Effects of centrally acting ACE inhibitors on the rate of cognitive decline in dementia

Abstract

ObjectivesThere is growing evidence that antihypertensive agents, particularly centrally acting ACE inhibitors (CACE-Is), which cross the blood–brain barrier, are associated with a reduced rate of cognitive decline. Given this, we compared the rates of cognitive decline in clinic patients with dementia receiving CACE-Is (CACE-I) with those not currently treated with CACE-Is (NoCACE-I), and with those who started CACE-Is, during their first 6 months of treatment (NewCACE-I).DesignObservational case–control study.Setting2 university hospital memory clinics.Participants817 patients diagnosed with Alzheimer's disease, vascular or mixed dementia. Of these, 361 with valid cognitive scores were included for analysis, 85 CACE-I and 276 NoCACE-I.MeasurementsPatients were included if the baseline and end-point (standardised at 6 months apart) Standardised Mini-Mental State Examination (SMMSE) or Quick Mild Cognitive Impairment (Qmci) scores were available. Patients with comorbid depression or other dementia subtypes were excluded. The average 6-month rates of change in scores were compared between CACE-I, NoCACE-I and NewCACE-I patients.ResultsWhen the rate of decline was compared between groups, there was a significant difference in the median, 6-month rate of decline in Qmci scores between CACE-I (1.8 points) and NoCACE-I (2.1 points) patients (p=0.049), with similar, non-significant changes in SMMSE. Median SMMSE scores improved by 1.2 points in the first 6 months of CACE treatment (NewCACE-I), compared to a 0.8 point decline for the CACE-I (p=0.003) group and a 1 point decline for the NoCACE-I (p=0.001) group over the same period. Multivariate analysis, controlling for baseline characteristics, showed significant differences in the rates of decline, in SMMSE, between the three groups, p=0.002.ConclusionsCognitive scores may improve in the first 6 months after CACE-I treatment and use of CACE-Is is associated with a reduced rate of cognitive decline in patients with dementia.

Tolerability of Antihypertensive Medications in Older Adults

“…Studies are few, with little convincing evidence supporting benefit, harm, and safety for any agent, suggesting that providers must use the same judgment as in the non-demented [124]. Centrally acting ACEIs may be associated with a reduced rate of cognitive decline [125]. With both hypertension and dementia being common, there is uncertainty over whether the benefit in prevention of cognitive impairment is secondary to a lowering of BP or is a specific drug class benefit [97].…”

Antihypertensive drug use and risk of cognitive decline in the very old

“…Relationships between blood pressure lowering and dementia risk are less well understood [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22], particularly in very old age [3]. Systematic reviews [10][11][12], clinical trials [13,14,19] and observational studies [15][16][17][18][20][21][22] variably report antihypertensive drug use as associated with decreased risk of dementia/cognitive decline [14][15][16][17][18][19][20][21], increased risk [22], or no impact [10][11][12][13]. The majority of double-blind randomized placebo controlled trials show no relationships.…”

“…However, two trials in the young old (below age 70) report reductions in incident dementia: from an angiotensin-converting enzyme-inhibitor (ACE-I) plus optional diuretic, but only in those with prior stroke/transient ischaemic attack and concurrent stroke, mean age 64 years [14]; and from calcium channel blockers (CCB), mean age 69.9 years [19,20]. Observational literature shows beta-blockers, CCBs, ACE-I and diuretics as associated with some positive cognitive outcomes, again mostly in the younger old (mean age at baseline ranged from $68 to 78 years) [15][16][17][18]. Evidence is strongest for CCBs with the suggestion that their impact may be independent of blood pressure lowering [11,12].…”

ACE I/D genotype-related increase in ACE plasma activity is a better predictor for schizophrenia diagnosis than the genotype alone

“…Several studies suggested an involvement of the renin-angiotensin system (RAS) and ACE on cognitive performance, as improved cognition and delayed dementia progression were associated with the use of ACE inhibitors (Ohrui et al, 2004;Kehoe and Wilcock, 2007;Yamada et al, 2011;Gao et al, 2013). Thus, considering that cognitive impairments are central features of SCZ (Kahn and Keefe, 2013), these results might direct future studies on the ACE roles on cognition in SCZ patients.…”