Vascular cognitive impairment, a cardiovascular complication

Table 1 Research studies on antihypertensive use and cognitive impairment

Ref.	Sample size	Treatment option	Primary outcome	Treatment period	Result
Tzourio et al[64]	6108	Participants were assigned to either active treatment (perindopril and indapamide) or matching placebo(s)	Dementia (using DSM-IV criteria) and cognitive decline (a decline of 3 or more points in the Mini-Mental State Examination score)	3.9 yr	Dementia was documented in 193 (6.3%) of the 3051 randomized participants in the actively treated group and 217 (7.1%) of the 3054 randomized participants in the placebo group [relative risk reduction, 12% (95%CI: -8% to 28%); P = 0.2]. Cognitive decline occurred in 9.1% of the actively treated group and 11.0% of the placebo group [risk reduction, 19% (95%CI: 4% to 32%); P = 0.01]. The risks of the composite outcomes of dementia with recurrent stroke and of cognitive decline with recurrent stroke were reduced by 34% (95%CI: 3% to 55%) (P = 0.03) and 45% (95%CI: 21% to 61%) (P < 0.001), respectively, with no clear effect on either dementia or cognitive decline in the absence of recurrent stroke
Dufouil et al[65]	192	Participants were assigned to a combination of perindopril plus indapamide or their placebos or to single therapy with perindopril or placebo	Cerebral MRI both at baseline and after a mean follow-up time of 36 mo WMHs were graded with a visual rating scale from A (no WMH) to D (severe WMH)	36 mo	Twenty-four subjects (12.5%) developed new WMHs at follow-up. The risk of new WMH was reduced by 43% (95%CI: -7% to 89%) in the active treatment group compared with the placebo group (P = 0.17). The mean total volume of new WMHs was significantly reduced in the active treatment group [0.4 mm3 (SE = 0.8)] compared with the placebo group [2.0 mm3 (SE = 0.7); P = 0.012)]
Hajjar et al[62]	53	Lisinopril, candesartan, or hydrochlorothiazide	Cerebral blood flow velocity (BFV; transcranial Doppler ultrasonography during rest, sitting, standing, hypercapnia, and hypocapnia), cognition (trail making test), and blood pressure	12 mo	There was a tendency toward an increase in BFV in the candesartan group and a decrease in the lisinopril and hydrochlorothiazide groups (between-group P = 0.57) that was significant in those with low BFV at baseline (< median 27.6 cm/s, between-group P = 0.03). The candesartan group also had the greatest improvement in executive function (Trail Making Test Part B improved by 17.1 s, vs hydrochlorothiazide improved by 4.2 s and lisinopril worsened by 14.4 s, P = 0.008). Carbon dioxide vasoreactivity and vasomotor range declined significantly in the lisinopril (within-group P = 0.001 for vasoreactivity and 0.02 for vasomotor range) and hydrochlorothiazide groups (within-group P = 0.10 and 0.009, respectively) but not in the candesartan group (within-group P = 0.25 and 0.38, respectively; between-group P = 0.30 and 0.46, respectively)
Gelber et al[61]	2197	Different classes of antihypertensive medication	Cognitive function was assessed at 7 standardized examinations using the CASI	5.8 yr	854 men developed cognitive impairment (median follow-up, 5.8 yr). β-blocker use as the sole antihypertensive drug at baseline was consistently associated with a lower risk of cognitive impairment (IRR 0.69; 95%CI: 0.50-0.94), as compared with men not taking any antihypertensive medications. The use of diuretics, calcium channel blockers, angiotensin-converting enzyme inhibitors, or vasodilators alone was not significantly associated with cognitive impairment

CASI: Cognitive Abilities Screening Instrument; MRI: Magnetic resonance imaging; WMH: White matter hyperintensities; IRR: Incidence rate ratio.