Antihypertensive Drug Therapy and Risk of Dementia: Real-World Evidence From a Large Old Population

Objective: Evidence exists that lowering high blood pressure reduces the risk of dementia. However, the generalizability of this evidence to very old and frail patients remains uncertain. The aim of this study was to evaluate the protective effect of adherence to antihypertensive treatment on the risk of dementia in a large and heterogeneous general population. Design and method: A nested case–control study was carried out by including the cohort of 215,547 patients from Lombardy (Italy), aged >=65 years, who started antihypertensive drug therapy during 2009-2012. Cases were the 13,812 patients who developed dementia or Alzheimer’s disease during follow-up (up to 2019). Up to five controls were selected for each case. Adherence to drug therapy was measured by considering the proportion of days of the follow-up covered by the drug prescriptions. Conditional logistic regression was used to model the risk of outcome associated with adherence to antihypertensive drugs. Sensitivity analyses were performed to account for possible sources of systematic uncertainty. Results: The incidence of dementia showed a progressive increase with age, while the incidence of Alzheimer’s disease showed the highest incidence among patients aged 80-84 years. Progressive increase in adherence to treatment was associated with a progressive decrease in the risk of dementia. Compared to patients with very low adherence, those with high adherence exhibited a 24% risk reduction. This was also the case in each stratum of sex, age, and clinical status, including very old subjects (>=85 years) and those characterized by a very high risk of early mortality (36% at 1 year). Similar results were obtained when outcomes were decomposed, i.e. Alzheimer’s disease and other dementias were separately analysed. Conclusions: In elderly hypertensive patients from a general population, increased adherence to antihypertensive drugs was associated with a reduction in the risk of dementia regardless of the patients’ clinical status and age.