Methylphenidate for Apathy in Alzheimer's Dementia: A Controlled Study: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Methylphenidate for Apathy in Alzheimer's Dementia: A Controlled Study (NCT00495820), a randomized phase 4 study. The primary outcome is Apathy Evaluation Scale Score at 12 Weeks.

2. Clinical Question

The study also described hypotheses concerning instrumental activities of daily living and caregiver burden. Those are not among the outcome results posted in the registry record. The listed secondary outcomes are the Mini-mental State Examination at 12 weeks and Clinical Global Impression. The record does not describe additional hypotheses or how those secondary measures were intended to relate to the primary question.

The central statistical question is about a difference between randomized groups at a defined follow-up, not simply whether either group changed from its own starting point. The registry record posts group means and standard deviations for the primary measure, along with a sponsor-reported mixed models analysis. A simple unadjusted comparison can help describe the posted summary statistics, but it is not a substitute for the sponsor's analysis. The record identifies a discrepancy between the re-calculation and sponsor analysis, so the sponsor's own analysis takes precedence for interpreting the trial's inferential result.

3. Trial Design

This was a phase 4, randomized, triple-masked, parallel-group study sponsored by the VA Office of Research and Development. The registry record lists 60 participants, with 30 in the methylphenidate group and 30 in the placebo group. The study status is completed. The listed study start is 2007-08, and primary completion is 2010-03.

In general, random allocation is intended to create groups whose baseline characteristics are comparable on average, while masking is intended to reduce the influence of treatment knowledge on trial conduct, outcome assessment, or participant reporting. The registry record identifies masking as triple, but does not specify which people or roles were masked. It describes a parallel model, meaning participants were assigned to a group and followed in that group rather than being described as crossing between treatments. Details of allocation sequence generation, concealment, and masking procedures are not reported in the registry record.

The primary endpoint was measured at 12 weeks. The record does not state the treatment schedule or provide a broader follow-up schedule for all outcomes. It lists a total of three outcome measures: the primary Apathy Evaluation Scale score and the two secondary outcomes. Enrollment is reported as 60, and the posted group results each include 30 participants. The record does not report the number screened, exclusions after randomization, withdrawals, or the number contributing to each analysis beyond the group counts attached to the outcome results.

The original trial's sample-size assumptions and design justification are not reported in the registry record. The planning illustrations associated with the posted effects are separate from that original design information and should not be taken as evidence about how the trial was planned.

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 Apathy Evaluation Scale Score at 12 Weeks, measured over At 12 weeks.

The primary endpoint was the Apathy Evaluation Scale score at 12 weeks, recorded in units on a scale and summarized as a mean with standard deviation. The AES is described in the registry record as an 18 item instrument developed to assess apathy and distinguish it from depression. It covers behavioral, cognitive, and emotional domains over the previous four weeks. Scores range from 18 to 72, and higher scores indicate worsening apathy.

Apathy is the target construct in the study question, so a scale specifically developed to assess apathy is directly relevant to the stated purpose. The score condenses information across several domains into a measure that can be compared between randomized groups. The four-week reference period also means that the score reflects reported apathy over a defined period rather than a single moment.

Because higher scores indicate worse apathy, lower group averages are in the direction of less severe apathy on this scale. That direction makes the sign of a mean difference meaningful, but the scale score alone does not establish the importance of a difference to patients or caregivers. The registry record does not report a threshold for a clinically meaningful change or a responder definition. It also does not provide the population field for this outcome. Those omissions limit interpretation of what size of score difference would represent a meaningful individual benefit.

7. Results Posted in the Registry

• Methylphenidate Group: mean 38.20 versus 43.60 on control; difference -5.40 (95% CI -9.62 to -1.18), standardized effect d = -0.65; z-test p = 0.012.

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.

Mini-mental State Examination (MMSE) at 12 Weeks

• 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:
  • Methylphenidate Group: mean 25.80 versus 23.60 on control; difference 2.20 (95% CI 0.47 to 3.93), standardized effect d = 0.64; z-test p = 0.013.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically higher for Methylphenidate Group than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Clinical Global Impression

• 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:
  • Methylphenidate Group: mean 3.90 versus 4.80 on control; difference -0.90 (95% CI -1.35 to -0.45), standardized effect d = -1.02; z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for Methylphenidate Group than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

The registry record lists the Mini-mental State Examination and Clinical Global Impression as secondary outcomes, both at 12 weeks. Their posted group summaries produce simple unadjusted contrasts that show separation between the groups. The reported direction of each contrast depends on its own scale and coding; the registry record does not provide enough scale interpretation for Clinical Global Impression to assign a clinical meaning to its numeric direction. These outcomes add context, but do not change what the primary AES endpoint measures.

The reported analysis for the Mini-mental State Examination is a Mixed Models Analysis with p =0.01. A sponsor-reported analysis is not listed for Clinical Global Impression, although a simple unadjusted re-calculation is posted. The record does not give model estimates or confidence intervals for the reported secondary model analysis. As with the primary result, the re-calculations and any sponsor model results should be kept distinct.

The overall pattern is that both secondary measures have a posted group contrast, alongside the primary endpoint's group separation. This is not the same as independent confirmation of the primary result: secondary measures may capture different constructs, and their statistical evidence is less secure when multiple outcomes are examined without a reported adjustment for multiple testing. No multiplicity procedure is reported in the registry record. The secondary findings are therefore best treated as additional descriptive evidence, with less weight than the prespecified primary question, rather than as a collection of separate definitive conclusions.

The study's hypotheses also mention instrumental activities of daily living and caregiver burden, but the registry record does not post results for those outcomes. Their status in the analysis plan, whether they were measured, and any results are not reported in the registry record. The posted secondary outcomes should not be taken as substitutes for those stated hypotheses.

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

• Mini-mental State Examination (MMSE) at 12 Weeks
• Clinical Global Impression

9. Statistical Interpretation

10. Statistical Methods Explained

The primary outcome is continuous: it is a scale score summarized by a mean and standard deviation. The posted group summaries are 38.2 with standard deviation 9.1 for methylphenidate, and 43.6 with standard deviation 7.5 for placebo, with 30 participants in each group. A mean difference expresses the separation between the group averages in the scale's original units. The posted re-calculation gives -5.4 for methylphenidate relative to placebo. Because higher AES scores indicate worse apathy, a negative contrast corresponds to a lower average score in the methylphenidate group.

What does an unadjusted comparison represent?

In general, an unadjusted comparison uses the available group summaries without accounting for covariates or repeated measurements in a fitted model. It is straightforward to interpret in the outcome's original units, but it may not reproduce an analysis that uses participant-level observations, baseline values, or correlations across repeated measurements. The registry record identifies the re-calculations as simple unadjusted comparisons and reports a Mixed Models Analysis as the sponsor's method for the primary comparison. The full model specification is not reported in the registry record.

The displayed standard deviations describe the spread of individual scores around each group mean. They are not standard errors of the means and do not directly describe the uncertainty in the group contrast. In general, a standard error quantifies the sampling uncertainty of an estimate; it depends on the spread of outcomes and the amount of information in the groups. The confidence interval for the mean difference expresses a range of values compatible with the estimate under the calculation's assumptions.

Why can a mixed model differ from a summary-statistic calculation?

In general, mixed models can account for correlation among repeated observations from the same participant and can combine information across measurement occasions. Their estimate and uncertainty may depend on the model structure, included observations, covariates, and missing-data assumptions. The registry record gives the method name and a p-value for the primary comparison, but does not report enough details to identify those model choices or reproduce the sponsor estimate. Consequently, the simple re-calculation and the sponsor result need not match. Since the record flags a discrepancy, the sponsor's own analysis takes precedence.

What does the p-value say?

In general, a p-value measures how incompatible the observed data are with a specified null hypothesis under the analysis assumptions. It is not the probability that the null hypothesis is true, nor does it measure the size or importance of an effect. For the primary endpoint, the re-calculated p-value is 0.012, while the sponsor analysis is reported as p <0.05. These values come from different analyses and should not be treated as interchangeable. The sponsor's reported significance statement does not supply an effect estimate or confidence interval in the registry record.

For the primary re-calculation, the standardized effect size is reported as -0.648, based on a pooled standard deviation of 8.338. A standardized effect expresses the mean contrast in standard-deviation units, allowing scale differences to be put on a common statistical scale. It does not establish clinical importance; that requires a meaningful interpretation of the scale and the effect in the intended population. The record does not report a clinical threshold for the AES.

Why does over-dispersion matter in general?

In general, over-dispersion means that the observed variation is greater than a model assumes. When a model understates variation, its standard errors can be too small, making confidence intervals too narrow and p-values too low. Over-dispersion is especially discussed for count data, where a simple probability model may not capture participant-to-participant variability. The primary endpoint in this study is a continuous scale score, and the registry record does not report an over-dispersion assessment. It should not be inferred as a trial-specific issue from the information posted.

The analysis record does not state whether the primary comparison followed an intention-to-treat principle, how missing values were handled, or whether any participants were excluded from the sponsor analysis. Those details matter because an analysis can be influenced by which randomized participants contribute data and by assumptions about unavailable outcomes. The posted group counts are informative, but are not a substitute for a participant flow or a description of the analysis population.

11. Confidence Intervals and Precision

The re-calculated primary mean difference is -5.4, with a 95% confidence interval from -9.62 to -1.18. In general, a confidence interval describes uncertainty around an estimate under the method's assumptions. It is not a guarantee that the true difference falls within the interval, and it does not describe the range of individual participant scores. The interval's endpoints are both below zero, so the re-calculation indicates a difference in the direction of a lower mean AES score in the methylphenidate group.

The interval also makes clear that the estimate is not a single known quantity. A range of mean differences is compatible with the re-calculated data under the interval procedure. Whether any part of that range represents a clinically important difference cannot be determined from the registry record because no threshold for meaningful AES change is reported. The individual score distributions may also overlap even when group means differ; group means and confidence intervals do not describe how many participants had a particular outcome.

These precision statements apply to the simple unadjusted re-calculation. The sponsor's Mixed Models Analysis is reported as p <0.05, without a posted model estimate or confidence interval. The registry record flags a discrepancy, so the sponsor's own analysis takes precedence for the trial's inference. The re-calculated interval should therefore be read as a statistical description of the posted summary statistics, not as the sponsor's model-based uncertainty interval.

The same distinction matters for the secondary outcomes: their simple contrasts have their own uncertainty, but the registry record does not report sponsor model estimates and intervals for all of them. None of the posted intervals can establish clinical importance on its own. Precision concerns the uncertainty of an estimated group difference, while importance concerns what that difference means on the outcome and to the people measured.

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 report participants per arm, not a total number of events. They use the observed effect as a starting point and show planning for 100%, 75%, and 50% of that effect. The assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation; the effect to detect is 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 indicates the number of participants per arm that the planning calculation estimates would be needed to have an 80% chance of detecting the specified effect, if the assumptions hold. The 90% power column gives the corresponding planning count for a 90% chance. These are design-planning quantities, not guarantees: realized power and precision depend on the true effect, variability, analysis, and available outcome data.

Smaller target effects require more participants because a weaker group separation is harder to distinguish from random variation. Thus, planning for 75% or 50% of the observed effect gives larger per-arm counts than planning for the full observed effect. The estimates are illustrations based on observed trial contrasts and do not establish the sample-size rationale used when this trial was designed. They are not observed power.

The assumptions behind these illustrations are not the same as the unknown original planning assumptions. The registry record does not report the trial's original target effect, planned power, or design calculation. Read the displayed participant counts as hypothetical planning guidance under the stated calculation assumptions, rather than as evidence that the completed study was adequately or inadequately sized.

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 = -5.400; pooled standard deviation σ = 8.338.
2. n = 2 × (1.96 + 0.842)² × 8.338² / -5.400² = 37.4, rounded up to 38 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 <- -5.4                      # observed difference in means
sigma <- 8.33846508657319                     # 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(495820)
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 = 38 (80% power), 51 (90% power)
 75% of observed effect: n per arm = 67 (80% power), 90 (90% power)
 50% of observed effect: n per arm = 150 (80% power), 201 (90% power)
power.t.test: 38.4 
Simulated power at n = 38 per arm: 0.791 (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

For the primary outcome, the registry record reports a sponsor analysis using Mixed Models Analysis and gives p <0.05. It does not post the model-based estimate or confidence interval. The simple unadjusted re-calculation from the group summary statistics gives a mean difference of -5.4, a 95% confidence interval from -9.62 to -1.18, and p = 0.012.

These are not two presentations of an identical calculation. A mixed model may use participant-level repeated measurements and model assumptions that are not captured by a calculation from endpoint means and standard deviations. The model specification and analysis details needed to reconstruct the sponsor result are not reported in the registry record. The record explicitly flags a discrepancy between the sponsor analysis and the re-calculation.

Accordingly, the sponsor's own analysis takes precedence when describing the trial's inferential result. The re-calculation remains useful for showing what follows from the posted group summaries, but it should not be used to replace or claim to verify the sponsor's model. Because the sponsor's estimate and interval are absent, the size and precision of its model-based effect cannot be evaluated from the registry record alone.

15. Multiplicity, Missing Data and Analysis Populations

The registry record identifies a primary outcome and two secondary outcomes, but does not report a multiplicity adjustment or a testing hierarchy across outcomes. When several outcomes are examined, each test creates an opportunity for a chance finding. In general, multiplicity procedures control how the overall error rate is interpreted across a family of tests, often by adjusting thresholds or organizing tests in a prespecified sequence. Without a reported approach, the secondary p-values should not be read as if they were the only tests conducted.

The primary endpoint remains the central trial question, but the record does not report whether the primary outcome and analysis were prespecified in a detailed statistical analysis plan or whether any analyses were changed. The registry record also does not report a protocol-level decision rule for interpreting the primary outcome. Such details would help distinguish planned analyses from exploratory analyses.

Missing-data handling is not reported in the registry record. The group results include 30 participants per arm, but that does not establish whether all randomized participants contributed to every endpoint or whether all available repeated measurements were used. The record does not state how missing endpoint values were treated, whether imputation was used, or what assumptions were made about missingness. It does not report a sensitivity analysis for missing data.

The analysis population is also not stated. The record does not specify whether the sponsor analysis included all randomized participants, only participants with observed outcomes, or another population. It does not report participant flow, exclusions, or protocol deviations relevant to the analysis. Without that information, the relationship between randomization and the analyzed groups cannot be fully assessed.

These omissions do not establish that a particular method was absent from the study; they mean the method is not reported in the registry record. They limit independent evaluation of the robustness of the sponsor analysis, especially alongside the noted discrepancy between that analysis and the summary-statistic re-calculation.

16. Safety Results

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

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 3% reporting threshold.

Most frequent non-serious adverse event terms

The registry record lists zero serious adverse events among 30 participants at risk in the methylphenidate group and zero among 30 participants at risk in the placebo group. It lists other adverse events for 14 participants in the methylphenidate group and 16 in the placebo group, each with 30 at risk. These are counts of participants affected, not descriptions of event severity or duration beyond the serious-versus-other categories used in the record.

No serious adverse event terms are listed. Death counts are not reported in the registry record. The record does not provide event-level descriptions for the other adverse events, their timing, relationship to treatment, or the criteria used to classify them. It also does not provide enough detail to evaluate whether participants had multiple events or how event collection was conducted.

These figures should be read as the safety counts posted for the study, not as proof that serious events could not occur or as a complete assessment of risk. The registry record's limited event detail means the counts cannot characterize the nature or clinical importance of individual events.

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

The primary endpoint results describe lower average AES scores at 12 weeks in the methylphenidate group than in the placebo group, with the scale definition indicating that higher scores represent worsening apathy. The sponsor's mixed-model analysis is reported as p <0.05, while the simple unadjusted re-calculation gives a mean difference of -5.4 with a 95% confidence interval from -9.62 to -1.18. Because the registry record flags a discrepancy, the sponsor's own analysis takes precedence for the trial's inference.

The numerical result does not by itself establish how much difference matters to participants, caregivers, or clinicians. The registry record does not report a threshold for a clinically meaningful AES difference, responder criteria, or participant-level change distributions. It also does not provide baseline AES summaries in the posted outcome information. The endpoint summaries therefore describe a group contrast at follow-up rather than a complete account of individual change.

The findings do not establish that every participant in one group had a better outcome than every participant in the other. Group means can differ while individual scores overlap. Nor do the registry results establish a lasting effect beyond the reported 12-week endpoint. Longer-term outcomes are not reported in the registry record.

The two secondary outcomes provide additional measures but do not answer the same question as the primary apathy scale. Their results should be interpreted cautiously because multiplicity handling is not reported and their clinical scale directions are not fully described in the registry record. The stated hypotheses about instrumental activities of daily living and caregiver burden are not accompanied by posted results.

Overall, the registry record supports a carefully bounded statistical description: the reported primary group summaries differ in the direction of lower apathy scores in the methylphenidate group, and the sponsor reports a statistically significant mixed-model comparison. The information posted does not establish clinical importance, explain the discrepancy with the simple re-calculation, or support conclusions about outcomes and populations not reported.

18. Why This Trial Matters Statistically

This trial illustrates why statistical interpretation should keep the outcome definition, analysis method, and reporting completeness connected. The primary AES is directly targeted to apathy, and its scoring direction makes the sign of the group difference interpretable. At the same time, a mean difference is not self-interpreting: clinical importance requires a meaningful scale threshold or other context, which the registry record does not provide.

It also demonstrates the distinction between a sponsor's model-based result and a simple re-calculation from summary statistics. The posted means and standard deviations permit a transparent unadjusted comparison, while the sponsor reports a mixed-model p-value. Since those results are flagged as discrepant and the model estimate is not posted, readers need to avoid treating the re-calculation as a reconstruction of the sponsor's analysis. The sponsor analysis takes precedence for the trial's own inferential result, but the missing estimate and interval limit assessment of its size and precision.

The study's small posted group counts make clear why effect estimates and uncertainty matter alongside p-values. A significance statement does not communicate clinical meaning, and a planning illustration based on the observed effect does not establish the original study's design rationale. The record also illustrates how the absence of multiplicity details, missing-data methods, and analysis-population information affects the strength of conclusions that can be drawn from secondary outcomes.

Finally, registry reporting is not only a list of endpoint values. Information about the model, participant flow, missing outcomes, clinically meaningful thresholds, and the stated functional hypotheses would help readers judge how robustly statistical findings connect to the study's broader clinical question.

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.

Several limitations are specific to the information reported for this trial. The primary outcome results are presented at 12 weeks, and later outcome results are not reported in the registry record. The record gives no baseline AES summaries, so endpoint values cannot be compared with baseline values using the posted information. It also does not report a threshold for clinically meaningful AES change or a responder definition, limiting interpretation of the difference's practical importance.

The trial enrolled 60 participants, with 30 reported in each group. This is the posted study size, but the registry record does not provide the original sample-size justification, target effect, or planned power. The planning illustrations based on observed effects do not fill that gap. The record also lacks participant flow and does not specify whether every randomized participant contributed to each outcome analysis.

The sponsor's primary analysis is identified as a Mixed Models Analysis, but its model specification, estimate, and confidence interval are not reported. The simple unadjusted re-calculation differs from the sponsor analysis, and the record flags that discrepancy. Without further model details, the sponsor result cannot be independently reconstructed from the registry record.

Additional reporting gaps include the treatment dose and schedule, eligibility criteria, baseline participant characteristics, the analysis population, missing-data procedures, multiplicity handling, and the masking roles. The registry record mentions hypotheses about instrumental activities of daily living and caregiver burden but does not post results for them. Death counts and detailed adverse-event descriptions are also not reported. These gaps constrain interpretation; they do not establish that the study did not collect or analyze the information.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Methylphenidate for Apathy in Alzheimer's Dementia: A Controlled Study — NCT00495820.
• Registry record last updated 2015-11-20; status last verified 2015-10.
• Results first posted 2015-11-20.
• 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

NCT00495820 is a completed phase 4 randomized, triple-masked, parallel-group study sponsored by the VA Office of Research and Development. It enrolled 60 participants to compare methylphenidate with placebo for apathy in Alzheimer's dementia, with 30 participants reported in each group. The primary outcome was the Apathy Evaluation Scale score at 12 weeks.

The posted primary group means were 38.2 for methylphenidate and 43.6 for placebo. The sponsor reports a Mixed Models Analysis with p <0.05. A simple unadjusted re-calculation gives a mean difference of -5.4, with a 95% confidence interval from -9.62 to -1.18; the registry record flags a discrepancy, so the sponsor's own analysis takes precedence. Two secondary outcomes are listed, while results for the stated hypotheses about instrumental activities of daily living and caregiver burden are not reported in the registry record.

The record lists zero serious adverse events in both groups and other adverse events affecting 14 participants in the methylphenidate group and 16 in the placebo group. More detailed safety information, analysis methods, and missing-data handling are not reported in the registry record.