Assessing the Impact of Calcium Channel Blockers on COGnitive Function in the Very Elderly (AI-COG): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Assessing the Impact of Calcium Channel Blockers on COGnitive Function in the Very Elderly (AI-COG) (NCT01868165), a registered phase not stated study. The primary outcome is Change in Cognitive Function as Measured Using the Extended Mini Mental State Exam.

2. Clinical Question

The clinical motivation recorded for AI-COG is that high blood pressure and cognitive decline are concerns in older adults, while the effect of calcium channel blockers on cognitive function in those aged 80 and over is described as unclear. The study therefore focuses on an association in this age group. Because allocation is not stated and the record explicitly says this is not a randomized comparison, the question is not equivalent to asking what would happen if otherwise similar participants were assigned to different drugs. Differences between people taking different antihypertensives could also be relevant to interpretation, but the registry record does not describe how such differences were handled.

3. Trial Design

AI-COG is registered as completed, with Imperial College London listed as sponsor. The registry records enrollment of 337 and describes a cohort of adults aged 80 and over treated with antihypertensive drugs. The study start is listed as 2013-06 and primary completion as 2015-02. The primary outcome timeframe is 12 months.

The record describes regression analysis of change in cognitive function, with results intended for participants taking calcium channel blocker antihypertensives over follow-up. This is not presented as a randomized trial: allocation is not stated, and the registry warns that the arms are not a like-for-like control comparison. The record does not give a detailed description of how participants entered particular medication groups, whether medication use changed during follow-up, or how a comparator was defined.

These design details matter because a regression association in a cohort has a different interpretation from a randomized contrast. In a randomized comparison, allocation is intended to make treatment groups comparable on average. In this record, no such assignment is reported. Regression can account for measured variables included in a model, but it cannot by itself ensure comparability or eliminate the influence of unmeasured differences.

The registry lists one primary outcome measure and one analysis. It does not report a detailed protocol, model specification, covariates, treatment-group sizes, recruitment procedures, or the statistical analysis plan. It also does not provide the primary outcome estimate. The completion status and enrollment entry describe the registry record, but they do not establish how many participants contributed usable cognitive assessments to the 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.

Before assignment: Participants had hypertension and treatment with antihypertensives.The study examined the cognitive change in older adults taking antihypertensives with a particular focus on Calcium Channel Blockers (CCB). Cognitive function was tested at 0 \& 12 months. Participation in the study had no impact on treatment.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Regression analysis examining change in cognitive function in older adults taking antihypertensives, results are reported for those taking calcium channel blocker antihypertensives over one year of follow up.

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 Cognitive Function as Measured Using the Extended Mini Mental State Exam, measured over 12 months.

The primary endpoint is change in cognitive function measured using the extended Mini Mental State Exam, with change expressed on a scale. The registry describes the exam as an extended screening test that assesses several areas of cognitive function. Scores range from 0 to 100, with higher scores indicating better performance; people without cognitive impairment would be expected to score close to the maximum. The stated assessment period is 12 months.

A change score is intended to describe how a participant's measured performance differs over follow-up, rather than only describing performance at a single assessment. Comparing changes can be useful when the question concerns whether cognitive performance changes over time in relation to medication exposure. The measure is a screening assessment, however, and the registry does not describe it as a diagnostic determination of dementia or another condition.

The record specifies that the outcome is a mean of a continuous measure and that the reported dispersion is a 95% confidence interval. A mean gives an average change across the analyzed observations; it does not describe every participant's experience. The confidence interval is intended to express uncertainty around that estimated mean. Although the measure and reporting format are described, the actual mean change and confidence interval are not reported in the registry record. Consequently, the direction, size, and precision of the primary outcome cannot be read from the posted results.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a mean change represent?

The registry classifies the primary outcome as a mean of a continuous measure. In general, a mean change is calculated by measuring an outcome at more than one time and averaging the within-person changes among the observations included in an analysis. It summarizes the center of the measured changes, not the full spread of individual responses. A group mean can therefore coexist with substantial variation between participants.

For AI-COG, the measure is the extended Mini Mental State Exam, and the reported unit is change on a scale. The registry says higher scores are better and gives the scale range as 0 to 100. The primary timeframe is 12 months. These details define what an estimate would mean, but the mean change itself is not reported in the registry record.

How should a confidence interval be read?

In general, a confidence interval describes statistical uncertainty around an estimate. A narrower interval indicates greater precision under the analysis assumptions, while a wider interval indicates less precision. It is not a range that contains every participant's change, and it does not show the distribution of individual scores. The registry specifies a 95% confidence interval for the primary outcome but does not report its endpoints. Its precision and compatibility with different possible mean changes therefore cannot be assessed from the posted results.

What does regression contribute?

The registry says the primary analysis is a regression analysis examining change in cognitive function among older adults taking antihypertensives, with results reported for those taking calcium channel blocker antihypertensives. In general, regression relates an outcome to one or more explanatory variables and can adjust an estimate for variables included in the model. The registry does not state which variables were included, how they were selected, what model form was used, or how assumptions were assessed. It is therefore not possible to evaluate the adjustment strategy from the record.

Regression does not automatically make groups comparable. In a nonrandomized cohort, medication use is not assigned by chance according to the registry description. Measured factors included in a model may be accounted for, but unmeasured or poorly measured factors can still affect an association. The record itself cautions that the arms are not a like-for-like control comparison. This limits causal interpretation regardless of the statistical method.

Why does the outcome scale matter?

In general, a continuous score preserves more gradation than reducing performance to a simple category. The extended Mini Mental State Exam is described as a screening test covering several areas of cognitive function. A score change can summarize measured performance over time, but interpretation depends on the measurement properties and context. The registry does not report a threshold for meaningful change, a minimal important difference, or a separate clinical interpretation rule. The score should therefore be read as a measured scale outcome, not as a direct diagnosis.

The registry's description says that people without cognitive impairment would be expected to score close to the maximum. This is context for the scale, not a result for the study participants. The record does not report their baseline score distribution or the observed follow-up scores. Without these, the amount of room for scores to rise or the pattern of starting performance cannot be assessed.

What can planning illustrations tell readers?

In general, sample-size planning asks how many participants per arm would be needed under specified assumptions to detect a chosen effect with a chosen power. Such calculations depend on assumptions about the target effect, variability, allocation, and statistical test. They are planning illustrations, not evidence about the power achieved by an already completed study and not a description of the observed result.

The registry's planning assumptions describe a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and effects expressed as fractions of the observed effect. However, the posted registry record does not report the primary observed effect needed to interpret those illustrations. In addition, the study description does not identify a randomized, like-for-like two-arm comparison. A planning calculation based on equal allocation should not be mistaken for the study's actual allocation or analysis design.

Overall, the methods information identifies the outcome type, measure, timeframe, and broad analysis approach. It does not supply the model details or numerical estimate needed for a full statistical appraisal. General explanations of means, confidence intervals, and regression clarify how such results would ordinarily be read, but they cannot replace the missing result and analysis details.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists one primary outcome measure and one analysis. That is useful scope information, but it does not establish that no other outcomes, models, subgroup analyses, or statistical tests were considered. A multiplicity plan describing whether and how multiple comparisons were handled is not reported in the registry record.

In general, testing many hypotheses can increase the chance of obtaining at least one apparently notable result by chance. Prespecifying a primary outcome and analysis can help readers distinguish the principal question from exploratory work. The registry identifies a primary cognitive outcome, but it does not provide enough detail to determine whether the reported analysis followed a prespecified plan or whether adjustment for multiplicity was used.

Missing-data handling is not reported in the registry record. The record does not state how many participants had cognitive assessments available at each time, how incomplete follow-up was treated, whether any values were imputed, or whether sensitivity analyses were performed. These details matter because an analysis based only on participants with observed measurements may differ from one that accounts for missing outcomes under explicit assumptions.

The analysis population is also not described in detail. The enrollment entry is 337, but that does not establish the number included in the cognitive analysis. The registry does not give an analysis denominator or describe exclusions from the outcome model. As a result, readers cannot assess the extent to which the analyzed participants represent everyone enrolled or determine how missing observations may have influenced the estimate.

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 registry's serious-adverse-event record lists the Older Adult Cohort with 292 at risk and 0 affected by a serious adverse event. It also lists 292 at risk and 0 affected for other adverse events, and records 0 deaths. No top serious-event terms are listed. These are the counts recorded in the registry, not a comparison between randomized treatment groups.

The denominator of 292 is the safety denominator in this record; it should not be assumed to be the enrollment count or the number included in the cognitive analysis. The registry does not explain the relationship between that safety denominator and the enrollment entry of 337.

Zero recorded events does not establish that an event was impossible or that there was no risk. It means that the registry reports no affected participants for the listed category in the stated safety record. The registry does not describe the event-collection methods, the observation period for safety outcomes, or whether adverse events were collected and attributed by medication group. Without those details, these counts should be read narrowly as registry entries rather than as evidence of comparative safety.

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

AI-COG asks about change in cognitive function among adults aged 80 and over who take antihypertensive drugs, with a particular focus on calcium channel blocker use. Its primary measure is change in the extended Mini Mental State Exam over 12 months. The registry describes the outcome and a regression analysis, but it does not report the estimated mean change or its 95% confidence interval. The posted record therefore does not show the direction, magnitude, or precision of the cognitive result.

The study is not described as a randomized comparison. Allocation is not stated, and the registry cautions that the arms are not a like-for-like control comparison. If an association were available, it would need to be interpreted in light of possible differences between people taking different antihypertensives. Regression may adjust for variables included in its model, but model details are not reported and adjustment cannot establish that all relevant differences have been accounted for.

The record also does not report the number included in the cognitive analysis, missing-data methods, or the analysis population. This prevents assessment of how complete follow-up was and how closely the analyzed participants correspond to those enrolled. The safety counts are reported separately and should not be used as a substitute for cognitive analysis denominators.

Accordingly, the registry record establishes that a cohort study was completed and specifies the intended cognitive outcome and broad analysis focus. It does not, in the posted information, establish whether cognitive scores changed in a particular direction or whether calcium channel blocker use was associated with a particular amount of change. Nor can the record support a causal conclusion about medication effects. The absence of a posted estimate is a limit on what can be concluded from this registry entry, not evidence that the study found no change.

13. Why This Trial Matters Statistically

This study raises a statistical question where outcome measurement and design interpretation need to be kept distinct. The extended Mini Mental State Exam provides a continuous score, and the registry defines change over 12 months as the primary outcome. A continuous outcome can describe average movement in measured performance, while its confidence interval conveys uncertainty. But those summaries are useful only when the numerical estimate and its uncertainty are available; neither is reported in the registry record.

AI-COG also illustrates why a regression result from a cohort should not automatically be read as a treatment effect. The registry explicitly notes that the comparison is not randomized and that the arms are not like-for-like controls. Statistical adjustment can address measured variables in a model, but the record does not identify the model variables or establish that all relevant differences were measured. The design and model details are therefore central to how any association should be interpreted.

Another important issue is the connection between enrollment, outcome follow-up, and analysis. The registry records enrollment of 337 and a safety denominator of 292, but it does not report the cognitive analysis denominator or missing-data approach. Without a flow account, readers cannot assess which participants contributed to the primary outcome or whether incomplete measurements could affect the estimate.

Finally, a registry can define a question and outcome without making the numerical result available. This record identifies its cognitive measure, timeframe, outcome type, and broad method, but does not post the mean change or confidence interval. That distinction is statistically important: a completed study and a specified endpoint do not, on their own, communicate the result or its precision.

14. Limitations

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

The primary limitation of the registry record for interpreting the main question is that it does not report the numerical cognitive outcome. The mean change and 95% confidence interval are absent, so neither the estimated direction nor the magnitude or precision can be assessed. The record also does not provide baseline or follow-up score summaries.

The comparison is nonrandomized according to the registry, and the record warns that the arms are not a like-for-like control comparison. It does not explain how medication groups were defined, how participants came to take particular antihypertensives, or whether medication use changed during follow-up. These omissions limit the ability to interpret an association as attributable to calcium channel blocker use.

Further analysis details are not reported in the registry record. These include the regression model specification, adjustment variables, assumptions, missing-data procedures, and analysis population. The record does not give the cognitive outcome denominator or a participant flow description. The relationship between enrollment and the safety denominator is not explained.

The endpoint is a screening measure of cognitive function, and the registry does not provide a threshold for clinically meaningful change or describe how score changes should be interpreted for individual participants. It also does not report a detailed multiplicity plan or whether analyses beyond the listed primary analysis were conducted. These limitations apply to interpretation of the posted registry record; they do not establish what may be available in other study materials.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Assessing the Impact of Calcium Channel Blockers on COGnitive Function in the Very Elderly (AI-COG) — NCT01868165.
• Registry record last updated 2019-09-23; status last verified 2019-08.
• Results first posted 2019-09-23.
• 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.

18. Record Summary

AI-COG (NCT01868165) is listed as completed and sponsored by Imperial College London. The registry records enrollment of 337, a study start of 2013-06, and primary completion in 2015-02. The study concerns adults aged 80 and over treated with antihypertensive drugs, with a particular focus on calcium channel blocker use.

The primary outcome is mean change in the extended Mini Mental State Exam over 12 months, reported with a 95% confidence interval. The registry describes a regression analysis and states that the study is not a randomized, like-for-like comparison. The primary mean change and confidence interval are not reported in the registry record. The record lists 292 at risk and 0 affected for serious adverse events, 292 at risk and 0 affected for other adverse events, and 0 deaths.