LMDA New & Noteworthy, March 2018

Contents include: Q & A: Robert Blacker; Q & A: Chava Kokhleffel.https://soundideas.pugetsound.edu/lmdanewsletter/1016/thumbnail.jp

A QTL genome scan of the metabolic syndrome and its component traits

BACKGROUND: Because high blood pressure, altered lipid levels, obesity, and diabetes so frequently occur together, they are sometimes collectively referred to as the metabolic syndrome. While there have been many studies of each metabolic syndrome trait separately, few studies have attempted to analyze them combined, i.e., as one composite variable, in quantitative trait linkage or association analysis. We used genotype and phenotype data from the Framingham Heart Study to perform a full-genome scan for quantitative trait loci underlying the metabolic syndrome. RESULTS: Heritability estimates for all of the covariate-adjusted and age- and gender-standardized individual traits, and the composite metabolic syndrome trait, were all fairly high (0.39–0.62), and the composite trait was among the highest at 0.61. The composite trait yielded no regions with suggestive linkage by Lander and Kruglyak's criteria, although there were several noteworthy regions for individual traits, some of which were also observed for the composite variable. CONCLUSION: Despite its high heritability, the composite metabolic syndrome trait variable did not increase the power to detect or localize linkage peaks in this sample. However, this strategy and related methods of combining correlated individual traits deserve further investigation, particularly in settings with complex causal pathways

Carbohydrate vs protein supplementation for recovery of neuromuscular function following prolonged load carriage

<p>Abstract</p> <p>Background</p> <p>This study examined the effect of carbohydrate and whey protein supplements on recovery of neuromuscular function after prolonged load carriage.</p> <p>Methods</p> <p>Ten male participants (body mass: 81.5 ± 10.5 kg, age: 28 ± 9 years, <inline-formula><graphic file="1550-2783-7-2-i1.gif"/></inline-formula> O₂max: 55.0 ± 5.5 ml·kg^-1·min^-1) completed three treadmill walking tests (2 hr, 6.5 km·h^-1), carrying a 25 kg backpack consuming 500 ml of either: (1) Placebo (flavoured water) [PLA], (2) 6.4% Carbohydrate Solution [CHO] or (3) 7.0% Whey Protein Solution [PRO]. For three days after load carriage, participants consumed two 500 ml supplement boluses. Muscle performance was measured before and at 0, 24, 48 and 72 h after load carriage, during voluntary and electrically stimulated contractions.</p> <p>Results</p> <p>Isometric knee extension force decreased immediately after load carriage with no difference between conditions. During recovery, isometric force returned to pre-exercise values at 48 h for CHO and PRO but at 72 h for PLA. Voluntary activation decreased immediately after load carriage and returned to pre-exercise values at 24 h in all conditions (<it>P </it>= 0.086). During recovery, there were no differences between conditions for the change in isokinetic peak torque. Following reductions immediately after load carriage, knee extensor and flexor peak torque (60°·s^-1) recovered to pre-exercise values at 72 h. Trunk extensor and flexor peak torque (15°·s^-1) recovered to pre-exercise values at 24 h (<it>P </it>= 0.091) and 48 h (<it>P </it>= 0.177), respectively.</p> <p>Conclusion</p> <p>Recovery of neuromuscular function after prolonged load carriage is improved with either carbohydrate or whey protein supplementation for isometric contractions but not for isokinetic contractions.</p

Clinical Characteristics and Longitudinal Changes of Informal Cost of Alzheimer's Disease in the Community

Most estimates of the cost of informal caregiving in patients with Alzheimer's disease (AD) remain cross-sectional. Longitudinal estimates of informal caregiving hours and costs are less frequent and are from assessments covering only short periods of time. The objectives of this study were to estimate long-term trajectories of the use and cost of informal caregiving for patients with AD and the effects of patient characteristics on the use and cost of informal caregiving. The sample is drawn from the Predictors Study, a large, multicenter cohort of patients with probable AD, prospectively followed annually for up to 7 years in three university-based AD centers in the United States (n=170). Generalized linear mixed models were used to estimate the effects of patient characteristics on use and cost of informal caregiving. Patients' clinical characteristics included cognitive status (Mini-Mental State Examination), functional capacity (Blessed Dementia Rating Scale (BDRS)), comorbidities, psychotic symptoms, behavioral problems, depressive symptoms, and extrapyramidal signs. Results show that rates of informal care use and caregiving hours (and costs) increased substantially over time but were related differently to patients' characteristics. Use of informal care was significantly associated with worse cognition, worse function, and higher comorbidities. Conditional on receiving informal care, informal caregiving hours (and costs) were mainly associated with worse function. Each additional point on the BDRS increased informal caregiving costs 5.4%. Average annual informal cost was estimated at $25,381 per patient, increasing from$20,589 at baseline to $43,030 in Year 4

Longitudinal Study of Effects of Patient Characteristics on Direct Costs in Alzheimer Disease

OBJECTIVES: To estimate long-term trajectories of direct cost of caring for patients with Alzheimer disease (AD) and examine the effects of patients' characteristics on cost longitudinally. METHODS: The sample is drawn from the Predictors Study, a large, multicenter cohort of patients with probable AD, prospectively followed up annually for up to 7 years in three university-based AD centers in the United States. Random effects models estimated the effects of patients' clinical and sociodemographic characteristics on direct cost of care. Direct cost included cost associated with medical and nonmedical care. Clinical characteristics included cognitive status (measured by Mini-Mental State Examination), functional capacity (measured by Blessed Dementia Rating Scale [BDRS]), psychotic symptoms, behavioral problems, depressive symptoms, extrapyramidal signs, and comorbidities. The model also controlled for patients' sex, age, and living arrangements. RESULTS: Total direct cost increased from approximately 9,239 dollars per patient per year at baseline, when all patients were at the early stages of the disease, to 19,925 dollars by year 4. After controlling for other variables, a one-point increase in the BDRS score increased total direct cost by 7.7%. One more comorbid condition increased total direct cost by 14.3%. Total direct cost was 20.8% lower for patients living at home compared with those living in an institutional setting. CONCLUSIONS: Total direct cost of caring for patients with Alzheimer disease increased substantially over time. Much of the cost increases were explained by patients' clinical and demographic variables. Comorbidities and functional capacity were associated with higher direct cost over time

Home Health and Informal Care Utilization and Costs over Time in Alzheimer's Disease

OBJECTIVES: To (1) compare home health and informal (unpaid) services utilization among patients with Alzheimer's disease (AD), (2) examine longitudinal changes in services use, and (3) estimate possible interdependence of home health and informal care utilization. METHODS: The sample is drawn from the Predictors Study, a large, multicenter cohort of patients with probable AD, prospectively followed annually for up to 7 years in three university-based AD centers. Bivariate probit models estimated the effects of patient characteristics on home health and informal care utilization. RESULTS: A large majority of the patients (80.6%) received informal care with a smaller proportion (18.6%) receiving home health services. Home health services utilization increased from 9.9% at baseline to 34.5% in year 4. Among users, number of days that services were provided in three-month recall increased from 21.9 to 56 days over time. Home health services utilization was significantly associated with function, depressive symptoms, being female, and not living with a spouse. Informal care utilization was significantly associated with cognition, function, comorbidities, and living with a spouse or child. CONCLUSIONS: Home health and informal care utilization relate differently to patient characteristics. Utilization of home health care or informal care was not influenced by utilization of the other

Clinical Features Associated with Costs in Early AD: Baseline Data from the Predictors Study

BACKGROUND: Few studies on cost of caring for patients with Alzheimer disease (AD) have simultaneously considered multiple dimensions of disease costs and detailed clinical characteristics. OBJECTIVE: To estimate empirically the incremental effects of patients' clinical characteristics on disease costs. METHODS: Data are derived from the baseline visit of 180 patients in the Predictors Study, a large, multicenter cohort of patients with probable AD followed from early stages of the disease. All patients initially lived at home, in retirement homes, or in assisted living facilities. Costs of direct medical care included hospitalizations, outpatient treatment and procedures, assistive devices, and medications. Costs of direct nonmedical care included home health aides, respite care, and adult day care. Indirect costs were measured by caregiving time. Patients' clinical characteristics included cognitive status, functional capacity, psychotic symptoms, behavioral problems, depressive symptoms, extrapyramidal signs, comorbidities, and duration of illness. RESULTS: A 1-point increase in the Blessed Dementia Rating Scale score was associated with a $1,411 increase in direct medical costs and a$2,718 increase in unpaid caregiving costs. Direct medical costs also were $3,777 higher among subjects with depressive symptoms than among those who were not depressed. CONCLUSIONS: Medical care costs and unpaid caregiving costs relate differently to patients' clinical characteristics. Poorer functional status is associated with higher medical care costs and unpaid caregiving costs. Interventions may be particularly useful if targeted in the areas of basic and instrumental activities of daily living

Diabetes causes marked inhibition of mitochondrial metabolism in pancreatic β-cells

Diabetes is a global health problem caused primarily by the inability of pancreatic β-cells to secrete adequate levels of insulin. The molecular mechanisms underlying the progressive failure of β-cells to respond to glucose in type-2 diabetes remain unresolved. Using a combination of transcriptomics and proteomics, we find significant dysregulation of major metabolic pathways in islets of diabetic βV59M mice, a non-obese, eulipidaemic diabetes model. Multiple genes/proteins involved in glycolysis/gluconeogenesis are upregulated, whereas those involved in oxidative phosphorylation are downregulated. In isolated islets, glucose-induced increases in NADH and ATP are impaired and both oxidative and glycolytic glucose metabolism are reduced. INS-1 β-cells cultured chronically at high glucose show similar changes in protein expression and reduced glucose-stimulated oxygen consumption: targeted metabolomics reveals impaired metabolism. These data indicate hyperglycaemia induces metabolic changes in β-cells that markedly reduce mitochondrial metabolism and ATP synthesis. We propose this underlies the progressive failure of β-cells in diabetes.Peer reviewe

Seizures in Alzheimer Disease. Who, When, and How Common?

Background: Transient symptoms in Alzheimer disease (AD) are frequent and include seizures, syncope, and episodes of inattention or confusion. The incidence of seizures in AD and predictors of which patients with AD might be more predisposed to them is based primarily on retrospective studies and is not well established. Objective: To determine the incidence and predictors of new-onset unprovoked seizures. Design: Prospective cohort study. Setting: Three academic centers. Patients: Four hundred fifty-three patients with probable AD observed prospectively from mild disease stages since 1992. Main Outcome Measure: Informant interviews every 6 months included questions about whether the patient had a seizure (convulsion, fainting, or “funny” spell) and whether diagnosis or treatment for epilepsy or seizure was made. Two epileptologists independently retrospectively reviewed all available medical records for 52 patients with positive responses to either of these questions, and using a specific checklist form, events were diagnosed as to whether they were unprovoked seizures (intrarater concordance, κ = 0.67). Diagnosis of unprovoked seizures constituted the event in survival analyses. Potential predictors included sex, age, race/ethnicity, educational achievement, duration of illness, baseline cognition and function, depression, medical comorbidities, and time-dependent use of cholinesterase inhibitors and neuroleptic agents, apolipoprotein E genotype, and previous electroencephalographic findings. Results: Over the course of 3518 visit-assessments (per patient: mean, 7.8; maximum, 27), 7 patients (1.5%) developed seizures. Younger age was associated with higher risk (hazard ratio, 1.23; 95% confidence interval, 1.08-1.41; P = .003 for each additional year of age) of seizure incidence. No other predictor was significant. The overall incidence of seizures was low (418 per 100 000 person-years of observation) although significantly higher than expected for idiopathic unprovoked seizures in similar age ranges of the general population (hazard ratio, 8.06; 95% confidence interval, 3.23-16.61). Conclusions: Unprovoked seizures are uncommon in AD, but they do occur more frequently than in the general population. Younger age is a risk factor for seizures in AD