<b><i>Background:</i></b> Midlife hypertension followed by late life hypotension resulting from neurodegeneration increases amyloidogenesis and tauopathy. <b><i>Methods:</i></b> Consecutive outpatients with late-onset Alzheimer's disease (AD) at various stages and their respective caregivers were assessed for score variations in 1 year of tests assessing caregiver burden, functionality and cognition according to blood pressure (BP) variations and <i>APOE</i> haplotypes, while also taking into account differential effects of angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, β-blockers, calcium channel blockers, diuretics, or no antihypertensive medication on score changes. The diagnosis and treatment of arterial hypertension followed the JNC 7 report. <b><i>Results:</i></b> Variations in systolic BP (-11.76 ± 17.1 mm Hg), diastolic BP (-4.92 ± 10.3 mm Hg) and pulse pressure (-6.84 ± 12.6 mm Hg) were significant after 1 year (n = 191; &#x03C1; < 0.01). For APOE4+ carriers, rises in systolic or diastolic BP improved Clinical Dementia Rating Scale Sum of Boxes scores (&#x03C1; < 0.04), with marginally significant improvements in Mini-Mental State Examination scores resulting from risen systolic (&#x03C1; = 0.069) or diastolic BP (&#x03C1; = 0.079), and in basic independence only regarding risen diastolic BP (&#x03C1; = 0.055). APOE4- carriers resisted any functional or cognitive effects of BP variations. No differences were found regarding any antihypertensive class for variations in BP or any test scores, regardless of <i>APOE</i> haplotypes. <b><i>Conclusions:</i></b> Targeting mild BP elevations brings better functional and cognitive results for APOE4+ carriers with AD.