Exercise Effects on Brain Health and Learning From Minutes to Months: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Exercise Effects on Brain Health and Learning From Minutes to Months (NCT03114150), a randomized na study. The primary outcome is Change in Hippocampal-dependent Learning.

2. Clinical Question

3. Trial Design

NCT03114150 is recorded as a completed, randomized, double-masked, parallel-group study with 122 participants enrolled. The listed phase is NA. The sponsor is Michelle W. Voss. The record gives a start date of 2018-05-01 and a primary completion date of 2023-06-21. The condition listed is sedentary lifestyle.

The two interventions were behavioral exercise programs. Cardiorespiratory fitness training was described as a supervised cycling program lasting 24 weeks and designed to improve cardiorespiratory fitness. Functional fitness training was also supervised for 24 weeks and focused on functional flexibility and mobility. The posted descriptions do not contain complete details of the orientation provided by the exercise training specialist, and further exercise dose and adherence information is not reported in the registry record.

The primary outcome was measured at baseline and 24 weeks. Its analysis population is described as participants with both pre- and post-intervention measurements. The outcome summaries list 48 participants in the cardiorespiratory training group and 45 in the functional fitness group. These outcome counts need not equal the enrollment count: the registry does not provide enough information to explain participant flow, reasons for unavailable measurements, or exclusions from this outcome analysis.

The record also lists hippocampal-cortical functional connectivity and cardiorespiratory fitness as secondary outcomes. The connectivity outcome has a 30-minute timeframe, while cardiorespiratory fitness is assessed at baseline and 24 weeks. One secondary outcome title is repeated in the registry's list. Detailed allocation procedures, the method used to maintain masking, and the trial's original sample-size justification are not reported in the registry record.

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.

Crossover: One Week

Randomized Trial: 24 Weeks

Analysis population for the primary outcome, as defined in the registry: Participants with both pre- and post-intervention measurements.

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 Change in Hippocampal-dependent Learning, measured over Baseline, 24-weeks.

The primary endpoint is change in hippocampal-dependent learning, expressed as a learning-rate slope for the wayfinding condition of a spatial navigation task. The measure is based on the proportion of items correctly recalled on a map over four learning trials. For each trial, the proportion correct can range from 0 to 1; a higher value represents faster learning. The reported endpoint is the change in slope from baseline to 24 weeks, in participants with measurements at both time points.

The registry describes this task as related to hippocampal structure and function and places it among learning constructs examined in animal models. The endpoint is therefore a task-specific measure of learning rather than a direct measure of all cognitive abilities, brain health, or everyday functioning. A change in its slope summarizes the pattern of recall across the task's learning trials; it does not by itself identify the biological mechanism that might account for a group difference.

Using a defined task and timepoint makes the outcome measurable and comparable between the randomized groups. Interpretation still depends on the analysis and the precision of the estimate. The registry record does not report further validation information or explain how the endpoint was selected relative to other possible measures.

7. Results Posted in the Registry

• Functional Fitness Training: mean 0.00 versus -0.00 on control; difference 0.01 (95% CI -0.01 to 0.02), standardized effect d = 0.22; z-test p = 0.294.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Change in Hippocampal-cortical Functional Connectivity

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard errors.
• Result:
  • Light Intensity Aerobic Exercise: mean -0.01 versus 0.00 on control; difference -0.01 (95% CI -0.02 to 0.01), standardized effect d = -0.11; z-test p = 0.396.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Light Intensity Aerobic Exercise and the control. The interval gives the range of effects that remain compatible with the data.

Change in Cardiorespiratory Fitness

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Functional Fitness Training: mean 0.53 versus 2.33 on control; difference -1.80 (95% CI -2.75 to -0.85), standardized effect d = -0.77; z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for Functional Fitness Training than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

The secondary outcomes address related but distinct aspects of the study: hippocampal-cortical functional connectivity and cardiorespiratory fitness. Their assessment times also differ. Connectivity is recorded at 30 minutes, while cardiorespiratory fitness is assessed over the longer intervention period. This set of outcomes does not present one uniform statistical pattern: the simple connectivity comparison is uncertain, while the simple fitness comparison is more clearly separated. The registry's own mixed-model summaries do not map straightforwardly onto those simple estimates in every case.

These measures can provide context for the primary learning outcome, but they are not substitutes for it. Connectivity is a brain-network measure, cardiorespiratory fitness is a physical fitness measure, and wayfinding learning is a task-specific behavioral outcome. A result in one domain does not establish a corresponding result in another, and the registry does not report an analysis showing that changes in one outcome explain changes in another.

Secondary findings generally carry less confirmatory weight when the record does not specify a multiplicity strategy or a prespecified hierarchy for interpreting them. Examining multiple outcomes can produce some small p-values by chance, and the reported analyses may not all have the same status in the study's original plan. The registry does not report whether the secondary outcomes were adjusted for multiple comparisons. Their findings are useful for describing the broader pattern of posted results, but should be treated as exploratory or supportive rather than as independent proof of a broad effect.

The connectivity title appears twice in the registry's secondary-outcome list, while the posted results include a connectivity analysis and a fitness analysis. That duplication makes it especially important to avoid inferring a complete outcome hierarchy from the list alone. Details of the planned secondary analyses and their role in the study's conclusions are not reported in the registry record.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Change in Hippocampal-cortical Functional Connectivity
• Change in Hippocampal-cortical Functional Connectivity
• Change in Cardiorespiratory Fitness

9. Statistical Interpretation

10. Statistical Methods Explained

What does a mean difference represent?

For a continuous outcome, a mean difference compares the average value in one group with the average value in another. In this analysis, the unadjusted primary contrast is functional fitness training relative to cardiorespiratory fitness training. Its positive estimate means the posted group mean change is higher in the functional fitness group under that contrast ordering. The sign alone does not establish that the difference is important, precise, or attributable to a particular mechanism. The outcome's units and definition matter: this is a learning-rate slope, not a general cognitive score.

The simple comparison is calculated from the posted group summary statistics, without adjustment for other variables. It is useful as a transparent comparison of the reported means, but it is not necessarily the same estimand or model as the sponsor's mixed-model analysis. A model can account for repeated observations or other structure, depending on its specification. The registry names mixed models for its reported analyses, but the details needed to determine exactly what was modeled are not reported in the registry record.

What does a confidence interval communicate?

A confidence interval describes the uncertainty around an estimate under the assumptions of the analysis. It gives a range of values reasonably compatible with the observed data and the method used; it does not mean that the true value has a stated probability of falling in that particular interval. For the primary simple comparison, the 95% interval extends from -0.007 to 0.022. Because it crosses zero, the posted summary does not clearly distinguish a difference in one direction from no difference or a difference in the other direction. The range also indicates that the estimate should not be interpreted as an exact effect size.

Intervals depend on the data, sample size, variability, and analysis assumptions. A narrower interval would indicate greater precision for the estimate under the same framework; a wider interval leaves more uncertainty. Precision and importance are separate questions: a precisely estimated difference could still be small in practical terms, while an imprecise estimate may include differences that would matter. The registry does not state a threshold for a meaningful change in this learning measure.

Why can a reported p-value and interval seem at odds?

A p-value measures how surprising data at least as incompatible with a specified null model would be, assuming that model and its assumptions. It is not the probability that the null hypothesis is true, nor a measure of effect size. In a conventional two-sided analysis, a 95% confidence interval that crosses the null value of zero would ordinarily align with a p-value that is not below .05. The primary mixed-model result in the registry reports p <.05 while its 95% interval crosses zero. The record does not explain this apparent tension, so readers should not try to resolve it by assuming an unreported test, contrast, or modeling choice.

The unadjusted p-value of 0.294 for the simple primary comparison is consistent with its interval spanning zero. It indicates that the simple analysis does not provide strong evidence against a zero mean difference under its assumptions. It does not prove that the groups have identical effects or establish that the observed difference is unimportant.

Why can results from two analyses differ?

A re-calculation from group means and variability is intentionally simple and unadjusted. A mixed model can use a different structure, such as repeated measurements, and may estimate a different quantity or account for covariance. The registry does not report enough detail to determine whether that explains the different primary estimates. The estimates should therefore be described as results from different analyses, not combined as though they were identical. The record's mixed-model report is relevant, but its apparent interval and p-value tension needs to remain visible to the reader.

Contrast direction is also important. Reversing which group is subtracted from which changes the sign of a mean difference but not the underlying separation. For the fitness secondary outcome, the simple contrast is functional fitness relative to cardiorespiratory fitness, whereas the mixed-model value is reported as a positive estimate without enough accompanying detail to confirm the same ordering. The signs should not be compared as if they necessarily use identical contrast conventions.

What role does variability play?

Standard deviations describe spread among individual measurements around a group mean. Standard errors describe uncertainty in an estimated mean, and are generally affected by both variability and the amount of information available. They are not interchangeable. The primary endpoint is reported with standard deviations, while the short-term connectivity outcome is reported with standard errors. A reader should interpret each spread measure according to the label attached to that outcome rather than compare the numerical spread values directly across outcomes.

The simple comparisons use the posted means and variability to estimate group contrasts and confidence intervals. These calculations depend on assumptions, including how the measurements behave and how observations contribute to the estimate. General statistical methods often use models to address outcome structure and account for uncertainty, but the exact assumptions and diagnostics for the registry's mixed models are not reported in the registry record.

Why does multiplicity matter?

When several outcomes or analyses are examined, the chance of finding at least one apparently unusual result can increase, even if none represents a reliable underlying effect. This is the general reason to interpret secondary findings cautiously and to distinguish planned primary analyses from additional comparisons. The registry lists multiple outcomes and reports several analyses. A procedure for controlling multiplicity, a hierarchy among secondary outcomes, and a complete statistical analysis plan are not reported in the registry record. The reported secondary p-values should therefore not automatically be treated as confirmatory.

These methods explain how to read the reported estimates, not why participants were assigned to particular groups or whether the exercise programs produce broad clinical effects. Randomization supports comparisons between assigned groups, but interpretation also depends on follow-up, outcome availability, analysis choices, and transparent reporting. The posted summaries do not answer every question about those features.

11. Confidence Intervals and Precision

The primary simple comparison estimates a mean difference of 0.008, with a 95% confidence interval from -0.007 to 0.022. The interval covers zero and includes values on both sides of it. Thus, the observed estimate is not precise enough to rule out no mean difference, nor to rule out differences in either direction within the interval. The interval should be read as an uncertainty range for the specified simple analysis, not as a guarantee that the true effect lies within it.

The group summaries for this outcome are based on 48 participants in the cardiorespiratory fitness training group and 45 in the functional fitness training group. The registry defines the primary outcome population as participants with both pre- and post-intervention measurements. It does not explain why the outcome counts are below the enrolled total or provide a detailed account of missing measurements. That prevents a complete assessment of whether unavailable outcomes could affect the estimate.

The reported mixed-model interval for the primary outcome runs from -.04 to .01, with a reported p-value of <.05. As that interval crosses zero, its combination with the p-value has a reporting tension that cannot be reconciled from the registry entries. The interval and the re-calculated interval also describe analyses that are not established as identical. Precision should therefore be discussed separately for each analysis, not inferred by choosing whichever result appears more decisive.

A confidence interval addresses statistical uncertainty, not the importance of a difference. No threshold for a meaningful change in learning rate is reported in the registry record. Nor does the interval account for uncertainty from unreported choices such as the full model specification, missing-data handling, or multiplicity procedures. The available estimate is informative about the posted data, while leaving substantial uncertainty about the size and interpretation of the underlying group difference.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The planning illustrations express sample size as participants per arm, not total events. They use the observed unadjusted effect as a reference and show planning for 100% of that observed effect, 75% of the observed effect, and 50% of the observed effect. The assumptions listed for these calculations are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The calculations are planning illustrations; the trial's own original sample-size assumptions and justification are not reported in the registry record.

The 80% power column gives the estimated participants per arm for a future study to have 80% power to detect the stated effect under those assumptions. The 90% power column gives the corresponding participants per arm for 90% power. In plain terms, power describes the chance that a study using the assumed design would detect an effect of the specified size under the model if that effect were present. These columns are not a description of what the completed study observed.

The rows illustrate that smaller target effects require more participants per arm. For example, planning for 75% or 50% of the observed effect requires larger sample sizes than planning for the full observed effect. This pattern follows from the general relationship between effect size and precision: smaller differences are harder to distinguish from sampling variability using the same design assumptions.

These figures are not observed power. They are conditional planning calculations based on the posted effect estimate and specified assumptions, and they do not show the probability that the trial's findings are true. Since the observed effect itself is uncertain, sample-size planning based directly on it can also be uncertain. The original protocol's planning rationale is not reported in the registry record.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = 0.008; pooled standard deviation σ = 0.035.
2. n = 2 × (1.96 + 0.842)² × 0.035² / 0.008² = 325.4, rounded up to 326 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
delta <- 0.00773                      # observed difference in means
sigma <- 0.0351917822575319                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(3114150)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 326 (80% power), 436 (90% power)
 75% of observed effect: n per arm = 579 (80% power), 775 (90% power)
 50% of observed effect: n per arm = 1,302 (80% power), 1,743 (90% power)
power.t.test: 326.3 
Simulated power at n = 326 per arm: 0.800 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Analyses Reported by the Sponsor

The registry's own primary analysis is described as a mixed-model analysis of slope. It reports a value of -0.02, a 95% confidence interval from -.04 to .01, and p <.05. The simple re-calculation from the posted group summaries instead gives a mean difference of 0.008, a 95% confidence interval from -0.007 to 0.022, and an unadjusted p-value of 0.294. The calculations differ in both the estimate and the reported inference, and the registry does not give enough model detail to establish that they target exactly the same quantity.

The sponsor's analysis should be understood as the registry's reported model-based result; the simple calculation is a separate, unadjusted comparison of posted summary statistics. The registry's primary mixed-model interval crosses zero even though its p-value is reported as below .05. Without further analysis details, that apparent reporting tension cannot be resolved. Neither result should be silently substituted for the other, and the re-calculation should not be presented as a correction to the sponsor's analysis.

The secondary outcomes likewise include registry mixed-model reports and separate simple comparisons. Differences between these estimates may reflect the analysis method, outcome, or contrast direction, but the record does not establish the explanation. The posted model specification and analysis plan are not reported in the registry record.

15. Multiplicity, Missing Data and Analysis Populations

Multiplicity arises when an analysis considers several outcomes, comparisons, timepoints, or statistical tests. Even if each test is evaluated using the same nominal threshold, the chance of obtaining at least one apparently positive result can rise as tests accumulate. Statistical plans may address this through an adjustment, an ordered testing strategy, or clear designation of primary and secondary outcomes. Which approach is appropriate depends on the study objectives and plan.

The registry identifies a primary learning outcome and lists secondary outcomes for connectivity and cardiorespiratory fitness. It also posts several registry analyses. A multiplicity adjustment, a testing hierarchy, and a complete statistical analysis plan are not reported in the registry record. Therefore, isolated secondary p-values should be interpreted cautiously, especially where the corresponding confidence interval includes zero or where the model and simple re-calculation differ.

The primary outcome population is described as participants with both pre- and post-intervention measurements. The posted primary summaries include 48 participants in one group and 45 in the other, while total enrollment is 122. The record does not report enough participant-flow information to explain these counts, the reasons measurements may be missing, or whether missingness differed by group. It also does not describe the method used to handle missing outcomes beyond defining the population with both measurements.

Complete-case analyses can be affected if participants with missing measurements differ in relevant ways from those with observed outcomes. This is a general concern, not evidence that such a bias occurred in this trial. Assessing it would require details about follow-up, reasons for missingness, and any sensitivity analyses, which are not reported in the registry record.

Random allocation and a parallel-group design are stated, but the record does not give the allocation sequence method, concealment procedures, or full details of masking. It also does not report the original sample-size justification or whether interim analyses were planned or conducted. Those details matter to a complete assessment of the analysis plan, but they should not be inferred from the posted estimates.

16. 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

The registry's serious adverse event summaries report zero serious events in each of the listed groups, and zero deaths in each group. These counts describe the events recorded in the registry; they do not establish that no unrecorded events occurred or that the programs have no risks. The record does not provide event definitions or further narrative about surveillance and attribution.

The safety groups are labeled moderate intensity aerobic exercise, light intensity aerobic exercise, cardiorespiratory fitness training, and functional fitness training. Those labels do not map cleanly onto the two intervention descriptions used for the primary outcome. The recorded numbers at risk also differ across the safety groups. The registry does not explain this difference or provide enough information to reconcile the safety populations with the primary outcome populations.

Other, non-serious adverse events are reported as 22 in the cardiorespiratory fitness training group and 8 in the functional fitness training group; the other listed safety groups each report zero. These are event-affecting counts, not evidence that events were caused by the intervention. The record does not identify the event terms in the posted summary. No rates or comparisons are inferred from these counts.

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

The primary data describe a randomized comparison of two supervised exercise programs and a task-specific measure of wayfinding learning. The simple unadjusted estimate is small relative to the uncertainty represented by its interval, which includes zero and values in either direction. The sponsor's mixed-model result is also posted, but its p-value and confidence interval appear to be in tension. Taken together, the registry record does not support a simple, unqualified conclusion about the size or direction of the primary group difference.

This does not show that the programs are equivalent, nor does it establish that there is no effect. A non-significant unadjusted p-value can arise when a true difference is absent, but also when the estimate is too imprecise to distinguish a difference from zero. Equivalence or non-inferiority would require a prespecified margin and an appropriate analysis, neither of which is reported in the registry record.

The trial's outcomes represent different constructs. A wayfinding learning slope is not a complete measure of memory or cognition; functional connectivity is not the same as learning performance; and cardiorespiratory fitness is not a direct clinical outcome. The registry's stated interest in exercise effects on brain health and learning provides context, but the posted outcome summaries alone do not establish broad changes in cognitive health or identify a biological mechanism.

The secondary findings add information but have limitations in interpretation. Their analyses span distinct measures and timeframes, and a multiplicity procedure is not reported. The available result summaries also do not resolve questions about missing measurements, detailed analysis choices, or the alignment between simple comparisons and mixed-model results. These limitations should temper any attempt to generalize from an individual estimate.

Accordingly, the results are best read as estimates from this specific comparison and set of posted outcomes. They do not determine how an individual should exercise, and they are not medical advice. Broader claims would require evidence beyond the registry summaries, including transparent analysis details and results across relevant populations and outcomes.

18. Why This Trial Matters Statistically

This trial illustrates why a reported estimate should be read alongside its uncertainty and analysis definition. The primary simple comparison gives a mean difference and confidence interval, while the registry also reports a mixed-model result. Those are not automatically interchangeable. The difference makes clear that understanding the model, contrast, and outcome definition is part of interpreting the result, not a technical afterthought.

The apparent inconsistency between the primary mixed-model confidence interval and p-value is also a useful lesson in statistical reporting. A p-value should not be read alone, and a confidence interval should not be ignored when it gives a conflicting signal. Transparent reporting of model specifications, contrast conventions, and the relationship between tests and intervals helps readers determine what the results mean.

The trial also provides a practical example of how confidence intervals distinguish uncertainty from certainty. A point estimate is one summary of observed data; its interval conveys how much the estimate could vary under the analysis assumptions. In this case the simple primary interval includes zero and extends in either direction, so the observed estimate does not settle the question of the underlying difference.

Finally, a study with multiple outcomes needs clear handling of multiplicity and missing data. The registry provides a primary learning outcome and several secondary measures, but does not report a multiplicity plan or full missing-data account. Those omissions do not invalidate the posted numbers, but they limit the strength of claims that can be built from individual secondary findings. The distinction between descriptive results and confirmatory evidence is central to sound clinical-trial interpretation.

19. 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 primary outcome analysis includes participants with both pre- and post-intervention measurements, and the reason the posted outcome group counts are below the enrolled total is not reported in the registry record. Without participant-flow details, reasons for unavailable measurements, and missing-data sensitivity analyses, it is not possible to assess how the outcome population compares with all randomized participants.

The posted primary analyses differ: a simple unadjusted re-calculation and a mixed-model result are both available, but the model specification and contrast details are not. The mixed-model primary result also pairs a reported p-value below .05 with a 95% confidence interval that crosses zero. The record does not explain this tension. This makes precise interpretation of the sponsor-reported analysis difficult.

The registry does not report a multiplicity strategy despite several outcomes and analyses. Secondary findings should therefore be treated cautiously, particularly when considering them alongside the primary result. The original sample-size justification, any interim-analysis plan, and the full statistical analysis plan are also not reported in the registry record.

The safety summaries use group labels and denominators that do not align transparently with the two primary-outcome intervention groups. Event terms and further safety follow-up details are not reported in the posted summary. The intervention descriptions themselves are incomplete in the orientation details. In addition, the primary outcome is a task-specific learning measure, and the listed outcomes do not establish broad cognitive or clinical effects. These limitations constrain conclusions about generalizability and mechanism.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Exercise Effects on Brain Health and Learning From Minutes to Months — NCT03114150.
• Registry record last updated 2025-08-13; status last verified 2025-07.
• Results first posted 2025-08-13.
• 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.

23. Record Summary

NCT03114150 is recorded as a completed randomized, double-masked, parallel-group study with 122 participants enrolled. It compares supervised cardiorespiratory fitness training with supervised functional fitness training, each described as lasting 24 weeks. The primary outcome is change in wayfinding learning rate from baseline to 24 weeks among participants with both pre- and post-intervention measurements.

The unadjusted primary comparison estimates a mean difference of 0.008, with a 95% confidence interval from -0.007 to 0.022 and p = 0.294. A mixed-model result is also posted, but its reported p-value and confidence interval appear inconsistent by conventional interpretation. Secondary findings address connectivity and cardiorespiratory fitness, with no multiplicity plan reported. Serious adverse events and deaths are recorded as zero in the listed groups; interpretation is limited by differences in safety-group labels and denominators.