Clinical importance in Alzheimer's disease: effects of anchor agreement and disease severity.

OBJECTIVES: Methods of evaluating clinically meaningful decline are critical in research on Alzheimer's disease. A common method of quantifying clinically meaningful change is to calculate an anchor-based minimal clinically important difference (MCID) score. In this approach, individuals who report a meaningful change serve as the "anchors", and the mean level of change for this group serves as the MCID. In research on Alzheimer's disease, there are several possible anchors, including patients, knowledgeable observers (e.g., a family member), and clinicians. The goal of this study was to examine the extent to which agreement among anchors impacts MCID estimation and whether this relationship is moderated by cognitive severity status. METHODS: Analyses were completed on a longitudinal sample of 2247 adults, aged 50-103, from the Uniform Data Set. Outcome measures included the Montreal Cognitive Assessment, Clinical Dementia Rating-Sum of Boxes, and Functional Activities Questionnaire. RESULTS: For all of the outcomes, the MCID estimate was significantly higher when meaningful decline was endorsed by all of the anchors compared to when there was disagreement among the anchors. In addition, the MCID estimate was higher with increasing severity of cognitive impairment. Finally, cognitive severity status moderated the influence of agreement among anchors on MCID estimation; as disease severity increased, anchor agreement demonstrated less influence on the MCID. CONCLUSIONS: MCID estimates based on one anchor may underestimate meaningful change, and researchers should consider the viewpoints of multiple anchors in constructing MCIDs, particularly in the early stages of cognitive decline.

Effect of exercise engagement and cardiovascular risk on neuronal injury.

INTRODUCTION: Neuronal health as a potential underlying mechanism of the beneficial effects of exercise has been understudied in humans. Furthermore, there has been limited consideration of potential moderators (e.g., cardiovascular health) on the effects of exercise. METHODS: Clinically normal middle-aged and older adults completed a validated questionnaire about exercise engagement over a 10-year period (n = 75; age 63 ± 8 years). A composite estimate of neuronal injury was formulated that included cerebrospinal fluid-based measures of visinin-like protein-1, neurogranin, synaptosomal-associated protein 25, and neurofilament light chain. Cardiovascular risk was estimated using the Framingham Risk Score. RESULTS: Cross-sectional analyses showed that greater exercise engagement was associated with less neuronal injury in the group with lower cardiovascular risk (p = 0.008), but not the group with higher cardiovascular risk (p = 0.209). DISCUSSION: Cardiovascular risk is an important moderator to consider when examining the effects of exercise on cognitive and neural health, and may be relevant to personalized exercise recommendations. HIGHLIGHTS: We examined the association between exercise engagement and neuronal injury. Vascular risk moderated the association between exercise and neuronal injury. Cardiovascular risk may be relevant to personalized exercise recommendations.

The impact of technology-based compensatory behaviors on subjective cognitive decline in older adults with a family history of dementia.

The current study examined whether greater use of technology to help with daily tasks is associated with less subjective cognitive decline (SCD), especially in individuals with a family history of Alzheimer's disease (AD). Individuals over the age of 50 (n = 102; age range 50-85) completed surveys about their digital and analog approaches to daily tasks, physical activity, and SCD. Participants with and without family histories of AD were matched on age, education, sex, and family history of AD using the R package MatchIt. There was no main effect of technology-based behavioral strategies on SCD (p = 0.259). However, a family history of AD moderated the association between technology use and SCD even when controlling for another protective lifestyle factor, physical activity. In individuals with a family history of AD, more reliance on technology-based behavioral strategies was associated with less SCD (p = 0.018), but this relationship was not significant in individuals without family history of AD (p = 0.511). Our findings suggest that technology-based behavioral strategies are associated with less SCD in individuals with a family history of AD, independent of another protective lifestyle factor. Future recommendations provided by healthcare providers to address SCD in cognitively unimpaired older adults might include focusing on technological assistance.

Determinants of physical activity engagement in older adults.

In order to increase engagement in physical activity, it is important to determine which factors contribute to physical activity engagement in older adults. The current study examined the relative predictive ability of several potential determinants, in terms of both the concurrent level as well as longitudinal trajectories. Clinically normal adults aged 61-92 completed the Physical Activity Scale for the Elderly (n = 189 for cross-sectional models; n = 214 for longitudinal models). Potential determinants included age, gender, education, physical health, sensory health, mood, cardiovascular health, cognitive status, and biomarkers of Alzheimer disease (AD). We observed a novel finding that both concurrent physical health (p < 0.001) and change in physical health (p < 0.001) were significant predictors above and beyond other determinants. Concurrent mood predicted levels of physical activity (p = 0.035), particularly in females. These findings suggest that poor physical health and low mood might be important to consider as potential barriers to physical activity engagement in older adults.

Physical Exercise and Longitudinal Trajectories in Alzheimer Disease Biomarkers and Cognitive Functioning.

INTRODUCTION: Associations of physical exercise with Alzheimer disease (AD) biomarkers and cognitive functioning have been observed cross-sectionally. However, the effects of exercise on longitudinal change in AD biomarkers have not been thoroughly investigated. The current study examined whether individuals with higher baseline exercise exhibited less longitudinal change in AD biomarkers and cognitive functioning, and whether APOE and/or brain-derived neurotrophic factor (BDNF) genotypes moderated the effects of exercise on longitudinal changes. METHODS: Clinically normal individuals completed a questionnaire on physical exercise over the prior 10-year period at baseline. Ninety-five individuals had serial cerebrospinal fluid samples collected to examine Aß42, ptau181 and total tau; 181 individuals underwent multiple assessments of amyloid positron emission tomography imaging with Pittsburgh Compound-B; 327 individuals underwent multiple cognitive assessments, including measures of episodic memory, executive functions, verbal fluency, and processing speed. RESULTS: Greater exercise was associated with less steep decline in processing speed. Baseline exercise did not robustly impact longitudinal change for any other outcomes. Neither APOE nor BDNF genotype robustly moderated the effect of exercise on trajectories of AD biomarkers or cognitive decline. INTERPRETATION: Results suggest that self-reported physical exercise may be limited as a moderator of changes in AD biomarkers.

Global Public Health Surveillance Using Media Reports: Redesigning GPHIN.

Global public health surveillance relies on reporting structures and transmission of trustworthy health reports. But in practice, these processes may not always be fast enough, or are hindered by procedural, technical, or political barriers. GPHIN, the Global Public Health Intelligence Network, was designed in the late 1990s to scour mainstream news for health events, as that travels faster and more freely. This paper outlines the next generation of GPHIN, which went live in 2017, and reports on design decisions underpinning its new functions and innovations.

Spatial navigation ability predicts progression of dementia symptomatology.

INTRODUCTION: Spatial navigation deficits are observed in Alzheimer's disease cross-sectionally, but prediction of longitudinal clinical decline has been less examined. METHODS: Cognitive mapping (CM) was assessed in 95 participants and route learning (RL) was assessed in 65 participants at baseline. Clinical progression over an average of 4 to 5 years was assessed using the clinical dementia rating (CDR) scale. Relative predictive ability was compared to episodic memory, hippocampus, and cerebrospinal fluid biomarkers (phosphorylated tau/amyloid ß 42 (ptau181 /Aß42 ) ratio). RESULTS: CM and RL were predictors of clinical progression (P's < 0.032). All measures, except RL-Learning remained predictors with episodic memory in models (P's < 0.048). Only RL-Retrieval remained a predictor when ptau181 /Aß42 was included (P < 0.001). CM interacted with hippocampus and ptau181 /Aß42 in prediction (P's < 0.013). CM, RL, and episodic memory evidenced strong diagnostic accuracy (area under the curve (AUC) = 0.894, 0.794, and 0.735, respectively); CM tended to perform better than episodic memory (P = 0.056). DISCUSSION: Baseline spatial navigation performance may be appropriate for assessing risk of clinical progression.