Dataset Information

Does Testing More Frequently Shorten the Time to Detect Disease Progression?

ABSTRACT:

Purpose

With the rise of smartphone devices to monitor health status remotely, it is tempting to conclude that sampling more often will provide a more sensitive means of detecting changes in health status earlier over time, when interventions may improve outcomes.

Methods

The answer to this question is derived in the context of a model where observations are generated from a linear-trend model with independent as well as autocorrelated autoregressive-moving average, or ARMA(1,1), errors.

Results

The results imply a cautionary message that an increase in the sampling frequency may not always lead to a faster detection of trend changes. The benefit of rapid successive observations depends on how observations, taken closely together in time, are correlated.

Conclusions

Shortening the observation period by half can be accomplished by increasing the number of independent observations to maintain the same power for detecting change over time. However, a strategy to detect progression of disease sooner by taking numerous closely spaced measurements over a shortened interval is limited by the degree of autocorrelation among adjacent observations. We provide a statistical model of disease progression that allows for autocorrelation among successive measurements, and obtain the power of detecting a linear change of specified magnitude when equal-spaced observations are taken over a given time interval.

Translational relevance

New emerging technology for home monitoring of visual function will provide a means to monitor sensory status more frequently. The model proposed here takes into account how successive measurements are correlated, which impacts the number of measurements needed to detect a significant change in status.

SUBMITTER: Ledolter J

PROVIDER: S-EPMC5412967 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Introduction: We investigated whether monthly assessments of a computerized cognitive composite (C3) could aid in the detection of differences in practice effects (PE) in clinically unimpaired (CU) older adults, and whether diminished PE were associated with Alzheimer's disease (AD) biomarkers and annual cognitive decline. Materials and Methods: N = 114 CU participants (age 77.6 ± 5.0, 61% female, MMSE 29 ± 1.2) from the Harvard Aging Brain Study completed the self-administered C3 monthly, at-home, on an iPad for one year. At baseline, participants underwent in-clinic Preclinical Alzheimer's Cognitive Composite-5 (PACC5) testing, and a subsample (n = 72, age = 77.8 ± 4.9, 59% female, MMSE 29 ± 1.3) had 1-year follow-up in-clinic PACC5 testing available. Participants had undergone PIB-PET imaging (0.99 ± 1.6 years before at-home baseline) and Flortaucipir PET imaging (n = 105, 0.62 ± 1.1 years before at-home baseline). Linear mixed models were used to investigate change over months on the C3 adjusting for age, sex, and years of education, and to extract individual covariate-adjusted slopes over the first 3 months. We investigated the association of 3-month C3 slopes with global amyloid burden and tau deposition in eight predefined regions of interest, and conducted Receiver Operating Characteristic analyses to examine how accurately 3-month C3 slopes could identify individuals that showed >0.10 SD annual decline on the PACC-5. Results: Overall, individuals improved on all C3 measures over 12 months (β = 0.23, 95% CI [0.21-0.25], p < 0.001), but improvement over the first 3 months was greatest (β = 0.68, 95% CI [0.59-0.77], p < 0.001), suggesting stronger PE over initial repeated exposures. However, lower PE over 3 months were associated with more global amyloid burden (r = -0.20, 95% CI [-0.38 - -0.01], p = 0.049) and tau deposition in the entorhinal cortex (r = -0.38, 95% CI [-0.54 - -0.19], p < 0.001) and inferior-temporal lobe (r = -0.23, 95% CI [-0.41 - -0.02], p = 0.03). 3-month C3 slopes exhibited good discriminative ability to identify PACC-5 decliners (AUC 0.91, 95% CI [0.84-0.98]), which was better than baseline C3 (p < 0.001) and baseline PACC-5 scores (p = 0.02). Conclusion: While PE are commonly observed among CU adults, diminished PE over monthly cognitive testing are associated with greater AD biomarker burden and cognitive decline. Our findings imply that unsupervised computerized testing using monthly retest paradigms can provide rapid detection of diminished PE indicative of future cognitive decline in preclinical AD.