Medication Changes Among Older Drivers Involved in Motor Vehicle Crashes.

Importance: Although older adults may use potentially driver-impairing (PDI) medications that can produce psychomotor impairment, little is known about changes to PDI medication use among older adults from the time before to the time after a motor vehicle crash (MVC). Objective: To quantify use of and changes in PDI medications among older adults before and after an MVC. Design, Setting, and Participants: This cohort study used linked Medicare claims and police-reported MVC data on 154 096 person-crashes among 121 846 older drivers. Eligible persons were drivers aged 66 years or older, involved in a police-reported MVC in New Jersey from May 1, 2007, through December 31, 2017, and with continuous enrollment in Medicare fee-for-service Parts A and B for at least 12 months and Part D for at least 120 days prior to the MVC. Data were analyzed from January 2022 to May 2024. Main Outcomes and Measures: Use of benzodiazepines, nonbenzodiazepine hypnotics, opioid analgesics, and other PDI medications in the 120 days before and 120 days after the MVC. Because each person could contribute multiple MVCs during the study period if they met eligibility criteria, the unit of analysis was the number of person-crashes. The proportion of person-crashes after which PDI medications were started, discontinued, or continued was quantified as well. Results: Among 154 096 eligible person-crashes, the mean (SD) age of the drivers was 75.2 (6.7) years at the time of the MVC. Of 121 846 unique persons, 51.6% were women. In 80.0% of the person-crashes, drivers used 1 or more PDI medications before the crash, and in 81.0% of the person-crashes, drivers used 1 or more PDI medications after the crash. Use of benzodiazepines (8.1% before the crash and 8.8% after the crash), nonbenzodiazepine hypnotics (5.9% before the crash and 6.0% after the crash), and opioid analgesics (15.4% before the crash and 17.5% after the crash) was slightly higher after the MVC. After the MVC, drivers in 2.1% of person-crashes started benzodiazepines and 1.4% stopped benzodiazepines, drivers in 1.2% of person-crashes started nonbenzodiazepine hypnotics and 1.2% stopped nonbenzodiazepine hypnotics, and drivers in 8.4% of person-crashes started opioid analgesics and 6.3% stopped opioid analgesics. Conclusions and Relevance: This cohort study suggests that most older drivers involved in MVCs did not use fewer PDI medications after crashes than before crashes. Qualitative research of perceived risks vs benefits of PDI medications is necessary to understand the reasons why MVCs do not appear to motivate clinicians to deprescribe PDI medications as a strategy to avert potential harms, including additional MVCs.

Implications of using administrative healthcare data to identify risk of motor vehicle crash-related injury: the importance of distinguishing crash from crash-related injury.

BACKGROUND: Administrative healthcare databases, such as Medicare, are increasingly used to identify groups at risk of a crash. However, they only contain information on crash-related injuries, not all crashes. If the driver characteristics associated with crash and crash-related injury differ, conflating the two may result in ineffective or imprecise policy interventions. METHODS: We linked 10 years (2008-2017) of Medicare claims to New Jersey police crash reports to compare the demographics, clinical diagnoses, and prescription drug dispensings for crash-involved drivers ≥ 68 years with a police-reported crash to those with a claim for a crash-related injury. We calculated standardized mean differences to compare characteristics between groups. RESULTS: Crash-involved drivers with a Medicare claim for an injury were more likely than those with a police-reported crash to be female (62.4% vs. 51.8%, standardized mean difference [SMD] = 0.30), had more clinical diagnoses including Alzheimer's disease and related dementias (13.0% vs. 9.2%, SMD = 0.20) and rheumatoid arthritis/osteoarthritis (69.5% vs 61.4%, SMD = 0.20), and a higher rate of dispensing for opioids (33.8% vs 27.6%, SMD = 0.18) and antiepileptics (12.9% vs 9.6%, SMD = 0.14) prior to the crash. Despite documented inconsistencies in coding practices, findings were robust when restricted to claims indicating the injured party was the driver or was left unspecified. CONCLUSIONS: To identify effective mechanisms for reducing morbidity and mortality from crashes, researchers should consider augmenting administrative datasets with information from police crash reports, and vice versa. When those data are not available, we caution researchers and policymakers against the tendency to conflate crash and crash-related injury when interpreting their findings.

Non-benzodiazepine Hypnotics and Police-Reported Motor Vehicle Crash Risk among Older Adults: A Sequential Target Trial Emulation.

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.

Geographic Variation of Antidementia and Antipsychotic Medication Use Among US Nursing Home Residents With Dementia.

BACKGROUND: Several antidementia medications have been approved for symptomatic treatment of cognitive and functional impairment due to Alzheimer disease. Antipsychotics are often prescribed off-label for behavioral symptoms. OBJECTIVE: The aim of this study was to describe the basis for regional variation in antidementia and antipsychotic medication use. SETTING: US nursing homes (n=9735), hospital referral regions (HRR; n=289). SUBJECTS: Long-stay residents with dementia (n=273,004). METHODS: Using 2018 Minimum Data Set 3.0 linked to Medicare data, facility information, and Dartmouth Atlas files, we calculated prevalence of use and separate multilevel logistic models [outcomes: memantine, cholinesterase inhibitor (ChEI), antipsychotic use] estimated adjusted odds ratios (aOR) and 95% CIs for resident, facility, and HRR characteristics. We then fit a series of cross-classified multilevel logistic models to estimate the proportional change in cluster variance (PCV). RESULTS: Overall, 20.9% used antipsychotics, 16.1% used memantine, and 23.3% used ChEIs. For antipsychotics, facility factors [eg, use of physical restraints (aOR: 1.08; 95% CI: 1.05-1.11) or poor staffing ratings (aOR: 1.10; 95% CI: 1.06-1.14)] were associated with more antipsychotic use. Nursing homes in HRRs with the highest health care utilization had greater antidementia drug use (aOR memantine: 1.68; 95% CI: 1.44-1.96). Resident/facility factors accounted for much regional variation in antipsychotics (PCV STATE : 27.80%; PCV HRR : 39.54%). For antidementia medications, HRR-level factors accounted for most regional variation (memantine PCV STATE : 37.44%; ChEI PCV STATE : 39.02%). CONCLUSION: Regional variations exist in antipsychotic and antidementia medication use among nursing home residents with dementia suggesting the need for evidence-based protocols to guide the use of these medications.

Hypothalamic transcriptome response to simulated diel earthen pond hypoxia cycles in channel catfish (Ictalurus punctatus).

Commercial culture of channel catfish (Ictalurus punctatus) occurs in earthen ponds that are characterized by diel swings in dissolved oxygen concentration that can fall to severe levels of hypoxia, which can suppress appetite and lead to suboptimal growth. Given the significance of the hypothalamus in regulating these processes in other fishes, an investigation into the hypothalamus transcriptome was conducted to identify specific genes and expression patterns responding to hypoxia. Channel catfish in normoxic water were compared with catfish subjected to 12 h of hypoxia (20% oxygen saturation; 1.8 mg O2/L; 27°C) followed by 12 h of recovery in normoxia to mimic 24 h in a catfish aquaculture pond. Fish were sampled at 0-, 6-, 12-, 18-, and 24-h timepoints, with the 6- and 12-h samplings occurring during hypoxia. A total of 190 genes were differentially expressed during the experiment, with most occurring during hypoxia and returning to baseline values within 6 h of normoxia. Differentially expressed genes were sorted by function into Gene Ontology biological processes and revealed that most were categorized as "response to hypoxia," "sprouting angiogenesis," and "cellular response to xenobiotic stimulus." The patterns of gene expression reported here suggest that transcriptome responses to hypoxia are broad and quickly reversibly with the onset of normoxia. Although no genes commonly reported to modulate appetite were found to be differentially expressed in this experiment, several candidates were identified for future studies investigating the interplay between hypoxia and appetite in channel catfish, including adm, igfbp1a, igfbp7, and stc2b.NEW & NOTEWORTHY Channel catfish are an economically important species that experience diel episodic periods of hypoxia that can reduce appetite. This is the first study to investigate their transcriptome from the hypothalamus in a simulated 24-h span in a commercial catfish pond, with 12 h of hypoxia and 12 h of normoxia. The research revealed functional groups of genes relating to hypoxia, angiogenesis, and glycolysis as well as individual target genes possibly involved in appetite regulation.

Elevated Amyloid-ß PET Scan and Cognitive and Functional Decline in Mild Cognitive Impairment and Dementia of Uncertain Etiology.

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.

Association between neuropsychological assessment and amyloid status in a clinical setting.

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).

Changes in Antidementia Medications upon Admission to the Nursing Home: Who Decides and Why? Results From a National Survey of Nursing Home Administrators.

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.

Antidementia Medication Use in Nursing Home Residents.

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.

Changes in the burden of medications that may impair driving among older adults before and after a motor vehicle crash.

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.

Effect of hypoxia duration and pattern on channel Catfish (Ictalurus punctatus) neuropeptide gene expression and hematology.

Commercial aquaculture production of channel catfish (Ictalurus punctatus) occurs in shallow ponds with daily cycling of dissolved oxygen concentration ranging from supersaturation to severe hypoxia. Once daily minimum dissolved oxygen concentration falls below 3.0 mg O2/L, channel catfish have a reduced appetite, leading to reduced growth rates. In other fishes, upregulation of the neuropeptides corticotropin-releasing factor (CRF) and urotensin I (UI) have been implicated as initiating the mechanism responsible for decreasing appetite once an environmental stressor is detected. Channel catfish maintained at 27 °C in aquaria were subjected to varying durations and patterns of hypoxia (1.75 ± 0.07 mg O2/L) to evaluate underlying physiological responses to hypoxia and determine if hypothalamic CRF and UI are responsible for hypoxia-induced anorexia in channel catfish. During a short exposure to hypoxia (12 h), venous PO2 was significantly lower within 6 h and was coupled with an increase of hematocrit and decrease of blood osmolality, yet all responses reversed within 12 h after returning to normoxia. When this pattern of hypoxia and normoxia was repeated cyclically for 5 days, these physiological responses repeated daily. Extended periods of hypoxia (5 days) resulted in similar hematological responses, which did not recover to baseline values during the hypoxia exposure. This study did not find a significant change in hypothalamic transcription of CRF and UI during hypoxia challenges but did identify multiple physiological adaptive responses that work together to reduce the severity of experimentally induced hypoxia in channel catfish.

Distance From Home to Motor Vehicle Crash Location: Implications for License Restrictions Among Medically-At-Risk Older Drivers.

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.

No association between APOE genotype and lipid lowering with cognitive function in a randomized controlled trial of evolocumab.

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.

Healthy Lifestyle Behaviors and Viewpoints Among Members of an Alzheimer Prevention Registry.

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.

Feasibility of a Yoga Intervention for Individuals with Mild Cognitive Impairment: A Randomized Controlled Trial.

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.

Effectiveness of barrier devices, high-volume evacuators, and extraoral suction devices on reducing dental aerosols for the dental operator: A pilot study.

BACKGROUND: The COVID-19 pandemic has increased the importance of minimizing exposure to aerosols generated during dental procedures. The authors' objective was to measure the aerosolized particles in the breathing zone of operators using several facial protection and filtration methods. METHODS: Twenty-one dentists performed maxillary anterior incisor veneer preparations using a microscope and drape and loupes with or without a face shield. In each test condition, the following 3 levels of filtration were tested: no filtration, a high-volume evacuator [HVE], and an HVE with an extraoral suction device. Measurements were made using a mass monitor attached to the operator's chest with inlet within 10 inches of the operator's face. RESULTS: The authors found that the microscope and drape provided the lowest levels of aerosolized particles compared with loupes with or without a face shield (P < .001). There was no detectable difference in the concentration of particles between operators wearing a face shield and wearing loupes alone (P = .47). The particles in each test condition were lowered when an HVE was used (P < .001) and further lowered with an extraoral suction device. CONCLUSIONS: The findings of this study suggest that the use of a surgical microscope and bag barrier drape, HVE, and extraoral suction device result in the lowest concentration of aerosolized particles. The face shield did not appear to offer any protection from aerosolized particles. HVE and extraoral suction were effective in decreasing aerosols regardless of the type of facial protection used. PRACTICAL IMPLICATIONS: Dentists can reduce exposure to aerosols with a drape, HVE, and extraoral suction.

Novel blood test for early biomarkers of preeclampsia and Alzheimer's disease.

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.

Peripheral Markers of Vascular Endothelial Dysfunction Show Independent but Additive Relationships with Brain-Based Biomarkers in Association with Functional Impairment in Alzheimer's Disease.

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.

Video feedback intervention for cognitively impaired older drivers: A randomized clinical trial.

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.

The relationship between cerebral and retinal microbleeds in cerebral amyloid angiopathy (CAA): A pilot study.

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.