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1.
Alzheimers Dement ; 20(5): 3305-3321, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38539269

RESUMO

INTRODUCTION: Published norms are typically cross-sectional and often are not sensitive to preclinical cognitive changes due to dementia. We developed and validated demographically adjusted cross-sectional and longitudinal normative standards using harmonized outcomes from two Alzheimer's disease (AD) risk-enriched cohorts. METHODS: Data from the Wisconsin Registry for Alzheimer's Prevention and the Wisconsin Alzheimer's Disease Research Center were combined. Quantile regression was used to develop unconditional (cross-sectional) and conditional (longitudinal) normative standards for 18 outcomes using data from cognitively unimpaired participants (N = 1390; mean follow-up = 9.25 years). Validity analyses (N = 2456) examined relationships between percentile scores (centiles), consensus-based cognitive statuses, and AD biomarker levels. RESULTS: Unconditional and conditional centiles were lower in those with consensus-based impairment or biomarker positivity. Similarly, quantitative biomarker levels were higher in those whose centiles suggested decline. DISCUSSION: This study presents normative standards for cognitive measures sensitive to pre-clinical changes. Future directions will investigate potential clinical applications of longitudinal normative standards. HIGHLIGHTS: Quantile regression was used to construct longitudinal norms for cognitive tests. Poorer percentile scores were related to concurrent diagnosis and Alzheimer's disease biomarkers. A ShinyApp was built to display test scores and norms and flag low performance.


Assuntos
Doença de Alzheimer , Biomarcadores , Testes Neuropsicológicos , Humanos , Doença de Alzheimer/diagnóstico , Masculino , Idoso , Feminino , Testes Neuropsicológicos/normas , Testes Neuropsicológicos/estatística & dados numéricos , Estudos Longitudinais , Wisconsin , Estudos Transversais , Disfunção Cognitiva/diagnóstico , Estudos de Coortes , Cognição/fisiologia , Idoso de 80 Anos ou mais , Pessoa de Meia-Idade
2.
Alzheimers Dement ; 19(1): 343-352, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-35757902

RESUMO

Episodes of lucidity (ELs) in Alzheimer's disease and Alzheimer's disease-related dementias (AD/ADRD), have garnered increasing attention as an important area of research. Efforts to study lucidity suffer from a lack of clear definitional criteria, inconsistent conceptualization, and diverse approaches to operationalizing features of these events. To advance systematic investigation of ELs in AD/ADRD, there is a need for clarity and precision in labeling event attributes, markers, and specific measurement strategies that enable operational harmonization across distinct approaches to investigating the relatively broad and nascent phenomenon. To that end, we propose a preliminary research framework to guide harmonization of approaches to investigating ELs in AD/ADRD. Our goal is to provide an initial schematic that encourages uniform labeling of operational decisions about ELs.


Assuntos
Doença de Alzheimer , Demência , Humanos , Cognição
3.
Brain ; 143(1): 320-335, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31886494

RESUMO

This study investigated differences in retrospective cognitive trajectories between amyloid and tau PET biomarker stratified groups in initially cognitively unimpaired participants sampled from the Wisconsin Registry for Alzheimer's Prevention. One hundred and sixty-seven initially unimpaired individuals (baseline age 59 ± 6 years; 115 females) were stratified by elevated amyloid-ß and tau status based on 11C-Pittsburgh compound B (PiB) and 18F-MK-6240 PET imaging. Mixed effects models were used to determine if longitudinal cognitive trajectories based on a composite of cognitive tests including memory and executive function differed between biomarker groups. Secondary analyses investigated group differences for a variety of cross-sectional health and cognitive tests, and associations between 18F-MK-6240, 11C-PiB, and age. A significant group × age interaction was observed with post hoc comparisons indicating that the group with both elevated amyloid and tau pathophysiology were declining approximately three times faster in retrospective cognition compared to those with just one or no elevated biomarkers. This result was robust against various thresholds and medial temporal lobe regions defining elevated tau. Participants were relatively healthy and mostly did not differ between biomarker groups in health factors at the beginning or end of study, or most cognitive measures at study entry. Analyses investigating association between age, MK-6240 and PiB indicated weak associations between age and 18F-MK-6240 in tangle-associated regions, which were negligible after adjusting for 11C-PiB. Strong associations, particularly in entorhinal cortex, hippocampus and amygdala, were observed between 18F-MK-6240 and global 11C-PiB in regions associated with Braak neurofibrillary tangle stages I-VI. These results suggest that the combination of pathological amyloid and tau is detrimental to cognitive decline in preclinical Alzheimer's disease during late middle-age. Within the Alzheimer's disease continuum, middle-age health factors likely do not greatly influence preclinical cognitive decline. Future studies in a larger preclinical sample are needed to determine if and to what extent individual contributions of amyloid and tau affect cognitive decline. 18F-MK-6240 shows promise as a sensitive biomarker for detecting neurofibrillary tangles in preclinical Alzheimer's disease.


Assuntos
Encéfalo/diagnóstico por imagem , Disfunção Cognitiva/diagnóstico por imagem , Placa Amiloide/diagnóstico por imagem , Idoso , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/metabolismo , Doença de Alzheimer/fisiopatologia , Doença de Alzheimer/psicologia , Peptídeos beta-Amiloides/metabolismo , Compostos de Anilina , Encéfalo/metabolismo , Radioisótopos de Carbono , Disfunção Cognitiva/metabolismo , Disfunção Cognitiva/fisiopatologia , Disfunção Cognitiva/psicologia , Feminino , Radioisótopos de Flúor , Humanos , Isoquinolinas , Estudos Longitudinais , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Emaranhados Neurofibrilares/metabolismo , Testes Neuropsicológicos , Placa Amiloide/metabolismo , Tomografia por Emissão de Pósitrons , Sintomas Prodrômicos , Tiazóis , Proteínas tau/metabolismo
4.
Alzheimers Dement ; 17(2): 255-270, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33215876

RESUMO

INTRODUCTION: Non-pharmacological treatments (NPTs) have the potential to improve meaningful outcomes for older people at risk of, or living with dementia, but research often lacks methodological rigor and continues to produce mixed results. METHODS: In the current position paper, experts in NPT research have specified treatment targets, aims, and ingredients using an umbrella framework, the Rehabilitation Treatment Specification System. RESULTS: Experts provided a snapshot and an authoritative summary of the evidence for different NPTs based on the best synthesis efforts, identified main gaps in knowledge and relevant barriers, and provided directions for future research. Experts in trial methodology provide best practice principles and recommendations for those working in this area, underscoring the importance of prespecified protocols. DISCUSSION: We conclude that the evidence strongly supports various NPTs in relation to their primary targets, and discuss opportunities and challenges associated with a unifying theoretical framework to guide future efforts in this area.


Assuntos
Envelhecimento/fisiologia , Demência , Terapia Cognitivo-Comportamental , Demência/reabilitação , Demência/terapia , Exercício Físico , Humanos , Meditação , Musicoterapia
5.
Behav Res Methods ; 52(4): 1681-1699, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32128696

RESUMO

The verbal fluency task-listing words from a category or words that begin with a specific letter-is a common experimental paradigm that is used to diagnose memory impairments and to understand how we store and retrieve knowledge. Data from the verbal fluency task are analyzed in many different ways, often requiring manual coding that is time intensive and error-prone. Researchers have also used fluency data from groups or individuals to estimate semantic networks-latent representations of semantic memory that describe the relations between concepts-that further our understanding of how knowledge is encoded. However computational methods used to estimate networks are not standardized and can be difficult to implement, which has hindered widespread adoption. We present SNAFU: the Semantic Network and Fluency Utility, a tool for estimating networks from fluency data and automatizing traditional fluency analyses, including counting cluster switches and cluster sizes, intrusions, perseverations, and word frequencies. In this manuscript, we provide a primer on using the tool, illustrate its application by creating a semantic network for foods, and validate the tool by comparing results to trained human coders using multiple datasets.


Assuntos
Web Semântica , Semântica , Comportamento Verbal , Humanos , Memória , Testes Neuropsicológicos
6.
J Int Neuropsychol Soc ; 25(1): 1-14, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30482257

RESUMO

OBJECTIVES: A major challenge in cognitive aging is differentiating preclinical disease-related cognitive decline from changes associated with normal aging. Neuropsychological test authors typically publish single time-point norms, referred to here as unconditional reference values. However, detecting significant change requires longitudinal, or conditional reference values, created by modeling cognition as a function of prior performance. Our objectives were to create, depict, and examine preliminary validity of unconditional and conditional reference values for ages 40-75 years on neuropsychological tests. METHOD: We used quantile regression to create growth-curve-like models of performance on tests of memory and executive function using participants from the Wisconsin Registry for Alzheimer's Prevention. Unconditional and conditional models accounted for age, sex, education, and verbal ability/literacy; conditional models also included past performance on and number of prior exposures to the test. Models were then used to estimate individuals' unconditional and conditional percentile ranks for each test. We examined how low performance on each test (operationalized as <7th percentile) related to consensus-conference-determined cognitive statuses and subjective impairment. RESULTS: Participants with low performance were more likely to receive an abnormal cognitive diagnosis at the current visit (but not later visits). Low performance was also linked to subjective and informant reports of worsening memory function. CONCLUSIONS: The percentile-based methods and single-test results described here show potential for detecting troublesome within-person cognitive change. Development of reference values for additional cognitive measures, investigation of alternative thresholds for abnormality (including multi-test criteria), and validation in samples with more clinical endpoints are needed. (JINS, 2019, 25, 1-14).


Assuntos
Doença de Alzheimer/prevenção & controle , Envelhecimento Cognitivo/fisiologia , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/fisiopatologia , Testes Neuropsicológicos , Sistema de Registros , Adulto , Idoso , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Valores de Referência , Wisconsin
7.
J Int Neuropsychol Soc ; 25(2): 119-133, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30522545

RESUMO

OBJECTIVES: Prior research has identified numerous genetic (including sex), education, health, and lifestyle factors that predict cognitive decline. Traditional model selection approaches (e.g., backward or stepwise selection) attempt to find one model that best fits the observed data, risking interpretations that only the selected predictors are important. In reality, several predictor combinations may fit similarly well but result in different conclusions (e.g., about size and significance of parameter estimates). In this study, we describe an alternative method, Information-Theoretic (IT) model averaging, and apply it to characterize a set of complex interactions in a longitudinal study on cognitive decline. METHODS: Here, we used longitudinal cognitive data from 1256 late-middle aged adults from the Wisconsin Registry for Alzheimer's Prevention study to examine the effects of sex, apolipoprotein E (APOE) ɛ4 allele (non-modifiable factors), and literacy achievement (modifiable) on cognitive decline. For each outcome, we applied IT model averaging to a set of models with different combinations of interactions among sex, APOE, literacy, and age. RESULTS: For a list-learning test, model-averaged results showed better performance for women versus men, with faster decline among men; increased literacy was associated with better performance, particularly among men. APOE had less of an association with cognitive performance in this age range (∼40-70 years). CONCLUSIONS: These results illustrate the utility of the IT approach and point to literacy as a potential modifier of cognitive decline. Whether the protective effect of literacy is due to educational attainment or intrinsic verbal intellectual ability is the topic of ongoing work. (JINS, 2019, 25, 119-133).


Assuntos
Disfunção Cognitiva/epidemiologia , Alfabetização/estatística & dados numéricos , Modelos Teóricos , Sistema de Registros , Adulto , Idoso , Doença de Alzheimer/prevenção & controle , Apolipoproteína E4/genética , Disfunção Cognitiva/genética , Escolaridade , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Fatores de Proteção , Fatores Sexuais , Wisconsin/epidemiologia
8.
J Int Neuropsychol Soc ; 22(10): 1016-1025, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27903330

RESUMO

OBJECTIVES: Intraindividual cognitive variability (IICV) has been shown to differentiate between groups with normal cognition, mild cognitive impairment (MCI), and dementia. This study examined whether baseline IICV predicted subsequent mild to moderate cognitive impairment in a cognitively normal baseline sample. METHODS: Participants with 4 waves of cognitive assessment were drawn from the Wisconsin Registry for Alzheimer's Prevention (WRAP; n=684; 53.6(6.6) baseline age; 9.1(1.0) years follow-up; 70% female; 74.6% parental history of Alzheimer's disease). The primary outcome was Wave 4 cognitive status ("cognitively normal" vs. "impaired") determined by consensus conference; "impaired" included early MCI (n=109), clinical MCI (n=11), or dementia (n=1). Primary predictors included two IICV variables, each based on the standard deviation of a set of scores: "6 Factor IICV" and "4 Test IICV". Each IICV variable was tested in a series of logistic regression models to determine whether IICV predicted cognitive status. In exploratory analyses, distribution-based cutoffs incorporating memory, executive function, and IICV patterns were used to create and test an MCI risk variable. RESULTS: Results were similar for the IICV variables: higher IICV was associated with greater risk of subsequent impairment after covariate adjustment. After adjusting for memory and executive functioning scores contributing to IICV, IICV was not significant. The MCI risk variable also predicted risk of impairment. CONCLUSIONS: While IICV in middle-age predicts subsequent impairment, it is a weaker risk indicator than the memory and executive function scores contributing to its calculation. Exploratory analyses suggest potential to incorporate IICV patterns into risk assessment in clinical settings. (JINS, 2016, 22, 1016-1025).


Assuntos
Doença de Alzheimer/diagnóstico , Disfunção Cognitiva/diagnóstico , Função Executiva/fisiologia , Transtornos da Memória/diagnóstico , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Sistema de Registros , Wisconsin
9.
Alzheimers Dement (Amst) ; 16(1): e12524, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38239330

RESUMO

We propose a novel method to assess delayed primacy in the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) memory test. We then examine whether this measure predicts post mortem Alzheimer's disease (AD) neuropathology in individuals who were clinically unimpaired at baseline. A total of 1096 individuals were selected from the Rush Alzheimer's Disease Center database registry. All participants were clinically unimpaired at baseline, and had subsequently undergone brain autopsy. Average age at baseline was 78.8 (6.92). A Bayesian regression analysis was carried out with global pathology as an outcome; demographic, clinical, and apolipoprotein E (APOE) data as covariates; and cognitive predictors, including delayed primacy. Global AD pathology was best predicted by delayed primacy. Secondary analyses showed that delayed primacy was mostly associated with neuritic plaques, whereas total delayed recall was associated with neurofibrillary tangles. Sex differential associations were observed. We conclude that CERAD-derived delayed primacy is a useful metric for early detection and diagnosis of AD in unimpaired individuals. Highlights: We propose a novel method to analyse serial position in the CERAD memory test.We analyse data from 1096 individuals who were cognitively unimpaired at baseline.Delayed primacy predicts post mortem pathology better than traditional metrics.

10.
Clin Neuropsychol ; 38(2): 453-470, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-37349970

RESUMO

Objective: Process-based scores of episodic memory tests, such as the recency ratio (Rr), have been found to compare favourably to, or to be better than, most conventional or "traditional" scores employed to estimate memory ability in older individuals (Bock et al., 2021; Bruno et al., 2019). We explored the relationship between process-based scores and hippocampal volume in older adults, while comparing process-based to traditional story recall-derived scores, to examine potential differences in their predictive abilities. Methods: We analysed data from 355 participants extracted from the WRAP and WADRC databases, who were classified as cognitively unimpaired, or exhibited mild cognitive impairment (MCI) or dementia. Story Recall was measured with the Logical Memory Test (LMT) from the Weschler Memory Scale Revised, collected within twelve months of the magnetic resonance imaging scan. Linear regression analyses were conducted with left or right hippocampal volume (HV) as outcomes separately, and with Rr, Total ratio, Immediate LMT, or Delayed LMT scores as predictors, along with covariates. Results: Higher Rr and Tr scores significantly predicted lower left and right HV, while Tr showed the best model fit of all, as indicated by AIC. Traditional scores, Immediate LMT and Delayed LMT, were significantly associated with left and right HV, but were outperformed by both process-based scores for left HV, and by Tr for right HV. Conclusions: Current findings show the direct relationship between hippocampal volume and all the LMT scores examined here, and that process-based scores outperform traditional scores as markers of hippocampal volume.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Humanos , Idoso , Testes Neuropsicológicos , Disfunção Cognitiva/patologia , Hipocampo/patologia , Memória de Curto Prazo , Análise de Regressão , Imageamento por Ressonância Magnética , Doença de Alzheimer/psicologia
11.
Neurobiol Aging ; 133: 87-98, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37925995

RESUMO

Neuropsychological measures sensitive to decline in the preclinical phase of Alzheimer's disease are needed. We previously demonstrated that higher amyloid-beta (Aß) assessed by positron emission tomography in adults without cognitive impairment was associated with recall of fewer proper names in Logical Memory story recall. The current study investigated the association between proper names and cerebrospinal fluid biomarkers (Aß42/40, phosphorylated tau181 [pTau181], neurofilament light) in 223 participants from the Wisconsin Registry for Alzheimer's Prevention. We assessed associations between biomarkers and delayed Logical Memory total score and proper names using binary logistic regressions. Sensitivity analyses used multinomial logistic regression and stratified biomarker groups. Lower Logical Memory total score and proper names scores from the most recent visit were associated with biomarker positivity. Relatedly, there was a 27% decreased risk of being classified Aß42/40+/pTau181+ for each additional proper name recalled. A linear mixed effects model found that longitudinal change in proper names recall was predicted by biomarker status. These results demonstrate a novel relationship between proper names and Alzheimer's disease-cerebrospinal fluid pathology.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Humanos , Doença de Alzheimer/patologia , Proteínas tau/líquido cefalorraquidiano , Estudos Longitudinais , Progressão da Doença , Disfunção Cognitiva/psicologia , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Biomarcadores/líquido cefalorraquidiano , Fragmentos de Peptídeos/líquido cefalorraquidiano
12.
bioRxiv ; 2023 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-37425732

RESUMO

INTRODUCTION: We propose a novel method to assess delayed primacy in the CERAD memory test. We then examine whether this measure predicts post mortem Alzheimer's disease (AD) neuropathology in individuals who were clinically unimpaired at baseline. METHODS: A total of 1096 individuals were selected from the Rush Alzheimer's Disease Center database registry. All participants were clinically unimpaired at baseline, and had subsequently undergone brain autopsy. Average age at baseline was 78.8 (6.92). A Bayesian regression analysis was carried out with global pathology as outcome; demographic, clinical and APOE data as covariates; and cognitive predictors, including delayed primacy. RESULTS: Global AD pathology was best predicted by delayed primacy. Secondary analyses showed that delayed primacy was mostly associated with neuritic plaques, whereas total delayed recall was associated with neurofibrillary tangles. DISCUSSION: We conclude that CERAD-derived delayed primacy is a useful metric for early detection and diagnosis of AD in unimpaired individuals.

13.
Brain Sci ; 13(11)2023 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-38002491

RESUMO

The association between depressive symptomatology and cognitive decline has been examined using the Centre for Epidemiologic Studies-Depression Scale (CES-D); however, concerns have been raised about this self-report measure. Here, we examined how the CES-D total score from the 14- and 10-item versions compared to the 20-item version in predicting progression to cognitive decline from a cognitively unimpaired baseline. Data from 1054 participants were analysed using ordinal logistic regression, alongside moderator and receiver-operating characteristics curve analyses. All baseline total scores significantly predicted progression to cognitive decline. The 14-item version was better than the 20-item version in predicting consensus diagnosis, as shown by their AICs, while also showing the highest accuracy when discriminating between participants by diagnosis at last visit. We did not find sex to moderate the relationship between CES-D score and cognitive decline. Current findings suggest the 10- and 14-item versions of the CES-D are comparable to the 20-item version, and that the 14-item version may be better at predicting longitudinal consensus diagnosis compared to the 20-item version.

14.
Gerontologist ; 63(1): 13-27, 2023 01 24.
Artigo em Inglês | MEDLINE | ID: mdl-35797987

RESUMO

BACKGROUND AND OBJECTIVES: Episodes of lucidity (ELs), or a transient return of abilities believed to be lost in people living with dementia, are a growing area of interest. These events hold important implications for care, caregiving, and our understanding of underlying etiologies. Research on ELs is largely limited to retrospective reports. The perspectives of professional and family caregivers on ELs and research approaches can inform efforts to define and study lucidity. The present study examined family caregiver and hospice clinician experiences with and perspectives on ELs in people living with dementia and observational approaches to studying these events. RESEARCH DESIGN AND METHODS: This exploratory, descriptive qualitative study employed semistructured interviews (N = 20 caregivers, N = 6 clinicians). Data were analyzed using Rapid Identification of Themes and subsequent duplicate review of interview data to enhance trustworthiness. RESULTS: Most participants readily recalled events they perceived as ELs, describing a transient return of abilities they felt was significant and/or meaningful. Defining features, interpretations, and the perceived impact of ELs varied, although ELs were commonly conceptualized as a manifestation of self. Caregivers described extensive efforts to detect patterns and supportive social conditions for ELs. Participants supported use of audiovisual observation to study ELs and provided recommendations for privacy, workflow, and caregiver engagement. DISCUSSION AND IMPLICATIONS: Interpretations of ELs are heterogeneous, and recognition of these events may necessitate close familiarity with the person living with dementia. Participants endorse observational approaches and integration of caregivers in this research.


Assuntos
Cuidadores , Demência , Humanos , Estudos Retrospectivos , Cognição , Pesquisa Qualitativa
15.
Front Behav Neurosci ; 17: 1294648, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38322496

RESUMO

Background: Alzheimer's disease (AD) is a progressive neurologic disease and the most common cause of dementia. Classic pathology in AD is characterized by inflammation, abnormal presence of tau protein, and aggregation of ß-amyloid that disrupt normal neuronal function and lead to cell death. Deficits in communication also occur during disease progression and significantly reduce health, well-being, and quality of life. Because clinical diagnosis occurs in the mid-stage of the disease, characterizing the prodrome and early stages in humans is currently challenging. To overcome these challenges, we use the validated TgF344-AD (F344-Tg(Prp-APP, Prp-PS1)19/Rrrc) transgenic rat model that manifests cognitive, behavioral, and neuropathological dysfunction akin to AD in humans. Objectives: The overarching goal of our work is to test the central hypothesis that pathology and related behavioral deficits such as communication dysfunction in part manifest in the peripheral nervous system and corresponding target tissues already in the early stages. The primary aims of this study are to test the hypotheses that: (1) changes in ultrasonic vocalizations (USV) occur in the prodromal stage at 6 months of age and worsen at 9 months of age, (2) inflammation as well as AD-related pathology can be found in the thyroarytenoid muscle (TA) at 12 months of age (experimental endpoint tissue harvest), and to (3) demonstrate that the TgF344-AD rat model is an appropriate model for preclinical investigations of early AD-related vocal deficits. Methods: USVs were collected from male TgF344-AD (N = 19) and wildtype (WT) Fischer-344 rats (N = 19) at 6 months (N = 38; WT: n = 19; TgF344-AD: n = 19) and 9 months of age (N = 18; WT: n = 10; TgF344-AD: n = 8) and acoustically analyzed for duration, mean power, principal frequency, low frequency, high frequency, peak frequency, and call type. RT-qPCR was used to assay peripheral inflammation and AD-related pathology via gene expressions in the TA muscle of male TgF344-AD rats (n = 6) and WT rats (n = 6) at 12 months of age. Results: This study revealed a significant reduction in mean power of ultrasonic calls from 6 to 9 months of age and increased peak frequency levels over time in TgF344-AD rats compared to WT controls. Additionally, significant downregulation of AD-related genes Uqcrc2, Bace2, Serpina3n, and Igf2, as well as downregulation of pro-inflammatory gene Myd88 was found in the TA muscle of TgF344-AD rats at 12 months of age. Discussion: Our findings demonstrate early and progressive vocal deficits in the TgF344-AD rat model. We further provide evidence of dysregulation of AD-pathology-related genes as well as inflammatory genes in the TA muscles of TgF344-AD rats in the early stage of the disease, confirming this rat model for early-stage investigations of voice deficits and related pathology.

16.
Neuropsychology ; 37(6): 628-635, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35604714

RESUMO

OBJECTIVE: The preeminent in vivo cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease (AD) are amyloid ß 1-42 (Aß42), phosphorylated Tau (p-tau), and total Tau (t-tau). The goal of this study was to examine how well traditional (total and delayed recall) and process-based (recency ratio [Rr]) measures derived from Rey's Auditory Verbal Learning test (AVLT) were associated with these biomarkers. METHOD: Data from 235 participants (Mage = 65.5, SD = 6.9), who ranged from cognitively unimpaired to mild cognitive impairment, and for whom CSF values were available, were extracted from the Wisconsin Registry for Alzheimer's Prevention. Bayesian regression analyses were carried out using CSF scores as outcomes, AVLT scores as predictors, and controlling for demographic data and diagnosis. RESULTS: We found moderate evidence that Rr was associated with both CSF p-tau (Bayesian factor [BFM] = 5.55) and t-tau (BFM = 7.28), above and beyond the control variables, while it did not correlate with CSF Aß42 levels. In contrast, total and delayed recall scores were not linked with any of the AD biomarkers, in separate analyses. When comparing all memory predictors in a single regression, Rr remained the strongest predictor of CSF t-tau levels (BFM = 3.57). CONCLUSIONS: Our findings suggest that Rr may be a better cognitive measure than commonly used AVLT scores to assess CSF levels of p-tau and t-tau in nondemented individuals. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Humanos , Idoso , Peptídeos beta-Amiloides , Estudos Transversais , Teorema de Bayes , Proteínas tau/líquido cefalorraquidiano , Doença de Alzheimer/psicologia , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/psicologia , Aprendizagem Verbal , Biomarcadores/líquido cefalorraquidiano
17.
Cortex ; 159: 167-174, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36630749

RESUMO

Recency refers to the information learned at the end of a study list or task. Recency forgetting, as tracked by the ratio between recency recall in immediate and delayed conditions, i.e., the recency ratio (Rr), has been applied to list-learning tasks, demonstrating its efficacy in predicting cognitive decline, conversion to mild cognitive impairment (MCI), and cerebrospinal fluid (CSF) biomarkers of neurodegeneration. However, little is known as to whether Rr can be effectively applied to story recall tasks. To address this question, data were extracted from the database of the Alzheimer's Disease Research Center at the University of Wisconsin - Madison. A total of 212 participants were included in the study. CSF biomarkers were amyloid-beta (Aß) 40 and 42, phosphorylated (p) and total (t) tau, neurofilament light (NFL), neurogranin (Ng), and α-synuclein (a-syn). Story Recall was measured with the Logical Memory Test (LMT). We carried out Bayesian regression analyses with Rr, and other LMT scores as predictors; and CSF biomarkers (including the Aß42/40 and p-tau/Aß42 ratios) as outcomes. Results showed that models including Rr consistently provided best fits with the data, with few exceptions. These findings demonstrate the applicability of Rr to story recall and its sensitivity to CSF biomarkers of neurodegeneration, and encourage its inclusion when evaluating risk of neurodegeneration with story recall.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Humanos , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/psicologia , Peptídeos beta-Amiloides , Teorema de Bayes , Biomarcadores , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/psicologia , Proteínas tau , Neurônios
18.
J Aging Health ; 35(7-8): 455-465, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-36412130

RESUMO

ObjectivesDetermine associations of hearing loss (HL) and hearing aid (HA) use with cognition, health-related quality of life (HRQoL), and depressive symptoms. Methods: Participants were from the Epidemiology of Hearing Loss Study or Beaver Dam Offspring Study. HL was defined as pure-tone average (.5-4.0 kHz) > 25 dB. A principal component analysis of 5 cognitive tasks measured cognition. The SF-12 measured mental and physical HRQoL. The Centers for Epidemiological Studies Depression Scale measured depressive symptoms (score ≥ 16). Regression models returned beta (B) coefficients or odds ratios (OR) with 95% confidence intervals. Results: This study included 3574 participants. HL (vs. none) was associated with poorer cognition (B-.12 [-.18, -.06]), mental (B-.99 [-1.65, -.33]) and physical (B-.76 [-1.50, -.03]) HRQoL, and increased odds of depressive symptoms (OR 1.49 [1.16, 1.91]). HA users had better cognition than non-users. Discussion: HL likely impacts cognition and well-being. HA use may have cognitive benefits.


Assuntos
Auxiliares de Audição , Perda Auditiva , Humanos , Depressão/epidemiologia , Depressão/psicologia , Qualidade de Vida , Perda Auditiva/psicologia , Cognição
19.
J Clin Exp Neuropsychol ; 45(8): 763-769, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37571873

RESUMO

BACKGROUND: Wordlist and story recall tests are routinely employed in clinical practice for dementia diagnosis. In this study, our aim was to establish how well-standard clinical metrics compared to process scores derived from wordlist and story recall tests in predicting biomarker determined Alzheimer's disease, as defined by CSF ptau/Aß42 ratio. METHODS: Data from 295 participants (mean age = 65 ± 9.) were drawn from the University of Wisconsin - Madison Alzheimer's Disease Research Center (ADRC) and Wisconsin Registry for Alzheimer's Prevention (WRAP). Rey's Auditory Verbal Learning Test (AVLT; wordlist) and Logical Memory Test (LMT; story) data were used. Bayesian linear regression analyses were carried out with CSF ptau/Aß42 ratio as outcome. Sensitivity analyses were carried out with logistic regressions to assess diagnosticity. RESULTS: LMT generally outperformed AVLT. Notably, the best predictors were primacy ratio, a process score indexing loss of information learned early during test administration, and recency ratio, which tracks loss of recently learned information. Sensitivity analyses confirmed this conclusion. CONCLUSIONS: Our study shows that story recall tests may be better than wordlist tests for detection of dementia, especially when employing process scores alongside conventional clinical scores.


Assuntos
Doença de Alzheimer , Humanos , Pessoa de Meia-Idade , Idoso , Doença de Alzheimer/diagnóstico , Teorema de Bayes , Biomarcadores , Aprendizagem , Rememoração Mental
20.
Am J Speech Lang Pathol ; 31(1): 67-83, 2022 01 18.
Artigo em Inglês | MEDLINE | ID: mdl-34694868

RESUMO

INTRODUCTION: Adults with mild traumatic brain injury (mTBI) are at risk for communication disorders, yet studies exploring cognitive-communication performance are currently lacking. AIMS: This aim of this study was to characterize discourse-level performance by adults with mTBI on a standardized elicitation task and compare it to (a) healthy adults, (b) adults with orthopedic injuries (OIs), and (c) adults with moderate to severe TBI. METHOD: This study used a cross-sectional design. The participants included mTBI and OI groups recruited prospectively from an emergency medicine department. Moderate to severe TBI and healthy data were acquired from TalkBank. One-way analyses of variance were used to compare mean linguistic scores. RESULTS: Seventy participants across all groups were recruited. Groups did not differ on demographic variables. The study found significant differences in both content and productivity measures among the groups. Variables did not appear sensitive to differentiate between mTBI and OI groups. DISCUSSION: Cognitive and language performance of adults with mTBI is a pressing clinical issue. Studies exploring language with carefully selected control groups can influence the development of sensitive measures to identify individuals with cognitive-communication deficits.


Assuntos
Concussão Encefálica , Lesões Encefálicas Traumáticas , Adulto , Concussão Encefálica/complicações , Concussão Encefálica/diagnóstico , Lesões Encefálicas Traumáticas/complicações , Lesões Encefálicas Traumáticas/diagnóstico , Lesões Encefálicas Traumáticas/psicologia , Estudos Transversais , Humanos , Idioma , Testes de Linguagem
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