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OBJECTIVE: To evaluate the construct validity of the NIH Toolbox Cognitive Battery (NIH TB-CB) in the healthy oldest-old (85+ years old). METHOD: Our sample from the McKnight Brain Aging Registry consists of 179 individuals, 85 to 99 years of age, screened for memory, neurological, and psychiatric disorders. Using previous research methods on a sample of 85 + y/o adults, we conducted confirmatory factor analyses on models of NIH TB-CB and same domain standard neuropsychological measures. We hypothesized the five-factor model (Reading, Vocabulary, Memory, Working Memory, and Executive/Speed) would have the best fit, consistent with younger populations. We assessed confirmatory and discriminant validity. We also evaluated demographic and computer use predictors of NIH TB-CB composite scores. RESULTS: Findings suggest the six-factor model (Vocabulary, Reading, Memory, Working Memory, Executive, and Speed) had a better fit than alternative models. NIH TB-CB tests had good convergent and discriminant validity, though tests in the executive functioning domain had high inter-correlations with other cognitive domains. Computer use was strongly associated with higher NIH TB-CB overall and fluid cognition composite scores. CONCLUSION: The NIH TB-CB is a valid assessment for the oldest-old samples, with relatively weak validity in the domain of executive functioning. Computer use's impact on composite scores could be due to the executive demands of learning to use a tablet. Strong relationships of executive function with other cognitive domains could be due to cognitive dedifferentiation. Overall, the NIH TB-CB could be useful for testing cognition in the oldest-old and the impact of aging on cognition in older populations.
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Cognição , Função Executiva , Adulto , Humanos , Idoso de 80 Anos ou mais , Idoso , Estados Unidos , Reprodutibilidade dos Testes , Envelhecimento , Memória de Curto Prazo , Testes Neuropsicológicos , National Institutes of Health (U.S.)RESUMO
OBJECTIVE: The objective of this study was to examine the effect of treatment timing on risk of institutionalization of Medicaid patients with Alzheimer's disease (AD) and to estimate the economic implications of earlier diagnosis and treatment initiation. METHODS: New Jersey Medicaid claims data (1997-2009) were used retrospectively to study the effect of treatment on time to institutionalization. Observed Medicaid payments were used to calculate savings from delayed institutionalization, adjusting for cost offsets resulting from concurrent changes in use of other medical services. RESULTS: Initiation of existing therapies at earliest symptomatic onset is predicted to delay institutionalization by 91 days, reducing Medicaid costs by $19,108/institutionalized patient. Incorporating an 18.5% cost offset from increased use of other medical services as well as drug costs associated with earlier treatment results in net savings of $12,687/patient. Projected annual Medicaid savings exceed $1 billion. CONCLUSION: Earlier treatment leads to a small delay in institutionalization among AD patients, resulting in significant costs savings to Medicaid.
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Doença de Alzheimer , Institucionalização/economia , Medicare/economia , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/economia , Doença de Alzheimer/terapia , Redução de Custos , Feminino , Custos de Cuidados de Saúde/estatística & dados numéricos , Humanos , Institucionalização/métodos , Classificação Internacional de Doenças , Masculino , Medicare/estatística & dados numéricos , New Jersey , Avaliação de Resultados em Cuidados de Saúde , Escalas de Graduação Psiquiátrica , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Estados UnidosRESUMO
Blood-based biomarkers of Alzheimer disease (AD) may facilitate testing of historically under-represented groups. The Study of Race to Understand Alzheimer Biomarkers (SORTOUT-AB) is a multi-center longitudinal study to compare AD biomarkers in participants who identify their race as either Black or white. Plasma samples from 324 Black and 1,547 white participants underwent analysis with C2N Diagnostics' PrecivityAD test for Aß42 and Aß40. Compared to white individuals, Black individuals had higher average plasma Aß42/40 levels at baseline, consistent with a lower average level of amyloid pathology. Interestingly, this difference resulted from lower average levels of plasma Aß40 in Black participants. Despite the differences, Black and white individuals had similar longitudinal rates of change in Aß42/40, consistent with a similar rate of amyloid accumulation. Our results agree with multiple recent studies demonstrating a lower prevalence of amyloid pathology in Black individuals, and additionally suggest that amyloid accumulates consistently across both groups.
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Doença de Alzheimer , Peptídeos beta-Amiloides , Biomarcadores , Fragmentos de Peptídeos , População Branca , Humanos , Peptídeos beta-Amiloides/sangue , Masculino , Feminino , Doença de Alzheimer/sangue , Doença de Alzheimer/etnologia , Estudos Longitudinais , Idoso , Fragmentos de Peptídeos/sangue , Biomarcadores/sangue , Negro ou Afro-Americano , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , População NegraRESUMO
Medical error is costly, in terms of the health and wellbeing of the patient, their family, and the financial burden placed on the medical system. Reducing medical error is paramount to minimizing harm and improving outcomes. One potential source of medical error is physician cognitive impairment. Determining how to effectively assess and mange physician cognitive impairment is an important, albeit difficult problem to address. There have been calls and attempts to implement age-based cognitive screening, but this approach is not optimal. Instead, we propose that neuropsychological assessment is the gold standard for fitness-for-duty evaluations and that there is a need for the development of physician-based, normative data to improve these evaluations. Here, we outline the framework of our research protocol in a large, academic medical center, in partnership with hospital leadership and legal counsel, which can be modeled by other medical centers. With high rates of physician burnout and an aging physician population, the United States is facing a looming public health crisis that requires proactive management.
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Disfunção Cognitiva , Médicos , Humanos , Envelhecimento , Esgotamento Psicológico , Disfunção Cognitiva/diagnóstico , Exercício FísicoRESUMO
BACKGROUND: Access to specialists facilitates appropriate Alzheimer's disease and related dementia (ADRD) medication use and adherence. However, there is little information on the impact of specialists' availability on ADRD medication adherence, especially in regions of the United States (US) where specialists are scarce, e.g., the Deep South (DS). OBJECTIVE: To ascertain whether the availability of specialty physicians in the DS and other US regions predicts ADRD medication adherence among community-dwelling older adultsMethods:We conducted secondary analyses of claims data for 54,194 Medicare beneficiaries with ADRD in 2013-2015. Medication adherence was measured using the proportion of days covered (PDC). Multivariable-adjusted Modified Poisson regression was used to examine associations of adherence with physicians' availability by region. RESULTS: The race/ethnicity distribution was 81.44% white, 9.17% black, 6.24% Hispanic, 2.25% Asian, and 1% other; 71.81% were female, and 42.36% were older than 85 years. Beneficiaries across regions differed in all individual and contextual characteristics except sex and comorbidities. Neurologists and psychiatrists' availability was not significantly associated with adherence (DSâ=â1.00, 0.97-1.03 & non-DSâ=â1.01, 1.00-1.01). Race and having ≥1 specialist visits were associated with a lower risk of adherence in both regions (pâ<â0.0001). Advanced age, dual Medicare/Medicaid eligibility, and living in non-large metropolitan areas, were associated with adherence in the non-DS region. CONCLUSION: Among older Americans with ADRD, a context defined by specialist availability does not affect adherence, but other context characteristics related to socioeconomic status may. Research should further examine the influence of individual and contextual factors on ADRD treatment among older adults.
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Doença de Alzheimer , Medicare , Humanos , Feminino , Idoso , Estados Unidos/epidemiologia , Masculino , Doença de Alzheimer/epidemiologia , Comorbidade , Vida Independente , Adesão à MedicaçãoRESUMO
Background: Family caregivers are often inexperienced and require information from clinic visits to effectively provide care for patients. Despite reported deficiencies, 68% of health systems facilitate sharing information with family caregivers through the patient portal. The patient portal is especially critical in the context of serious illnesses, like advanced cancer and dementia, where caregiving is intense and informational needs change over the trajectory of disease progression. Objective: The objective of our study was to analyze a large, nationally representative sample of family caregivers from the National Study of Caregiving (NSOC) to determine individual characteristics and demographic factors associated with patient portal use among family caregivers of persons living with dementia and those living with cancer. Methods: We conducted a secondary data analysis using data from the 2020 NSOC sample of family caregivers linked to National Health and Aging Trends Study. Weighted regression analysis by condition (ie, dementia or cancer) was used to examine associations between family caregiver use of the patient portal and demographic variables, including age, race or ethnicity, gender, employment status, caregiver health, education, and religiosity. Results: A total of 462 participants (representing 4,589,844 weighted responses) were included in our analysis. In the fully adjusted regression model for caregivers of persons living with dementia, Hispanic ethnicity was associated with higher odds of patient portal use (OR: 2.81, 95% CI 1.05-7.57; P=.04), whereas qualification lower than a college degree was associated with lower odds of patient portal use by family caregiver (OR 0.36, 95% CI 0.18-0.71; P<.001. In the fully adjusted regression model for caregivers of persons living with cancer, no variables were found to be statistically significantly associated with patient portal use at the .05 level. Conclusions: In our analysis of NSOC survey data, we found differences between how dementia and cancer caregivers access the patient portal. As the patient portal is a common method of connecting caregivers with information from clinic visits, future research should focus on understanding how the portal is used by the groups we have identified, and why.
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Demência , Neoplasias , Portais do Paciente , Humanos , Cuidadores , Demência/epidemiologia , Análise de Regressão , Neoplasias/terapiaRESUMO
We collected and analyzed genomic sequencing data from individuals with clinician- diagnosed early-onset or atypical dementia. Thirty-two patients were previously described, with sixty-eight newly described in this report. Of those sixty-eight, sixty-two patients reported Caucasian, non-Hispanic ethnicity and six reported as African American, non-Hispanic. Fifty-three percent of patients had a returnable variant. Five patients harbored a pathogenic variant as defined by the American College of Medical Genetics criteria for pathogenicity. A polygenic risk score was calculated for Alzheimer's patients in the total cohort and compared to the scores of a late-onset Alzheimer's cohort and a control set. Patients with early-onset Alzheimer's had higher non- APOE polygenic risk scores than patients with late onset Alzheimer's, supporting the conclusion that both rare and common genetic variation associate with early-onset neurodegenerative disease risk.
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We collected and analyzed genomic sequencing data from individuals with clinician-diagnosed early-onset or atypical dementia. Thirty-two patients were previously described, with 68 newly described in this report. Of those 68, 62 patients self-reported white, non-Hispanic ethnicity and 6 reported as African-American, non-Hispanic. Fifty-three percent of patients had a returnable variant. Five patients harbored a pathogenic variant as defined by the American College of Medical Genetics criteria for pathogenicity. A polygenic risk score (PRS) was calculated for Alzheimer's patients in the total cohort and compared to the scores of a late-onset Alzheimer's cohort and a control set. Patients with early-onset Alzheimer's had higher non-APOE PRSs than patients with late-onset Alzheimer's, supporting the conclusion that both rare and common genetic variation associate with early-onset neurodegenerative disease risk.
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Doença de Alzheimer , Doenças Neurodegenerativas , Humanos , Doença de Alzheimer/genética , Apolipoproteínas E/genética , Fatores de RiscoAssuntos
Glucosilceramidase/genética , Doença de Parkinson , Cognição , Doença de Gaucher , Humanos , Mutação , alfa-SinucleínaRESUMO
BACKGROUND/AIMS: A large multicenter trial of donepezil 23 mg/day versus donepezil 10 mg/day for moderate-to-severe Alzheimer's disease allowed patients taking concomitant memantine. We evaluated the efficacy/safety of donepezil 23 and 10 mg/day in this trial, with respect to concomitant memantine use. METHODS: Prespecified analysis of data from a 24-week, randomized, double-blind trial. Patients were randomized to donepezil doses (23 vs. 10 mg/day) and stratified by concomitant memantine use (yes or no). Efficacy and safety were assessed for each donepezil dose in subgroups taking or not taking concomitant memantine. RESULTS: At week 24, donepezil 23 mg/day provided significant cognitive benefits over 10 mg/day (p < 0.01) on the Severe Impairment Battery, with or without concomitant memantine (ANCOVA adjusted for baseline score, country and treatment). The higher dose showed no benefit on the global function, Mini-Mental State Examination or activities of daily living measures in either memantine subgroup. Rates of treatment-emergent adverse events (AEs) were higher for donepezil 23 mg/day with memantine (80.7%) than 23 mg/day without memantine (69.7%) or 10 mg/day with/without memantine (66.7/62.0%); across all treatment groups, most events were mild/moderate in severity. Individual rates of serious AEs were low (<1.0%), regardless of concomitant memantine use. CONCLUSION: In this population, concomitant memantine use did not alter the response profile of donepezil 23 vs. 10 mg/day. Donepezil 23 mg was generally safe and well tolerated among patients receiving donepezil alone and among patients receiving a combination of donepezil and memantine therapy.
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Doença de Alzheimer/tratamento farmacológico , Indanos , Memantina , Piperidinas , Atividades Cotidianas , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/psicologia , Donepezila , Relação Dose-Resposta a Droga , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Avaliação Geriátrica/métodos , Humanos , Indanos/administração & dosagem , Indanos/efeitos adversos , Testes de Inteligência , Masculino , Memantina/administração & dosagem , Memantina/efeitos adversos , Piperidinas/administração & dosagem , Piperidinas/efeitos adversos , Escalas de Graduação Psiquiátrica , Resultado do TratamentoRESUMO
More than 1 million people in the United States have Parkinson disease (PD), more than are diagnosed as having multiple sclerosis, amyotrophic lateral sclerosis, muscular dystrophy, and myasthenia gravis combined. PD affects approximately 1 in 100 Americans older than 60 years. It burdens patients, their care partners, and the overall healthcare system. This article reviews the epidemiology, clinical features, putative environmental risk and protective factors, neuropathological aspects, heterogeneity, medical management, and recent studies regarding genetics and PD. The article suggests that based on new research, the prevalence of PD varies in different regions of the United States. Some progress has been made in identifying the risk and protective factors of PD, and a newly emphasized area of study in PD is genetics. Patient care recommendations, based on American Academy of Neurology practice guidelines, are outlined to show the state of contemporary medical management of PD and related disorders.
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Doença de Parkinson/terapia , Progressão da Doença , Dopaminérgicos/uso terapêutico , Humanos , Doença de Parkinson/epidemiologia , Doença de Parkinson/genética , Doença de Parkinson/fisiopatologia , Prognóstico , Qualidade de Vida , Fatores de Risco , Estados Unidos/epidemiologiaRESUMO
OBJECTIVE: To characterize factors contributing to quality of life (QOL) in families providing care to people with dementia. BACKGROUND: Assessing QOL in dementia has proved difficult. Individuals with dementia often possess limited insight, leading them to self-rate QOL differently from those who provide care for them. A majority of people with dementia receive care in the context of family units, but measures of whole-family QOL have not been previously described in the literature on dementia. The concept of family quality of life (FQOL) was developed and validated among families caring for children with developmental disabilities. FQOL measures have the potential to improve determinations of effectiveness in dementia care. DESIGN/METHODS: Fifty-four questionnaires requesting information on priorities for care were collected from families of patients obtaining care at an academic dementia clinic. Forms were completed by family members, patients, or both. The mean age of the patients was 73.6 years; 61% were women. Qualitative analyses of the responses were conducted by two evaluators. Comments from 54 questionnaires were assigned by consensus to five categories based on domains validated for FQOL in families of individuals with developmental disabilities. Eleven cases from the 54 were rated by both evaluators to assess inter-rater reliability. RESULTS: Five domains were identified as follows: (1) family interactions, (2) direct care/activities of daily living support, (3) emotional/behavioral well-being, (4) physical and cognitive well-being, and (5) disability-related support/medical care. Not surprisingly for clinic encounters, medical care requests and inquiries were expressed by a high proportion of families. Concerns about physical and cognitive well-being were expressed nearly as often. Issues regarding family interactions and emotional well-being were less frequently raised. CONCLUSIONS/RELEVANCE: A FQOL model developed for developmental disability provided useful information for qualitative characterization of priorities among families receiving dementia care. Ongoing research will be useful to explore the validity and utility of the FQOL concept in dementia, especially in domains not well addressed by the current questionnaire.
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Atitude Frente a Saúde , Demência/psicologia , Família/psicologia , Qualidade de Vida , Perfil de Impacto da Doença , Centros Médicos Acadêmicos , Idoso , Idoso de 80 Anos ou mais , Cognição , Pessoas com Deficiência/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ambulatório Hospitalar , Inquéritos e QuestionáriosRESUMO
BACKGROUND AND OBJECTIVES: People with Alzheimer's disease and related dementias (ADRD) exhibit losses in daily function, as well as behavioral and psychological symptoms, that place a great deal of burden on family caregivers and exert a major influence on the quality of life of these individuals and their families. Despite years of intervention research in the field, there are few studies related to the impact of providing care for a person with ADRD on the family as the unit of analysis. While numerous findings have reported the effects of the chronic stress of caregiving for an individual, analysis of family quality of life is a concept that has been generally overlooked in the ADRD field. The purpose of the present study was to develop and test the Family Quality of Life in Dementia (FQOL-D) scale. RESEARCH DESIGN AND METHODS: Face validity was obtained via a Delphi survey of a multidisciplinary team of dementia providers and researchers; initial psychometric evaluation of the instrument was obtained via family respondents (N = 244). RESULTS: Internal consistency and reliability were established for the instrument. The FQOL-D scale exhibited excellent factorability and concurrent validity with existing scales assessing family psychosocial measures. DISCUSSION AND IMPLICATIONS: The initial psychometric testing of the FQOL-D instrument is favorable. Additional use of the FQOL-D instrument in health care settings is warranted to evaluate further the clinical utility of the instrument.
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Demência , Qualidade de Vida , Cuidadores , Família , Humanos , Psicometria , Reprodutibilidade dos Testes , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Use of specialists and recommended drugs has beneficial effects for older adults living with Alzheimer's disease and related dementia (ADRD). Gaps in care may exist for minorities, e.g., Blacks, and especially in the United States (U.S.) Deep South (DS), a poor U.S. region with rising ADRD cases and minority overrepresentation. Currently, we have little understanding of ADRD care utilization in diverse populations in this region and elsewhere in the U.S. (non-DS), and the factors that adversely impact it. OBJECTIVE: To examine utilization of specialists and ADRD drugs (outcomes) in racial/ethnic groups of older adults with ADRD and the personal or context-level factors affecting these outcomes in DS and non-DS. METHODS: We obtained outcomes and personal-level covariates from claims for 127,512 Medicare beneficiaries with ADRD in 2013-2015, and combined county-level data in exploratory factor analysis to define context-level covariates. Adjusted analyses tested significant association of outcomes with Black/White race and other factors in DS and non-DS. RESULTS: Across racial/ethnic groups, 33%-43% in DS and 43%-50% in non-DS used specialists; 47%-55% in DS and 41%-48% in non-DS used ADRD drugs. In adjusted analyses, differences between Blacks and Whites were not significant. Vascular dementia, comorbidities, poverty, and context-level factor "Availability of Medical Resources" were associated with specialist use; Alzheimer's disease and senile dementia, comorbidities, and specialist use were associated with drug use. In non-DS only, other individual, context-level covariates were associated with the outcomes. CONCLUSION: We did not observe significant gaps in ADRD care in DS and non-DS; however, research should further examine determinants of low specialist and drug use in these regions.
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Demência , Acessibilidade aos Serviços de Saúde/estatística & dados numéricos , Disparidades em Assistência à Saúde , Grupos Raciais , Idoso , Demência/tratamento farmacológico , Demência/etnologia , Feminino , Humanos , Masculino , Medicare , Estudos Retrospectivos , Fatores Socioeconômicos , Sudeste dos Estados Unidos , Especialização/estatística & dados numéricos , Estados UnidosRESUMO
Alzheimer's disease and related dementias (ADRD) often result in communication deficits that can lead to negative health outcomes as well as complications for caregiving and clinical care. Although augmentative and alternative communication (AAC) devices have demonstrated efficacy in assisting persons living with dementia (PLWD) in communicating, few devices offer customization for the person's care preferences (e.g., clothing, food, activities) or are designed for integration into clinical care and caregiving. To address this issue, our research team is developing a novel electronic AAC prototype with a touchscreen to promote communication and personhood for PLWD. The current article describes the development of this technology and uses the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) 2013 Statement to describe the clinical trial that is planned to test its efficacy. TARGETS: PLWD and their care partners. INTERVENTION DESCRIPTION: Use of AAC Plus to promote communication and personhood for PLWD. MECHANISMS OF ACTION: AAC Plus will provide PLWD and care partners a way to communicate PLWD's daily preferences and provide clinical data for health care providers. OUTCOMES: Determine whether enhanced communication of daily preferences of PLWD will improve quality of life of PLWD and their care partners. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04571502 (Date of registration October 1, 2020). [Research in Gerontological Nursing, 14(5), 225-234.].
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Demência , Informática Médica , Cuidadores , Demência/terapia , Humanos , Pessoalidade , Qualidade de VidaRESUMO
BACKGROUND: Cognitive processing speed is important for performing everyday activities in persons with mild cognitive impairment (MCI). However, its role in daily function has not been examined while simultaneously accounting for contributions of Alzheimer's disease (AD) risk biomarkers. We examine the relationships of processing speed and genetic and neuroimaging biomarkers to composites of daily function, mobility, and driving. METHOD: We used baseline data from 103 participants on the MCI/mild dementia spectrum from the Applying Programs to Preserve Skills trial. Linear regression models examined relationships of processing speed, structural magnetic resonance imaging (MRI), and genetic risk alleles for AD to composites of performance-based instrumental activities of daily living (IADLs), community mobility, and on-road driving evaluations. RESULTS: In multivariable models, processing speed and the brain MRI neurodegeneration biomarker Spatial Pattern of Abnormality for Recognition of Early Alzheimer's disease (SPARE-AD) were significantly associated with functional and mobility composite performance. Better processing speed and younger age were associated with on-road driving ratings. Genetic risk markers, left hippocampal atrophy, and white matter lesion volumes were not significant correlates of these abilities. Processing speed had a strong positive association with IADL function (p < .001), mobility (p < .001), and driving (p = .002). CONCLUSIONS: Cognitive processing speed is strongly and consistently associated with critical daily functions in persons with MCI in models including genetic and neuroimaging biomarkers of AD risk. SPARE-AD scores also significantly correlate with IADL performance and mobility. Results highlight the central role of processing speed in everyday task performance among persons with MCI/mild dementia.
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Disfunção Cognitiva , Demência , Atividades Cotidianas , Doença de Alzheimer/genética , Biomarcadores , Cognição , Humanos , Testes NeuropsicológicosRESUMO
Importance: Basket-design clinical trials that allow investigation of treatment effects on different clinical syndromes that share the same molecular pathophysiology have not previously been attempted in neurodegenerative disease. Objective: To assess the safety, tolerability, and pharmacodynamics of the microtubule stabilizer TPI-287 (abeotaxane) in Alzheimer disease (AD) or the 4-repeat tauopathies (4RT) progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS). Design, Setting, and Participants: Two parallel-design, double-blind, placebo-controlled phase 1 randomized clinical trials in AD and 4RT were conducted from December 20, 2013, through May 4, 2017, at the University of California, San Francisco, and University of Alabama at Birmingham. A total of 94 patients with clinically diagnosed AD (n = 39) and 4RT (n = 55) were screened; of these, 3 refused to participate, and 10 with AD and 11 with 4RT did not meet inclusion criteria. A total of 29 patients with AD, 14 with PSP, and 30 with ß-amyloid-negative CBS (determined on positron emission tomography findings) were enrolled. Data were analyzed from December 20, 2013, through May 4, 2017, based on modified intention to treat. Interventions: Randomization was 8:3 drug to placebo in 3 sequential dose cohorts receiving 2.0, 6.3, or 20.0 mg/m2 of intravenous TPI-287 once every 3 weeks for 9 weeks, with an optional 6-week open-label extension. Main Outcomes and Measures: Primary end points were safety and tolerability (maximal tolerated dose) of TPI-287. Secondary and exploratory end points included TPI-287 levels in cerebrospinal fluid (CSF) and changes on biomarker, clinical, and neuropsychology measures. Results: A total of 68 participants (38 men [56%]; median age, 65 [range, 50-85] years) were included in the modified intention-to-treat analysis, of whom 26 had AD (14 women [54%]; median age, 63 [range, 50-76] years), and 42 had 4RT (16 women [38%]; median age, 69 [range, 54-83] years). Three severe anaphylactoid reactions occurred in TPI-287-treated patients with AD, whereas none were seen in patients with 4RT, leading to a maximal tolerated dose of 6.3 mg/m2 for AD and 20.0 mg/m2 for 4RT. More falls (3 in the placebo group vs 11 in the TPI-287 group) and a dose-related worsening of dementia symptoms (mean [SD] in the CDR plus NACC FTLD-SB [Clinical Dementia Rating scale sum of boxes with frontotemporal dementia measures], 0.5 [1.8] in the placebo group vs 0.7 [1.6] in the TPI-287 group; median difference, 1.5 [95% CI, 0-2.5]; P = .03) were seen in patients with 4RT. Despite undetectable TPI-287 levels in CSF, CSF biomarkers demonstrated decreased chitinase-3-like protein-1 (YKL-40) levels in the 4RT treatment arm (mean [SD], -8.4 [26.0] ng/mL) compared with placebo (mean [SD], 10.4 [42.3] ng/mL; median difference, -14.6 [95% CI, -30.0 to 0.2] ng/mL; P = .048, Mann-Whitney test). Conclusions and Relevance: In this randomized clinical trial, TPI-287 was less tolerated in patients with AD than in those with 4RT owing to the presence of anaphylactoid reactions. The ability to reveal different tau therapeutic effects in various tauopathy syndromes suggests that basket trials are a valuable approach to tau therapeutic early clinical development. Trial Registration: ClinicalTrials.gov identifiers: NCT019666666 and NCT02133846.
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Doença de Alzheimer/tratamento farmacológico , Doenças Neurodegenerativas/tratamento farmacológico , Paralisia Supranuclear Progressiva/tratamento farmacológico , Taxoides/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/líquido cefalorraquidiano , Biomarcadores/líquido cefalorraquidiano , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doenças Neurodegenerativas/líquido cefalorraquidiano , Paralisia Supranuclear Progressiva/líquido cefalorraquidiano , Taxoides/efeitos adversos , Taxoides/uso terapêutico , Resultado do TratamentoRESUMO
Objective: We assessed the clinical utility of the Alabama Brief Cognitive Screener (ABCs), an alternative to the Mini-Mental State Examination (MMSE), for cognitive screening in a new electronic medical record. Other available nonproprietary instruments were determined to be more tuned to milder deficits than the MMSE. Methods: The ABCs was administered as part of routine clinical assessment in the University of Alabama at Birmingham memory disorders clinics from April 30, 2012, to April 30, 2015. Outpatients (N = 1,589) with clinician diagnoses (ICD-9-CM) of memory loss, mild cognitive impairment, neurodegenerative cognitive impairment, Alzheimer's dementia, or dementia not otherwise specified were included in the analysis. Memory disorder clinicians used multiple sources of information for assignment of diagnoses, including interviews with patients and caregivers, the ABCs, figure copy, semantic fluencies, phonemic fluencies, ratings of daily function, imaging, laboratory tests, and medical records. Results: Scoring distribution by diagnosis was mild cognitive impairment (n = 310): mean (SD) = 25.47 (3.37), median = 26; Alzheimer's dementia (n = 208): mean (SD) = 16.42 (6.33), median = 17; cerebral degeneration (n = 371): mean (SD) = 20.61 (5.90), median = 21; memory loss (n = 583): mean (SD) = 24.90 (5.09), median = 27; and dementia (n = 117): mean (SD) = 15.18 (6.34), median = 15. Mean ABCs scores differed by diagnosis (Wilcoxon signed-ranks Z = 483.5, P < .001). This finding was consistent with a meta-analysis of MMSE performance between groups. Conclusions: ABCs scores vary appropriately by diagnosis and resemble MMSE scoring distributions. The ABCs provides a nonproprietary alternative to the MMSE to assess the severity of cognitive deficits.
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Disfunção Cognitiva/diagnóstico , Demência/diagnóstico , Transtornos da Memória/diagnóstico , Doenças Neurodegenerativas/diagnóstico , Testes Neuropsicológicos , Idoso , Cognição , Registros Eletrônicos de Saúde , Feminino , Humanos , Masculino , Atenção Primária à SaúdeRESUMO
Family caregivers of persons with dementia encounter resistance to care behaviors (RCBs). The purpose of this methods paper was to describe the process and content of six weekly 60-min caregiver coaching sessions delivered synchronously through an online platform to 26 family caregivers of persons with dementia. All session notes were analyzed for process; two coaching sessions from five purposely-selected participants were transcribed and analyzed thematically for content. The six sessions followed an overall pattern. The first session included the most teaching and goal-setting; the coaches also queried the family caregiver about the premorbid personality, work history, and interpersonal attributes of the person with dementia. Sessions two through five were the most active coaching sessions; previously suggested strategies were evaluated and tailored; caregivers also role-played with the coaches and developed scripts designed to curtail RCB. The sixth session served as a review of successful caregiver strategies and concluded the coaching relationship. Four primary content themes emerged in the coaching process: (1) education; (2) caregiver communication; (3) affirmation of the caregiver; and (4) individualized strategies. These four content categories were used throughout the coaching process and were interwoven with each other so that the participant knew why the behavior was occurring, how to verbally address it, how to use a strategy effectively, and affirmation of the result. The coaching process and content demonstrated alignment with person-centered practices and relationship-centered care.
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BACKGROUND: Progressive supranuclear palsy is a rare neurodegenerative disease associated with dysfunctional tau protein. BIIB092 is a humanised monoclonal antibody that binds to N-terminal tau and is thus being assessed as a potential novel treatment for progressive supranuclear palsy. We aimed to investigate the safety and tolerability of BIIB092 in individuals with progressive supranuclear palsy. METHODS: This 12-week, double-blind, randomised, placebo-controlled, multiple ascending dose, phase 1b trial was done at 13 outpatient sites in the USA. Participants aged 41-86 years with probable or possible progressive supranuclear palsy with a score of 20 or greater on the Mini-Mental State Examination (MMSE) were enrolled. Three BIIB092 dose escalation cohorts (150 mg, 700 mg, or 2100 mg; eight participants per cohort) were tested sequentially. For each dose cohort, the first two participants were randomly assigned by a computer-generated scheme to receive either BIIB092 or placebo intravenously every 4 weeks for 57 days. After 2 days, the six remaining participants in each cohort were randomly assigned (5:1) to receive BIIB092 or placebo for 57 days. An additional expansion panel of 24 patients was randomly assigned (3:1) to receive 2100 mg or placebo every 4 weeks for 57 days. All participants were followed up to day 85. The primary outcome was safety, which was analysed in the treated population (all enrolled participants who received at least one dose of the study drug). This trial is registered with ClinicalTrials.gov, NCT02460094. FINDINGS: Between Oct 2, 2015, and Oct 19, 2016, 48 participants were enrolled and randomly assigned to the BIIB092 (n=36) and placebo (n=12) groups. No apparent demographic differences were observed between the two groups at baseline. All 48 participants completed the treatment phase of the study. Adverse events were generally mild to moderate in severity; the most common in the placebo and BIIB092 groups were falls (in two [17%] of 12 patients and in ten [28%] of 36 patients), urinary tract infections (in one [8%] of 12 and in six [17%] of 36), contusions (in one [8%] of 12 and in five [14%] of 36), and headaches (in none and in five [14%] of 36). Four serious adverse events resulting in admission to hospital were reported in three participants who received BIIB092 2100 mg: two severe adverse events of urinary tract infection, one severe adverse event of change in mental status, and one moderate adverse event of aspiration pneumonia. None was considered to be related to the study drug, all were resolved, and no deaths were reported. INTERPRETATION: Repeated administration of the anti-tau monoclonal antibody BIIB092, at doses of up to 2100 mg, appears to be well tolerated in participants with progressive supranuclear palsy. Results of this phase 1b trial have informed the design of the ongoing phase 2 PASSPORT (NCT03068468) study to examine the efficacy and safety of BIIB092. FUNDING: Bristol-Myers Squibb, Biogen.