Imaging Tau in Alzheimer's Disease and Normal Aging: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Imaging Tau in Alzheimer's Disease and Normal Aging (NCT03373604), a non-randomized phase 2 study. The primary outcome is 18F-MK-6240 Binding.

2. Clinical Question

3. Trial Design

This is a completed Phase 2 study with a parallel-group structure and non-randomized allocation. The registry record lists enrollment of 71 and describes groups with cognitive impairment and no cognitive impairment. The cognitive-impairment group includes people with mild cognitive impairment or mild-stage Alzheimer’s disease dementia; the no-cognitive-impairment group is described as healthy controls. These are participant categories, not randomized treatment assignments. Differences between the groups therefore cannot be attributed to an assigned treatment based on this design alone.

The listed intervention is 18F-MK-6240. The study summary describes PET imaging to measure abnormal tau accumulation in the brain, along with brain MRI and tests of memory and thinking. Lumbar puncture is listed as optional. The registry’s primary outcome is 18F-MK-6240 binding, expressed as SUVr, with a one-day timeframe. A secondary outcome concerns correlation between tau, neurodegeneration and inflammation using PET and cerebrospinal-fluid biomarkers.

The registry lists the study as completed. Its recorded start date is 2017-12-11, and its primary completion date is 2022-05-11. Masking is listed as none. The record does not report further details about how participants entered each group, whether specific covariates were used to account for group differences, or the statistical plan used to analyze the outcome. Those omissions limit what can be concluded about the design and its analysis beyond the registered characteristics.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

6. Primary Endpoint

The registry lists the primary outcome as 18F-MK-6240 Binding, measured over 1 day.

The primary endpoint is 18F-MK-6240 binding, measured as a standardized uptake value ratio (SUVr). The registry specifies a mean as the summary measure and standard deviation as the measure of dispersion, with a one-day timeframe. In general, a PET binding measure is used to describe tracer uptake in brain tissue; in this study, the stated purpose of PET was to measure abnormal accumulation of tau protein.

A mean describes the average measured value in a group, while a standard deviation describes how spread out individual values are around that average. The mean can help describe the typical binding level, and the standard deviation gives context about variability among participants. Neither statistic alone establishes whether group differences are precise or meaningful: interpretation also depends on the actual values, the analysis, and uncertainty estimates.

The registry record does not report the numerical SUVr means or standard deviations, nor does it provide an estimated group contrast or confidence interval. Consequently, the registered endpoint can be described, but its observed magnitude and precision cannot be assessed from the record. The secondary outcome is described as correlation between tau, neurodegeneration and inflammation using PET and CSF biomarkers; numerical correlation results are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registered primary measure is a continuous outcome summarized as a mean and standard deviation. In general, continuous outcomes can take a range of values rather than being limited to categories. A mean is a measure of central tendency, while the standard deviation describes the spread of observed values around that mean. A small standard deviation indicates less observed spread than a larger one, but whether a particular amount of spread is small or large depends on the outcome’s scale and context. The registry identifies SUVr as the unit for the primary endpoint.

What would an uncertainty interval add?

In general, a confidence interval expresses uncertainty around an estimate. It gives a range of values compatible with the data and the statistical method used, under that method’s assumptions. A narrow interval indicates greater precision than a wide interval, though precision is not the same as clinical importance. The registry record does not report a confidence interval for the primary outcome, so its precision cannot be judged from the record.

What would a group comparison mean?

A contrast between group means would describe the observed difference in average SUVr between the cognitive-impairment and no-cognitive-impairment groups, if such a contrast were reported. In general, an unadjusted contrast compares the observed groups without accounting for other characteristics. An adjusted contrast attempts to account for specified characteristics through a statistical model. The registry record does not report a contrast, an adjustment method, or covariates included in any model. It is therefore not possible to determine whether the posted result is adjusted or unadjusted, or to interpret the result as accounting for possible group differences.

Non-randomized group allocation is central to interpretation. In general, randomization can help balance measured and unmeasured characteristics between assigned groups, while non-randomized comparisons may retain confounding. Here, the group definitions are based on cognitive impairment status, and the groups are not randomized treatment arms. Any observed association would need to be interpreted in light of that design. The registry record does not report a strategy for controlling confounding.

What do the planning assumptions describe?

The sample-size planning illustration is described as using a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. It considers effects stated as fractions of the observed effect. These are planning assumptions, not evidence that the study was originally designed using those assumptions. The registry record does not report the trial’s own sample-size justification.

In general, a sample-size calculation estimates how many participants per arm might be needed to detect an assumed effect under specified conditions. Such a calculation depends on the chosen effect, variability, significance level, allocation, and analysis assumptions. A planning illustration based on an observed effect is not observed power and does not show that a study had a particular probability of detecting an effect after results are known. The sample-size information should be read as a planning exercise, not as a new trial result. The registry record does not report an interim analysis plan or other details about how the planning assumptions relate to the original protocol.

What analysis details are missing?

The registry record lists zero analyses. It does not report a statistical test, model specification, handling of missing observations, analysis population, or multiplicity procedure. These details matter because different choices can affect estimates and uncertainty. For example, a model can account for specified participant characteristics, while a complete-case analysis excludes participants without the required measurements. The record does not say whether either approach, or another approach, was used.

Multiplicity arises when many outcomes or comparisons are tested. In general, assessing multiple results can increase the chance of at least one apparently notable finding if no adjustment or prioritization is used. The registry lists two outcome measures, but does not report a multiplicity strategy or analysis results. The existence of multiple outcomes alone does not reveal how they were handled.

Over-dispersion is a general concern for some outcome types when observed variability exceeds what a chosen model expects. The primary measure is described as a continuous mean, and the record does not identify a model for which over-dispersion is relevant. It would not be appropriate to claim that over-dispersion occurred or that a particular correction was used. More broadly, methods should be interpreted from the analysis actually reported; those details are not reported in the registry record.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("No Cognitive Impairment", "Cognitive Impairment")
n   <- c(43, 28)
m   <- c(1.41, 2.3)
sp  <- c(0.43, 0.92)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  No Cognitive Impairment  43  1.410  0.430  1.278  1.542
CARM  Cognitive Impairment  28  2.300  0.920  1.943  2.657

11. Multiplicity, Missing Data and Analysis Populations

The registry lists two outcome measures, including the primary 18F-MK-6240 binding measure and a secondary outcome concerning correlations between tau, neurodegeneration and inflammation using PET and CSF biomarkers. It does not report a multiplicity procedure, such as a method to account for testing multiple outcomes or comparisons. The record also lists zero analyses, so it does not show which comparisons were conducted or how results were prioritized. Without that information, the statistical handling of multiple outcomes cannot be evaluated.

Missing-data methods are not reported in the registry record. The record does not state how unavailable or unusable PET, MRI, cognitive-test, or CSF measurements were handled, whether any participants were excluded from an analysis, or how many observations contributed to the primary endpoint. The analysis population is also not reported. These details matter because an analysis based only on participants with complete measurements may differ from an analysis that uses other methods to handle missing observations.

The registry record does not report an interim analysis plan, a prespecified statistical model, or a sample-size justification for the original study. The planning illustration describes a two-sided significance level of 0.05, equal allocation, and a normal approximation, with effects expressed as fractions of the observed effect. Those planning assumptions do not establish the study’s original analysis plan. In the absence of an analysis record, readers cannot assess whether the posted outcome reporting follows prespecified methods or how missing data and multiple outcomes were addressed.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent non-serious adverse event terms

For the no-cognitive-impairment group, the registry records zero serious adverse events among 43 at risk and 4 other adverse events among 43 at risk. For the cognitive-impairment group, it records zero serious adverse events among 28 at risk and 4 other adverse events among 28 at risk. The death count is zero in each group.

These are descriptive registry counts. The record does not give the terms or descriptions of the other adverse events, and the list of top serious adverse-event terms is empty. It also does not provide detail on event timing, severity definitions, attribution, or whether events were considered related to the intervention. The figures therefore cannot establish what the events were or why they occurred.

A zero serious-event count in these groups is not proof that serious events could not occur, nor does it address events that may not have been captured or reported. The counts are also not a randomized comparison of safety: allocation was non-randomized, and the groups represent different cognitive-status categories. These data should be read as the adverse-event figures recorded for the study groups, not as evidence that the intervention caused or prevented an event.

13. What the Result Does, and Does Not, Mean

The study’s registered focus is tau imaging in Alzheimer’s disease and normal aging. It uses 18F-MK-6240 PET binding as its primary outcome and describes groups with and without cognitive impairment. The record also identifies MRI, tests of memory and thinking, and an optional lumbar puncture. These details establish the study’s measurement aims and the kinds of information it sought to collect.

The record does not report numerical results for the primary endpoint. It therefore does not show the observed SUVr mean or standard deviation in either group, the size or direction of a group difference, or the precision of any estimate. No conclusion about the strength of an association or the degree of separation between groups can be drawn from the outcome description alone. The secondary correlation outcome is also named without numerical results.

Because the study is non-randomized, even a reported group difference would need to be interpreted as an association unless the analysis supported stronger causal conclusions. In general, groups defined by cognitive status can differ in other ways, and those differences may affect an imaging measure. The registry record does not report an adjusted analysis or enough methods detail to assess how such factors were handled.

The adverse-event counts provide a separate descriptive view of events recorded in the groups. They do not answer whether 18F-MK-6240 binding differs by cognitive status, and the absence of recorded serious events does not prove the absence of risk. In short, the registry record identifies a completed imaging study and its intended outcomes, but it does not provide the endpoint results or analysis details needed to judge the statistical evidence.

14. Why This Trial Matters Statistically

This trial is statistically relevant because it applies a quantitative imaging measure to a question about tau in Alzheimer’s disease and normal aging. The primary outcome is defined as a mean SUVr, with standard deviation describing variability. Clearly specifying the measurement and summary statistics is a necessary starting point for assessing whether imaging measurements differ across clinically described groups.

The non-randomized design also illustrates why design and interpretation must be considered together. The groups are defined by cognitive status rather than randomized assignment. In general, a difference between such groups can reflect the characteristic used to define them, other participant characteristics, or a combination. Statistical adjustment can sometimes address measured differences, but the record does not report whether adjustment was used. A numerical difference alone would not settle the causal interpretation.

The registry’s secondary outcome links PET and CSF biomarkers with neurodegeneration and inflammation. Such relationships can be studied through associations, but statistical association does not by itself establish causal direction. Appropriate interpretation depends on the measurements, analysis, and uncertainty, none of which are reported numerically for that outcome in the registry record.

The record also demonstrates the distinction between a registered outcome and a reported analysis. Although the primary measure and secondary outcome are identified, the registry lists zero analyses and does not give numerical endpoint results. Thus, the study question can be understood, but the evidence’s magnitude and precision cannot be assessed from the registry record. That distinction is important for researchers interpreting registry entries: design and measurement details are informative, but they do not substitute for estimates and their uncertainty.

15. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The central limitation for statistical interpretation is that the registry record does not report numerical results for the primary SUVr endpoint. Means, standard deviations, a group contrast, and an uncertainty estimate are not available in the record. Without them, readers cannot assess the direction, size, variability, or precision of the primary result. The secondary correlation outcome is also listed without numerical estimates.

Although enrollment is reported as 71, the record does not state how many participants contributed usable data to each outcome or analysis. Analysis populations and missing-data handling are not reported. It is therefore not possible to determine whether all enrolled participants had endpoint measurements, or how unavailable measurements were treated.

The non-randomized design limits causal interpretation. The arm descriptions identify groups by cognitive status, but the record does not report whether participant characteristics were balanced, which covariates were measured, or whether an adjusted analysis was performed. The registry also does not report eligibility details beyond the group descriptions, or the statistical model and test used for the endpoint.

Other relevant methods are not reported in the registry record, including a multiplicity strategy, interim analysis plan, and original sample-size justification. The listed adverse-event counts lack event descriptions and further context on timing or attribution. These omissions do not establish that methods were absent from the full study conduct; they mean those details cannot be assessed from the registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Imaging Tau in Alzheimer's Disease and Normal Aging — NCT03373604.
• Registry record last updated 2025-05-08; status last verified 2025-04.
• Results first posted 2025-05-08.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

19. Record Summary

The registry identifies NCT03373604 as a completed Phase 2 study titled “Imaging Tau in Alzheimer’s Disease and Normal Aging,” with the official title “Imaging Tau in Alzheimer’s Disease and Normal Aging With 18F-MK-6240.” It records non-randomized allocation, no masking, a parallel model, enrollment of 71, a start date of 2017-12-11, and a primary completion date of 2022-05-11.

The primary outcome is 18F-MK-6240 binding, measured as mean SUVr with standard deviation and a one-day timeframe. The groups are described as cognitive impairment and no cognitive impairment. A secondary outcome concerns correlations among tau, neurodegeneration and inflammation using PET and CSF biomarkers. The registry record does not report numerical outcome results or analysis estimates. It lists zero analyses. Serious adverse-event counts are zero in both groups; other adverse events are recorded as 4 in each group.