Publications by authors named "Chiadi Onyike"

US clinical practice guidelines for the diagnostic evaluation of cognitive impairment due to Alzheimer's disease (AD) or a related dementia (ADRD) are two decades old. This evidence-based guideline was developed to empower all clinicians to implement a structured approach for evaluating a patient with symptoms that may represent clinical AD/ADRD. An expert workgroup conducted a review of 7374 publications (133 met inclusion criteria) and developed recommendations as steps in an evaluation process.

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US clinical practice guidelines for the diagnostic evaluation of cognitive impairment due to Alzheimer's disease (AD) or AD and related dementias (ADRD) are decades old and aimed at specialists. This evidence-based guideline was developed to empower all-including primary care-clinicians to implement a structured approach for evaluating a patient with symptoms that may represent clinical AD/ADRD. Through a modified-Delphi approach and guideline-development process (7374 publications were reviewed; 133 met inclusion criteria) an expert workgroup developed recommendations as steps in a patient-centered evaluation process.

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US clinical practice guidelines for the diagnostic evaluation of cognitive impairment due to Alzheimer's Disease (AD) or AD and related dementias (ADRD) are decades old and aimed at specialists. This evidence-based guideline was developed to empower all-including primary care-clinicians to implement a structured approach for evaluating a patient with symptoms that may represent clinical AD/ADRD. As part of the modified Delphi approach and guideline development process (7374 publications were reviewed; 133 met inclusion criteria) an expert workgroup developed recommendations as steps in a patient-centered evaluation process.

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Introduction: Psychotropic medication (PM) use in behavioral-variant frontotemporal dementia (bvFTD) is higher than in other dementias. However, no information exists on whether PM use differs between sporadic and genetic bvFTD.

Methods: We analyzed data from sporadic and genetic bvFTD participants with PM prescriptions in the Advancing Research and Treatment in Frontotemporal Lobar Degeneration/Longitudinal Evaluation of Familial Frontotemporal Dementia Subjects study.

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Introduction: Early-onset Alzheimer's disease (EOAD) manifests prior to the age of 65, and affects 4%-8% of patients with Alzheimer's disease (AD). The current analyses sought to examine longitudinal cognitive trajectories of participants with early-onset dementia.

Methods: Data from 307 cognitively normal (CN) volunteer participants and those with amyloid-positive EOAD or amyloid-negative cognitive impairment (EOnonAD) were compared.

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Introduction: Early-onset Alzheimer's disease (EOAD) and late-onset Alzheimer's disease (LOAD) share similar amyloid etiology, but evidence from smaller-scale studies suggests that they manifest differently clinically. Current analyses sought to contrast the cognitive profiles of EOAD and LOAD.

Methods: Z-score cognitive-domain composites for 311 amyloid-positive sporadic EOAD and 314 amyloid-positive LOAD participants were calculated from baseline data from age-appropriate control cohorts.

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Frontotemporal dementia (FTD) is one of the leading causes of young-onset dementia before age 65, typically manifesting as abnormal behavior (in behavioral variant FTD) or language impairment (in primary progressive aphasia). Although FTD affects all populations across the globe, knowledge regarding the pathophysiology and genetics derives primarily from studies conducted in North America and Western Europe. Globally, biomedical research for FTD is hindered by variable access to diagnosis, discussed in this group's earlier article, and by reduced access to expertise, funding, and infrastructure.

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Article Synopsis
  • Behavioral variant frontotemporal dementia (bvFTD) is characterized by a range of neuropsychiatric symptoms (NPS) that occur frequently both early and late in the illness, impacting emotional and behavioral aspects.
  • A study involving 354 participants identified four main clusters of NPS—affective, disinhibited, compulsive, and psychosis—showing that some symptoms fluctuate while others remain stable over time.
  • The findings suggest that NPS could be linked to specific brain network disruptions, providing insight for potential treatments, although the variability in symptoms indicates they may not be reliable indicators of disease progression.
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Objective: Spinocerebellar ataxia type 2 (SCA2) is a rare, inherited neurodegenerative disease characterised by progressive deterioration in both motor coordination and cognitive function. Atrophy of the cerebellum, brainstem, and spinal cord are core features of SCA2, however the evolution and pattern of whole-brain atrophy in SCA2 remain unclear. We undertook a multi-site, structural magnetic resonance imaging (MRI) study to comprehensively characterize the neurodegeneration profile of SCA2.

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Introduction: Delay in diagnosis of posterior cortical atrophy (PCA) syndrome is common, and the lack of familiarity with assessment tools for identifying visual cortical dysfunction is a contributing factor. We propose recommendations for the approach to the evaluation of PCA clinical features during the office visit, the neuropsychological evaluation, and the research setting. A recommended screening battery for eye clinics is also proposed.

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Article Synopsis
  • The study investigates the role of the genetic variant rs1990622 as a potential modifier of disease risk in frontotemporal lobar degeneration (FTLD), particularly among those with pathogenic variants.
  • Researchers enrolled participants from the ALLFTD study, analyzing the impact of rs1990622 on gray matter volume and cognitive function across various genetic groups related to FTD.
  • Results indicate that carriers of the minor allele of rs1990622 show increased gray matter volume and better cognitive performance, especially in the thalamus and among presymptomatic individuals.
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  • Clinical trials for spinocerebellar ataxias (SCA) need better endpoints to measure early disease progression and effectiveness of treatments, as current measures focus on later stages.
  • The READISCA consortium found that advanced multimodal magnetic resonance imaging (MRI) can track changes in brain structure and function over 6 months in participants with early-stage SCA mutations, indicating disease progression.
  • Results showed significant differences in microstructural changes between SCA patients and controls, suggesting that diffusion MRI could reduce the sample size needed for future trials compared to traditional assessments like the Scale for Assessment and Rating of Ataxia (SARA).
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Frontotemporal lobar degeneration with neuronal inclusions of the TAR DNA-binding protein 43 (FTLD-TDP) is a fatal neurodegenerative disorder with only a limited number of risk loci identified. We report our comprehensive genome-wide association study as part of the International FTLD-TDP Whole-Genome Sequencing Consortium, including 985 cases and 3,153 controls, and meta-analysis with the Dementia-seq cohort, compiled from 26 institutions/brain banks in the United States, Europe and Australia. We confirm as the strongest overall FTLD-TDP risk factor and identify as a novel FTLD-TDP risk factor.

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We present the case of a 62-year-old woman with probable behavioral variant of frontotemporal dementia (bvFTD) with cognitive/language deficits who demonstrated improved performance on cognitive/language testing and in functional tasks following long-term, home-based transcranial direct current stimulation (tDCS) coupled with computerized cognitive training (CCT). The patient underwent home-based tDCS (anode on the left prefrontal cortex and cathode on the right homologue) for 46 sessions over 10 weeks along with CCT. On post-treatment testing, the patient improved by 3 points on the Mini-Mental State Exam (MMSE) (23 to 26).

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Background: Identifying the characteristics of individuals who demonstrate response to an intervention allows us to predict who is most likely to benefit from certain interventions. Prediction is challenging in rare and heterogeneous diseases, such as primary progressive aphasia (PPA), that have varying clinical manifestations. We aimed to determine the characteristics of those who will benefit most from transcranial direct current stimulation (tDCS) of the left inferior frontal gyrus (IFG) using a novel heterogeneity and group identification analysis.

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Article Synopsis
  • The study investigates the effect of a specific genetic modifier on gray matter volume and cognitive function in patients with Frontotemporal Lobar Degeneration (FTLD), including both mutation carriers and sporadic cases.
  • Participants were recruited from the ALLFTD study and were genotyped for the rs1990622 SNP to assess the relationship between this genetic variant and cognitive outcomes across different genetic groups.
  • Findings indicate that the minor allele of rs1990622 is associated with increased gray matter volume and better cognitive scores in mutation carriers, especially affecting the thalamus, suggesting it may play a role in modifying the risk and impact of FTLD.
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Background: Fatigue is a prevalent and debilitating symptom in neurological disorders, including spinocerebellar ataxias (SCAs). However, the risk factors of fatigue in the SCAs as well as its impact have not been well investigated.

Objectives: To study the prevalence of fatigue in SCAs, the factors contributing to fatigue, and the influence of fatigue on quality of life.

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Cerebellar atrophy is the neuropathological hallmark of most ataxias. Hence, quantifying the volume of the cerebellar grey and white matter is of great interest. In this study, we aim to identify volume differences in the cerebellum between spinocerebellar ataxia type 1 (SCA1), SCA3 and SCA6 as well as multiple system atrophy of cerebellar type (MSA-C).

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Introduction: The pace of innovation has accelerated in virtually every area of tau research in just the past few years.

Methods: In February 2022, leading international tau experts convened to share selected highlights of this work during Tau 2022, the second international tau conference co-organized and co-sponsored by the Alzheimer's Association, CurePSP, and the Rainwater Charitable Foundation.

Results: Representing academia, industry, and the philanthropic sector, presenters joined more than 1700 registered attendees from 59 countries, spanning six continents, to share recent advances and exciting new directions in tau research.

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The Cerebellar Cognitive Affective/Schmahmann Syndrome (CCAS) manifests as impaired executive control, linguistic processing, visual spatial function, and affect regulation. The CCAS has been described in the spinocerebellar ataxias (SCAs), but its prevalence is unknown. We analyzed results of the CCAS/Schmahmann Scale (CCAS-S), developed to detect and quantify CCAS, in two natural history studies of 309 individuals Symptomatic for SCA1, SCA2, SCA3, SCA6, SCA7, or SCA8, 26 individuals Pre-symptomatic for SCA1 or SCA3, and 37 Controls.

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Background: Cerebellar atrophy is the neuropathological hallmark of most ataxias. Hence, quantifying the volume of the cerebellar grey and white matter is of great interest. In this study, we aim to identify volume differences in the cerebellum between spinocerebellar ataxia type 1 (SCA1), SCA3 and SCA6 as well as multiple system atrophy of cerebellar type (MSA-C).

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Article Synopsis
  • Researchers developed an MRI-based signature to identify brain atrophy linked to sporadic early-onset Alzheimer's disease (EOAD) using two patient samples, one small (n=25) and another larger (n=211).
  • The study found consistent atrophy patterns in specific brain regions, like the caudal lateral temporal cortex and inferior parietal lobule, while the medial temporal lobe was relatively spared.
  • The EOAD-signature atrophy correlates with cognitive impairment severity, suggesting it's a reliable biomarker for Alzheimer’s-related neurodegeneration in clinical trials.
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Article Synopsis
  • The LEADS study focuses on understanding the genetic causes of early-onset Alzheimer's Disease (EOAD), specifically in individuals aged 40-64, by screening for known pathogenic variants.
  • *Whole exome sequencing of 299 participants found pathogenic variants in 1.35% of EOAD cases and 6.58% of early-onset non-Alzheimer's disease cases, but no gene showed a significant enrichment for rare functional variants.
  • *The findings suggest that LEADS may include new genetic variants related to early-onset cognitive impairment, making it an important resource for ongoing Alzheimer's research.*
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