Dataset Information

Alzheimer's disease severity, objectively determined and measured.

ABSTRACT:

Introduction

With expansion of clinical trials to individuals across the spectrum of Alzheimer disease (AD) from preclinical to symptomatic phases, it is increasingly important to quantify AD severity using methods that capture underlying pathophysiology.

Methods

We derived an AD severity measure based on biomarkers from brain imaging, neuropathology, and cognitive testing using latent variable modeling. We used data from ADNI-1 (N = 822) and applied findings to BIOCARD study (N = 349). We evaluated criterion validity for distinguishing diagnostic groups and construct validity by evaluating rates of change in AD severity.

Results

The AD severity factor cross-sectionally distinguishes cognitively normal participants from MCI (AUC = 0.87) and AD dementia (AUC = 0.94). Among ADNI MCI subjects, worsening scores predict faster progression to AD dementia (HR = 1.17; 95% CI, 1.13-1.22). In ADNI and BIOCARD, the pace of change in AD severity is steepest among progressors, with persisting differences by baseline diagnosis.

Discussion

Our content-valid latent variable measurement model is a reasonable approach for grading AD severity across a broad spectrum beginning at preclinical stages of AD.

SUBMITTER: Gross AL

PROVIDER: S-EPMC5078784 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Publications

Alzheimer's disease severity, objectively determined and measured.

Gross Alden L AL Mungas Dan M DM Leoutsakos Jeannie-Marie S JS Albert Marilyn S MS Jones Richard N RN

Alzheimer's & dementia (Amsterdam, Netherlands) 20161014

<h4>Introduction</h4>With expansion of clinical trials to individuals across the spectrum of Alzheimer disease (AD) from preclinical to symptomatic phases, it is increasingly important to quantify AD severity using methods that capture underlying pathophysiology.<h4>Methods</h4>We derived an AD severity measure based on biomarkers from brain imaging, neuropathology, and cognitive testing using latent variable modeling. We used data from ADNI-1 (N = 822) and applied findings to BIOCARD study (N = ...[more]

PMID: 27830173

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Project description:IntroductionThe disease burden of nonalcoholic fatty liver disease (NAFLD) increases rapidly, in line with the obesity pandemic. Physical activity has been linked to a lower risk of NAFLD. However, the impact of different intensities of activity and sedentary behavior and whether their effects on NAFLD are explained by metabolic health remain unclear.MethodsWe performed cross-sectional analyses within the population-based Rotterdam Study cohort. Abdominal ultrasound and accelerometry data were collected between 2009 and 2014. NAFLD was defined as hepatic steatosis diagnosed by ultrasound, in the absence of secondary causes for steatosis: viral hepatitis, steatogenic drugs, and excessive alcohol. We categorized accelerometry data into sedentary time and light, moderate, and vigorous physical activities.ResultsWe included 667 participants (aged 63.3 ± 6.3 years, 53% female individuals), and 34.3% had NAFLD. Total physical activity was associated with lower NAFLD prevalence adjusted for demographic, lifestyle, and socioeconomic factors (odds ratio: 0.958 per 10 min/d, 95% confidence interval [CI]: 0.929-0.986). More intensive physical activity was more strongly associated with lower NAFLD prevalence: odds ratios for light, moderate, and vigorous physical activities were 0.931 (95% CI: 0.882-0.982), 0.891 (95% CI: 0.820-0.967), and 0.740 (95% CI: 0.600-0.906) per 10 min/d, respectively. These associations were explained by metabolic health, particularly homeostatic model assessment of insulin resistance (proportion mediated: 0.59, P < 0.001) and waist circumference (proportion mediated: 1.08, P < 0.001). Beyond this indirect effect, no direct effect could be demonstrated (P = 0.282-0.827).DiscussionPhysical activity at each intensity is inversely associated with NAFLD prevalence, with larger effects for higher intensities of physical activity. This association is mediated by better metabolic health, mainly lower insulin resistance and waist circumference. Physical activity should therefore be incorporated into NAFLD disease management and prevention programs.

Dataset Information

Alzheimer's disease severity, objectively determined and measured.

Introduction

Methods

Results

Discussion

Publications

Alzheimer's disease severity, objectively determined and measured.

Similar Datasets

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