Methods:

The investigators used a nested case-control study design with a cohort of 215,547 patients residing in Lombardy, Italy, who were aged ≥65 years and had started antihypertensive medications within the time frame of 2009–2012. Patients were identified through the health care databases of Lombardy, which account for 16% of Italy’s population (10 million individuals, predominantly of White race). Cases were defined as patients who developed dementia or Alzheimer’s disease during follow-up, with a date of onset defined as the date corresponding to the first event among: 1) hospitalization with a diagnosis of dementia or Alzheimer’s disease, 2) prescription of anti-dementia drugs (galantamine, rivastigmine, donepezil, and memantine), and 3) exemption from the copayment for drugs and other health services for dementia or Alzheimer’s disease.

For each case patient, five controls were identified from the cohort as individuals with the same sex, age at cohort entry (±3 years), clinical status, and index date (±30 days) of the corresponding case patient. Adherence to treatment, and thus exposure to antihypertensive drugs, was assessed by the ratio between the number of days in which the antihypertensive drug therapy was available and the days of follow-up, a measure defined as the “proportion of days covered” (PDC) by prescriptions. Four categories of adherence or exposure to antihypertensive drugs were considered: very low (PDC ≤25%), low (26%–50%), intermediate (51%–75%), and high (>75%).