Wharton et al.88. Wharton W, Goldstein FC, Zhao L, Steenland K, Levey AI, Hajjar I. Modulation of renin-angiotensin system may slow conversion from mild cognitive impairment to Alzheimer’s disease. J Am Geriatr Soc. 2015;63(9):1749-56. https://doi.org/10.1111/jgs.13627
https://doi.org/10.1111/jgs.13627...
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83 individuals with MCI who were taking an antihypertensive at baseline.
38 RAS users. Age: 82.6±7.2 years. Sex: 45% male. Black: 13.9%.
45 RAS non-users. Age: 83.7±5.9 years. Sex: 20% male. Black: 4.4%. |
38 participants were allocated in the RAS (renin-angiotensin system) users. They received ACEI (angiotensin converting enzyme inhibitors) or ARB (angiotensin receptor blockers).
45 participants were allocated in the non-RAS users. They received beta blocker, diuretics or calcium channel blockers.
Both groups were accompanied for 4 years. |
Progression from MCI to AD (Alzheimer’s disease:
RAS users=3 (7.9%).
Non-RAS users=11 (24.4%).
Neuropathological changes:
Absolute numbers of plaques in hippocampus CA1 and entorhinal cortex were significantly lower in non-RAS-AHM group. In the fully adjusted model, RAS users had significantly fewer overall neurofibrillary tangles (NFTs) (p<0.01) and fewer tangles in all prespecified regions of interest including the hippocampal CA1 region (p<0.01), the entorhinal cortex (p<0.01), and the average number of NFT in brain regions, including the angular gyrus, inferior temporal, mid-frontal cortex, and superior frontal (p=0.06). RAS users also had higher brain weight (p=0.03) and fewer diffuse plaques (p=0.02). RAS-AHM and non-RAS-AHM users did not differ on neuropathological indices of NIA Reagan, amyloid burden, arteriolosclerosis, Lewy body disease, chronic, micro, or gross infarcts, Braak, or CERAD scores. |
The association between use of RAS-AHM and conversion to AD remains significant (p=0.0285).
RAS users had significantly fewer overall NFTs (p<0.01) and fewer tangles in all prespecified regions of interest. |
Wharton et al.1010. Wharton W, Zhao L, Steenland K, Goldstein FC, Schneider JA, Barnes LL, et al. Neurofibrillary tangles and conversion to mild cognitive impairment with certain antihypertensives. J Alzheimers Dis. 2019;70(1):153-61. https://doi.org/10.3233/JAD-190011
https://doi.org/10.3233/JAD-190011...
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RAS acting: 488 (312 were taking BBB-crossing medications and 124 were taking non-BBB-crossing formulations). African-American: 90; Caucasians: 398. Age: 74.6±8 years. Male: 46%.
Non RAS: 296 (113 were taking a calcium channel blocker, 174 a beta-blocker, and 108 a diuretic). African-American: 117; Caucasians: 552. Age: 75.5±8.8 years. Male: 49%. |
488 were allocated in the RAS-acting group, taking ACEI or ARB.
296 were allocated in the non RAS group, taking calcium channel blockers, diuretics, or beta-blockers.
Both groups had a follow-up of 3 years. |
Conversion rates to AD as a function of RAS-acting medication use:
280 of the 784 participants taking an antihypertensive medication converted to AD. 161 were RAS-acting medication users (33.0%), 119 non-users (40.2%), 98 centrally acting medication users (30.7%), and 48 non-centrally acting medication users (40.0%) converted to AD. |
Participants taking BBB-crossing RAS-acting medications would have greater cognitive protection than those taking non-centrally acting medications. Results regarding the rate of decline showed beneficial cognitive and functional effects on the Boston Naming Test (p<0.01), MMSE (p<0.01), and Clinical Dementia Rating-Sum of Boxes (CDR-SOB p<0.01). |
Peters et al.99. Peters R, Beckett N, Fagard R, Thijs L, Wang JG, Forette F, et al. Increased pulse pressure linked to dementia: further results from the Hypertension in the Very Elderly Trial - HYVET. J Hypertens. 2013;31(9):1868-75. https://doi.org/10.1097/HJH.0b013e3283622cc6
https://doi.org/10.1097/HJH.0b013e328362...
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Participants were recruited from Eastern European countries and from China. 60% woman. Age 83.5 years (3.1).
Active group n=1,623.
Placebo group n=1,580. |
Placebo-controlled trial comparing indapamide SR 1.5 mg or matching placebo with the optional addition of 2 or 4 mg perindopril, or matching placebo to reach a goal BP of less than 150/80 mmHg. |
There were 263 cases of incident dementia (3.8/100 patient-years in the placebo compared with 3.3/100 in the actively treated group).
Placebo: For SBP and DBP, there was no significant relationship with later dementia (p=0.13 and p=0.43, respectively). For PP, higher PP was associated with increased risk (p=0.032).
Intervention: There was no significant relationship between SBP and later dementia (p=0.36). Diastolic pressure showed a clearer and statistically significant U-shaped relationship with later dementia with a calculated nadir of 87.5 mmHg (p=0.0195). Higher PP was associated with increased risk (p=0.0046). |
The HYVET trial also collected data relating to incident dementia and found no difference between the active and placebo groups with regard to this endpoint, although there were 8% fewer cases in the actively treated group. That SBP shows no clear relationship with dementia (…) |
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