Bladder Antimuscarinics and Cognitive Decline in Elderly Patients

Introduction: The evidence on the impact of bladder antimuscarinics initiation on cognitive function in older adults is inconsistent. Methods: A retrospective analysis of data from the National Alzheimer\u27s Coordinating Center (NACC) on enrollees 65 years and older evaluated the association between antimuscarinic initiation and cognitive decline. We defined decline from baseline (yes/no) for cognitive assessments included in the NACC Uniform Data Set 2.0 battery. New users were matched on year of enrollment and time in the cohort to randomly selected nonusers. Analyses were conducted using inverse probability of treatment weights based on baseline propensity scores. Results: Our analyses included 698 new users and 7037 nonusers. The odds ratio (OR) and 95% confidence interval for cognitive decline in users as compared to nonusers was 1.4 (1.19–1.65) for Mini–Mental State Examination (MMSE), and 1.21 (1.03–1.42) for Clinical Dementia Rating; in addition, the odds of decline were 20% higher in users compared to nonusers for semantic memory/language and executive function. The effect estimate for MMSE was 1.94 (1.3–2.91) for those with mild cognitive impairment, 1.26 (0.99–1.62) in those with normal cognition, and 1.44 (1.04–1.99) in those with dementia at baseline. Discussion: Our results show that antimuscarinic initiation is associated with cognitive decline and raise questions about their use, especially in those with impaired cognition

The Association of Gabapentin Initiation and Neurocognitive Changes in Older Adults with Normal Cognition

Background: Gabapentin is increasingly prescribed to older adults, which raises concerns about its potential to cause neurocognitive changes. Therefore, we aimed to examine the association of gabapentin use with neurocognitive changes (i.e., cognitive decline, functional status decline, and motor function change) in older adults. Methods: We conducted a retrospective cohort study using the National Alzheimer’s Coordinating Center Uniform Data Set (UDS; September 2005-March 2021 data freeze). From the eligible sample (≥age 65 years), we identified cognitively normal new-users of gabapentin and the visit they initiated gabapentin (i.e., index visit). Initiators were matched to randomly selected nonusers on year of UDS enrollment and visit number from enrollment to index. Cognitive decline was defined as any increase in the Clinical Dementia Rating global score (CDRGLOB) and as a 1-point increase in CDR sum of boxes (CDR-SB). Functional status decline was defined as a 3-point increase in the sum of the Functional Activities Questionnaire (FAQ) and as 0.3-point increase in mean FAQ. Decline in motor function was defined as new clinician reports of gait disorder, falls, and slowness. To mitigate confounding and selection bias, we used joint stabilized inverse probability of treatment weights and stabilized inverse probability of censoring weights. All analyses were conducted comparing index to index+1 and index+2 visits. Results: From the eligible UDS participants (N = 23,059), we included 480 initiators (mean age [SD]: 78.7 [6.9]; male 34.4%); 4,320 nonusers (78.3 [7.0]; 34.4%). Gabapentin initiation was significantly associated with cognitive/functional status decline: worsening CDRGLOB at index+1 visit (odds ratio [95% confidence interval]: 1.55 [1.07, 2.25]); CDR-SB at index+1 visit (1.94 [1.22, 3.09]); and mean of FAQ at index+2 visit (1.78 [1.12, 2.83]). After excluding initiators with extant motor dysfunction (n = 21), we identified 459 initiators (78.7 [6.9]; 34.0%) and 4,131 nonusers (78.2 [6.9]; 34.7%); in this sample, gabapentin initiation was associated with increased falls at the index+2 visit (2.51 [1.19, 5.31]). Conclusion: Gabapentin initiation was significantly associated with deleterious neurocognitive changes among older adults with initially normal cognition. Further studies are needed to examine the risk/benefit of prescribing gabapentin in older adults

Simple surface functionalization strategy for immunosensing detection of aflatoxin B1

This paper describes the strategy of functionalization of gold electrodes surfaces in aim to obtain a new impedimetric immunosensor for the detection of aflatoxin B1, a common toxic food contaminant. The immunosensor elaboration is based on immobilization of anti-aflatoxin antibody on gold electrodes modified with a cross-linked film of bovine serum albumin, by a four-step protocol. The immunosensor is based on a simple design and requires small volumes of toxic aflatoxin solution. All the steps of the immunosensor elaboration and the immunochemical reaction between aflatoxin and antibody were followed using atomic force microscopy (AFM) and electrochemical impedance spectroscopy (EIS). The resistance to charge transfer (Rct) was the most sensitive parameter to changes induced to the interfacial properties of the immunosensor by the incubation with aflatoxin and varied linearly with aflatoxin concentration in the range 1-20 ng/mL. The immunosensor was applied for the detection of aflatoxin in spiked plant extracts with good recovery factors

Predictors of Chronic Opioid Therapy in Medicaid Beneficiaries with HIV Who Initiated Antiretroviral Therapy

The factors associated with chronic opioid therapy (COT) in patients with HIV is understudied. Using Medicaid data (2002-2009), this retrospective cohort study examines COT in beneficiaries with HIV who initiated standard combination anti-retroviral therapy (cART). We used generalized estimating equations on logistic regression models with backward selection to identify significant predictors of COT initiation. COT was initiated among 1014 out of 9615 beneficiaries with HIV (male: 10.4%; female: 10.7%). Those with older age, any malignancy, Hepatitis C infection, back pain, arthritis, neuropathy pain, substance use disorder, polypharmacy, (use of) benzodiazepines, gabapentinoids, antidepressants, and prior opioid therapies were positively associated with COT. In sex-stratified analyses, multiple predictors were shared between male and female beneficiaries; however, chronic obstructive pulmonary disease, liver disease, any malignancy, and antipsychotic therapy were unique to female beneficiaries. Comorbidities and polypharmacy were important predictors of COT in Medicaid beneficiaries with HIV who initiated cART

Ochratoxin A Detection on Antibody- Immobilized on BSA-Functionalized Gold Electrodes

Ochratoxin A (OTA)-a toxin produced by Aspergillus carbonarius, Aspergillus ochraceus, and Penicillium verrucosum-is one of the most-abundant food-contaminating mycotoxins. To avoid the risk of OTA consumption for humans and animals, the rapid detection and quantitation of OTA level in different commodities are of great importance. In this work, an impedimetric immunosensor for ochratoxin A (OTA) detection, a common toxic botanical contaminant, was developed via the immobilization of anti-OTA antibody on bovine serum albumin modified gold electrodes. A four-step reaction protocol was tested to modify the gold electrode and obtain the sensing substrate. All the steps of the immunosensor elaboration and also the immunochemical reaction between surface-bound antibody and ochratoxin A were analyzed using cyclic voltammetry and electrochemical impedance spectroscopy. Modification of the impedance due to the specific antigen-antibody reaction at immunosensor surface, was used in order to detect ochratoxin A. Linear proportionality of the charge transfer resistance to the concentration of OTA allows ochratoxin A detection in the range of 2.5-100 ng/mL

Optimizing Medication Appropriateness in Older Adults: A Randomized Clinical Interventional Trial to Decrease Anticholinergic Burden

Background The complexity of medication therapy in older adults with multiple comorbidities often leads to inappropriate prescribing. Drugs with anticholinergic properties are of particular interest because many are not recognized for this property; their use may lead to increased anticholinergic burden resulting in significant health risks, as well as negatively impacting cognition. Medication therapy management (MTM) interventions showed promise in addressing inappropriate medication use, but the effectiveness of targeted multidisciplinary team interventions addressing anticholinergic medications in older populations is yet to be determined. Methods We conducted an 8-week, parallel-arm, randomized trial to evaluate whether a targeted patient-centered pharmacist–physician team MTM intervention (“targeted MTM intervention”) reduced the use of inappropriate anticholinergic medications in older patients enrolled in a longitudinal cohort at University of Kentucky’s Alzheimer’s Disease Center. Study outcomes included changes in the medication appropriateness index (MAI) targeting anticholinergic medications and in the anticholinergic drug scale (ADS) score from baseline to the end of study. Results Between October 1, 2014 and September 30, 2015 we enrolled and randomized 50 participants taking at least one medication with anticholinergic properties. Of these, 35 (70%) were women, 45 (90%) were white, and 33 (66%) were cognitively intact (clinical dementia rating [CDR] = 0); mean age was 77.7 ± 6.6 years. At baseline, the mean MAI was 12.6 ± 6.3; 25 (50%) of the participants used two or more anticholinergics, and the mean ADS score was 2.8 ± 1.6. After randomization, although no statistically significant difference was noted between groups, we identified a potentially meaningful imbalance as the intervention group had more participants with intact cognition, and thus included CDR in all of the analyses. The targeted MTM intervention resulted in statistically significant CDR adjusted differences between groups with regard to improved MAI (change score of 3.6 (1.1) for the MTM group as compared with 1.0 (0.9) for the control group, p = 0.04) and ADS (change score of 1.0 (0.3) for the MTM group as compared with 0.2 (0.3) for the control group, p = 0.03). Conclusions Our targeted MTM intervention resulted in improvement in anticholinergic medication appropriateness and reduced the use of inappropriate anticholinergic medications in older patients. Our results show promise in an area of great importance to ensure optimum outcomes for medications used in older adults. Trial registration ClinicalTrials.gov NCT02172612. Registered 20 June 2014

Environmental Illness May Have Contributed to the Origins of Transylvanian Vampire Myths

Field and ethnographic data are utilized to illustrate that significant contamination of rural wells with nitrates, bacteria and protozoa both currently and in the past are fertile ground for the development of myths surrounding spirit and blood stealing mythical creatures. The very real problem of methemoglobinemia, an environmentally induced hypoxia, in rural Transylvania is an ideal situation for physiological confirmation of and, perhaps, cultural etiology determination of the myth of vampirism. Ethnographic accounts of vampire and werewolf myths are correlated with the field data

Clinical and laboratory features of anti-MAG neuropathy without monoclonal gammopathy

Antibodies against myelin-associated glycoprotein (MAG) almost invariably appear in the context of an IgM monoclonal gammopathy associated neuropathy. Very few cases of anti-MAG neuropathy lacking IgM-monoclonal gammopathy have been reported. We investigated the presence of anti-MAG antibodies in 69 patients fulfilling diagnostic criteria for CIDP. Anti-MAG antibodies were tested by ELISA and confirmed by immunohistochemistry. We identified four (5.8%) anti-MAG positive patients without detectable IgM-monoclonal gammopathy. In two of them, IgM-monoclonal gammopathy was detected at 3 and 4-year follow-up coinciding with an increase in anti-MAG antibodies titers. In conclusion, anti-MAG antibody testing should be considered in chronic demyelinating neuropathies, even if IgM-monoclonal gammopathy is not detectable

INtervention for Cognitive Reserve Enhancement in Delaying the Onset of Alzheimer\u27s Symptomatic Expression (INCREASE), a Randomized Controlled Trial: Rationale, Study Design, and Protocol

BACKGROUND: The course of Alzheimer\u27s disease (AD) includes a 10-20-year preclinical period with progressive accumulation of amyloid β (Aβ) plaques and neurofibrillary tangles in the absence of symptomatic cognitive or functional decline. The duration of this preclinical stage in part depends on the rate of pathologic progression, which is offset by compensatory mechanisms, referred to as cognitive reserve (CR). Comorbid medical conditions, psychosocial stressors, and inappropriate medication use may lower CR, hastening the onset of symptomatic AD. Here, we describe a randomized controlled trial (RCT) designed to test the efficacy of a medication therapy management (MTM) intervention to reduce inappropriate medication use, bolster cognitive reserve, and ultimately delay symptomatic AD. METHODS/DESIGN: Our study aims to enroll 90 non-demented community-dwelling adults ≥ 65 years of age. Participants will undergo positron emission tomography (PET) scans, measuring Aβ levels using standardized uptake value ratios (SUVr). Participants will be randomly assigned to MTM intervention or control, stratified by Aβ levels, and followed for 12 months via in-person and telephone visits. Outcomes of interest include: (1) medication appropriateness (measured with the Medication Appropriateness Index (MAI)); (2) scores from Trail Making Test B (TMTB), Montreal Cognitive Assessment (MoCA), and California Verbal Learning Test (CVLT); (3) perceived health status (measured with the SF-36). We will also evaluate pre- to post-intervention change in: (1) use of inappropriate medications as measured by MAI; 2) CR Change Score (CRCS), defined as the difference in scopolamine-challenged vs unchallenged cognitive scores at baseline and follow-up. Baseline Aβ SUVr will be used to examine the relative impact of preclinical AD (pAD) pathology on CRCS, as well as the interplay of amyloid burden with inappropriate medication use. DISCUSSION: This manuscript describes the protocol of INCREASE ( INtervention for Cognitive Reserve Enhancement in delaying the onset of Alzheimer\u27s Symptomatic Expression ): a randomized controlled trial that investigates the impact of deprescribing inappropriate medications and optimizing medication regimens on potentially delaying the onset of symptomatic AD and AD-related dementias. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02849639. Registered on 29 July 2016