Clinical impact of 11C-Pittsburgh compound-B positron emission tomography in addition to magnetic resonance imaging and single-photon emission computed tomography on diagnosis of mild cognitive impairment to Alzheimer's disease

This study aimed to evaluated the clinical impact of adding [¹¹C] Pittsburgh compound-B (¹¹C-PiB) PET for clinical diagnosis of mild cognitive impairment (MCI) to Alzheimer''s disease (AD) dementia.Twenty six (mean age 78.5 ± 5.18 years, 21 females) AD (n = 7), amnestic MCI (n = 12), non-amnestic MCI (n = 3), vascular dementia, progressive supranuclear palsy (PSP) with frontotemporal dementia (FTD), FTD (n = 1 each), and normal (n = 1) patients underwent ¹¹C-PiB-PET, MRI, and SPECT scanning. ¹¹C-PiB-PET was compared with MRI and SPECT for clinical impact.¹¹C-PiB-PET showed positivity in 6, 9, and 0 of the AD, amnestic MCI, and non-amnestic MCI patients, respectively, and 0 of those with another disease. Parahippocampal atrophy at VSASD was observed in 5 AD patients, 6 amnestic and PiB-positive MCI patients, 1 amnestic and PiB-negative MCI patient, and 1 vascular dementia patient. Parietal lobe hypoperfusion in SPECT findings was observed in 6, 4, and 2 of those, respectively, as well as 1 each of non-amnestic MCI, vascular dementia, and normal cases. Sensitivity/specificity/accuracy for selecting PiB-positive patients among the 15 MCI patients for ¹¹C-PiB-PET were 100% (9/9)/100% (6/6)/100% (15/15), for VSRAD were 66.7% (6/9)/83.3% (5/6)/73.3% (11/15), and for SPECT were 44.4% (4/9)/50.0% (3/6)/46.7% (7/15), while those were 88.9% (8/9)/33.3% (2/6)/66.7% (10/15)/for combined VSRAD and SPECT. ¹¹C-PiB-PET accuracy was significantly higher than that of SPECT.¹¹PiB-PET alone may be useful for selecting patients who will progress from MCI to AD in the future, although follow-up study is necessary to clarify the outcome of MCI patients.     

Conversion pattern and predictive factor of mild cognitive impairment in elderly Koreans

ObjectiveWe aimed to understand conversion characteristics of mild cognitive impairment (MCI) in elderly Koreans.MethodsWe analyzed clinical data of 760 individuals who participated in a two-year follow-up study. Neuropsychological assessments and clinical examination were conducted in the follow-ups. Logistic regression model was used to estimate predictive risk factors of MCI conversion.ResultThe participants at baseline (n = 760) represented 462 cognitively normal individuals (60.8%), 286 individuals with MCI (37.6%), and 12 individuals with dementia (1.6%). Among the cognitively normal individuals (n = 462), 108 (23.4%) progressed to MCI during the two-year follow-up period, including 92 with amnestic mild cognitive impairment (aMCI; 19.9%) and 16 with non-amnestic mild cognitive impairment (non-aMCI; 3.5%). Interestingly, 3.7% of participants with aMCI converted to non-aMCI, while 45.5% of participants with non-aMCI converted to aMCI. Moreover, a higher proportion of non-aMCI (27.3%) reverted to a cognitively normal state, compared to aMCI participants (18.6%), indicating that non-amnestic cognitive impairment is more unstable than amnestic cognitive impairment, and probably converges toward aMCI. Additionally, we found that weight loss was associated with incident MCI and future MCI. Weight loss was negatively correlated with Clinical Dementia Rating (p = 0.005), and significantly associated with a higher risk of MCI conversion from a cognitively normal state (OR = 1.10, 95% CI: 1.00–1.21, p = 0.042).ConclusionThis study supports that non-amnestic MCI is prone to converge toward amnestic MCI, and the elderly people with weight loss are at risk for developing cognitive decline.     

Elevation of plasma soluble amyloid precursor protein beta in Alzheimer’s disease

IntroductionBeta-amyloid is considered to be a pathophysiological marker in Alzheimer's disease (AD). Soluble amyloid precursor proteins (sAPPs) –α (sAPPα) and –β (sAPPβ), which are the byproducts of non-amyloidogenic and amyloidogenic process of APP, respectively, have been repeatedly observed in the cerebrospinal fluids (CSF) of AD patients. The present study focused on the determination of sAPP levels in peripheral blood.MethodsThe plasma protein levels of sAPPα and sAPPβ were measured with ELISA. Plasma from 52 AD patients, 98 amnestic mild cognitive impairment (MCI) patients, and 114 cognitively normal controls were compared.ResultsThe plasma level of sAPPβ was significantly increased in AD patients than in cognitively healthy controls. However, no significant change in plasma sAPPα was observed among the three groups. Furthermore, the plasma sAPPβ levels significantly correlated with cognitive assessment scales, such as clinical dementia rating (CDR), and mini-mental status examination (MMSE). Interestingly, sAPPα and sAPPβ had a positive correlation with each other in blood plasma, similar to previous studies on CSF sAPP. This correlation was stronger in the MCI and AD groups than in the cognitively healthy controls.ConclusionsThese results suggest that individuals with elevated plasma sAPPβ levels are at an increased risk of AD; elevation in these levels may reflect the progression of disease.     

Trospium chloride for overactive bladder may induce central nervous system adverse events

BackgroundAnticholinergic drugs constitute the first-line pharmacologic treatment for overactive bladder (OAB). Of the various anticholinergic agents available, trospium chloride appears to have potentially favorable chemical and pharmacologic properties leading to reduce the incidence of central nervous system (CNS) adverse reactions, since their ability to cross the blood-brain barrier is reduced (relative to other drugs in this therapeutic class).ObjectiveThe objective of the present survey was to establish whether or not CNS adverse reactions may be associated with trospium exposure by evaluating spontaneous reports made to the French pharmacovigilance database (FPVD).MethodsAll serious adverse drug reactions, specifically confusion, hallucinations, agitation and cognitive impairment, associated with trospium (the immediate-release form only) recorded in the FPVD between September 2005 to September 2011 were identified and analyzed.ResultsWe identified 15 cases of CNS adverse events, according to at least one of the following terms: confusion (n = 9), hallucinations (n = 6), cognitive impairment (n = 4) and agitation (n = 2) and in which trospium chloride was suspected to have a causal link according to their imputability evaluation. The reports concerned 10 women and 5 men, with a mean age of 81 years (range: 62 to 96 years). The symptoms varied from relatively acute states of confusion and/or hallucinations to more progressive cognitive changes. In all these cases, CNS symptoms resolved rapidly after treatment discontinuation.ConclusionDespite the drug's favorable physiochemical properties, we have found pharmacovigilance data indicating that trospium chloride prescribed for OAB can induce CNS adverse reactions, such as confusion, hallucinations, agitation and/or cognitive impairment. Physicians should consider withdrawing trospium chloride if CNS symptoms suggestive of anticholinergic adverse effects occur in patients treated with this drug.     

Spatial navigation deficit in amnestic mild cognitive impairment

Patients with Alzheimer's disease (AD) frequently have difficulties with spatial orientation in their day-to-day life. Although AD is typically preceded by amnestic mild cognitive impairment (MCI), spatial navigation has not yet been studied in MCI. Sixty-five patients were divided into five groups: probable AD (n = 21); MCI, further classified as amnestic MCI single domain (n = 11); amnestic MCI multiple domain (n = 18), or nonamnestic MCI (n = 7), and subjective memory complaints (n = 8). These patients, together with a group of healthy control subjects (n = 26), were tested by using a four-subtests task that required them to locate an invisible goal inside a circular arena. Each subtest began with an overhead view of the arena showed on a computer monitor. This was followed by a real navigation inside of the actual space, an enclosed arena 2.9 m in diameter. Depending on the subtest, the subjects could use the starting position and/or cues on the wall for navigation. The subtests thus were focused on allocentric and egocentric navigation. The AD group and amnestic MCI multiple-domain group were impaired in all subtests. The amnestic MCI single-domain group was impaired significantly in subtests focused on allocentric orientation and at the beginning of the real space egocentric subtest, suggesting impaired memory for allocentric and real space configurations. Our results suggest that spatial navigation impairment occurs early in the development of AD and can be used for monitoring of the disease progression or for evaluation of presymptomiatic AD.     

Chinese herbal medicine for mild cognitive impairment using mini-mental state examination: A systematic review and meta-analysis

Introduction:The prevalence of mild cognitive impairment (MCI) in the elderly population aged 60 to 84 years ranges from 6.7% to 25.2%, and the effective prevention and reversal of MCI progression to Alzheimer disease (AD) is crucial. The mini mental state examination (MMSE) is the most commonly used screening tool in Chinese outpatient clinics, with sufficient sensitivity and specificity to allow useful stratification from average to abnormal with adequate consideration of age and education.Objective:To investigate the clinical significance of Chinese herbs on MMSE scores in MCI patients and discuss the effectiveness of Chinese herbs through pharmacology.Methods:Three English databases and 4 Chinese databases we have searched, and the risk of bias was assessed according to the Cochrane tool. Statistics will be used for heterogeneity assessment, sensitivity analysis, data synthesis, funnel plot generation and subgroup analysis. If sufficiently homogeneous studies are found, a Meta-analysis will be performed, with subgroups describing any differences.Results:A total of 21 studies were included, 4 studies were placebo-controlled, 14 Chinese Herbal Medicines (CHMs) were compared with other cognitive improvements, 3 CHMs were combined with other medications, and the results of 17 studies favored the herbal group.Conclusion:The results indicate that herbal medicine can improve MMSE scores, and herbal medicine combined with other drugs that can improve cognition can significantly improve MMSE scores, but there are methodological flaws in the study. Experimental studies have found a basis for the ability of herbs to improve cognition and memory impairment, and herbal medicine has great potential to improve MCI cognition. Keywords mild cognitive impairment, herbal medicine, MMSE, systematic evaluation, meta-analysis. PROSPERO international prospective register of systematic reviews protocol registration number: CRD42020202368     

The effect of severity of white matter hyperintensities on loss of functional independency in patients with mild cognitive impairment: A CREDOS-LTCI (clinical research center for dementia of South Korea-long term card insurance) study

ObjectiveBy combining data from the Clinical Research Center for Dementia of South Korea(CREDOS) study and long-term care insurance(LTCI), we aimed to assess whether the severity of white matter hyperintensity(WMH) predicted functional decline in cases of amnestic mild cognitive impairment(MCI).MethodsWMH was evaluated in 3,569 patients with amnestic MCI using the visual rating scale developed for the CREDOS study. The participants were classified as having amnestic MCI with minimal WMH change(aMCI), with moderate WMH change(maMCI) and with severe WMH change(saMCI) according to the severity of the WMH measurements. A Kaplan–Meier survival probability estimate was used to compute median time from the diagnosis of MCI to LTCI enrollment for the three MCI groups. The effect of various risk factors of LTCI enrollment was evaluated using Cox’s proportional hazards model, adjusted for covariates.ResultsAs compared with aMCI cases, maMCI and saMCI patients required help with daily activities of living at a younger age. The saMCI and maMCI patients had higher risk of LTCI enrollment as compared with that of the aMCI patients. Younger patients(≤ 65y) with MCI had a 3.201 times higher risk of early LTCI enrollment than older patients(> 65y) did. High clinical dementia rating score and female sex were also risk factors of early LTCI enrollment.ConclusionsWMH predicted the rate of global functional decline and loss of independence in patients with MCI. The findings support the use of neuroimaging of WMH, in conjunction with biomarkers, as a tool in predicting functional decline in patients with MCI.     

Monotherapy with mirabegron had a better tolerance than the anticholinergic agents on overactive bladder: A systematic review and meta-analysis

Background:We conducted this meta-analysis to explore the tolerance of monotherapy with mirabegron (50 mg) on an overactive bladder, compared with a common dosage of anticholinergic agents.Materials and methods:A comprehensive search for all randomized controlled trials that evaluated the safety of mirabegron and anticholinergic agents on overactive bladder was performed, and we searched the Cochrane Central Register of Controlled trials databases, Pubmed, Embase, and relevant trials from 2013.02 to 2019.10.Results:Eight studies included 5500 patients with treatment of monotherapy on overactive bladder were identified. The total number of treatment-emergent adverse events had no significantly difference between two monotherapies (RR = 0.88 95%CI: 0.76–1.01; P = .08); however, patients would have a better tolerance with mirabegron (50 mg) in adverse events of dry mouth (RR = 0.42; 95%CI: 0.33–0.53; P < .01) and tachycardia (RR = 0.52; 95%CI: 0.29–0.94; P = .03); and there were no significant differences between two groups in hypertension (RR = 1.02; 95%CI: 0.80–1.30; P = .90), constipation (RR = 0.91; 95%CI: 0.65–1.26; P = 0.57), blurred vision (RR = 1.03; 95%CI: 0.60–1.77; P = 0.92), and urinary tract infection (RR = 0.90; 95%CI: 0.70–1.16; P = .41).Conclusions:Treatment-emergent adverse events in patients with overactive bladder who underwent monotherapy of mirabegron (50 mg) or the anticholinergic agents had no significant differences, but mirabegron has a better tolerance in the aspect of dry mouth and tachycardia.     

Impact of anticholinergic burden on emergency department visits among older adults in Korea: A national population cohort study

ObjectivesThis study aimed to evaluate the impact of high anticholinergic burden on overall emergency department (ED) visits and ED visits related to adverse effects of anticholinergic drugs among older adults.MethodsFor this retrospective cohort study, we used claims data from older adults with high representativeness. The average daily Anticholinergic Risk Scale (ARS) score was calculated based on the dosage, treatment duration, and potency of anticholinergic drugs during three months. A high-exposure group (ARS ≥ 2) and a non-exposure group were included in this analysis. The primary outcome was the first ED visit during the follow-up period. Anticholinergic ED visits were defined as ED visits with a main diagnosis of a fall, fracture, dizziness, delirium, constipation, or urinary retention.ResultsIn total, 118,750 subjects (43.6% male) were included in this study. The mean age was 75.4 ± 6.6 years. The adjusted hazard ratios (aHRs) for all-cause and anticholinergic ED visits among those with high ARS scores were 1.28 (95% CI: 1.20–1.36) and 1.55 (95% CI: 1.38–1.74), respectively. The high-exposure group was at higher risk than the non-exposure group for ED visits for falls or fractures (aHR: 1.31, 95% CI: 1.07–1.60), dizziness (aHR: 1.71, 95% CI: 1.36–2.14), delirium (aHR: 2.05, 95% CI: 1.13–3.73), constipation (aHR: 1.65, 95% CI: 1.35–2.02) and urinary retention (aHR: 1.66, 95% CI: 1.30–2.12).ConclusionsThis study demonstrated that a high anticholinergic burden in older adults increased the risk of all-cause ED visits, anticholinergic ED visits and specific-cause ED visits.     

Azathioprine-induced toxoplasma gondii infection in a patient with Crohn's disease with NUDT15 variation: A case report

Introduction:Azathioprine (AZA) has been widely used for the treatment of various immune-related diseases and has become a mainstay in the treatment of inflammatory bowel disease. However, patients with genetic mutations may experience severe adverse events when treated with azathioprine. Most of the previous literature focused on the TPMP gene-related adverse reactions, herein, we report a case of Crohn''s disease patient with nucleoside diphosphate-linked moiety X motif 15 gene (NUDT15) variation and wild-type TPMP gene who developed toxoplasma gondii infection after azathioprine treatment.Patient concerns:A 56-year-old Crohn''s disease patient developed toxoplasma gondii infection within 2 months after the administration of azathioprine; however, he had no relevant high-risk factors.Diagnosis:Subsequent genetic testing revealed that the patient was heterozygous for NUDT15. Therefore, it was reasonable to consider that the patient''s genetic mutation resulted in reduced tolerance to azathioprine, leading to low immunity and eventually toxoplasma infection.Interventions:AZA was then discontinued; after anti-infection, antipyretic and other supportive treatments were administered, the patient''s condition gradually improved.Outcomes:The patient was followed up at 1, 3, and 6 months after discharge; fortunately, he was in good health.Conclusion:We report a case of Crohn''s disease in a patient who developed severe pneumonia caused by toxoplasma gondii infection due to the administration of AZA, with normal TPMP gene but NUDT15 gene mutation. This indicates that NUDT15 variation may contribute to severe adverse events in patients treated with azathioprine, and we suggest that NUDT15 genotype be detected before the use of azathioprine in order to provide personalized therapy and reduce side effects.     

Association between plasminogen activator inhibitor-1 (PAI-1) 4G/5G polymorphism and risk of Alzheimer's disease,metabolic syndrome,and female infertility: A meta-analysis

Background:Plasminogen activator inhibitor-1 (PAI-1) is considered to be involved in the physiopathological mechanisms of Alzheimer''s disease (AD), metabolic syndrome (MetS), and female infertility. Previous studies investigating the association between PAI-14G/5G (rs1799889) gene polymorphism and the risk of AD, MetS, and female infertility have reported inconsistent results. The aim of the present study was to investigate possible associations.Methods:Eligible studies were retrieved through PubMed, Medline, EMBASE, CNKI, and WANFANG databases. The odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the associations. Subgroup analyses by ethnicity and mean age, sensitivity analyses, and publication bias were performed.Results:Five studies (four articles) for AD, six studies (six articles) for MetS, and four studies (four articles) for female infertility were included in this meta-analysis. Our results showed no significant associations between the PAI-14G/5G polymorphism and the risk of AD and female infertility in five genetic models. For the risk of MetS, the PAI-1 4G/5G (rs1799889) polymorphism may be associated with the risk of MetS (4G vs 5G, OR = 1.31, 95%CI = 1.04–1.64, P = .021), especially in Asians (4G/4G vs 4G/5G+5G/5G, OR = 1.38, 95%CI = 1.01–1.87, P = .041) and patients with mean age > 50 years old (4G/4G vs 4G/5G+5G/5G, OR = 1.36, 95%CI = 1.03–1.78, P = .029).Conclusion:The present meta-analysis suggested that the PAI-1 4G/5G polymorphism might be associated with the risk of MetS, but no evidence was detected for AD and female infertility.     

Effects of perioperative interventions for preventing postoperative delirium: A protocol for systematic review and meta-analysis of randomized controlled trials

Background:Postoperative delirium (POD) not only increases the medical burden but also adversely affects patient prognosis. Although some cases of delirium can be avoided by early intervention, there is no clear evidence indicating whether any of these measures can effectively prevent POD in specific patient groups.Objective:The aim of this meta-analysis was to compare the efficacy and safety of the existing preventive measures for managing POD.Methods:The PubMed, OVID (Embase and MEDLINE), Web of Science, and the Cochrane Library databases were searched for articles published before January 2020. The relevant randomized controlled trials (RCTs) were selected based on the inclusion and exclusion criteria. Data extraction and methodological quality assessment were performed according to a predesigned data extraction form and scoring system, respectively. The interventions were compared on the basis of the primary outcome like incidence of POD, and secondary outcomes like duration of delirium and the length of intensive care unit and hospital stay.Results:Sixty-three RCTs were included in the study, covering interventions like surgery, anesthesia, analgesics, intraoperative blood glucose control, cholinesterase inhibitors, anticonvulsant drugs, antipsychotic drugs, sleep rhythmic regulation, and multi-modal nursing. The occurrence of POD was low in 4 trials that monitored the depth of anesthesia with bispectral index during the operation (P < .0001). Two studies showed that supplementary analgesia was useful for delirium prevention (P = .002). Seventeen studies showed that perioperative sedation with α₂-adrenergic receptor agonists prevented POD (P = .0006). Six studies showed that both typical and atypical antipsychotic drugs can reduce the incidence of POD (P = .002). Multimodal nursing during the perioperative period effectively reduced POD in 6 studies (P < .00001). Furthermore, these preventive measures can reduce the duration of delirium, as well as the total and postoperative length of hospitalized stay for non-cardiac surgery patients. For patients undergoing cardiac surgery, effective prevention can only reduce the length of intensive care unit stay.Conclusion:Measures including intraoperative monitoring of bispectral index, supplemental analgesia, α₂-adrenergic receptor agonists, antipsychotic drugs, and multimodal care are helpful to prevent POD effectively. However, larger, high-quality RCTs are needed to verify these findings and develop more interventions and drugs for preventing postoperative delirium.     

PIN-1 promoter polymorphisms in mild cognitive impairment and susceptibility to Alzheimer's disease: a preliminary report

BACKGROUND AND AIMS: Peptydil prolyl cis-trans isomerase (PIN-1), which specifically regulates the conformational changes following phosphorylation of several proteins, targets the inactive hyper-phosphorylated tau on the Thr231-Pro motif and directly restores its biological function. Interestingly, PIN-1 is oxidatively inhibited not only in Alzheimer's disease brain but also in the hippocampi of mild cognitive impairment (MCI) subjects. The PIN-1 gene is characterized by two single nucleotide polymorphisms (SNPs) in the promoter region which are associated with the risk of Alzheimer's disease. The aim of this study was to analyse the genotype and allele distributions of these PIN-1 SNPs in MCI subjects diagnosed respectively as amnestic MCI (a-MCI) and multiple impaired cognitive domains (mcd-MCI) on the basis of cognitive features. METHODS: -667 T/C and -842 C/G SNPs were genotyped by polymerase chain reaction (PCR) amplification and direct sequencing in 43 MCI subjects, with the intention of comparing -667 and -842 SNP frequencies with those previously described in 111 Alzheimer's disease patients (AD) and 73 healthy controls (HC). RESULTS: The allele frequencies of the -842 C/G SNP in a-MCI subjects are similar to those of AD subjects, while those of mcd-MCI are comparable to HC (G allele 83% in both a-MCI and AD; 95% and 94% in mcd-MCI and HC, respectively). A similar trend is also observed in -842 C/G genotypes. CONCLUSIONS: Since a-MCI is thought to be the preclinical form of AD, the similar genotype distribution of -842 SNP in AD and a-MCI, but not in mcd-MCI, suggests that it is potentially involved in the conversion of a-MCI to AD. In conclusion, these findings support the theory that polymorphisms of the PIN-1 gene can affect neurodegeneration and its clinical progression.     

Effect of Nusinersen in a late onset spinal muscular atrophy patient for 14 months: A case report

Rationale:Spinal muscular atrophy (SMA) is a genetic disorder caused by genetic defect of SMN1 gene. SMA was an untreatable disease until 2016, when Nusinersen an antisense oligonucleotide therapy was approved for treatment. We report the effect of Nusinersen in a late onset SMA for 14 months.Patient concerns:A 13-year-old boy who was diagnosed as SMA with progressive proximal limb weakness was treated with intrathecal injection of Nusinersen.Diagnosis:The patient had progressive proximal limb weakness after 2 years of age. The patient had elevated creatine kinase level and shoed neurogenic changes in the needle electromyography study. After genetic analysis, homozygous deletion in Exon 7 and 8 of SMN1 protein was found and he was diagnosed as late onset SMA.Interventions:Intrathecal Nusinersen was administered per protocol.Outcomes:After 14 months of treatment, the patient showed significant clinical improvement in the revised Hammersmith functional rating scale and 6-minute walk test.Lessons:Although there is limited data on the effect of Nusinersen in late onset SMA patients, our case adds on the effectiveness even in late onset SMA. More studies are needed to consolidate the effects and adverse events of Nusinersen in late onset SMA.     

Effects of Bojungikgi-tang on anorexic patients with atopic dermatitis: A protocol for a randomized,usual care-controlled,assessor-blinded,parallel, pilot clinical trial

Background:Anorexia and atopic dermatitis (AD) are highly prevalent diseases, and the herbal medicine Bojungikgi-tang (BJT) has been frequently used for the treatment of both anorexia and AD. However, no study has simultaneously evaluated the effects of BJT for both anorexia and AD.Methods:A prospective, randomized, usual care-controlled, assessor-blinded. parallel, pilot clinical trial has been designed to explore the feasibility, preliminary effectiveness, and safety of BJT for the treatment of anorexic patients with AD. Forty anorexic patients with AD will be randomly assigned (1:1) to BJT or the usual care group. The BJT group will be administered BJT granules twice a day for 8 weeks and followed up for 4 weeks whereas the usual care group will not receive BJT granules. All participants in both groups will be provided with over-the-counter topical corticosteroids as a relief drug. Data will be collected at baseline and at 4, 8, and 12 weeks after randomization. The primary outcome is the score on the anorexia visual analog scale at 8 weeks post-treatment. The secondary outcomes include body weight, body fat percentage, body fat mass, skeletal muscle mass, SCORing of Atopic Dermatitis index, Validated Investigator Global Assessment scale for Atopic Dermatitis, Dermatology Life Quality Index, EuroQoL 5 Dimension 5 Level, deficiency and excess pattern identification questionnaire, total immunoglobulin E, eosinophil count, and frequency and amount of use of topical corticosteroids. Adverse events and laboratory test results will be monitored to assess safety. Fecal samples to check for gut microbiome changes and blood samples to check immune and metabolic markers will be collected before and after taking BJT.Discussion:This is the first trial that explores the preliminary effectiveness and safety of BJT for the treatment of anorexic patients with AD. The results of this pilot study will provide the basic evidence for large-scale, confirmatory, multicenter, high-quality clinical trials.Trial registration:Clinical Research Information Service, KCT0006784 (registered on November 26, 2021).     

Stages of mild cognitive impairment and Alzheimer’s disease can be differentiated by declines in timed up and go test: A systematic review and meta-analysis

Motor dysfunction increases in the moderate and severe stages of dementia. However, there is still no consensus on changes in mobility during its early stages. This meta-analysis aimed to measure the level of single-task functional mobility in older subjects with mild cognitive impairment (MCI) and/or Alzheimer’s disease (AD). In a search of the PubMed, ISI Web of Knowledge, and Scopus databases, 2728 articles were identified. At the end of the selection, a total of 18 studies were included in the meta-analysis. Functional mobility was investigated using the timed up and go (TUG) test in all studies. When compared to healthy elderly (HE) adults, the following mean differences (MD) in seconds were found for the investigated subgroups: no amnestic MCI (MD = 0.26; CI_95% = -0.77, 1.29), amnestic MCI (MD = 0.86; CI_95% = -0.02, 1.73), very mild AD (MD = 1.32; CI_95% = 0.63, 2.02), mild AD (MD = 2.43; CI_95% = 1.84, 3.01), mild-moderate AD (MD = 3.01; CI_95% = 2.47, 3.55), and mild-severe AD (MD = 4.51; CI_95% = 1.14, 7.88); for the groups, the following MD were found: MCI (MD = 0.97; CI_95% = 0.51, 1.44) and AD (MD = 2.66; CI_95% = 2.16, 3.15). These results suggest a transition period in motor capacity between healthy aging and dementia, wherein functional mobility analysis in a single-task (TUG) can contribute to the diagnosis and staging of predementia states and AD.     

The anticholinergic risk scale and anticholinergic adverse effects in older persons

BACKGROUND: Adverse effects of anticholinergic medications may contribute to events such as falls, delirium, and cognitive impairment in older patients. To further assess this risk, we developed the Anticholinergic Risk Scale (ARS), a ranked categorical list of commonly prescribed medications with anticholinergic potential. The objective of this study was to determine if the ARS score could be used to predict the risk of anticholinergic adverse effects in a geriatric evaluation and management (GEM) cohort and in a primary care cohort. METHODS: Medical records of 132 GEM patients were reviewed retrospectively for medications included on the ARS and their resultant possible anticholinergic adverse effects. Prospectively, we enrolled 117 patients, 65 years or older, in primary care clinics; performed medication reconciliation; and asked about anticholinergic adverse effects. The relationship between the ARS score and the risk of anticholinergic adverse effects was assessed using Poisson regression analysis. RESULTS: Higher ARS scores were associated with increased risk of anticholinergic adverse effects in the GEM cohort (crude relative risk [RR], 1.5; 95% confidence interval [CI], 1.3-1.8) and in the primary care cohort (crude RR, 1.9; 95% CI, 1.5-2.4). After adjustment for age and the number of medications, higher ARS scores increased the risk of anticholinergic adverse effects in the GEM cohort (adjusted RR, 1.3; 95% CI, 1.1-1.6; c statistic, 0.74) and in the primary care cohort (adjusted RR, 1.9; 95% CI, 1.5-2.5; c statistic, 0.77). CONCLUSION: Higher ARS scores are associated with statistically significantly increased risk of anticholinergic adverse effects in older patients.     

Leukocyte telomere length (LTL) is reduced in stable mild cognitive impairment but low LTL is not associated with conversion to Alzheimer's disease: a pilot study

Leukocyte telomere length (LTL) is associated with the aging process and may be related to cognitive aging. Previous studies have shown conflicting results whether LTL is affected in patients with Alzheimer's disease (AD). In this pilot study, we investigated LTL in a well-defined homogeneous mono-center population. Sixty consecutive patients admitted for cognitive impairment to a memory clinic were recruited. The participants included patients with AD or mild cognitive impairment (MCI) diagnosed with AD upon follow-up (n=32), patients with stable MCI (n=13), patients with other dementias diagnosed at primary evaluation or upon follow-up (n=15), and healthy controls (n=20). LTL was determined using a quantitative PCR assay. Patients with AD had similar LTL as healthy controls. Patients with stable MCI had reduced LTL both compared to AD patients (p=0.02) and controls (p=0.008). Subanalyses within the AD group showed that patients with MCI that later converted to AD had similar LTL as patients with clinical diagnosis of AD at primary evaluation and healthy controls whereas the LTL was longer compared to the stable MCI group (p=0.02). There were no correlations between LTL and the core AD biomarkers Aβ(1-42), T-tau and P-tau. In conclusion, in this pilot study, patients with AD or MCI that later converted to AD had similar LTL as healthy controls. Patients with stable MCI that did not progress to dementia had reduced LTL compared to controls, which might suggest a more marked biological aging as a cause of the cognitive symptoms in this group.     

Development of bullous pemphigoid following radiation therapy combined with nivolumab for renal cell carcinoma: A case report of abscopal toxicities

Rationale:Concern for immune-related adverse events from immunotherapy and radiation therapy are well-documented; however, side effects are mostly mild to moderate. However, high-grade, potentially life-threatening adverse events are increasing. While case reports regarding immunotherapy-related bullous pemphigoid (BP) have been rising, only 1 has described BP following concomitant use of both nivolumab and radiation therapy (RT). For that patient, nivolumab was used for 10 weeks prior to RT and development of PB followed 7 weeks later. This case presents a patient who tolerated nivolumab well for 38 months prior to developing BP less than 2 weeks after completing RT.Patient concerns:We present the case of DH, a 67-year-old gentleman on nivolumab for metastatic renal cell carcinoma to the lung since May of 2017. Following progressing lung nodules, the patient had his nivolumab paused and completed a course of short-beam radiation therapy. After restarting nivolumab post-radiation, the patient presented with itchy rash and blisters on his arm, legs, and trunk.Diagnosis:DH consulted dermatology following development of rash and was diagnosed with bullous dermatosis, likely bullous pemphigoid. Bullous pemphigoid following concomitant nivolumab (OPDIVO), despite prior tolerance and no history of autoimmune disease, was confirmed by biopsy a month later.Interventions:Initial treatment was betamethasone 0.05% cream mixed 1:1 with powder to form paste applied twice daily. Given progressive symptoms and confirmatory biopsy of BP, nivolumab was held and 100 mg doxycycline and 80 mg prednisone daily was prescribed for a week, reduced to 60 mg during the second week.Outcomes:A week following discontinuation of nivolumab and beginning of doxycycline and prednisone, the blistering and rash was almost entirely resolved. Four months later, nivolumab was restarted and the patient continued low-dose tapering of prednisone until December. Since completing prednisone, the patient has shown no recurrence of bullous pemphigoid and has not developed any other immune-related adverse events to nivolumab upon rechallenge. Follow-up through October 2021 demonstrates the patient''s sites of disease, both in- and out-field, have remained responsive to treatment.Lessons:Treating physicians should be aware of off-target effects of radiotherapy for oligoprogressive disease, which may include abscopal toxicities and the development of new immune-related adverse effects.     

Physical performance across the cognitive spectrum and between dementia subtypes in a population-based sample of older adults: The HUNT study

BackgroundLiterature on physical performance in older adults across the cognitive spectrum remains inconclusive, and knowledge on differences between dementia subtypes is lacking. We aim to identify distinct physical-performance deficits across the cognitive spectrum and between dementia subtypes.Methods11,466 persons were included from the 70-year-and-older cohort in the fourth wave of the Trøndelag Health Study (HUNT4 70+). Physical performance was assessed with the Short Physical Performance Battery (SPPB), 4-meter gait speed, five-times-sit-to-stand (FTSS), grip strength and one-leg-standing (OLS). Clinical experts diagnosed dementia per DSM-5 criteria. Multiple linear and logistic regression were performed to analyze differences between groups. Age, sex, education, somatic comorbidity, physical activity and smoking status were used as covariates.ResultsGait speed declined across the cognitive spectrum, beginning in people with subjective cognitive decline (SCD). Participants with mild cognitive impairment (MCI) additionally showed reduced lower-limb muscle strength, balance and grip strength. Those with dementia scored lowest on all physical-performance measures. Participants with Alzheimer's disease (AD) had a higher SPPB sum score and faster gait speed than participants with vascular dementia (VaD) and Lewy body dementia (LBD); participants with VaD and LBD had lower odds of being able to perform FTSS and OLS than participants with AD.ConclusionsPhysical performance declined across the spectrum from cognitively healthy to SCD to MCI and to dementia. Participants with AD performed better on all assessments except grip strength than participants with VaD and LBD. Stage of cognitive impairment and dementia subtype should guide exercise interventions to prevent mobility decline and dependency.