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1.
Am J Epidemiol ; 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38957996

RESUMO

Non-benzodiazepine hypnotics ( "Z-drugs") are prescribed for insomnia, but might increase risk of motor vehicle crash (MVC) among older adults through prolonged drowsiness and delayed reaction times. We estimated the effect of initiating Z-drug treatment on the 12-week risk of MVC in a sequential target trial emulation. After linking New Jersey driver licensing and police-reported MVC data to Medicare claims, we emulated a new target trial each week (July 1, 2007 - October 7, 2017) in which Medicare fee-for-service beneficiaries were classified as Z-drug-treated or untreated at baseline and followed for an MVC. We used inverse probability of treatment and censoring weighted pooled logistic regression models to estimate risk ratios (RR) and risk differences with 95% bootstrap confidence limits (CLs). There were 257,554 person-trials, of which 103,371 were Z-drug-treated and 154,183 untreated, giving rise to 976 and 1,249 MVCs, respectively. The intention-to-treat RR was 1.06 (95%CLs 0.95, 1.16). For the per-protocol estimand, there were 800 MVCs and 1,241 MVCs among treated and untreated person-trials, respectively, suggesting a reduced MVC risk (RR 0.83 [95%CLs 0.74, 0.92]) with sustained Z-drug treatment. Z-drugs should be prescribed to older patients judiciously but not withheld entirely over concerns about MVC risk.

2.
Neuropsychology ; 38(4): 337-346, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38330360

RESUMO

OBJECTIVE: Large research cohorts show robust associations between neuropsychological tests and Alzheimer's disease (AD) biomarkers, but studies in clinical settings are limited. The increasing availability of AD biomarkers to the practicing clinician makes it important to understand the relationship between comprehensive clinical neuropsychological assessment and biomarker status. This study examined concordance between practicing clinical neuropsychologists' diagnostic impressions and AD biomarker status in patients seen at an outpatient medical center, with a secondary aim of defining the characteristics of discordant cases. METHOD: Participants (N = 79) seen for clinical neuropsychological assessment who subsequently underwent lumbar puncture or amyloid positron emission tomography imaging were identified via retrospective chart review. Concordance between clinical neuropsychological diagnosis (non-AD, indeterminate, possible/probable AD) and AD biomarker status (negative, indeterminate, positive) was determined. Individual test score data were used to examine between-group differences based on amyloid status. RESULTS: AD biomarker positive and negative patients did not differ on individual neuropsychological tests after correcting for multiple comparisons, though the small number of AD biomarker indeterminate individuals performed better than biomarker positive patients. However, there was 76.7% concordance between neuropsychologists' diagnostic impressions and AD biomarker status (88% sensitivity and 55% specificity of neuropsychological assessment in detecting AD biomarker status). AD biomarker negative patients diagnosed as possible/probable AD (discordant) versus non-AD (concordant) had significantly lower Neuropsychological Assessment Battery Story Delayed Recall, higher Wechsler Adult Intelligence Scale-Fourth Edition Coding, and higher Trail-Making A (i.e., an amnestic memory profile). CONCLUSIONS: Comprehensive neuropsychological assessment showed modest concordance with AD biomarker status in patients seen in an outpatient medical center for routine clinical care. Low specificity for the clinical diagnosis of AD could be explained by the multiplicity of etiologies that cause memory impairment (i.e., TAR DNA-binding protein 43, suspected non-AD pathology). (PsycInfo Database Record (c) 2024 APA, all rights reserved).


Assuntos
Doença de Alzheimer , Biomarcadores , Testes Neuropsicológicos , Tomografia por Emissão de Pósitrons , Humanos , Feminino , Masculino , Doença de Alzheimer/diagnóstico , Idoso , Estudos Retrospectivos , Pessoa de Meia-Idade , Peptídeos beta-Amiloides , Idoso de 80 Anos ou mais
3.
J Alzheimers Dis ; 97(3): 1161-1171, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38306055

RESUMO

BACKGROUND: Elevated amyloid-ß (Aß) on positron emission tomography (PET) scan is used to aid diagnosis of Alzheimer's disease (AD), but many prior studies have focused on patients with a typical AD phenotype such as amnestic mild cognitive impairment (MCI). Little is known about whether elevated Aß on PET scan predicts rate of cognitive and functional decline among those with MCI or dementia that is clinically less typical of early AD, thus leading to etiologic uncertainty. OBJECTIVE: We aimed to investigate whether elevated Aß on PET scan predicts cognitive and functional decline over an 18-month period in those with MCI or dementia of uncertain etiology. METHODS: In 1,028 individuals with MCI or dementia of uncertain etiology, we evaluated the association between elevated Aß on PET scan and change on a telephone cognitive status measure administered to the participant and change in everyday function as reported by their care partner. RESULTS: Individuals with either MCI or dementia and elevated Aß (66.6% of the sample) showed greater cognitive decline compared to those without elevated Aß on PET scan, whose cognition was relatively stable over 18 months. Those with either MCI or dementia and elevated Aß were also reported to have greater functional decline compared to those without elevated Aß, even though the latter group showed significant care partner-reported functional decline over time. CONCLUSIONS: Elevated Aß on PET scan can be helpful in predicting rates of both cognitive and functional decline, even among cognitively impaired individuals with atypical presentations of AD.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Humanos , Incerteza , Disfunção Cognitiva/psicologia , Peptídeos beta-Amiloides , Doença de Alzheimer/psicologia , Cognição , Tomografia por Emissão de Pósitrons/métodos
4.
J Am Med Dir Assoc ; 25(1): 41-46.e5, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38173265

RESUMO

OBJECTIVE: Little is known about who is involved and what factors influence changes in antidementia medications for older adults living in nursing homes. The study sought to describe factors associated with initiation and discontinuation of antidementia medications in nursing home residents with dementia. DESIGN: National survey of nursing homes with ≥30 beds; homes with dementia units were oversampled. SETTINGS AND PARTICIPANTS: Nursing home administrators [eg, Directors of Nursing (DoNs)]. METHODS: In 2022, 1293 homes were surveyed (response rate: 26.6%, n = 340). Weighted analyses provided nationally representative results corrected for nonresponse (n = 14,455). RESULTS: DoNs reported that people always/almost always involved in antidementia medication decisions included nursing home prescriber (84.4%), nursing staff (33.2%), family (23.4%), resident (13.8%), community primary care provider (12.1%), and dementia specialist (5.8%). DoNs reported that antidementia medications were much more likely to be initiated if residents (55.8%) and family members (53.2%) wanted antidementia medications, a dementia specialist was involved (51.9%), resident had aggressive behaviors (44.8%), resisted care (31.6%), or had severe physical/cognitive impairment (22.3%). DoNs reported that antidementia medications were much more likely to be discontinued with dementia specialist involvement (46.5%), progression to severe impairment (39.2%), hospice involvement (31.5%), <6 months' prognosis (28.5%), emergence of aggressive behaviors (25.2%), or resisting care (19.0%) and much less likely to be discontinued if residents (30.2%) and family (27.3%) were reluctant to discontinue. One in 6 homes reported that residents had no immediate family/caregivers usually or almost always/always. CONCLUSIONS AND IMPLICATIONS: DoNs report that family/caregivers and dementia specialists have significant influence on antidementia medication decisions in nursing homes, but many residents lack their involvement. Real-world evidence on the risks and benefits of antidementia medications in nursing homes is needed to inform clinical guidance about appropriate use of antidementia medications in nursing homes.


Assuntos
Demência , Humanos , Idoso , Demência/psicologia , Casas de Saúde , Instituições de Cuidados Especializados de Enfermagem , Hospitalização
5.
J Geriatr Psychiatry Neurol ; 37(3): 194-205, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-37715795

RESUMO

BACKGROUND: Antidementia medication can provide symptomatic improvements in patients with Alzheimer's disease, but there is a lack of consensus guidance on when to start and stop treatment in the nursing home setting. METHODS: We describe utilization patterns of cholinesterase inhibitors (ChEI) and memantine for 3,50,197 newly admitted NH residents with dementia between 2011 and 2018. RESULTS: Overall, pre-admission use of antidementia medications declined from 2011 to 2018 (ChEIs: 44.5% to 36.9%; memantine: 27.4% to 23.2%). Older age, use of a feeding tube, and greater functional dependency were associated with lower odds of ChEI initiation. Coronary artery disease, parenteral nutrition, severe aggressive behaviors, severe cognitive impairment, and high functional dependency were associated with discontinuation of ChEIs. Comparison of clinical factors related to anti-dementia drug treatment changes from pre to post NH admission in 2011 and 2018 revealed a change toward lower likelihood of initiation of treatment among residents with more functional dependency and those with indicators of more complex illness as well as a change toward higher likelihood of discontinuation in residents having 2 or more hospital stays. CONCLUSIONS: These prescribing trends highlight the need for additional research on the effects of initiating and discontinuing antidementia medications in the NH to provide clear guidance for clinicians when making treatment decisions for individual residents.


Assuntos
Doença de Alzheimer , Memantina , Humanos , Memantina/uso terapêutico , Doença de Alzheimer/tratamento farmacológico , Casas de Saúde , Inibidores da Colinesterase/uso terapêutico , Cognição
6.
J Am Geriatr Soc ; 72(2): 444-455, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37905738

RESUMO

BACKGROUND: Medications are one of the most easily modifiable risk factors for motor vehicle crashes (MVCs) among older adults, yet limited information exists on how the use of potentially driver-impairing (PDI) medications changes following an MVC. Therefore, we examined the number and types of PDI medication classes dispensed before and after an MVC. METHODS: This observational study included Medicare fee-for-service beneficiaries aged ≥67 years who were involved in a police-reported MVC in New Jersey as a driver between 2008 and 2017. Analyses were conducted at the "person-crash" level because participants could be involved in more than one MVC. We examined the use of 36 PDI medication classes in the 120 days before and 120 days after MVC. We described the number and prevalence of PDI medication classes in the pre-MVC and post-MVC periods as well as the most common PDI medication classes started and stopped following the MVC. RESULTS: Among 124,954 person-crashes, the mean (SD) age was 76.0 (6.5) years, 51.3% were female, and 83.9% were non-Hispanic White. The median (Q1 , Q3 ) number of PDI medication classes was 2 (1, 4) in both the pre-MVC and post-MVC periods. Overall, 20.3% had a net increase, 15.9% had a net decrease, and 63.8% had no net change in the number of PDI medication classes after MVC. Opioids, antihistamines, and thiazide diuretics were the top PDI medication classes stopped following MVC, at incidences of 6.2%, 2.1%, and 1.7%, respectively. The top medication classes started were opioids (8.3%), skeletal muscle relaxants (2.2%), and benzodiazepines (2.1%). CONCLUSIONS: A majority of crash-involved older adults were exposed to multiple PDI medications before and after MVC. A greater proportion of person-crashes were associated with an increased rather than decreased number of PDI medications. The reasons why clinicians refrain from stopping PDI medications following an MVC remain to be elucidated.


Assuntos
Acidentes de Trânsito , Condução de Veículo , Humanos , Idoso , Feminino , Estados Unidos/epidemiologia , Masculino , Medicare , Fatores de Risco , Veículos Automotores , New Jersey
7.
J Aging Soc Policy ; : 1-15, 2022 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-36463560

RESUMO

In 30 states, licensing agencies can restrict the distance from home that "medically-at-risk" drivers are permitted to drive. However, where older drivers crash relative to their home or how distance to crash varies by medical condition is unknown. Using geocoded crash locations and residential addresses linked to Medicare claims, we describe how the relationship between distance from home to crash varies by driver characteristics. We find that a majority of crashes occur within a few miles from home with little variation across driver demographics or medical conditions. Thus, distance restrictions may not reduce crash rates among older adults, and the tradeoff between safety and mobility warrants consideration.

8.
PLoS One ; 17(4): e0266615, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35404972

RESUMO

APOE encodes a cholesterol transporter, and the ε4 allele is associated with higher circulating cholesterol levels, ß-amyloid burden, and risk of Alzheimer's disease. Prior studies demonstrated no significant differences in objective or subjective cognitive function for patients receiving the PCSK9 inhibitor evolocumab vs. placebo added to statin therapy. There is some evidence that cholesterol-lowering medications may confer greater cognitive benefits in APOE ε4 carriers. Thus, the purpose of this study was to determine whether APOE genotype moderates the relationships between evolocumab use and cognitive function. APOE-genotyped patients (N = 13,481; 28% ε4 carriers) from FOURIER, a randomized, placebo-controlled trial of evolocumab added to statin therapy in patients with stable atherosclerotic cardiovascular disease followed for a median of 2.2 years, completed the Everyday Cognition Scale (ECog) to self-report cognitive changes from the end of the trial compared to its beginning; a subset (N = 835) underwent objective cognitive testing using the Cambridge Neuropsychological Test Automated Battery as part of the EBBINGHAUS trial. There was a dose-dependent relationship between APOE ε4 genotype and patient-reported memory decline on the ECog in the placebo arm (p = .003 for trend across genotypes; ε4/ε4 carriers vs. non-carriers: OR = 1.46, 95% CI [1.03, 2.08]) but not in the evolocumab arm (p = .50, OR = 1.18, 95% CI [.83,1.66]). However, the genotype by treatment interaction was not significant (p = .30). In the subset of participants who underwent objective cognitive testing with the CANTAB, APOE genotype did not significantly modify the relationship between treatment arm and CANTAB performance after adjustment for demographic and medical covariates, (p's>.05). Although analyses were limited by the low population frequency of the ε4/ε4 genotype, this supports the cognitive safety of evolocumab among ε4 carriers, guiding future research on possible benefits of cholesterol-lowering medications in people at genetic risk for Alzheimer's disease.


Assuntos
Doença de Alzheimer , Anticolesterolemiantes , Inibidores de Hidroximetilglutaril-CoA Redutases , Doença de Alzheimer/genética , Anticorpos Monoclonais Humanizados , Anticolesterolemiantes/efeitos adversos , Apolipoproteína E4/genética , Cognição , Genótipo , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Testes Neuropsicológicos , Pró-Proteína Convertase 9/genética
9.
J Integr Complement Med ; 28(3): 250-260, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35294301

RESUMO

Background: Yoga is a potentially low risk intervention for cognitive impairment that combines mental and physical practice and includes instruction on breathing, stress reduction, and mindfulness meditation. Previous research documents that yoga can target modifiable risk factors for mild cognitive impairment (MCI) progression. The authors describe a randomized feasibility trial of yoga for individuals with MCI. Methods: Participants were 37 individuals with amnestic MCI who were randomly assigned to receive 12 weeks of twice-weekly yoga intervention (YI) or healthy living education (HLE) classes. Acceptability and feasibility were assessed by tracking adverse events, class attendance, and participant satisfaction. Participants completed neuropsychological and mood measures as well as measures of potential intervention mechanisms at baseline and immediately postintervention. Results: Participants in both conditions reported high levels of satisfaction and reasonable class attendance rates. Home practice rates were low. There were no adverse events deemed related to the YI. Results showed a medium effect size in favor of the YI in visuospatial skills. The yoga group also showed a large effect size indicating decline in perceived stress compared with the HLE group, whereas HLE resulted in greater reductions in depressive symptoms after the intervention (large effect size). Conclusions: Study findings indicated that the YI was safe, modestly feasible, and acceptable to older adults with MCI. The authors found preliminary evidence that yoga may improve visuospatial functioning in individuals with MCI. Results support stress reduction as a possible mechanism for the YI. Future studies should address a YI in a larger sample and include strategies to enhance engagement and home practice.


Assuntos
Disfunção Cognitiva , Meditação , Yoga , Afeto , Idoso , Disfunção Cognitiva/terapia , Estudos de Viabilidade , Humanos , Yoga/psicologia
10.
Alzheimer Dis Assoc Disord ; 36(2): 111-117, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35288521

RESUMO

BACKGROUND: Research on Alzheimer disease and related dementias is increasingly focused on preventative strategies to target modifiable risk factors (eg, exercise, diet, cognitive stimulation) to reduce risk of cognitive decline, though it remains difficult for adults to adopt and maintain these behaviors on their own. METHODS/PARTICIPANTS: In this survey study, we examined knowledge about modifiable risk factors for dementia, engagement in healthy lifestyle behaviors, and associated barriers/facilitators in an Alzheimer disease prevention registry of at-risk, cognitively normal adults (n=135: 77% female; 96% Caucasian and non-Hispanic; mean age=66.1; 79% with family history of dementia; 46% with subjective memory decline). RESULTS: Participants reported high levels of engagement in exercise (mean 3.4 d/wk), a healthy diet (60% with a healthy/balanced diet), and cognitive stimulation (52% engaging in cognitive stimulation 3 to 7 d/wk), and most (56% to 57%) reported moderate to high knowledge about dementia and modifiable risk factors. Family history of dementia was associated with greater knowledge of risk factors for dementia (P=0.017), but not with knowledge of lifestyle recommendations to reduce risk (P=0.85). Most participants (63%) reported a preference for walking/running over other types of aerobic exercise. On average, participants reported that they would be willing to increase healthy lifestyle behaviors to achieve "moderate" risk reduction for dementia (∼21% to 23%, on a scale from 0% to 40%, reflecting mildly to substantially reduced risk). CONCLUSION: Results broaden our understanding of current habits and willingness to engage in healthy lifestyle behaviors, which may inform individualized lifestyle interventions and/or design of prevention trials, particularly among at-risk adults with subjective or mild cognitive concerns, who may be especially motivated and able to engage in lifestyle interventions, to optimize brain health and reduce risk of cognitive decline.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Adulto , Idoso , Doença de Alzheimer/prevenção & controle , Disfunção Cognitiva/prevenção & controle , Feminino , Estilo de Vida Saudável , Humanos , Estilo de Vida , Masculino , Sistema de Registros
11.
Sci Rep ; 11(1): 15934, 2021 08 05.
Artigo em Inglês | MEDLINE | ID: mdl-34354200

RESUMO

A non-invasive and sensitive blood test has long been a goal for early stage disease diagnosis and treatment for Alzheimer's disease (AD) and other proteinopathy diseases. We previously reported that preeclampsia (PE), a severe pregnancy complication, is another proteinopathy disorder with impaired autophagy. We hypothesized that induced autophagy deficiency would promote accumulation of pathologic protein aggregates. Here, we describe a novel, sensitive assay that detects serum protein aggregates from patients with PE (n = 33 early onset and 33 late onset) and gestational age-matched controls (n = 77) as well as AD in both dementia and prodromal mild cognitive impairment (MCI, n = 24) stages with age-matched controls (n = 19). The assay employs exposure of genetically engineered, autophagy-deficient human trophoblasts (ADTs) to serum from patients. The aggregated protein complexes and their individual components, including transthyretin, amyloid ß-42, α-synuclein, and phosphorylated tau231, can be detected and quantified by co-staining with ProteoStat, a rotor dye with affinity to aggregated proteins, and respective antibodies. Detection of protein aggregates in ADTs was not dependent on transcriptional upregulation of these biomarkers. The ROC curve analysis validated the robustness of the assay for its specificity and sensitivity (PE; AUC: 1, CI: 0.949-1.00; AD; AUC: 0.986, CI: 0.832-1.00). In conclusion, we have developed a novel, noninvasive diagnostic and predictive assay for AD, MCI and PE.


Assuntos
Doença de Alzheimer/sangue , Análise Química do Sangue/métodos , Pré-Eclâmpsia/sangue , Adulto , Doença de Alzheimer/diagnóstico , Peptídeos beta-Amiloides , Biomarcadores/sangue , Proteínas Sanguíneas/análise , Disfunção Cognitiva/diagnóstico , Feminino , Testes Hematológicos/métodos , Humanos , Imuno-Histoquímica , Fragmentos de Peptídeos , Pré-Eclâmpsia/diagnóstico , Gravidez , Agregados Proteicos/fisiologia , Curva ROC , Trofoblastos/efeitos dos fármacos , alfa-Sinucleína , Proteínas tau
12.
Alzheimers Dement (Amst) ; 13(1): e12157, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33665347

RESUMO

INTRODUCTION: The goal of this study was to pilot a referral-based cognitive screening and genetic testing program for Alzheimer's disease (AD) risk assessment in a primary care setting. METHODS: Primary care providers (PCPs; N = 6) referred patients (N = 94; M = 63 years) to the Rhode Island Alzheimer's Disease Prevention Registry for apolipoprotein E (APOE) genotyping and cognitive screening. PCPs disclosed test results to patients and counseled them about risk factor modification. RESULTS: Compared to the Registry as a whole, participants were younger, more likely to be non-White, and had lower cognitive screening scores. Mild cognitive impairment participants correctly reported a higher perceived risk of developing AD. Patients who recalled being counseled about modifiable risk factors were more likely to report positive health behavior changes. DISCUSSION: A referral-based program for cognitive and genetic AD risk assessment in a primary care setting is feasible, acceptable to patients, and yielded a more demographically diverse sample than an AD prevention registry.

13.
J Neurol Sci ; 423: 117383, 2021 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-33684655

RESUMO

BACKGROUND: The standard in vivo diagnostic imaging technique for cerebral amyloid angiopathy (CAA) is costly and thereby of limited utility for point-of-care diagnosis and monitoring of treatment efficacy. Recent recognition that retinal changes may reflect cerebral changes in neurodegenerative disease provides an ideal opportunity for development of accessible and cost-effective biomarkers for point-of-care use in the detection and monitoring of CAA. In this pilot study, we examined structural and angiographic retinal changes in CAA patients relative to a control group, and compared retinal and cerebral pathology in a group of CAA patients. METHODS: We used spectral domain optical coherence tomography (SD-OCT) to image the retina and compared retinal microbleeds to both cerebral microbleeds and white matter hyperintensities (WMH) in CAA patients, as seen on MRI. We compared retinal angiographic changes, along with structural retinal neuronal layer changes in CAA patients and cognitively normal older adults, and examined the relationship between retinal and cerebral microbleeds and cognition in CAA patients. RESULTS: We found a trend level correlation between retinal and cerebral microbleeds in CAA patients. Moreover, we found a significant correlation between retinal microbleeds and episodic memory performance in CAA patients. There were no significant group differences between CAA patients and cognitively normal older adults on retinal angiographic or structural measurements. CONCLUSION: Retinal microbleeds may reflect degree of cerebral microbleed burden in CAA. This picture was complicated by systolic hypertension in the CAA group, which is a confounding factor for the interpretation of these data. Our results stimulate motivation for pursuit of a more comprehensive prospective study to determine the feasibility of retinal biomarkers in CAA.


Assuntos
Angiopatia Amiloide Cerebral , Doenças Neurodegenerativas , Idoso , Angiopatia Amiloide Cerebral/complicações , Angiopatia Amiloide Cerebral/diagnóstico por imagem , Hemorragia Cerebral/complicações , Hemorragia Cerebral/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Projetos Piloto , Estudos Prospectivos , Retina/diagnóstico por imagem
14.
Alzheimers Dement (N Y) ; 7(1): e12140, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33718583

RESUMO

INTRODUCTION: This clinical trial aimed to determine whether in-car video feedback about unsafe driving events (UDE) to cognitively impaired older drivers and family members leads to a reduction in such driving behaviors. METHODS: We randomized 51 cognitively impaired older drivers to receive either (1) a weekly progress report with recommendations and access to their videos, or (2) video monitoring alone without feedback over 3 months. RESULTS: UDE frequency/1000 miles was reduced by 12% in feedback (rate ratio [RR] = 0.88, 95% confidence interval [CI] = .58-1.34), while remaining constant with only monitoring (RR = 1.01, 95% CI = .68-1.51). UDE severity/1000 miles was reduced by 37% in feedback (RR = 0.63, 95% CI = .31-1.27), but increased by 40% in monitoring (RR = 1.40, 95% CI = .68-2.90). Cognitive impairment moderated intervention effects (P = .03) on UDE frequency. DISCUSSION: Results suggest the potential to improve driving safety among mild cognitively impaired older drivers using a behavior modification approach aimed at problem behaviors detected in their natural driving environment.

15.
J Alzheimers Dis ; 80(4): 1553-1565, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33720880

RESUMO

BACKGROUND: Cerebrovascular dysfunction confers risk for functional decline in Alzheimer's disease (AD), yet the clinical interplay of these two pathogenic processes is not well understood. OBJECTIVE: We utilized Alzheimer's Disease Neuroimaging Initiative (ADNI) data to examine associations between peripherally derived soluble cell adhesion molecules (CAMs) and clinical diagnostic indicators of AD. METHODS: Using generalized linear regression models, we examined cross-sectional relationships of soluble plasma vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), and E-Selectin to baseline diagnosis and functional impairment (clinical dementia rating sum-of-boxes, CDR-SB) in the ADNI cohort (n = 112 AD, n = 396 mild cognitive impairment (MCI), n = 58 cognitively normal). We further analyzed associations of these biomarkers with brain-based AD biomarkers in a subset with available cerebrospinal fluid (CSF) data (n = 351). p-values derived from main effects and interaction terms from the linear regressions were used to assess the relationship between independent and dependent variables for significance (significance level was set at 0.05 a priori for all analysis). RESULTS: Higher mean VCAM-1 (p = 0.0026) and ICAM-1 (p = 0.0189) levels were found in AD versus MCI groups; however, not in MCI versus cognitively normal groups. Only VCAM-1 was linked with CDR-SB scores (p = 0.0157), and APOE ɛ4 genotype modified this effect. We observed independent, additive associations when VCAM-1 and CSF amyloid-ß (Aß42), total tau, phosphorylated tau (P-tau), or P-tau/Aß42 (all < p = 0.01) were combined in a CDR-SB model; ICAM-1 showed a similar pattern, but to a lesser extent. CONCLUSION: Our findings indicate independent associations of plasma-based vascular biomarkers and CSF biomarkers with AD-related clinical impairment.


Assuntos
Doença de Alzheimer/patologia , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Disfunção Cognitiva/patologia , Molécula 1 de Adesão Intercelular/sangue , Fragmentos de Peptídeos/líquido cefalorraquidiano , Molécula 1 de Adesão de Célula Vascular/sangue , Proteínas tau/líquido cefalorraquidiano , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/sangue , Doença de Alzheimer/líquido cefalorraquidiano , Biomarcadores/sangue , Biomarcadores/líquido cefalorraquidiano , Encéfalo/patologia , Disfunção Cognitiva/sangue , Disfunção Cognitiva/líquido cefalorraquidiano , Disfunção Cognitiva/diagnóstico , Estudos Transversais , Bases de Dados Factuais , Feminino , Humanos , Modelos Lineares , Masculino , Neuroimagem
16.
J Gerontol A Biol Sci Med Sci ; 76(6): 1037-1043, 2021 05 22.
Artigo em Inglês | MEDLINE | ID: mdl-32886748

RESUMO

BACKGROUND: Anticholinergic/sedative drug use, measured by the Drug Burden Index (DBI), has been linked to cognitive impairment in older adults. Subjective cognitive decline (SCD) may be among the first symptoms patients with Alzheimer's disease (AD) experience. We examined whether DBI values are associated with SCD in older adults at risk of AD. We hypothesized that increased DBI would be associated with greater SCD at older ages. METHOD: Two-hundred-six community-dwelling, English-speaking adults (age = 65 ± 9 years) at risk of AD (42% apolipoprotein ε4 carriers; 78% with AD family history) were administered a single question to ascertain SCD: "Do you feel like your memory is becoming worse?" Response options were "No"; "Yes, but this does not worry me"; and "Yes, this worries me." DBI values were derived from self-reported medication regimens using older adult dosing recommendations. Adjusting for relevant covariates (comorbidities and polypharmacy), we examined independent effects of age and DBI on SCD, as well as the moderating effect of age on the DBI-SCD association at mean ± 1 SD of age. RESULTS: Both SCD and anticholinergic/sedative drug burden were prevalent. Greater drug burden was predictive of SCD severity, but age alone was not. A significant DBI*Age interaction emerged with greater drug burden corresponding to more severe SCD among individuals age 65 and older. CONCLUSION: Anticholinergic/sedative drug exposure was associated with greater SCD in adults 65 and older at risk for AD. Longitudinal research is needed to understand if this relationship is a pre-clinical marker of neurodegenerative disease and predictive of future cognitive decline.


Assuntos
Antagonistas Colinérgicos/efeitos adversos , Disfunção Cognitiva/induzido quimicamente , Hipnóticos e Sedativos/efeitos adversos , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/induzido quimicamente , Doença de Alzheimer/etiologia , Autoavaliação Diagnóstica , Relação Dose-Resposta a Droga , Feminino , Humanos , Masculino , Testes de Estado Mental e Demência , Pessoa de Meia-Idade , Fatores de Risco
17.
Front Psychol ; 11: 596257, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33192943

RESUMO

Cognitive impairment is a significant risk factor for hazardous driving among older drivers with Alzheimer's dementia, but little is known about how the driving behavior of mildly symptomatic compares with those in the preclinical, asymptomatic phase of Alzheimer's disease (AD). This study utilized two in-car technologies to characterize driving behavior in symptomatic and preclinical AD. The goals of this pilot study were to (1) describe unsafe driving behaviors in individuals with symptomatic early AD using G-force triggered video capture and (2) compare the driving habits of these symptomatic AD drivers to two groups of cognitively normal drivers, those with and those without evidence of cerebral amyloidosis (CN/A+ and CN/A-) using a global positioning system (GPS) datalogger. Thirty-three drivers (aged 60+ years) were studied over 3 months. G-force triggered video events captured instances of near-misses/collisions, traffic violations, risky driver conduct, and driving fundamentals. GPS data were sampled every 30 s and all instances of speeding, hard braking, and sudden acceleration were recorded. For the early AD participants, video capture identified driving unbelted, late response, driving too fast for conditions, traffic violations, poor judgment, and not scanning intersections as the most frequently occurring safety errors. When evaluating driving using the GPS datalogger, hard breaking events occurred most frequently on a per trip basis across all three groups. The CN/A+ group had the lowest event rate across all three event types with lower instances of speeding. Slower psychomotor speed (Trail Making Part A) was associated with fewer speeding events, more hard acceleration events, and more overall events. GPS tracked instances of speeding were correlated with total number of video-captured near-collisions/collisions and driving fundamentals. Results demonstrate the utility of electronic monitoring to identify potentially unsafe driving events in symptomatic and preclinical AD. Results suggest that drivers with preclinical AD may compensate for early, subtle cognitive changes by driving more slowly and cautiously than healthy older drivers or those with cognitive impairment. Self-regulatory changes in driving behavior appear to occur in the preclinical phase of AD, but safety concerns may not arise until symptoms of cognitive impairment emerge and the ability to self-monitor declines.

18.
Transl Vis Sci Technol ; 9(8): 14, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32855861

RESUMO

Purpose: Visually impaired people may be allowed to drive if they wear bioptic telescopes. Bioptic driving safety is debatable, especially given that the telescopes are seldom used by most bioptic drivers. This preliminary study examined bioptic safety based on critical events that occurred in naturalistic daily driving. Methods: Daily driving activities were recorded using in-car video recorders in 20 bioptic drivers (median age 55, visual acuity, 20/60-160) and 19 control subjects (median age 74) for two to eight weeks. In a secondary analysis, these subjects were compared with 44 cognitively impaired drivers with normal vision (median age 75). Results: In 292 hours of driving by bioptic drivers and 169 hours by control drivers, seven bioptic drivers and three control drivers had eight and four near-collisions, respectively. Near-collision survival times were not significantly different between the two groups (hazard ratio [HR] = 1.93, P = 0.591) according to Cox hazards regression. Even without compensation for bioptic drivers' longer driving exposure, their odds ratio (OR) was not statistically significant (OR = 2.88, P = 0.18). When including cognitively impaired drivers with normal vision, cognition was a significant predictor of near collisions (HR = 3.86, P = 0.036), but vision loss was not (HR = 0.47, P = 0.317). Conclusions: This preliminary study failed to find any evidence suggesting that bioptic drivers were more prone to near-collision than healthy drivers. Vision might be a less-significant factor than cognition. Translational Relevance: Given that bioptic drivers use the telescope for less than 2% of the driving time, this study suggests that driving safety might not be substantially affected even when visual acuity is in the low vision range.


Assuntos
Condução de Veículo , Telescópios , Baixa Visão , Pessoas com Deficiência Visual , Idoso , Pré-Escolar , Óculos , Humanos , Lactente , Pessoa de Meia-Idade
19.
Neuropsychology ; 34(6): 699-712, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32551739

RESUMO

OBJECTIVE: Accessing semantic representations of real-world objects requires integration of multimodal perceptual features that are represented across relevant neocortical areas. Early Alzheimer's disease (AD) neuropathology, including neurofibrillary tangles in the perirhinal cortex as well as disrupted cortico-cortical connectivity, would be expected to disrupt the integration of object features. This integration deficit may underlie AD patients' semantic memory deficits and would be predicted to be more prominent for living objects, which tend to be more defined by sensory features compared with nonliving objects. METHOD: Two experiments were conducted to assess feature integration in cognitively healthy older adults and patients with amnestic mild cognitive impairment (MCI). In both experiments, pictures of real-world objects were presented in congruent or incongruent colors. Participants were instructed to make a speeded color congruency judgment (Experiment 1) or name the presented surface color (Experiment 2). RESULTS: Across experiments, MCI patients showed a selective integration deficit for living, but not nonliving, objects across both experimental paradigms that was consistent with a deterioration in semantic structural representations rather than a deficit in controlled semantic retrieval. Planned secondary analyses with a subset of patients (Experiment 1) for whom PET imaging was available indicated that the degree of impairment was associated with the magnitude of cortical amyloid burden. CONCLUSIONS: These findings suggest that early AD pathology leads to impaired integration of distributed semantic object representations. The development of integration tasks as sensitive markers of early AD pathology may lead to more effective diagnostic tools for early detection and intervention. (PsycInfo Database Record (c) 2020 APA, all rights reserved).


Assuntos
Disfunção Cognitiva/psicologia , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/psicologia , Córtex Cerebral/diagnóstico por imagem , Disfunção Cognitiva/diagnóstico por imagem , Cor , Feminino , Humanos , Masculino , Rememoração Mental , Pessoa de Meia-Idade , Testes Neuropsicológicos , Estimulação Luminosa , Tomografia por Emissão de Pósitrons , Semântica
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