economic impact of AD therapies. Long-term, observational studies can provide complementary information to results from short-term clinical trials and more accurately assess practical long-term benefits, risks, costs, and effects on clinically meaningful end points. There is now accumulating and convergent evidence from short- and long-term RCTs, longer-term open-label extensions of RCTs, and long-term observational studies that ChEIs and memantine reduce decline in cognition and daily function, and delay nursing home placement. Optimal care in AD is multifactorial; it includes early diagnosis and multidisciplinary care with educational and nonpharmacological interventions, while ensuring safety, treating comorbidities, caring for caregivers, and appropriate initiation and maintenance of combination therapy.
    MeSH term(s) Alzheimer Disease/complications ; Alzheimer Disease/drug therapy ; Alzheimer Disease/pathology ; Cholinesterase Inhibitors/therapeutic use ; Cognition/drug effects ; Dementia ; Disease Progression ; Galantamine/therapeutic use ; Humans ; Indans/therapeutic use ; Memantine/therapeutic use ; Nootropic Agents/therapeutic use ; Phenylcarbamates/therapeutic use ; Piperidines/therapeutic use ; Rivastigmine ; Tacrine/therapeutic use ; Time Factors ; Treatment Outcome
    Chemical Substances Cholinesterase Inhibitors ; Indans ; Nootropic Agents ; Phenylcarbamates ; Piperidines ; Galantamine (0D3Q044KCA) ; Tacrine (4VX7YNB537) ; donepezil (8SSC91326P) ; Rivastigmine (PKI06M3IW0) ; Memantine (W8O17SJF3T)
    Language English
    Publishing date 2011-11
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 2035781-3
    ISSN 1936-2692 ; 1088-0224 ; 1096-1860
    ISSN (online) 1936-2692
    ISSN 1088-0224 ; 1096-1860
    Database MEDical Literature Analysis and Retrieval System OnLINE

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