Every row of the evidence table

Antihypertensive treatment improved cognitive scores by a small amount (SMD 0.06, moderate certainty) but the reduction in dementia incidence was not statistically significant (OR 0.89, low certainty). The drug-class rankings rest on one trial per class and are described as highly uncertain.

Significant for MCI and for the MCI-or-dementia composite; not significant for probable dementia alone (HR 0.86, 95% CI 0.72-1.02).

A large drop in blood pressure (22/9 mmHg) and fewer serious adverse events in the intervention villages.

Antihypertensive use tracked lower Alzheimer's risk but not lower non-Alzheimer dementia risk, where treated and untreated hypertension looked the same. A single baseline blood pressure reading predicted neither.

Individual participant data from five double-blind placebo-controlled trials, which is the strongest design in this table for this exposure.

Consistent across 14 trials (I-squared 0%) but small in absolute terms: 0.39 percentage points over about 4 years.

The authors state the data are compatible with anything from a 39% decrease to a 5% increase in risk, against DPP-4 inhibitors rather than no treatment.

For GLP-1 receptor agonists specifically: HR 0.95 (95% CI 0.87-1.04) against DPP4 inhibitors in the intention-to-treat analysis. Only the continuous-use analysis reached significance (HR 0.79).

Seven separate comparisons against seven other antidiabetic drugs, so the comparator is always another drug rather than no treatment.

Heterogeneity was near-total (I-squared 98.9%) and the estimate went to null in people newly diagnosed with diabetes (HR 1.01), which is where prevalent-user bias would be smallest.

Designed around new diabetes diagnoses with a landmark analysis and a one-year lag, which removes the prevalent-user advantage that inflates metformin's apparent benefit in the pooled cohorts.

Comparator is other oral antidiabetic drugs, not no treatment.

The split inside this one paper is the finding: the 41 observational studies show large benefits (SGLT2i OR 0.56, GLP-1RA OR 0.58) while the 23 randomised trials show no difference. When design and result disagree this cleanly, the trials are the ones to believe.

The exposure actually studied is STOPPING metformin early, which carried 21% higher dementia incidence than staying on it. Read as indirect support for metformin, not as a trial of it.

For SGLT2 inhibitors specifically: HR 0.86 (95% CI 0.79-0.94) against DPP4 inhibitors, and HR 0.70 in the as-treated analysis.

After the first year the data rule out more than a 3% change either way. Diagnoses were 46% higher in the first year, which the authors attribute to people being seen more often just after starting a statin. This sits against the Chicago cohort, which found benefit in APOE4 carriers.

Benefit was confined to APOE4 carriers (HR 0.60) and absent in non-carriers (HR 0.96). Observational, and it disagrees with the larger target-trial emulation that found nothing.