Publications by authors named "Mantyh W"

Introduction: Little is known about the factors underpinning discordant cerebrospinal fluid (CSF) amyloid beta (Aβ) versus p-tau181/Aβ or CSF Aβ versus Aβ positron emission tomography (PET).

Methods: We stratified 570 non-demented Alzheimer's Disease Neuroimaging Initiative (ADNI) participants by Aβ PET and further by CSF Aβ or p-tau181/Aβ. We used analysis of covariance testing adjusting for covariates, followed by Tukey post hoc pairwise comparisons, to compare CSF soluble triggering receptor expressed on myeloid cells-2 (sTREM2) across four participant groups: CSF+ with CSF- , CSF- with CSF+ , and concordant CSF/CSF.

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  • Cockayne syndrome (CS) is a rare genetic disorder causing premature aging and various neurological issues, but the clinical features of neurodegeneration, especially in later stages, are not well understood.
  • A study examined medical records of individuals with CS who lived beyond 18 years across three countries to identify common neurological complications, finding that most showed significant neurocognitive and physical decline.
  • Results indicated that nearly all participants experienced neurocognitive/neuropsychiatric symptoms, with high rates of tremors, peripheral neuropathy, and observable brain atrophy, suggesting a link between DNA repair defects in CS and broader neurodegenerative processes.
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Objectives: frequency varies by geography and ancestry. We provide data regarding the frequency of this allele in the Ojibwe people, the fifth largest Indigenous people in the United States.

Methods: Population study including 33 cognitively normal older individuals of an Ojibwe Tribal Nation (total population: 984; all with ≥25% Ojibwe ancestry).

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Non-pharmaceutical interventions (NPI) have great potential to improve cognitive function but limited investigation to discover NPI repurposing for Alzheimer's Disease (AD). This is the first study to develop an innovative framework to extract and represent NPI information from biomedical literature in a knowledge graph (KG), and train link prediction models to repurpose novel NPIs for AD prevention. We constructed a comprehensive KG, called ADInt, by extracting NPI information from biomedical literature.

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Background: The increasing needs of people living with dementia (PLWD) in Vietnam present an enormous public health challenge. Vietnam is an understudied country, and little is known regarding the overall unmet needs of caregivers or the demographic risk factors associated with unmet caregiving needs. This study aimed to determine the burden of unmet care needs of community-dwelling PLWD and identify sociodemographic risks associated with unmet care needs.

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Importance: Visual hallucinations are a core feature of dementia with Lewy bodies and primary psychiatric disease, yet identification of a hallucination vs normal spiritual experience depends on cultural context. Almost no information exists in the medical literature regarding normal spiritual experiences in American Indian participants in the context of a neurocognitive evaluation.

Objective: To assess the characteristics of a normal spiritual experience in an Ojibwe Tribal Nation.

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  • * A study applied a polygenic hazard score to early-onset AD patients and found that their scores were similar to those of late-onset patients, suggesting that genetic factors associated with late-onset AD do not explain early-onset cases.
  • * The research indicates that early-onset AD has a distinct genetic makeup compared to late-onset AD, highlighting the need for further investigation into unique genetic factors related to early-onset AD.
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  • Traumatic encephalopathy syndrome (TES) is linked to repetitive head impacts and presents cognitive symptoms similar to Alzheimer's disease (AD), complicating diagnosis due to overlapping neuropathological features.
  • A study of 154 participants compared cognitive performance, brain volume, and plasma biomarkers among those with TES, AD, and healthy controls, revealing that Aβ[+] TES patients performed worse on specific cognitive tests compared to Aβ[-] TES patients.
  • Results showed that both Aβ[+] and Aβ[-] TES groups had lower brain volumes in certain areas than healthy controls, but their volumes were similar to those of AD patients; additionally, Aβ[+] TES had higher levels of specific plasma biomarkers.
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Recently, computational drug repurposing has emerged as a promising method for identifying new pharmaceutical interventions (PI) for Alzheimer's Disease (AD). Non-pharmaceutical interventions (NPI), such as Vitamin E and Music therapy, have great potential to improve cognitive function and slow the progression of AD, but have largely been unexplored. This study predicts novel NPIs for AD through link prediction on our developed biomedical knowledge graph.

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Background And Objectives: Traumatic encephalopathy syndrome (TES) has overlapping clinical symptoms with Alzheimer disease (AD). AD pathology commonly co-occurs with chronic traumatic encephalopathy (CTE) pathology. There are currently no validated CTE biomarkers.

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Alzheimer's Disease (AD) is a neurodegenerative disorder that is still not fully understood. Sex modifies AD vulnerability, but the reasons for this are largely unknown. We utilize two independent electronic medical record (EMR) systems across 44,288 patients to perform deep clinical phenotyping and network analysis to gain insight into clinical characteristics and sex-specific clinical associations in AD.

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Objective: The clinical phenotype of the rare behavioural variant of Alzheimer's disease (bvAD) is insufficiently understood. Given the strong clinico-anatomical correlations of tau pathology in AD, we investigated the distribution of tau deposits in bvAD, in-vivo and ex-vivo, using positron emission tomography (PET) and postmortem examination.

Methods: For the tau PET study, seven amyloid-β positive bvAD patients underwent [F]flortaucipir or [F]RO948 PET.

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We investigated whether clinically normal older adults with remote, mild traumatic brain injury (mTBI) show evidence of higher cortical Aβ burden. Our study included 134 clinically normal older adults (age 74.1 ± 6.

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We report a group of patients presenting with a progressive dementia syndrome characterized by predominant dysfunction in core executive functions, relatively young age of onset and positive biomarkers for Alzheimer's pathophysiology. Atypical frontal, dysexecutive/behavioural variants and early-onset variants of Alzheimer's disease have been previously reported, but no diagnostic criteria exist for a progressive dysexecutive syndrome. In this retrospective review, we report on 55 participants diagnosed with a clinically defined progressive dysexecutive syndrome with F-fluorodeoxyglucose-positron emission tomography and Alzheimer's disease biomarkers available.

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Importance: Biomarkers for chronic traumatic encephalopathy (CTE) are currently lacking. The radiotracer fluorine F 18-labeled (18F)-flortaucipir (FTP) detects tau pathology in Alzheimer disease, and positron emission tomography (PET) with FTP shows elevated binding in individuals at risk for CTE. No study, however, has assessed the correlation between in vivo FTP PET and postmortem tau in CTE.

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See Gordon (doi:10.1093/brain/awy052) for a scientific commentary on this article.Predicting underlying pathology based on clinical presentation has historically proven difficult, especially in older cohorts.

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Historically, payment for cognitive, nonprocedural care has required provision of face-to-face evaluation and management as part of general ambulatory or inpatient care. Although non-face-to-face patient care (e.g.

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Objective: To describe the phenomenon of tau-negative amnestic dementia mimicking Alzheimer disease (AD) clinically and radiologically and to highlight the importance of biomarkers in AD research.

Methods: Eight participants with amnestic mild cognitive impairment or AD dementia were evaluated by a behavioral neurologist and had a standardized neuropsychological battery performed. All participants completed structural (MRI) and molecular (amyloid and tau PET) imaging.

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Importance: Erythromelalgia is a clinical diagnosis based on intermittent warmth, erythema, and pain in the distal extremities. One problem facing physicians is how to objectively test for this disease. Given that other painful conditions of the distal extremities (ie, neuropathy related to human immunodeficiency virus, diabetes, or Fabry disease) can be evaluated with a skin biopsy to visualize pathologically decreased densities of the small nerve fibers that innervate the epidermis, one hypothesis is that erythromelalgia could similarly be associated with a loss of epidermal nerve fiber density (ENFD).

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Study Objectives: Narcolepsy and idiopathic hypersomnia are commonly treated by sleep specialists and encountered by other medical providers. Although pharmacotherapy with modafinil and traditional stimulants is considered the mainstay of treatment, physicians are often uncomfortable with their prescription because of concerns regarding misuse. The goal of this study was to assess the frequency of stimulant misuse in this population.

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Objective: This study attempts to quantify the impact of the introduction of local second-level health services on nonmedical costs (NMCs) for residents of the rural Ecuadorian county of La Maná.

Methods: NMCs for patients accessing second-level health care were assessed by using a quasi-experimental pre- and postintervention study design. In 2007, before local second-level health care services existed, and then in 2008, after the introduction of second-level health care services in the form of a county hospital, 508 patients from the county who sought second-level health care were interviewed.

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Although skeletal pain is a leading cause of chronic pain and disability, relatively little is known about the specific populations of nerve fibers that innervate the skeleton. Recent studies have reported that therapies blocking nerve growth factor (NGF) or its cognate receptor, tropomyosin receptor kinase A (TrkA) are efficacious in attenuating skeletal pain. A potential factor to consider when assessing the analgesic efficacy of targeting NGF-TrkA signaling in a pain state is the fraction of NGF-responsive TrkA+ nociceptors that innervate the tissue from which the pain is arising, as this innervation and the analgesic efficacy of targeting NGF-TrkA signaling may vary considerably from tissue to tissue.

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