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Peripheral vestibular system: Age-related vestibular loss and associated deficits

Journal of Otology 2021年第4期16卷 258-265页

作者： Jennifer Coto Carmen L.Alvarez Ivette Cejas Brett M.Colbert Bonnie E.Levin Joshua Huppert Tatjana Rundek Carey Balaban Susan H.Blanton david J.Lee david loewenstein Michael Hoffer Xue Zhong Liu University of Miami Miller School of Medicine Department of OtolaryngologyMiamiFLUSA San Juan Bautista Medical School CaguasPRUSA Medical Scientist Training Program University of Miami Miller School of MedicineMiamiFLUSA University of Miami Miller School of Medicine Department of Neurology and the Evelyn F.McKnight Brain InstituteMiamiFLUSA University of Pittsburgh Departments of OtolaryngologyNeurobiologyCommunication Sciences&Disordersand BioengineeringPittsburghPAUSA University of Miami Miller School of Medicine Dr.John T.Macdonald Department of Human GeneticsMiamiFLUSA University of Miami Miller School of Medicine Department of Public Health SciencesMiamiFLUSA University of Miami Miller School of Medicine Department of Psychiatry and Behavioral SciencesMiamiFLUSA

Given the interdependence of multiple factors in age-related vestibular loss (e.g., balance, vision,cognition), it is important to examine the individual contributions of these factors with ARVL. While therelationship between the vestibular and visual systems has been well studied (Bronstein et al., 2015),little is known about the association of the peripheral vestibular system with neurodegenerative disorders (Cronin et al., 2017). Further, emerging research developments implicate the vestibular system asan opportunity for examining brain function beyond balance, and into other areas, such as cognition andpsychological functioning. Additionally, the bidirectional impact of psychological functioning is understudied in ARVL. Recognition of ARVL as part of a multifaceted aging process will help guide thedevelopment of integrated interventions for patients who remain at risk for decline. In this review, wewill discuss a wide variety of characteristics of the peripheral vestibular system and ARVL, how it relatesto neurodegenerative diseases, and correlations between ARVL and balance, vision, cognitive, and psychological dysfunction. We also discuss clinical implications as well as future directions for research, withan emphasis on improving care for patients with ARVL.

关键词： Peripheral vestibular system Age-related vestibular loss Balance Vision Cognitive Psychological

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Failure to Recover from Proactive Semantic Interference Differentiates Amnestic Mild Cognitive Impairment and PreMCI from Normal Aging after Adjusting for Initial Learning Ability

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Advances in Alzheimer's Disease 2018年第2期7卷 50-61页

作者： Rosie E.Curiel Elizabeth A.Crocco Arlene Raffo Salvador M.Guinjoan Charles Nemeroff Ailyn Penate Daema Piña david A.loewenstein Department of Psychiatry and Behavioral Sciences Center on AgingMiller School of MedicineUniversity of MiamiMiamiUSA FLENI Foundation University of Buenos Aires Schools of Medicine and PsychologyBuenos AiresArgentina Wien Center for Alzheimer’s Disease and Memory Disorders Mount Sinai Medical CenterMiami BeachUSA

Background: There is increasing evidence that the failure to recover from proactive semantic interference (frPSI) may be an early cognitive marker of preclinical Alzheimer’s disease (AD). However, it is unclear whether frPSI effects reflect deficiencies in an individual’s initial learning capacity versus the actual inability to learn new semantically related targets. Objective: The current study was designed to adjust for learning capacity and then to examine the extent to which frPSI, proactive semantic interference (PSI) and retroactive semantic interference (RSI) effects could differentiate between older adults who were cognitively normal (CN), and those diagnosed with either Pre-Mild Cognitive Impairment (PreMCI) or amnestic MCI (aMCI). Methods: We employed the LASSI-L cognitive stress test to examine frPSI, PSI and RSI effects while simultaneously controlling for the participant’s initial learning capacity among 50 CN, 35 aMCI, and 16 PreMCI participants who received an extensive diagnostic work-up. Results: aMCI and PreMCI participants showed greater frPSI deficits (50% and 43.8% respectively) compared to only 14% of CNparticipants. PSI effects were observed for aMCI but not PreMCI participants relative to their CN counterparts. RSI failed to differentiate between any of the study groups. Conclusion: By using participants as their own controls and adjusting for overall learning and memory, it is clear that frPSI deficits occur with much greater frequency in individuals at higher risk for Alzheimer’s disease (AD), and likely reflect a failure of brain compensatory mechanisms.

关键词： MCI Alzheimer’s Disease Semantic Interference Memory

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Regional patterns of atrophy on MRI in Alzheimer’s disease: Neuropsychological features and progression rates in the ADNI cohort

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Advances in Alzheimer's Disease 2013年第4期2卷 135-147页

作者： Ranjan Duara david A. loewenstein Qian Shen Warren Barker Maria T. Greig Daniel Varon Melissa E. Murray Dennis W. Dickson Department of Neurology Miller School of Medicine University of Miami Miami USA Herbert Wertheim College of Medicine Florida International University Miami USA Mayo Clinic Jacksonville USA Wien Center for Alzheimer’s Disease and Memory Disorders Mount Sinai Medical Center Miami Beach USA

Background: Discrete clinical and pathological subtypes of Alzheimer’s disease (AD) with variable presentations and rates of progression are well known. These subtypes may have specific patterns of regional brain atrophy, which are identifiable on MRI scans. Methods: To examine distinct regions which had distinct underlying patterns of cortical atrophy, factor analytic techniques applied to structural MRI volumetric data from cognitively normal (CN) (n = 202), amnestic mild cognitive impairment (aMCI) (n = 333) or mild AD (n = 146) subjects, in the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database was applied. This revealed the existence of two neocortical (NeoC-1 and NeoC-2), and a limbic cluster of atrophic brain regions. The frequency and clinical correlates of these regional patterns of atrophy were evaluated among the three diagnostic groups, and the rates of progression from aMCI to AD, over 24 months were evaluated. Results: Discernable patterns of regional atrophy were observed in about 29% of CN, 55% of aMCI and 83% of AD subjects. Heterogeneity in clinical presentation and APOE ε4 frequency were associated with regional patterns of atrophy on MRI scans. The most rapid progression rates to dementia among aMCI subjects (n = 224), over a 24-month period, were in those with NeoC-1 regional impairment (68.2%), followed by the Limbic regional impairment (48.8%). The same pattern of results was observed when only aMCI amyloid positive subjects were examined. Conclusions: The neuroimaging results closely parallel findings described recently among AD patients with the hippocampal sparing and limbic subtypes of AD neuropathology at autopsy. We conclude that NeoC-1, Limbic and other patterns of MRI atrophy may be useful markers for predicting the rate of progression of aMCI to AD and could have utility selecting individuals at higher risk for progression in clinical trials.

关键词： Subtypes Mild Cognitive Impairment MCI preMCI Amnestic MCI Alzheimer’s Disease Dementia MRI Hippocampal Volume Algorithmic Diagnosis Clinical Diagnosis Neuropsychological Tests Longitudinal Analysis Regional Atrophy

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A Novel Computerized Cognitive Test for the Detection of Mild Cognitive Impairment and Its Association with Neurodegeneration in Alzheimer’s Disease Prone Brain Regions

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Advances in Alzheimer's Disease 2023年第3期12卷 38-54页

作者： Rosie E. Curiel Cid D. Diane Zheng Marcela Kitaigorodsky Malek Adjouadi Elizabeth A. Crocco Mike Georgiou Christian Gonzalez-Jimenez Alexandra Ortega Mohammed Goryawala Natalya Nagornaya Pradip Pattany Efrosyni Sfakianaki Ubbo Visser david A. loewenstein Center for Cognitive Neuroscience and Aging and Department of Psychiatry and Behavioral Sciences Miller School of Medicine University of Miami Miami Florida USA Center for Advanced Technology and Education Department of Electrical and Computer Engineering College of Engineering and Computing Florida International University Miami Florida USA Department of Radiology and Nuclear Medicine Miller School of Medicine University of Miami Miami Florida USA Department of Computer Science University of Miami Miami Florida USA

During the prodromal stage of Alzheimer’s disease (AD), neurodegenerative changes can be identified by measuring volumetric loss in AD-prone brain regions on MRI. Cognitive assessments that are sensitive enough to measure the early brain-behavior manifestations of AD and that correlate with biomarkers of neurodegeneration are needed to identify and monitor individuals at risk for dementia. Weak sensitivity to early cognitive change has been a major limitation of traditional cognitive assessments. In this study, we focused on expanding our previous work by determining whether a digitized cognitive stress test, the loewenstein-Acevedo Scales for Semantic Interference and Learning, Brief Computerized Version (LASSI-BC) could differentiate between Cognitively Unimpaired (CU) and amnestic Mild Cognitive Impairment (aMCI) groups. A second focus was to correlate LASSI-BC performance to volumetric reductions in AD-prone brain regions. Data was gathered from 111 older adults who were comprehensively evaluated and administered the LASSI-BC. Eighty-seven of these participants (51 CU;36 aMCI) underwent MR imaging. The volumes of 12 AD-prone brain regions were related to LASSI-BC and other memory tests correcting for False Discovery Rate (FDR). Results indicated that, even after adjusting for initial learning ability, the failure to recover from proactive semantic interference (frPSI) on the LASSI-BC differentiated between CU and aMCI groups. An optimal combination of frPSI and initial learning strength on the LASSI-BC yielded an area under the ROC curve of 0.876 (76.1% sensitivity, 82.7% specificity). Further, frPSI on the LASSI-BC was associated with volumetric reductions in the hippocampus, amygdala, inferior temporal lobes, precuneus, and posterior cingulate.

关键词： Mild Cognitive Impairment Proactive Semantic Interference MRI Volume Cortical Thickness LASSI-L

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The computerized LASSI-BC Test versus the Standard LASSI-L Paper-and-Pencil Version in Community-Based-Samples

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Advances in Alzheimer's Disease 2024年第1期13卷 11-25页

作者： Rosie E. Curiel Cid Alexandra Ortega Ubbo Visser Marcela Kitaigorodsky D. Diane Zheng Diana Hincapie Kirsten Horne Crenshaw Ashleigh Beaulieu Brooke Bosworth Liz Gallardo Emory Neer Sofia Ramirez Elizabeth A. Crocco Mike Georgiou Efrosyni Sfakianaki david A. loewenstein Center for Cognitive Neuroscience and Aging and Department of Psychiatry and Behavioral Sciences Miller School of Medicine University of Miami Miami FL USA Department of Computer Sciences University of Miami Coral Gables FL USA Nova Southeastern University Fort Lauderdale FL USA Department of Radiology and Nuclear Medicine Miller School of Medicine University of Miami Miami FL USA

Proactive Semantic Interference (PSI) and failure to recover from PSI (frPSI), are novel constructs assessed by the LASSI-L. These measures are sensitive to cognitive changes in early Mild Cognitive Impairment (MCI) and preclinical AD determined by Aβ load using PET. The goal of this study was to compare a new computerized version of the LASSI-L (LASSI-Brief Computerized) to the standard paper-and-pencil version of the test. In this study, we examined 110 cognitively unimpaired (CU) older adults and 79 with amnestic MCI (aMCI) who were administered the paper-and-pencil form of the LASSI-L. Their performance was compared with 62 CU older adults and 52 aMCI participants examined using the LASSI-BC. After adjustment for covariates (degree of initial learning, sex, education, and language of evaluation) both the standard and computerized versions distinguished between aMCI and CU participants. The performance of CU and aMCI groups using either form was relatively commensurate. Importantly, an optimal combination of Cued B2 recall and Cued B1 intrusions on the LASSI-BC yielded an area under the ROC curve of .927, a sensitivity of 92.3% and specificity of 88.1%, relative to an area under the ROC curve of .815, a sensitivity of 72.5%, and a specificity of 79.1% obtained for the paper-and-pencil LASSI-L. Overall, the LASSI-BC was comparable, and in some ways, superior to the paper-and-pencil LASSI-L. Advantages of the LASSI-BC include a more standardized administration, suitability for remote assessment, and an automated scoring mechanism that can be verified by a built-in audio recording of responses.

关键词： Mild Cognitive Impairment Proactive Semantic Interference LASSI-L Computerized Cognitive Assessment

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