Non-invasive Nerve Stimulation and Cognitive Training to Improve Cognitive Performance in Healthy Older Adults: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Non-invasive Nerve Stimulation and Cognitive Training to Improve Cognitive Performance in Healthy Older Adults (NCT04276805), a randomized na study. The primary outcome is Hopkins Verbal Learning Test (Total Immediate Recall).

2. Clinical Question

3. Trial Design

This was a randomized, single-masked, parallel-group study sponsored by the University of Florida. The registry lists the study as completed, with an enrollment of 45 and phase recorded as not applicable. The study began on 2020-11-17, and primary completion was recorded as 2024-09-27. The registry record does not explain who was masked or provide further details about allocation procedures.

Both groups were assigned cognitive training over two weeks. The tVNS group paired training with active transcutaneous vagal nerve stimulation, while the Sham group paired training with sham stimulation. Participants completed assessments before and after the intervention. The primary endpoint’s timeframe describes the post-intervention assessment as approximately 2 to 3 weeks after baseline, depending on scheduling. No additional visit schedule is reported in the registry record.

This design can address the contrast between active and sham stimulation when both are paired with cognitive training, subject to the way outcomes were collected and analyzed. It does not, by itself, separate the effect of training from the effect of stimulation, because the described groups both received training. The registry record does not report a no-training group or another comparison that would estimate training’s independent contribution.

The record lists five outcome measures and no analyses. It does not report group-level primary-outcome results, a between-group estimate, a confidence interval, or a test result. The allocation, masking, and parallel structure describe the planned comparison, but they do not establish what the observed outcome data showed or how the analysis was conducted.

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 Hopkins Verbal Learning Test (Total Immediate Recall), measured over At baseline (intake assessment) and at the post-intervention assessment conducted following completion of the 2-week cognitive training intervention (approximately 2 to 3 weeks after baseline, depending on scheduling)..

The primary endpoint is total immediate recall on the Hopkins Verbal Learning Test (HVLT-R), expressed in units on a scale. The task uses a 12-item word list learned over three trials. The total immediate recall score is the sum of the correct words recalled after each learning trial, and the stated possible range is 0 to 36.

This measure is used to assess verbal learning and memory: it captures how many words a participant recalls across the learning trials. Measuring participants before and after the intervention allows assessment of performance at both time points. For the treatment question, however, the key evidence would be a clearly defined comparison of outcomes between the active-stimulation and sham groups, with its uncertainty. A within-group change alone would not establish that the groups differed.

The registry record identifies the measure, its scoring description, and its assessment timing, but it does not report the observed means, standard deviations, or an analysis comparing groups. Consequently, the size and precision of any difference in immediate recall cannot be described from the posted results.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

A randomized parallel-group design assigns participants to one of the study groups and compares their outcomes. In this trial, the described groups differed in whether cognitive training was paired with active tVNS or sham stimulation. Random allocation is intended, in general, to reduce systematic differences between groups at the time of assignment. It does not guarantee that every group characteristic is identical, particularly in a study with limited enrollment, and it does not remove the need to report the analysis and its uncertainty.

What does the primary measure represent?

The primary measure is a continuous score: total immediate recall on the HVLT-R. The registry describes a 12-item list learned over three trials and defines the score as the sum of correct words recalled across those trials, with a possible range from 0 to 36. A mean summarizes the average score in a group, while a standard deviation describes how spread out individual scores are around that mean. The registry identifies the mean and standard deviation as the measure’s summary types, but does not post the actual group summaries.

Why does the between-group comparison matter?

Participants were assessed at baseline and after the intervention. In general, a before-and-after design provides information about measurements at both times, but the treatment comparison depends on how outcomes across the randomized groups are contrasted. A difference observed within one group can reflect factors beyond the intervention, including changes over time. Comparing the randomized groups is the relevant framework for assessing whether outcomes differed between assignment groups. The registry record does not report whether the analysis used post-intervention scores, change from baseline, or another method.

What would a confidence interval communicate?

In general, a confidence interval gives a range of values compatible with the observed data under the assumptions of the analysis. It communicates precision as well as the estimated direction and size of a comparison. A narrow interval indicates greater precision than a wide interval, while an interval that includes values on both sides of no difference may leave the direction uncertain. No confidence interval for the primary outcome is reported in the registry record, so neither precision nor compatibility with different effect sizes can be assessed.

What can a significance test establish?

In general, a significance test evaluates how compatible the data are with a specified null hypothesis under the test’s assumptions. A p-value is not the probability that the null hypothesis is true, and it does not measure clinical importance. The sample-size assumptions mention a two-sided significance level of 0.05 for a planning illustration. That value is not a reported result and does not establish that the same threshold was used for an actual analysis. The registry record does not state the analysis model, test, or primary-outcome p-value.

Why can over-dispersion matter?

Over-dispersion is a general concern for data whose variability is greater than a statistical model assumes. If that extra variability is ignored, standard errors and uncertainty estimates can be too small, which can make results appear more precise than the data support. The primary outcome in this trial is described as a continuous score summarized by a mean and standard deviation; the registry record does not report a model or indicate that over-dispersion was assessed. This concept should not be taken as evidence that over-dispersion occurred in this study.

What do the planning assumptions mean?

The registry describes a planning illustration based on the observed effect, using a fraction of that effect, a two-sided significance level of 0.05, equal allocation between groups, and a normal approximation. For non-time-to-event outcomes, the stated convention is participants per arm. These assumptions explain the intended basis of a planning calculation, but no corresponding sample-size values or observed effect estimate are reported in the registry record. A planning illustration is not an observed power calculation and does not demonstrate that a study had adequate information to estimate its outcome precisely.

Most importantly, a statistical method cannot be reconstructed from the trial design alone. The model, handling of baseline measurements, analysis population, missing-data method, and any adjustment for multiple outcomes or tests are not reported in the registry record. Without those details and the primary-outcome results, the analysis cannot be independently interpreted from the registry entries.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists five outcome measures and no analyses. It identifies one primary measure, total immediate recall on the HVLT-R, but does not report results for that endpoint or explain how the other outcomes were treated in the statistical plan. The number of listed outcomes alone does not establish how many statistical tests were conducted, whether outcomes were tested, or whether any adjustment for multiple comparisons was planned.

When several outcomes or comparisons are examined, multiplicity can increase the chance of finding an apparently notable result by chance. In general, a prespecified strategy can clarify which outcome carries the primary inferential role and how additional tests are interpreted. The registry record does not report such a strategy, any multiplicity adjustment, or interim analyses. These details should therefore be regarded as not reported in the registry record, rather than inferred from the list of outcomes.

Missing-data handling is also not reported in the registry record. The record describes baseline and post-intervention assessments, but does not state how many participants completed each assessment, whether any primary-outcome values were missing, or how missing values were handled. It also does not describe an intention-to-treat, per-protocol, or other analysis population. The safety denominators do not establish the number included in the primary-outcome analysis.

These gaps limit the ability to assess bias and robustness. Without outcome completion counts and the analysis population, it is not possible to judge whether the analyzed participants represent those randomized. Without a stated missing-data approach or multiplicity plan, readers cannot evaluate those aspects of the analysis from the registry record.

11. 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 5% reporting threshold.

The registry lists serious adverse events for both groups. In the tVNS group, 24 participants were at risk and 0 were reported as affected; in the Sham group, 21 participants were at risk and 0 were reported as affected. Deaths are listed as 0 in each group. These are the serious-event figures recorded for the groups, not a complete description of every possible safety outcome.

The record also lists other adverse events: 24 participants at risk and 0 affected in the tVNS group, and 21 at risk and 0 affected in the Sham group. The registry record does not list serious adverse-event terms. The absence of reported affected participants in these entries should be read as a registry report of no events in the stated categories, not as proof that no adverse experiences of any kind occurred.

Safety counts do not establish the primary cognitive outcome or the comparative effect of the interventions. The registry record does not provide further detail about adverse-event collection, definitions, follow-up, or reporting procedures. These counts should therefore be interpreted within the limits of the categories and denominators recorded.

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

The record describes a completed randomized study of cognitive training paired either with active tVNS or with sham stimulation. Its primary outcome was total immediate recall on the HVLT-R, assessed before and after a two-week intervention. This establishes the intended comparison and the type of cognitive performance measured.

However, the registry record does not report group scores, a between-group estimate, a confidence interval, or an inferential result for the primary outcome. It therefore does not show whether the active and sham groups differed in immediate recall, in which direction any difference went, or how precisely a difference was estimated. The absence of a reported comparison is not evidence that the groups were the same, and it is not evidence that one approach performed better.

The intervention contrast also has a specific scope: both groups received cognitive training, while active versus sham stimulation differed. Results from such a comparison, if reported, would address the added contrast between active and sham stimulation in the setting of training. The design description alone does not estimate the separate contribution of cognitive training, because no no-training group is described.

The safety entries report no affected participants in the listed serious or other adverse-event categories, with group-specific denominators recorded. Those entries do not answer the cognitive-outcome question and should not be treated as evidence about all possible safety experiences.

Interpretation is further constrained by the lack of reported analysis methods, outcome completion counts, missing-data handling, and analysis populations. The registry record supports a description of the study’s intended design and recorded safety counts, but not a conclusion about the primary endpoint’s observed effect or its precision.

13. Why This Trial Matters Statistically

This trial is statistically informative as an example of the difference between a study design and a report of study results. Randomization, a defined primary endpoint, and assessments before and after an intervention make the intended comparison understandable. But statistical interpretation requires the outcome summaries and comparison, not only the design description.

The clinical contrast is also important to define carefully. Both groups received cognitive training; the group contrast is active tVNS paired with training versus sham stimulation paired with training. Keeping that distinction clear prevents attributing any hypothetical group difference to training alone or treating the study as a comparison of training with no training.

The endpoint is a continuous recall score with a defined scoring procedure. Reporting group summaries alongside an estimate of the between-group difference and its confidence interval would allow readers to assess both the scale of the observed result and its precision. The registry record does not report those statistics, so the intended outcome cannot be evaluated from the posted results.

The record also illustrates why transparent reporting of analysis choices matters. Information about missing assessments, analysis populations, the handling of multiple outcomes, and the statistical model helps readers judge how the findings were produced and how robust they may be. Those analysis details are not reported in the registry record.

These are not merely technical omissions: without outcome estimates and uncertainty, readers cannot distinguish a precise estimate near no difference from an imprecise estimate compatible with a range of possibilities. The study’s completion status and enrollment figure do not supply that information. Statistical interpretation must remain limited to the design and recorded safety entries unless primary-outcome results are reported.

14. 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 main limitation for interpreting this trial from its registry record is that primary-outcome results are not reported. The measure is defined, but group means, standard deviations, a between-group estimate, its confidence interval, and a test result are absent. This prevents assessment of the direction, magnitude, and precision of the primary comparison.

The registry describes assessments at baseline and after the intervention, but the analysis approach is not reported. It is not stated whether the comparison used post-intervention scores, change from baseline, or another method. The statistical model and any adjustment for baseline differences are also not reported in the registry record.

The record lists enrollment of 45, while the safety entries give denominators of 24 in the tVNS group and 21 in the Sham group. It does not report the number with available primary-outcome data or whether those safety denominators correspond to the primary analysis population. Missing assessments, withdrawals, and their handling are not reported.

Details relevant to interpreting the intervention are limited. The record identifies active and sham stimulation during two weeks of cognitive training, but does not further describe the stimulation or sham procedures, training regimen, or who was masked. Further eligibility details and the analyzed population are not reported in the registry record.

Finally, five outcome measures are listed, but the analysis plan, multiplicity approach, and interim analyses are not reported. The study is marked completed, yet that status does not resolve these reporting gaps. These limitations concern what can be concluded from the registry record; they do not establish that the study’s full results or methods were absent elsewhere.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Non-invasive Nerve Stimulation and Cognitive Training to Improve Cognitive Performance in Healthy Older Adults — NCT04276805.
• Registry record last updated 2026-07-27; status last verified 2025-04.
• Results first posted 2026-07-27.
• 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.

18. Record Summary

The University of Florida sponsored this completed randomized, single-masked, parallel-group study of cognitive training paired with active tVNS or sham stimulation in healthy older adults. The registry lists enrollment of 45 and identifies aging as the condition. The intervention lasted two weeks, with assessments before and after completion.

The primary endpoint was total immediate recall on the HVLT-R, a verbal learning and memory score based on correct recall across three learning trials. The registry lists five outcome measures and no analyses. It does not report the primary-outcome group results, a comparative estimate, or its uncertainty. Serious and other adverse-event entries list 0 affected participants in each group, with 24 at risk in the tVNS group and 21 in the Sham group. Analysis methods, missing-data handling, and analysis populations are not reported in the registry record.