Acute Exercise and the Cerebral Metabolic Response in Aging and Alzheimer's Disease: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Acute Exercise and the Cerebral Metabolic Response in Aging and Alzheimer's Disease (NCT04299308), a randomized na study. The primary outcome is Fluorodeoxyglucose (FDG) Positron Emission Tomography (PET) Metabolism (Standard Uptake Value Ratio).

2. Clinical Question

3. Trial Design

The registry record describes a randomized, parallel-group trial with no masking. It lists an enrollment of 60 and a completed status. The recorded start date was 2020-08-28, and the primary completion date was 2023-10-31. The sponsor was University of Kansas Medical Center. The phase entry is NA.

Participants were allocated to moderate-intensity or high-intensity aerobic exercise. The intensity descriptions use heart-rate reserve ranges: 45-55% for the moderate arm and 65-75% for the high-intensity arm. The registry record does not provide further details about the exercise session, the randomization procedure, concealment, or whether the intervention was delivered in one or more sessions.

The study’s stated overall goal was to characterize the acute exercise response in relation to brain glucose metabolism in aging and Alzheimer disease. It also planned to examine lactate metabolism, relationships with cognition, and the effect of exercise intensity. The primary endpoint was FDG PET metabolism expressed as SUVR. Lactate area under the curve and BDNF change were listed as secondary outcomes.

The endpoint summaries have different participant counts across outcomes. The primary summaries include 27 participants in the moderate-intensity arm and 31 in the high-intensity arm. The secondary summaries include 28 and 31 participants for each outcome. The registry record does not explain the differences in these counts, describe the analysis population, or report whether all randomized participants were included in each analysis.

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

Reasons for not completing this period:

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 Fluorodeoxyglucose (FDG) Positron Emission Tomography (PET) Metabolism (Standard Uptake Value Ratio), measured over Resting Vs acute exercise bout: ~1 month.

The primary endpoint was FDG PET metabolism reported as a standard uptake value ratio, or SUVR. FDG PET is used to assess glucose uptake in the brain; the registry description says the cerebral metabolism measure was standardized to uptake in the cerebellum. The SUVR values were calculated from regions of interest in native space.

A reference-region ratio expresses uptake in a region relative to uptake in a selected comparison region. This can help place regional PET measurements on a common scale, but it is still a specific imaging measure rather than a direct measure of every aspect of brain function. The registry record does not identify the particular regions of interest analyzed or explain how they were selected.

The timeframe was described as resting versus an acute exercise bout, assessed over about one month. The posted results give mean values and standard deviations for each exercise-intensity arm, along with a mean-difference estimate and an interval. They do not describe the exact calculation used to form the endpoint or whether the reported means represent change scores, visit-specific measurements, or another summary. That detail is not reported in the registry record.

The endpoint is relevant to the study’s stated aim because it quantifies an imaging marker of cerebral glucose metabolism around acute exercise. It should be interpreted as that measured PET outcome, not as a complete account of cognition or clinical status.

7. Results Posted in the Registry

• High Intensity Aerobic Exercise: mean -0.07 versus -0.05 on control; difference -0.02 (95% CI -0.03 to 0.00), standardized effect d = -0.51; z-test p = 0.053.

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.

Lactate Area Under the Curve

• 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:
  • High Intensity Aerobic Exercise: mean 97.00 versus 40.30 on control; difference 56.70 (95% CI 36.12 to 77.28), standardized effect d = 1.37; z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically higher for High Intensity Aerobic Exercise than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Brain-derived Neurotrophic Factor (BDNF) Change

• 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:
  • High Intensity Aerobic Exercise: mean 353.30 versus 610.20 on control; difference -256.90 (95% CI -662.80 to 149.00), standardized effect d = -0.34; z-test p = 0.215.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between High Intensity Aerobic Exercise and the control. The interval gives the range of effects that remain compatible with the data.

The secondary outcomes address related but distinct aspects of the acute exercise response. Lactate area under the curve characterizes a lactate measure across the recorded assessment period, while BDNF change is a separate biomarker outcome. The primary endpoint is an imaging measure of cerebral glucose metabolism. These outcomes may contribute complementary biological information, but the registry record does not report a formal model linking either secondary endpoint to the primary PET result.

The overall pattern is not uniform across secondary measures: the posted between-arm summaries differ in direction and in how precisely they estimate the contrast. That makes it inappropriate to treat the secondary outcomes as a single consistent signal or as confirmation of the primary result. They describe separate comparisons, each with its own scale, variability, and uncertainty.

Unadjusted secondary results carry less weight when several outcomes are examined because the chance of seeing an apparently notable result can increase with multiple tests. The registry record lists two secondary outcomes but does not report a multiplicity adjustment, a hierarchy of testing, or which outcomes were designated as confirmatory. The secondary p-values should therefore be read as unadjusted evidence and interpreted cautiously, rather than as definitive findings on their own.

The record also does not report whether secondary outcomes were specified before the study began, whether all measured outcomes were posted, or how missing observations were handled. These omissions limit assessment of selective reporting and the reliability of the comparisons. The secondary results can help frame follow-up questions about exercise intensity and biological response, but they do not resolve the uncertainty in the primary comparison.

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

• Lactate Area Under the Curve
• Brain-derived Neurotrophic Factor (BDNF) Change

9. Statistical Interpretation

10. Statistical Methods Explained

The posted outcome summaries describe continuous measures using a mean and a standard deviation. A mean is the arithmetic average of the recorded values in an arm. The standard deviation describes how dispersed those values are around their mean. It is not the same as the standard error: the standard deviation describes participant-to-participant variability, while the standard error describes uncertainty in an estimated mean. The registry record does not explain the exact procedures used to calculate or analyze these summaries.

What does the mean difference represent?

The comparison is expressed as the high-intensity mean minus the moderate-intensity mean. A negative estimate therefore indicates that the high-intensity arm’s reported mean is lower on the outcome scale than the moderate-intensity arm’s mean. The primary estimate is -0.015. This direction describes the observed contrast; whether a lower SUVR value has a particular clinical interpretation is not established by the registry summary.

The mean difference remains on the original measurement scale, which makes it interpretable in the endpoint’s units. The standardized effect estimate, d = -0.51 for the primary outcome, expresses the contrast relative to the pooled standard deviation. Standardization can help compare effect magnitudes across outcomes measured in different units, but it can be less directly interpretable than the original-scale difference. Neither estimate alone indicates whether the result is important for patients or clinically meaningful.

How should an interval be read?

An interval gives a range of values compatible with the estimate under the method used to construct it. A narrower interval indicates greater precision than a wider interval, all else being comparable. For the primary difference, the reported range is -0.031 to < 0.001. Because this range includes zero, the posted estimate is compatible with no between-arm mean difference as well as with differences in either direction within the stated range. The registry record does not identify the confidence level or method used to construct the interval.

What does an unadjusted p-value say?

A p-value describes how unusual data at least as discrepant as the observed data would be under a specified null model. It is not the probability that the null hypothesis is true, nor does it measure the size or clinical importance of an effect. The primary unadjusted p-value is 0.053. The registry record does not specify the full model or testing procedure underlying that value. It is therefore best read alongside the mean difference and interval, rather than as a stand-alone verdict.

“Unadjusted” matters because the posted value is not described as corrected for multiple outcome testing or other analysis choices. The registry record does not report whether covariates were included, whether baseline values were incorporated, or whether the comparison used a particular regression or repeated-measures model. Those details are not reported in the registry record. The displayed summaries should not be taken as evidence that a specific model was or was not used in the study’s full analysis.

Why do participant counts matter?

Precision depends in part on the amount of information contributing to an estimate, along with outcome variability and the analysis method. The primary group summaries use 27 participants in the moderate-intensity arm and 31 in the high-intensity arm. The secondary outcome summaries use different counts for the moderate-intensity arm. These counts describe the posted outcome summaries; they do not by themselves explain why participants may be absent from an endpoint or establish how missing data were handled.

The registry record lists 60 enrolled participants, but does not describe whether the posted analysis followed an intention-to-treat approach, used a per-protocol population, or applied another population definition. It also does not report imputation or sensitivity analyses for missing outcomes. No inference about the reason for different outcome counts is warranted from the counts alone.

What can be concluded from the posted analysis detail?

The registry record includes outcome means, standard deviations, mean differences, intervals, and unadjusted p-values. It does not provide a detailed statistical analysis plan, identify the method used for the intervals, or report a model specification. The secondary outcomes have no reported analysis entries. The record therefore supports a description of the posted group summaries and comparisons, but not a reconstruction of all analysis decisions.

General statistical interpretation also distinguishes estimation from decision-making. An estimate describes the observed contrast, and its interval communicates precision under a method. Whether a result meets a prespecified decision rule depends on a protocol or analysis plan. Such a primary decision rule is not reported in the registry record. The planning illustration uses a two-sided significance level of 0.05 for sample-size calculations, but that planning assumption does not establish the analysis rule used for the primary endpoint.

11. Confidence Intervals and Precision

The primary mean-difference estimate is -0.015, and its reported interval extends from -0.031 to < 0.001. The range is not especially narrow relative to the estimated contrast and includes zero, so the data summaries do not pin down a single direction with high precision. The interval also permits a small positive value at its upper end. The registry record does not state the confidence level or construction method for the interval, so its exact coverage interpretation cannot be assessed from the record alone.

The primary standard deviations are 0.03 in both arms. Those values describe variability in the outcome observations, not the uncertainty of the mean difference. The posted comparison also includes standard errors for the group means, but the registry record does not explain their derivation or identify the statistical model used for the comparison.

The point estimate should not be treated as though it were known exactly. An interval is useful because it makes uncertainty visible and highlights the range of differences consistent with the analysis. In this case, the interval crosses zero and the unadjusted p-value is 0.053. Neither statistic establishes the probability that one intensity is better, and neither indicates whether any difference would matter clinically.

Precision is limited by the information in the analyzed observations, the outcome’s variability, and the analysis method. The primary summaries include 27 participants in one arm and 31 in the other. The record does not report a precision target, a prespecified clinically important difference, or a confidence-interval method. It is therefore not possible to judge whether the study was designed to estimate the primary contrast to a desired degree of precision.

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 figures are participants per arm, not total participants or total events. They are illustrative calculations based on the observed effect, rather than the trial’s original design justification. The stated assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, a normal approximation, and an effect to detect set to the stated fraction of the observed effect. The original trial’s sample-size assumptions are not reported in the registry record.

The 80% power column gives the estimated number of participants per arm for a design with an 80% chance of detecting the specified effect under those assumptions, if that effect is real and the calculation’s conditions hold. The 90% power column uses a higher target chance of detection and therefore generally requires more participants for the same effect. For the primary outcome, planning for 100% of the observed effect gives 61 participants per arm for 80% power and 81 participants per arm for 90% power. Planning for 75% of the observed effect gives 108 and 144 participants per arm, respectively; planning for 50% gives 242 and 324.

The effect fractions describe planning scenarios, not different observed results. A smaller effect is harder to distinguish from random variation, so detecting it requires more participants under the same assumptions. These figures are planning illustrations, not observed power: observed power is not a measure of how persuasive or precise the completed trial results are.

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 = -0.015; pooled standard deviation σ = 0.030.
2. n = 2 × (1.96 + 0.842)² × 0.030² / -0.015² = 60.4, rounded up to 61 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 <- -0.0153                      # observed difference in means
sigma <- 0.03                     # 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(4299308)
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 = 61 (80% power), 81 (90% power)
 75% of observed effect: n per arm = 108 (80% power), 144 (90% power)
 50% of observed effect: n per arm = 242 (80% power), 324 (90% power)
power.t.test: 61.3 
Simulated power at n = 61 per arm: 0.795 (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. Multiplicity, Missing Data and Analysis Populations

The registry record lists a primary endpoint and two secondary outcomes. It does not report a multiplicity strategy, such as an adjustment for testing several outcomes or a prespecified hierarchy that would control how conclusions are drawn across them. The posted secondary p-values are unadjusted. Without a documented plan, the chance of false-positive findings across the set of outcomes cannot be evaluated from the record.

The record also does not report a detailed statistical analysis plan, the primary model, covariate adjustment, the method used to construct intervals, or a prespecified decision threshold for the primary result. The planning illustration specifies a two-sided significance level of 0.05 for its sample-size calculations; that information does not establish the trial’s original analysis plan.

Outcome counts vary: the primary summaries include 27 participants in the moderate-intensity arm and 31 in the high-intensity arm, while the secondary summaries include 28 in the moderate-intensity arm and 31 in the high-intensity arm. The registry record does not explain those differences. It does not report the amount or pattern of missing data, reasons for missing outcomes, imputation, or sensitivity analyses.

The analysis population is also not described. The registry record does not say whether analyses included everyone randomized, only participants who completed the exercise bout, or another defined group. It does not report whether randomization was stratified by healthy-aging or Alzheimer-disease status, or whether outcomes were analyzed separately by condition. These details matter for judging the reach and robustness of the estimates, but are not reported in the registry record.

15. 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 serious adverse event summaries report zero serious events among 29 participants at risk in the moderate-intensity arm and zero among 31 participants at risk in the high-intensity arm. The death count was zero in both arms. These are the counts recorded for the listed groups and should be read as observations in this trial, not as proof that serious events cannot occur.

The registry record also reports two other adverse events in each arm, among 29 and 31 participants at risk, respectively. The record does not provide further descriptions of those events or a list of serious-event terms. The absence of reported serious events is not the same as evidence of no adverse events, and the summaries do not establish comparative safety beyond the observed counts.

The safety counts and outcome-analysis counts are not identical for every endpoint. The record does not explain the difference, specify the adverse-event collection period, or provide details about event severity definitions or attribution. These limits should be kept in mind when interpreting the posted safety information.

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

The results describe a randomized comparison of moderate- and high-intensity acute aerobic exercise on a PET measure of cerebral metabolism, alongside secondary biological measures. For the primary outcome, the two reported group means are close in scale, the estimated mean difference is -0.015, and the interval ranges from -0.031 to < 0.001. The unadjusted p-value is 0.053. The interval includes zero, so the posted summary does not give a precise directional conclusion about the average difference between the intensity arms.

This comparison is not an exercise-versus-no-exercise test. It cannot show what would have happened without an exercise bout, because the posted arms both received aerobic exercise at different intensities. Nor do the group summaries establish that a change in the PET measure corresponds to a change in cognition, daily function, or disease progression. Although relationships with cognition were part of the stated study goal, cognition is not among the posted outcome results.

The results also do not establish whether the intensity contrast differs between healthy aging and Alzheimer disease. The conditions are listed in the registry record, but the posted summaries do not separate results by condition or report an interaction analysis. The record does not identify how many participants belonged to each condition group.

Secondary outcomes provide additional measurements, but they are distinct from the primary endpoint and their results are unadjusted. They should not be used to override the uncertainty in the primary comparison. The registry record does not report a multiplicity plan, detailed analysis methods, or an original sample-size rationale, which limits stronger claims about confirmatory evidence and study design.

In general, a measured biological response is not itself a clinical benefit or harm. The posted data are best understood as estimates of group-level biomarker and imaging outcomes in this particular randomized comparison, with uncertainty and reporting gaps that constrain interpretation.

17. Why This Trial Matters Statistically

This trial is statistically interesting because it compares two exercise intensities using an imaging endpoint intended to reflect cerebral glucose metabolism, while also measuring lactate and BDNF. That combination focuses attention on how physiological responses and brain-imaging measures may be studied together. The registry’s stated aims include examining relationships with cognition and the effect of exercise intensity, but the posted outcome summaries do not establish those relationships.

The primary result illustrates why an estimate should be read with its uncertainty. The mean difference is negative, but its interval reaches across zero and the unadjusted p-value is 0.053. Reporting the effect estimate, interval, and group variability gives more context than treating a p-value as a simple yes-or-no conclusion.

The record also highlights the importance of complete analysis reporting. The absence of a detailed statistical plan, a stated multiplicity approach, and a description of analysis populations makes it difficult to assess how the posted comparisons fit into the full analysis strategy. Different participant counts across outcomes add a further question about outcome availability that the record does not answer.

Finally, planning estimates based on the observed effect can help researchers consider the scale of a future study, but they are sensitive to the effect chosen and the assumptions used. They are not a substitute for a prospective design justification grounded in a meaningful target effect and a prespecified analysis. The registry’s planning illustration makes those assumptions explicit, while the original design assumptions remain unreported.

18. 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.

Several trial-specific limitations follow directly from what is and is not described in the registry record. The primary outcome is a PET SUVR measure, but the record does not identify the regions of interest, report separate region-level findings, or explain the exact calculation used for the posted means. The PET endpoint therefore cannot be interpreted beyond the stated imaging measure and comparison.

The enrollment was 60, while outcome summaries use different participant counts. The record does not explain missing observations or define the analysis populations. It also does not describe the randomization method, concealment, exercise-session details, adherence, or whether participants were assessed at the same intervals. These omissions limit evaluation of implementation and potential sources of bias.

The conditions of interest include healthy aging and Alzheimer disease, but the posted results do not provide group-specific estimates or show whether intensity effects differed by condition. The record does not report participant characteristics that would help assess how broadly the results apply. The primary interval’s confidence level and construction method are not identified, and the detailed analysis plan is not reported.

Secondary outcome comparisons are unadjusted, and no multiplicity procedure is reported. The record does not explain the different moderate-arm participant counts across outcomes or provide detailed safety-event descriptions. These limits leave uncertainty about missingness, the full set of analyses, and the interpretation of secondary findings.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Acute Exercise and the Cerebral Metabolic Response in Aging and Alzheimer's Disease — NCT04299308.
• Registry record last updated 2025-07-23; status last verified 2025-07.
• Results first posted 2025-07-23.
• 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.

22. Record Summary

NCT04299308, titled Acute Exercise and the Cerebral Metabolic Response in Aging and Alzheimer's Disease, is recorded as a completed randomized, parallel-group study with no masking and an enrollment of 60. The sponsor was University of Kansas Medical Center. Participants were assigned to moderate- or high-intensity aerobic exercise.

The primary outcome was FDG PET metabolism expressed as SUVR, with lactate area under the curve and BDNF change listed as secondary outcomes. The primary mean-difference estimate for high versus moderate intensity was -0.015, with an interval from -0.031 to < 0.001 and an unadjusted p-value of 0.053.

The registry record does not report a detailed statistical analysis plan, original sample-size assumptions, multiplicity handling, missing-data methods, or analysis-population definitions. Secondary analyses are not listed as reported analyses.