Combined tDCS and Cognitive Training in Alzheimer's: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Combined tDCS and Cognitive Training in Alzheimer's (NCT06861231), a randomized na study. The primary outcome is Mini-Mental State Examination (MMSE) Scores at Baseline, Post-intervention, and Follow up.

2. Clinical Question

The central comparison is whether adding active stimulation to cognitive training is associated with a different pattern of global cognitive-function scores than adding sham stimulation to cognitive training. Because both groups receive cognitive training, the comparison concerns the two combined approaches; it does not compare cognitive training with no training. The registry summary describes an expectation of improvement in both groups and a greater post-treatment improvement in the active-stimulation group, with gains expected to persist at follow-up. These statements are the study’s hypothesis, not reported findings.

The record lists an enrollment of 22 and describes a randomized, parallel-group study. The primary measure is the MMSE, collected at baseline, immediately after the intervention, and at follow-up. The endpoint description places post-intervention assessment at 2 weeks and follow-up at 6 weeks, four weeks after the post-intervention assessment. The brief summary instead describes follow-up as one month later. These timing descriptions are not fully aligned, so the endpoint-specific schedule is best read as the stated schedule for the primary measure.

No numerical MMSE results, group means, changes, uncertainty intervals, or inferential tests are reported in the registry record. Consequently, the registry does not establish whether the groups differed, how large any difference was, or how precisely it was estimated.

3. Trial Design

The registry describes a randomized, parallel-group trial with two groups. One group receives active tDCS together with cognitive training; the other receives sham tDCS together with cognitive training. The listed allocation is randomized, and the model is parallel. The record lists an enrollment of 22, and the study status is completed. The recorded start date is 2024-10-04, and the primary completion date is 2026-03-14.

The active-stimulation description specifies a constant current of 2 mA, delivered for 20 minutes daily for 10 days, with an initial and final ramp of 30 seconds. The sham description says that current is applied only during the initial and final ramps, intended to create the sensation of active stimulation. Cognitive training is included in both groups. The registry summary calls the design single-blind, while the masking entry says double. The record therefore contains conflicting masking descriptions, and it does not resolve which description is correct or identify who was masked.

The primary outcome is MMSE score at baseline, immediately post-intervention, and follow-up. The endpoint description specifies post-intervention at 2 weeks and follow-up at 6 weeks, while the brief summary describes a follow-up one month later. Secondary outcomes listed are WAIS-III digit scores and TAVEC memory scores, each assessed at baseline, post-intervention, and follow-up. The registry identifies five outcome measures, but the record does not give numerical results for them.

The trial’s phase is recorded as NA. The registry record does not report a statistical analysis plan, a sample-size justification, allocation-concealment procedures, or detailed participant eligibility criteria. The absence of these details limits assessment of how the planned design was implemented and how the reported outcomes, if available elsewhere, should be interpreted.

4. Participant Flow and Accounting

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

Overall Study

5. Baseline Characteristics

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

6. Primary Endpoint

The registry lists the primary outcome as Mini-Mental State Examination (MMSE) Scores at Baseline, Post-intervention, and Follow up, measured over Baseline, immediately post-intervention at 2 weeks, and follow-up at 6 weeks (4 weeks after post-intervention assessment).

The primary endpoint is the Mini-Mental State Examination (MMSE), used as an index of global cognitive functioning. The registry describes scores as ranging from 0 to 30, with higher scores indicating lower cognitive impairment and a better outcome. It also states that scores equal to or below 23 are considered cognitively impaired. The measure is intended to estimate the existence and severity of cognitive impairment.

Assessments are specified at baseline, immediately post-intervention at 2 weeks, and follow-up at 6 weeks, four weeks after the post-intervention assessment. The endpoint description says that post-intervention minus baseline difference scores were calculated. Positive differences indicate improvement, and the possible range of those difference scores is -30 to 30. The registry summary separately describes follow-up one month later, so readers should note that the timing language is not entirely consistent.

Repeated assessment allows the study to describe scores over time and compare the change patterns between active and sham stimulation when both are paired with cognitive training. A baseline-to-post-intervention change addresses short-term score movement; follow-up can describe whether scores are maintained or change after treatment ends. These are distinct questions, and a comparison at one time point does not by itself establish a lasting pattern.

No group-level MMSE means, standard deviations, change estimates, confidence intervals, or test results are reported in the registry record. The endpoint’s scale and assessment schedule are described, but the numerical outcome evidence needed to judge the size and precision of any group difference is not reported.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a continuous primary outcome summarized as a mean with standard deviation. This is appropriate as a way to describe the center and spread of a numerical score, but those summary statistics alone would not answer whether the active and sham groups differed. To interpret the comparison, readers would need the observed values or change estimates for each group, together with an estimate of uncertainty. Those results are not reported in the registry record.

What does a mean and standard deviation tell a reader?

In general, a mean describes the average score in a group. A standard deviation describes how much individual scores vary around that average. Neither statistic alone indicates how precisely a group average is estimated, and neither establishes whether two groups differ. Precision also depends on the amount of information available and on the variability in the data. Since the registry does not report MMSE group means or standard deviations, these features of the observed outcome cannot be assessed.

Why distinguish change within groups from a comparison between groups?

The endpoint description specifies post-intervention minus baseline change scores, where a positive value represents improvement. In general, within-group change describes how a group’s scores shifted over time. A treatment comparison asks whether the shifts differ between groups, or whether group scores differ at a specified assessment under an appropriate analysis. A change in one group is not, by itself, evidence that its change differs from the other group. Because both groups receive cognitive training, any between-group contrast concerns active versus sham stimulation in the context of that shared training.

The repeated assessments also raise a choice about how to represent time. An analysis might compare groups at a particular follow-up, compare changes from baseline, or model the pattern across all visits. These approaches answer related but not identical questions. The registry record does not report which inferential approach was planned or used, and it lists no analyses. No method should therefore be attributed to the investigators beyond the stated calculation of post-intervention minus baseline difference scores.

How should confidence intervals and p-values be understood?

In general, a confidence interval describes uncertainty around an estimated quantity, such as a difference in average change between groups. Its width communicates precision: a wider interval indicates greater uncertainty than a narrower interval. A p-value, when calculated under a specified statistical model, describes how compatible the observed data are with a stated null hypothesis. It does not measure the probability that a treatment works, nor does it convey the size or practical importance of a difference. Neither confidence intervals nor p-values for the primary outcome are reported in the registry record, so statistical significance and precision cannot be evaluated.

Why can over-dispersion matter?

In general, over-dispersion arises when the observed variability in data is greater than a statistical model expects. If an analysis assumes less variation than is present, its uncertainty estimates can be too small and its tests can appear more decisive than warranted. The MMSE endpoint is described as continuous, and the record does not report a model or evidence of over-dispersion. This concept is relevant as a general modeling consideration, not as a claim about this trial’s data.

What does the planning illustration mean?

The registry describes planning illustrations based on a fraction of the observed effect, using a two-sided significance level of 0.05, equal allocation, and a normal approximation. Such calculations are prospective planning aids: they illustrate how a hypothetical effect size and assumptions relate to a required sample size. They do not show the probability that this completed trial detected an effect, and they are not observed power. The registry record does not report the observed effect values or the numerical planning results. It also says these calculations are not the trial’s own design justification. No inference about the original sample-size rationale or the study’s power can be made from the record.

More generally, a statistical analysis needs to account for the outcome scale, the repeated observations, the intended comparison, and the handling of incomplete measurements. It should also identify the population included in each analysis and the assumptions used for uncertainty estimates. These details are not reported in the registry record. The available information supports a description of the outcome definition and the planned assessment times, but not a reconstruction of the inferential analysis.

10. Multiplicity, Missing Data and Analysis Populations

The primary outcome is measured at baseline, post-intervention, and follow-up, and the registry also lists secondary cognitive outcomes. Multiple outcomes and assessment times can create multiple opportunities to test hypotheses. In general, when many comparisons are examined, the chance of at least one apparently unusual result may increase unless the analysis plan accounts for the multiplicity or clearly identifies which comparisons are confirmatory. The registry record does not report a multiplicity strategy, a hierarchy of outcomes, or a prespecified primary contrast across the repeated assessments.

The primary outcome is described through several time points, and the record indicates that it was not reduced to a single comparison. No numerical analysis results are listed. The record does not say whether the investigators planned to compare post-intervention change, follow-up change, scores at each visit, or an overall trajectory. It also does not report whether secondary outcomes were intended as confirmatory or exploratory. These omissions prevent assessment of how the number of possible comparisons was handled.

Missing-data methods and analysis populations are also not reported in the registry record. There is no description of how incomplete assessments, withdrawals, or other unavailable measurements were handled, and no stated intention-to-treat, per-protocol, or other analysis population. The enrollment listing does not establish how many people contributed data to each outcome or assessment. Without those details, readers cannot assess whether exclusions or missing measurements might have affected the estimates.

In general, transparent reporting would identify the analyzed population, the amount and pattern of missing data, the method used to address missingness, and the prespecified comparisons. None of those details can be inferred from the completed status or the outcome schedule. The registry record therefore does not permit evaluation of multiplicity control, missing-data bias, or the relationship between the planned and analyzed populations.

11. Safety Results

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

Deaths

Other (non-serious) adverse events

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

The adverse-event information lists 0 serious adverse events in the active tDCS and cognitive-training group, among 11 participants at risk. It lists 0 serious adverse events in the sham tDCS and cognitive-training group, among 9 participants at risk. Deaths are listed as 0 in both groups. Other adverse events are also listed as 0 in both groups, using the same respective numbers at risk.

These are registry-record counts, not evidence that an adverse event is impossible or that no event could occur outside the recorded observation and reporting process. A zero count means that the registry lists no events of that category for the group; it does not quantify the uncertainty around the underlying risk. The record does not provide further information about event definitions, surveillance procedures, duration of safety observation, or whether all participants contributed safety data.

The listed participants at risk are safety denominators, and they should not be treated as the number assessed for the MMSE endpoint. The registry lists an enrollment of 22, but the safety groups have their own reported denominators. The record does not explain the relationship between those figures, so no reconciliation should be assumed. These safety counts also do not establish a comparative safety profile: the registry provides no inferential comparison or detailed event descriptions.

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

The registry record is useful for understanding the trial question: active tDCS plus cognitive training is compared with sham tDCS plus cognitive training, with MMSE scores assessed over time. It also identifies the expected direction of benefit as a hypothesis and describes the intervention and outcome schedule. Those details clarify what the researchers set out to investigate, but they do not show what the study found.

The record lists the study as completed, yet it does not report numerical primary-outcome results or statistical analyses. Completion should not be interpreted as evidence of a positive, negative, or conclusive result. Without group scores, changes, between-group estimates, or uncertainty intervals, the size and precision of any observed difference are unknown from the registry record. The stated hypothesis cannot fill that evidentiary gap.

The comparison is specifically active stimulation against sham stimulation when both are paired with cognitive training. It does not isolate the effect of cognitive training, because there is no training-free group described. Nor does the record report whether participants or assessors were masked consistently: one registry description says single-blind and another says double. This conflict limits interpretation of the intended protection against expectation or assessment effects.

The endpoint schedule contains a further ambiguity. The primary-outcome description gives follow-up at 6 weeks, four weeks after post-intervention assessment at 2 weeks, while the brief summary says follow-up one month later. The record does not clarify the discrepancy. The outcome timing should therefore be understood from the particular description being cited, rather than treated as an unambiguous schedule across all registry text.

The planning illustrations are not observed power and are not the trial’s stated design justification. They cannot establish that the study was adequately sized or that a nonsignificant result would indicate no effect. In general, estimates should be considered alongside their precision, study conduct, missing data, and analysis choices. Those details are not reported in the registry record. The most defensible conclusion is limited: the record documents a randomized completed study and its intended comparison, but does not report the outcome evidence needed to judge the primary question.

13. Why This Trial Matters Statistically

This trial is statistically interesting because it tests an add-on contrast. Both groups receive cognitive training, while the stimulation component differs between active and sham conditions. That design focuses the comparison on whether the active stimulation condition is associated with a different outcome pattern in the context of shared training. It avoids treating improvement within either group as the central contrast, which is important when both groups receive an intervention that may influence scores.

The repeated MMSE assessments make time part of the research question. Immediate post-intervention scores address short-term change, while follow-up is intended to describe whether the pattern persists or shifts after treatment. These assessments can support different estimands, such as change from baseline or a between-group difference at a particular visit. The registry defines the time points but does not report which comparison was selected for inference or provide estimates.

The record also illustrates why outcomes, analysis plans, and numerical results need to be reported together. A defined scale and schedule do not establish the size or precision of a group difference. Without effect estimates and uncertainty, readers cannot distinguish a small, imprecise difference from a larger, more precise one. The absence of an analysis description further limits assessment of repeated measurements, missing data, and multiplicity.

Finally, the inconsistent masking descriptions and follow-up wording are relevant to interpretation even though they do not determine the outcome. Clear reporting would make it easier to understand who was masked, when measurements occurred, and which analyses address the trial’s main question. The registry record establishes a meaningful randomized comparison and an outcome framework, but its statistical contribution cannot be evaluated fully without reported estimates and methods.

14. Limitations

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

A central limitation of the available record is the absence of numerical primary-outcome findings. Although the study status is completed and the MMSE is identified as the primary outcome, the registry record does not report group means, standard deviations, changes, comparative estimates, confidence intervals, or p-values. The analysis count is 0. As a result, the principal question cannot be answered from the posted results.

Several design and reporting details are unclear. The registry’s masking information says double, while the brief summary calls the study single-blind. The record does not resolve the discrepancy or specify who was masked. Follow-up is described as one month later in the summary and as 6 weeks in the primary endpoint description. These differences make the exact assessment schedule and masking arrangement uncertain.

The registry does not report a statistical analysis plan, sample-size justification, handling of missing data, or analysis populations. It does not give detailed eligibility criteria or explain how the safety denominators relate to the enrollment listing. The planning information describes illustrative calculations based on an observed effect, but does not report the numerical effect or planning results; it also states that these calculations are not the trial’s own design justification. Thus, the record does not support evaluation of the original design rationale or the precision that was anticipated.

The study compares active with sham stimulation while cognitive training is present in both groups. Consequently, the described design does not estimate cognitive training against no training. The record also lists secondary outcomes but does not report their findings or explain how multiple outcomes and time points were handled. These limitations concern the registry information available for interpretation; they should not be taken as claims about unreported study procedures.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Combined tDCS and Cognitive Training in Alzheimer's — NCT06861231.
• Registry record last updated 2026-06-16; status last verified 2026-04.
• Results first posted 2026-06-16.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

18. Record Summary

The registry record describes a randomized, parallel-group study of active or sham tDCS, with cognitive training in both groups, in people with mild cognitive impairment due to Alzheimer’s disease. It lists enrollment of 22, status completed, and the primary outcome as MMSE scores at baseline, post-intervention, and follow-up. The study’s hypothesis anticipates greater improvement with active stimulation, but this is not an observed result.

The registry lists 0 serious adverse events, 0 other adverse events, and 0 deaths in each safety group, with 11 participants at risk in the active group and 9 in the sham group. The masking description and follow-up timing are inconsistent across registry text. Numerical primary-outcome findings, inferential analyses, a missing-data approach, and an analysis plan are not reported in the registry record. Accordingly, the posted information describes the design and measurement framework but does not establish the direction, size, or precision of the primary outcome comparison.