Metformin, age-related cognitive decline, and brain pathology.

The objective of this study was to evaluate the relation of metformin with change in cognition and brain pathology. During a mean of 8 years (SD = 5.5) of annual follow-up visits, 262/3029 participants were using metformin at any time during the study. Using a linear-mixed effect model adjusted for age, sex, and education, metformin users had slower decline on a score of global cognition compared to non-users (estimate = 0.017, SE = 0.007, p = 0.027). Analyses of cognitive domains showed a slower decline in episodic memory and semantic memory specifically. In sensitivity analysis, when examining any diabetes medication use vs none, no association was observed of any diabetes medication use with cognitive function. In the autopsy subset of 1584 participants, there was no difference in the level of Alzheimer's disease (AD) pathology or the presence of infarcts (of any size or location) between groups of metformin users vs non-users. However, in additional analyses, metformin users had higher odds of subcortical infarcts, and lower odds of atherosclerosis and arteriosclerosis.

Association Between Triglycerides and Risk of Dementia in Community-Dwelling Older Adults: A Prospective Cohort Study.

BACKGROUND AND OBJECTIVES: It has been suggested that higher triglyceride levels were associated with a lower risk of Alzheimer disease. This study aimed to examine the association of triglycerides with dementia and cognition change in community-dwelling older adults. METHODS: This prospective longitudinal study used data from the Aspirin in Reducing Events in the Elderly (ASPREE) randomized trial of adults aged 65 years or older without dementia or previous cardiovascular events at enrollment. The main outcome was incident dementia. Other outcomes included changes in composite cognition and domain-specific cognition (global cognition, memory, language and executive function, and psychomotor speed). The association between baseline triglycerides and dementia risk was estimated using Cox proportional hazard models adjusting for relevant risk factors. Linear mixed models were used to investigate cognitive change. The analysis was repeated in a subcohort of participants with available APOE-ε4 genetic data with additional adjustment for APOE-ε4 carrier status and an external cohort (UK Biobank) with similar selection criteria applied. RESULTS: This study included 18,294 ASPREE participants and 68,200 UK Biobank participants (mean age: 75.1 and 66.9 years; female: 56.3% and 52.7%; median [interquartile range] triglyceride: 106 [80-142] mg/dL and 139 [101-193] mg/dL), with dementia recorded in 823 and 2,778 individuals over a median follow-up of 6.4 and 12.5 years, respectively. Higher triglyceride levels were associated with lower dementia risk in the entire ASPREE cohort (hazard ratio [HR] with doubling of triglyceride: 0.82, 95% CI 0.72-0.94). Findings were similar in the subcohort of participants with APOE-ε4 genetic data (n = 13,976) and in the UK Biobank cohort (HR was 0.82 and 0.83, respectively, all p ≤ 0.01). Higher triglycerides were also associated with slower decline in composite cognition and memory over time (p ≤ 0.05). DISCUSSION: Older adults with higher triglyceride levels within the normal to high-normal range had a lower dementia risk and slower cognitive decline over time compared with individuals with lower triglyceride levels. Higher triglyceride levels may be reflective of better overall health and/or lifestyle behaviors that would protect against dementia development. Future studies are warranted to investigate whether specific components within the total circulating pool of plasma triglycerides may promote better cognitive function, with the hope of informing the development of new preventive strategies.

Selective serotonin reuptake inhibitor use, age-related neuropathology and cognition in late-life.

The objective of this study was to evaluate an association of selective serotonin reuptake inhibitor (SSRI) use with late life cognitive decline and further investigate the association with brain pathology. Using the data are from two harmonized clinical-pathologic cohort studies with annual cognitive testing we found that SSRI use was associated with significantly faster global cognitive decline and this association was present in those with and without pre-existing cognitive impairment at the time of SSRI initiation. In separate analyses of persons who died during the study and underwent neuropathologic examination, SSRI use was related to higher level of paired helical filament tau tangles and faster rate of global cognitive decline. However, when SSRI use and tangles were included in the same model, the association of SSRI use with rate of global cognitive decline was reduced by more than 50% and no longer statistically significant. SSRI use was associated with higher postmortem level of tau tangles, possibly because SSRI are being used to treat neurobehavioral symptoms associated with dementia, and this relationship appears to partly account for the association of SSRI use with more rapid cognitive decline.

Population modeling of oilseed brassica aphids and their biocontrol agents with weather parameters in the north-west Himalayan region of India.

We studied the impact of weather parameters on the population build-up of Brevicoryne brassicae (L.) (Cabbage aphid), Lipaphis erysimi (Kalt.) (Mustard aphid), Myzus persicae (Sulzer) (Green peach aphid) and their biocontrol agents (coccinellids, syrphids, and a parasitoid, Diaeretiella rapae M'Intosh) on oilseed brassicas in Himachal Pradesh, India, during winters from 2016-2017 to 2018-2019. The temperature and sunshine resulted in the build-up of B. brassicae and their biocontrol agents' population, while rainfall and relative humidity caused a negative influence at surveyed locations. The L. erysimi and M. persicae populations showed an inverse correlation with the density-independent factors at most locations. Correlation coefficients indicated a negative correlation of the coccinellids population with the build-up of L. erysimi and M. persicae, while the predator population was positively related to the B. brassicae population at maximum locations. Parasitization by D. rapae showed a negative relationship with the aphid population. Stepwise regression analysis showed that minimum temperature and rainfall had a significant effect on the variability in the population of aphids. The predictive model could interpret more than 90% variation by minimum temperature in the coccinellid population at the surveyed locations. Further, regression analysis with temperature could explain up to 94% variability in parasitization by D. rapae. This study will contribute to predicting the changes that may occur in a population of aphids concerning the weather.

Validation of newly derived polygenic risk scores for dementia in a prospective study of older individuals.

INTRODUCTION: Recent genome-wide association studies identified new dementia-associated variants. We assessed the performance of updated polygenic risk scores (PRSs) using these variants in an independent cohort. METHODS: We used Cox models and area under the curve (AUC) to validate new PRSs (PRS-83SNP, PRS-SBayesR, and PRS-CS) compared with an older PRS-23SNP in 12,031 initially-healthy participants ≥70 years of age. Dementia was rigorously adjudicated according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria. RESULTS: PRS-83SNP, PRS-SBayesR, and PRS-CS were associated with incident dementia, with fully adjusted (including apolipoprotein E [APOE] ε4) hazard ratios per standard deviation (SD) of 1.35 (1.23-1.47), 1.37 (1.25-1.50), and 1.42 (1.30-1.56), respectively. The AUC of a model containing conventional/non-genetic factors and APOE was 74.7%. This was improved to 75.7% (p = 0.007), 76% (p = 0.004), and 76.1% (p = 0.003) with addition of PRS-83SNP, PRS-SBayesR, and PRS-CS, respectively. The PRS-23SNP did not improve AUC (74.7%, p = 0.95). CONCLUSION: New PRSs for dementia significantly improve risk-prediction performance, but still account for less risk than APOE genotype overall.

Determinants of initial insulin therapy for hospitalized patients with diabetes mellitus.

AIMS: Glycemic control immediately after hospital admission is difficult. This study aimed to develop an algorithm-based approach to initiate insulin therapy on admission. METHODS: Patients with history of diabetes mellitus admitted at UC Davis medical center, with any blood glucose (BG) value ≥ 180 mg/dL, or who received any insulin within the first 24 h of hospitalization were selected for a retrospective chart review. RESULTS: Total of 315 patient records were studied. Patients prescribed insulin prior to admission had higher 24-hour average BG and higher corrected total daily dose of insulin (CxTDD), compared with the patients who were not prescribed insulin prior to admission. For the patients not receiving home insulin and not given new glucocorticoids, first BG upon presentation correlated with the risk of first 24-hour average BG > 180 mg/dL. Factors associated with CxTDD were first BG, weight, oral intake, and glucocorticoid dose. Home insulin daily dose, opiate/intravenous pain medication and systemic inflammatory response syndrome were associated with CxTDD only in the patients receiving home insulin. CONCLUSIONS: A subgroup of patients can be given correction insulin as a sole initial treatment on admission. For patients requiring basal-bolus insulin, several factors associated with the initial insulin requirements are identified.

Occurrence and spread of Ceroplastes cirripediformis Comstock (Hemiptera: Coccomorpha: Coccidae) in India.

The notoriously destructive and invasive soft scale, Ceroplastes cirripediformis Comstock (Hemiptera: Coccomorpha: Coccidae), is recorded for the first time from India. The scale is redescribed to facilitate its identification and information on its host range, natural enemies and distribution is provided. An identification key to the Indian species in this genus is given. Management options in the event of an outbreak are discussed briefly. The establishment of this scale insect warrants special attention in India as it is a potentially damaging plant pest and has a broad host range across many plant families.

Different Cognitive Profiles Are Associated with Progression Rate and Age at Death in Probable Alzheimer's Disease.

BACKGROUND: Cognitive profiles characterized by primarily language or visuospatial deficits have been documented in individuals meeting diagnostic criteria for probable Alzheimer's disease (AD), but their association with progression rate or overall survival is not well described. OBJECTIVE: To compare time from diagnosis to severe disease stage and death in probable AD patients classified into three groups based on neuropsychological test performance: marked verbal impairment (Verb-PI) with relatively preserved visuospatial function, marked visuospatial impairment with preserved verbal function (Vis-PI), and balanced verbal and visuospatial impairments (Bal-PI). METHODS: This prospective cohort study included 540 probable AD patients attending an academic memory clinic who were enrolled from 1995-2013 and followed annually. Eligible individuals had a Mini-Mental State Exam (MMSE) score ≥10 at baseline, and at least one annual follow up visit. We used Cox proportional hazards modeling to analyze the association of cognitive profiles with time to decline in MMSE and CDR Global Score. RESULTS: Sixty-one (11.3%) individuals had a Verb-PI profile, 86 (16%) had a Vis-PI profile, and 393 (72.8%) a Bal-PI profile. MMSE decline to <10 was faster in Verb-PI than Vis-PI (HR 2.004, 95%CI, 1.062-3.780; p = 0.032). Progression to CDR-GS = 3 was faster in Verb-PI individuals compared to Bal-PI (HR 1.604, 95%CI, 1.022-2.515; p = 0.040) or Vis-PI (HR 2.388, 95%CI, 1.330-4.288; p = 0.004) individuals. Baseline cognitive profile did not affect mortality. CONCLUSION: A recognition of different AD profiles may help to personalize care by providing a better understanding of pathogenesis and expected progression.

The Design and Implementation of a Heart Disease Reversal Program in the Veterans Health Administration: Before and During the COVID-19 Pandemic.

BACKGROUND: Heart disease continues to be the leading cause of death in the US, and the number of people with cardiovascular disease (CVD) is rising. CVD is more prevalent among military veterans than nonveterans, and veteran status is associated with higher risk of incident heart disease after controlling for socioeconomic status, other medical diseases, depression, and lifestyle. Many patients seeking care in the Veterans Health Administration, including those who undergo cardiac catheterization, meet the criteria for multimorbidity (defined as ≥ 2 chronic diseases). OBSERVATIONS: The Heart Disease Reversal Program (HDRP) is a novel interdisciplinary, multicomponent lifestyle program at the US Department of Veterans Affairs (VA) Sacramento VA Medical Center. This program is a streamlined adaptation of behavioral/lifestyle interventions aimed at promoting partial reversal (regression) of atherosclerotic heart disease and achievement of comprehensive cardiovascular risk reduction. HDRP was developed and implemented within a VA behavioral medicine clinic and successfully adapted for delivery through videoconferencing during the COVID-19 pandemic. Patient satisfaction survey data indicate a very high level of patient acceptability. We found direct-to-patient clinical outreach an effective method for launching a disease reversal program. CONCLUSIONS: Beyond the clinical benefits to patients, there is significant value and benefit added to the health care system by offering an intervention within the disease reversal paradigm. Efforts of the health care team to reverse a disease can be considered the highest aim of medicine and health care.

Baseline Characteristics of Randomized Participants in the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE).

OBJECTIVE: GRADE (Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study) is a 36-center unmasked, parallel treatment group, randomized controlled trial evaluating four diabetes medications added to metformin in people with type 2 diabetes (T2DM). We report baseline characteristics and compare GRADE participants to a National Health and Nutrition Examination Survey (NHANES) cohort. RESEARCH DESIGN AND METHODS: Participants were age ≥30 years at the time of diagnosis, with duration of T2DM <10 years, HbA1c 6.8-8.5% (51-69 mmol/mol), prescribed metformin monotherapy, and randomized to glimepiride, sitagliptin, liraglutide, or insulin glargine. RESULTS: At baseline, GRADE's 5,047 randomized participants were 57.2 ± 10.0 years of age, 63.6% male, with racial/ethnic breakdown of 65.7% white, 19.8% African American, 3.6% Asian, 2.7% Native American, 7.6% other or unknown, and 18.4% Hispanic/Latino. Duration of diabetes was 4.2 ± 2.8 years, with mean HbA1c of 7.5 ± 0.5% (58 ± 5.3 mmol/mol), BMI of 34.3 ± 6.8 kg/m2, and metformin dose of 1,944 ± 204 mg/day. Among the cohort, 67% reported a history of hypertension, 72% a history of hyperlipidemia, and 6.5% a history of heart attack or stroke. Applying GRADE inclusion criteria to NHANES indicates enrollment of a representative cohort with T2DM on metformin monotherapy (NHANES cohort average age, 57.9 years; mean HbA1c, 7.4% [57 mmol/mol]; BMI, 33.2 kg/m2; duration, 4.2 ± 2.5 years; and 7.2% with a history of cardiovascular disease). CONCLUSIONS: The GRADE cohort represents patients with T2DM treated with metformin requiring a second diabetes medication. GRADE will inform decisions about the clinical effectiveness of the addition of four classes of diabetes medications to metformin.

Nonglycemic Effects of GLP-1 Agonists: From a Starling to Lizards to People.

With the approval of exenatide in 2005, physicians had a new class of hypoglycemic agents available for the treatment of type 2 diabetes-the glucagon-like peptide-1 receptor agonists (or GLP-1 receptor agonists). As of this writing, there are seven drugs in this class available in the United States. In addition to demonstrating either cardiovascular risk neutrality or overt benefit, as now mandated by the United States Food and Drug Administration (FDA), many of these drugs have other, unexpected actions. It is our goal to outline these actions, some beneficial, some not. We have reviewed English-language articles in this area, not for an exhaustive study, but rather a broad search to define current understanding and perhaps generate further investigation.

HYPOKALEMIC PERIODIC PARALYSIS IN A PATIENT WITH EUTHYROID GRAVES DISEASE AND CELIAC DISEASE.

OBJECTIVE: Thyrotoxic periodic paralysis is a sporadic form of hypokalemic periodic paralysis (HPP) that is most commonly seen in patients with Graves disease (GD) in association with acute thyrotoxicosis. A very few cases of HPP have been reported in patients with GD while the patient was euthyroid. METHODS: We describe a case of a 62-year-old Caucasian male with a history of GD, who presented with acute progressive bilateral lower extremity weakness. RESULTS: The patient was found to have severe hypokalemia, with no evidence of diarrhea or increased urinary potassium excretion. He was diagnosed as having HPP. He remained clinically and biochemically euthyroid during the admission. There was no history of high-carbohydrate meal intake, intense exercise, recent steroid exposure, or unusual stress. His symptoms improved gradually over the next 3 to 4 days with potassium supplementation. Nine months later, he progressed to overt hyperthyroidism and was treated with 25 mCi of iodine-131 and following that he has been on levothyroxine replacement for post-ablative hypothyroidism. Other unusual features in this patient were hypocalcemia, hypomagnesemia, and vitamin D deficiency during the acute presentation. Serum calcium and magnesium normalized 2 days after admission, while serum vitamin D continued to be low. He was later diagnosed to have celiac disease. CONCLUSION: Our case adds a rare presentation of HPP in a euthyroid patient with a known history of GD with associated celiac disease, hypomagnesemia, and hypocalcemia to the literature.

Telemedicine consultation for patients with diabetes mellitus: a cluster randomised controlled trial.

Introduction There is a widening discrepancy between the increasing number of patients with diabetes mellitus and the health care resources available to manage these patients. Telemedicine has been used in a number of instances to improve and deliver health care where traditional care delivery methods may encounter difficulty. We conducted a cluster randomised controlled trial of telemedicine consultation to manage patients with diabetes mellitus. Methods Eleven primary care centres attached to one Veteran Administration tertiary care centre were randomised to provide patients with diabetes consultation referral either by usual consultation in diabetes clinic or telemedicine consultations via videoconference. Results Altogether, 199 patients were managed by telemedicine consultation and 83 by usual consultation. Patients in both groups showed a small decrease in haemoglobin A1c, with no statistical difference between the groups (telemedicine consultation -1.01% vs usual consultation -0.68%, p = 0.19). Surveys of patients and semi-structured interviews with primary care providers showed better response and satisfaction with telemedicine consultations. Discussion This study shows similar clinical outcomes as measured by glycaemic control for patients with diabetes mellitus having a specialist consultation using real-time telemedicine consultation as compared to in-clinic consultation. Telemedicine consultation was also associated with better patient and primary care provider satisfaction.

Comparative Efficacy of Intrathecal Bupivacaine Alone and Combination of Bupivacaine with Clonidine in Spinal Anaesthesia.

INTRODUCTION: Clonidine is an α2 agonist agent that has been used as an adjuvant to local anaesthetics in regional anaesthesia. AIM: This study compared two combinations of bupivacaine and clonidine with bupivacaine alone for surgeries below the level of umbilicus in spinal anaesthesia. MATERIALS AND METHODS: We conducted a randomized double blind study on 90 patients of ASA I and ASA II aged 20-60 years, 30 in each group, undergoing surgery below the level of umbilicus in spinal anaesthesia. For intrathecal block, Group 1 received bupivacaine hydrochloride 12.5mg (2.5ml) in 8% dextrose (0.5% sensorcaine heavy) + 1ml (150µg) of preservative free clonidine. Group 2 received bupivacaine hydrochloride 12.5mg (2.5ml) in dextrose (0.5% sensorcaine heavy) + 0.5ml (75µg) of preservative free clonidine + 0.5ml of normal saline to make the volumes of all the groups same. Group 3 received bupivacaine hydrochloride 2.5ml in 8% dextrose (0.5% sensorcaine heavy) + 1ml of normal saline to make the volumes of all the groups same. Heart rate, NIBP, oxygen saturation and respiratory rate were monitored. The onset and duration of sensory block, the highest dermatomal level of sensory block, motor block, time to complete motor block recovery and duration of spinal anaesthesia were recorded. STATISTICAL ANALYSIS: The data of the study was recorded in the record chart and results were evaluated using statistical tests (ANOVA test, post-hoc turkey hsd test, paired t-test and chi-square test). RESULTS: Demographic data, the incidence and duration of bradycardia were comparable amongst the groups. The duration of sensory and motor block were greatest in group 1, followed by group 2 and group 3 (p <0.01). Decrease in the systolic blood pressure of group 2 and group 3 was noted as compared to group 1. No significant sedation or respiratory depression was observed in any group. CONCLUSION: Addition of clonidine to bupivacaine intrathecally is although a reliable method to prolong spinal anaesthesia but close monitoring for hypotension is desirable.

Diabetes nurse case management: Improving glucose control: 10 years of quality improvement follow-up data.

UNLABELLED: The purpose of this retrospective case-control review is to determine the effectiveness of a registered nurse case managers (RNCMs) certified diabetes educator (CDE) quality improvement case management program. RNCMs have a long tradition of providing chronic care intervention, particularly for the high-risk diabetes population with glycosylated hemoglobin (A1C) of 9% or more. However, limited data are available with regard to evaluation of such programs in a Veterans Health Administration population. RESULTS: A large population (N=3956) of high-risk veterans with a baseline A1C of 9% or more (mean=10.6%) was seen by the RNCM's. Paired T-tests of A1C after the last RNCM visit showed a statistically significant A1C reduction (p<0.001) (mean=8.5%), after 14-26 months of intervention. CONCLUSIONS: RNCMs clinical intervention demonstrated significant A1C reduction (~2%). This is an important finding for health care policy makers for planning interventions with respect to long-term management of diabetes mellitus.