Background/Objectives
Longitudinal studies have shown an increase in cognitive decline many years before clinical diagnosis of dementia. We sought to estimate changes, relative to “normal” aging, in ...the trajectory of scores on a global cognitive function test—the Cognitive Abilities Screening Instrument (CASI).
Design
A prospective cohort study.
Setting
Community‐dwelling members of a U.S. health maintenance organization.
Participants
Individuals aged 65 and older who had no dementia diagnosis at baseline and had at least two visits with valid CASI test score (N = 4,315).
Measurements
Average longitudinal trajectories, including changes in trajectory before clinical diagnosis in those who would be diagnosed with dementia, were estimated for CASI item response theory (IRT) scores. The impact of sex, education level, and APOE genotype on cognitive trajectories was assessed.
Results
Increased cognitive decline relative to “normal” aging was evident in CASI IRT at least 10 years before clinical diagnosis. Male gender, lower education, and presence of ≥1 APOE ε4 alleles were associated with lower average IRT scores. In those who would be diagnosed with dementia, a trajectory change point was estimated at an average of 3.1 years (95% confidence interval 3.0‐3.2) before clinical diagnosis, after which cognitive decline appeared to accelerate. The change point did not differ by sex, education level, or APOE ε4 genotype. There were subtle differences in trajectory slopes by sex and APOE ε4 genotype, but not by education.
Conclusion
Decline in average global cognitive function was evident at least 10 years before clinical diagnosis of dementia. The decline accelerated about 3 years before clinical diagnosis.
Objectives
To determine whether higher cumulative proton pump inhibitor (PPI) exposure is associated with greater dementia risk.
Design
Prospective population‐based cohort study.
Setting
Kaiser ...Permanente Washington, an integrated healthcare delivery system in Seattle, Washington.
Participants
Individuals aged 65 and older without dementia at study entry (N = 3,484).
Measurements
Participants were screened for dementia every 2 years, and those who screened positive underwent extensive evaluation. Dementia outcomes were determined using standard diagnostic criteria. Time‐varying PPI exposure was determined from computerized pharmacy data and consisted of total standardized daily doses (TSDDs) dispensed to an individual in the prior 10 years. We also assessed duration of use. Multivariable Cox regression was used to estimate the association between PPI exposure and time to dementia or Alzheimer's disease (AD).
Results
Over a mean follow‐up of 7.5 years, 827 participants (23.7%) developed dementia (670 with possible or probable AD). PPI exposure was not associated with risk of dementia (P = .66) or AD (P = .77). For dementia, the risk for specific levels of cumulative exposure compared to no use was: 365 TSDDs (HR 0.87, 95% CI 0.65–1.18), 1,095 TSDDs (HR 0.99, CI 0.75–1.30) and 1,825 TSDDs (HR 1.13, CI 0.82–1.56). These TSDD levels represent approximately 1, 3 and 5 years of daily use respectively. Duration of PPI use was not associated with dementia outcomes either.
Conclusion
Proton pump inhibitor use was not associated with dementia risk, even for people with high cumulative exposure. Although there are other safety concerns with long‐term PPI use, results from our study do not support that these medications should be avoided out of concern about dementia risk.
See related Editorial by Yu‐Xiao Yang.
Although self-rated health (SRH) and performance-based physical function (PPF) are both strong predictors of mortality, little research has investigated the relationships between them. The objective ...of this study was to evaluate longitudinal, bi-directional associations between SRH and PPF.
We evaluated longitudinal associations between SRH and PPF in 3,610 adults aged 65-89 followed for an average of 4.8 (standard deviation SD: 4.4) years between 1994 and July 2011 in the Adult Changes in Thought study, a population-based cohort in the Seattle area. SRH was assessed with a single-item question in the ACT study. Participants were asked at each evaluation to rate their health as "excellent", "very good", "good", "fair", or "poor" in response to the question "In general, how would you rate your health at this time". PPF scores (ranging from 0-16, with higher indicating better performance) included walking speed, chair rises, grip strength, and balance.
At the baseline visit, participants averaged 74.5 (SD: 5.8) years of age and 2,115 (58.6%) were female. In multivariable linear mixed models, PPF declined with age, with more rapid decreases associated with very good, good, and fair (vs. excellent) baseline SRH. Adjusted annual change in PPF was -0.17 points (95% confidence interval CI: -0.19, -0.15) for individuals with excellent baseline SRH and -0.21 points (95% CI: -0.22, -0.19) for participants with fair SRH. In multivariable generalized linear mixed models, lower baseline PPF quartiles were associated with lower odds of excellent/very good/good SRH at age 75, however, differences between baseline PPF quartiles diminished with age.
These results suggest that less than excellent SRH predicts decline in physical functioning, however, poor physical functioning may not predict change in SRH in a reciprocal fashion. SRH provides a simple assessment tool for identifying individuals at increased risk for decline in physical function.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Discovering an incidental finding (IF) or secondary finding (SF) is a potential result of genomic testing, but few data exist describing types and frequencies of SFs likely to appear in broader ...clinical populations.
The Electronic Medical Records and Genomics Network Phase III (eMERGE III) developed a CLIA-compliant sequencing panel of 109 genes and 1551 variants of clinical relevance or research interest and deployed this panel at ten clinical sites. We evaluated medically actionable SFs across 67 genes and 14 single-nucleotide variants (SNVs) in a diverse cohort of 21,915 participants drawn from a variety of settings (e.g., primary care, biobanks, specialty clinics).
Correcting for testing indication, we found a 3.02% overall frequency of SFs; 2.54% from 59 genes the American College of Medical Genetics and Genomics recommends for SF return, and 0.48% in other genes, primarily HFE and PALB2. SFs associated with cancer susceptibility were most frequent (1.38%), followed by cardiovascular diseases (0.87%), and lipid disorders (0.50%). After removing HFE, the frequency of SFs and proportion of pathogenic versus likely pathogenic SFs did not differ in those self-identifying as White versus others.
Here we present frequencies and types of medically actionable secondary findings to support informed decision making by patients, participants, and practitioners engaged in genomic medicine.
OBJECTIVE:The objective of this study was to determine differences in health care utilization, process of diabetes care, care satisfaction, and health status for Medicare Advantage (MA) and ...traditional Medicare (TM) beneficiaries with and without diabetes.
METHODS:Using the 2010–2016 Medicare Current Beneficiary Survey, we identified MA and TM beneficiaries with and without diabetes. To address the endogenous plan choice between MA and TM, we used an instrumental variable approach. Using marginal effects, we estimated differences in the outcomes between MA and TM beneficiaries with and without diabetes.
RESULTS:Our instrumental variable analysis showed that compared with TM beneficiaries with diabetes, MA beneficiaries with diabetes had less annual health care utilization, including −22.4 medical provider visits 95% confidence interval (CI)−23.6 to −21.1 and −3.4 outpatient hospital visits (95% CI−3.8 to −3.0). A significant difference between MA and TM beneficiaries without diabetes was only observed in medical provider visits and the difference was greater among beneficiaries with diabetes than beneficiaries without diabetes (−12.5 medical provider visits; 95% CI−15.9 to −9.2). While we did not detect significant differences in 5 measures of the process of diabetes care between MA and TM beneficiaries with diabetes, there were inconsistent results in the other 3 measures. There were no or marginal differences in care satisfaction and health status between MA and TM beneficiaries with and without diabetes.
CONCLUSIONS:MA enrollment was associated with lower health care utilization without compromising care satisfaction and health status, particularly for beneficiaries with diabetes. MA may have a more efficient care delivery system for beneficiaries with diabetes.
Glucose Levels and Risk of Dementia Crane, Paul K; Walker, Rod; Hubbard, Rebecca A ...
New England journal of medicine/The New England journal of medicine,
08/2013, Letnik:
369, Številka:
6
Journal Article
Recenzirano
Odprti dostop
Diabetes increases the risk of dementia. In this study, higher levels of glucose, even in persons without clinical diabetes, also increased the risk of dementia.
With the aging of the population, ...dementia has become a major threat to public health worldwide.
1
The rate of obesity is also increasing, with a parallel increase in the rate of diabetes.
2
The results of studies assessing the association between obesity or diabetes and the risk of dementia have been mixed.
3
,
4
It is imperative to understand the potential consequences of the obesity and diabetes epidemics for the incidence of dementia.
5
Any effects that obesity has on the risk of dementia are likely to include effects on metabolism. We evaluated extensive longitudinal clinical data from a prospective cohort with research-quality . . .
BACKGROUND:Coronary heart disease (CHD) is a leading cause of death globally. Although therapy with statins decreases circulating levels of low-density lipoprotein cholesterol and the incidence of ...CHD, additional events occur despite statin therapy in some individuals. The genetic determinants of this residual cardiovascular risk remain unknown.
METHODS:We performed a 2-stage genome-wide association study of CHD events during statin therapy. We first identified 3099 cases who experienced CHD events (defined as acute myocardial infarction or the need for coronary revascularization) during statin therapy and 7681 controls without CHD events during comparable intensity and duration of statin therapy from 4 sites in the Electronic Medical Records and Genomics Network. We then sought replication of candidate variants in another 160 cases and 1112 controls from a fifth Electronic Medical Records and Genomics site, which joined the network after the initial genome-wide association study. Finally, we performed a phenome-wide association study for other traits linked to the most significant locus.
RESULTS:The meta-analysis identified 7 single nucleotide polymorphisms at a genome-wide level of significance within the LPA/PLG locus associated with CHD events on statin treatment. The most significant association was for an intronic single nucleotide polymorphism within LPA/PLG (rs10455872; minor allele frequency, 0.069; odds ratio, 1.58; 95% confidence interval, 1.35–1.86; P=2.6×10). In the replication cohort, rs10455872 was also associated with CHD events (odds ratio, 1.71; 95% confidence interval, 1.14–2.57; P=0.009). The association of this single nucleotide polymorphism with CHD events was independent of statin-induced change in low-density lipoprotein cholesterol (odds ratio, 1.62; 95% confidence interval, 1.17–2.24; P=0.004) and persisted in individuals with low-density lipoprotein cholesterol ≤70 mg/dL (odds ratio, 2.43; 95% confidence interval, 1.18–4.75; P=0.015). A phenome-wide association study supported the effect of this region on coronary heart disease and did not identify noncardiovascular phenotypes.
CONCLUSIONS:Genetic variations at the LPA locus are associated with CHD events during statin therapy independently of the extent of low-density lipoprotein cholesterol lowering. This finding provides support for exploring strategies targeting circulating concentrations of lipoprotein(a) to reduce CHD events in patients receiving statins.
As individuals age, death is a competing risk for Alzheimer's disease (AD) but the reverse is not the case. As such, studies of AD can be placed within the semi‐competing risks framework. Central to ...semi‐competing risks, and in contrast to standard competing risks , is that one can learn about the dependence structure between the two events. To‐date, however, most methods for semi‐competing risks treat dependence as a nuisance and not a potential source of new clinical knowledge. We propose a novel regression‐based framework that views the two time‐to‐event outcomes through the lens of a longitudinal bivariate process on a partition of the time scales of the two events. A key innovation of the framework is that dependence is represented in two distinct forms, local and global dependence, both of which have intuitive clinical interpretations. Estimation and inference are performed via penalized maximum likelihood, and can accommodate right censoring, left truncation, and time‐varying covariates. An important consequence of the partitioning of the time scale is that an ambiguity regarding the specific form of the likelihood contribution may arise; a strategy for sensitivity analyses regarding this issue is described. The framework is then used to investigate the role of gender and having ≥1 apolipoprotein E (APOE) ε4 allele on the joint risk of AD and death using data from the Adult Changes in Thought study.
Glucose Levels and Risk of Frailty Zaslavsky, Oleg; Walker, Rod L; Crane, Paul K ...
The journals of gerontology. Series A, Biological sciences and medical sciences,
09/2016, Letnik:
71, Številka:
9
Journal Article
Recenzirano
Odprti dostop
The association between glucose levels and incident frailty in older persons remains unclear. We examined the extent to which higher glucose levels in older adults with and without diabetes are ...related to risk of frailty.
The data are from the Adult Changes in Thought study. We identified 1,848 individuals aged 65+ without dementia for whom glucose levels from laboratory measurements of glucose and glycated hemoglobin were available. Physical frailty using modified Fried's criteria was determined from biennial assessments. Frailty hazard was modeled as a function of time-varying measures of diabetes and average glucose levels using Cox regression.
A total of 578 incident frailty cases (94 with diabetes, 484 without) occurred during a median follow-up of 4.8 years. The adjusted hazard ratio for frailty comparing those with and without diabetes was 1.52 (95% confidence interval = 1.19-1.94). In participants without diabetes, modeling suggested elevated frailty risk with greater average glucose levels (p = .019); for example, a glucose level of 110mg/dL compared with 100mg/dL yielded a hazard ratio of 1.32 (95% confidence interval = 1.09-1.59). In participants with diabetes, glucose levels less than 160mg/dL and greater than 180mg/dL were related to increased risk of frailty (p = .001).
Higher glucose levels may be a risk factor for frailty in older adults without diabetes. The apparent U-shape association between glucose levels and frailty in people with diabetes is consistent with the literature on glycemia and mortality and deserves further examination.
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