too low blood pressure and cognitive decline in elderly

An Italian prospective cohort study of elderly patients (>65 yo) with baseline cognitive impairment assessed the association between achieved blood pressure in those who were hypertensive and the rate of cognitive decline (see htn low bp cognitive decline elderly jama intmed 2015 in dropbox, or JAMA Intern Med. 2015;175(4):578-585​). details:

--172 patients followed in 2 outpatient memory clinics, mean age 79, 63.4% female, mean mini-mental status exam (MMSE) baseline score of 22.1 (normal range 0-30, with scores of 21-24 indicating mild cognitive impairment, MCI, and 10-21 indicating moderate impairment). MMSE was assessed again after 9 months.

--baseline: 68.0% had dementia, 32.0% had MCI, and 73.3% had hypertension with 69.8% were on antihypertensive drugs. they also assessed an array of common morbidities (including diabetes, CHF, CAD, CKD) as well as ADLs/IADLs (activities of daily living, instrumental ADLs)

--primary outcome: assess the role of office BP, ambulatory blood pressure monitoring (ABPM), and BP meds in changes in cognitive function and progression of disabilities. secondary outcome: effect of office and ABPM on adverse events.

--patients in the lowest tertile of daytime systolic blood pressure by ABPM, SBP <=128 mmHg, had greater decrease in MMSE (-2.8) vs those in the intermediate tertile (SBP 129-144, with MMSE -0.7, p=0.002) vs highest tertile (SBP >=145, with MMSE -0.7, p=0.003)

--the association between SBP and MMSE decline was significant only in those on antihypertensive drugs, for both subgroups of those with MCI and dementia.

--in multivariate model (controlling for age, baseline MMSE, vascular comorbidities), interaction between daytime SBP and use of antihypertensives was independently associated with greater cognitive decline, for both MCI and dementia subgroups

--the association between office-based SBP and MMSE change was weaker than the ambulatory SBP, not reaching statistical significance.

--for the secondary outcome: both ADL and IADL decreased, but there was no relationship between any of the blood pressure measurements. 

--adverse events were pretty high: 26.2% had at least one fall, 6.8% had syncope, 23.7% were hospitalized. there was a nonsignificant trend for a higher incidence of syncope and hospitalization with decreasing daytime SBP (eg, the rates of syncope went from 10.5% in the lowest SBP tertile to 6.8% in the intermediate to 3.4% in the highest tertile. for hospitalizations, it went from 33.3% to 21.7% to 17.2%).  my guess is that this was too small a study to achieve statistical significance for these outcomes.

so, a few points:

--this was not an RCT, where patients were stratified to different blood pressure goals and cognitive decline was measured. so it is hard to draw firm conclusions. ie, did those with lower achieved SBP have more cognitive decline because those patients had their blood pressure lowered more easily (eg, their vasculature was fundamentally different, leading to lower achieved blood pressure in those having more cognitive decline -- and, by the way, there are some data finding that the onset of overt dementia is associated with spontaneous lowering of blood pressure)? and would the same group with more blood pressure lowering/more cognitive decline have had less cognitive decline if they were randomized to higher target blood pressures? one possible model is that more aggressively treating early hypertension is cognitively beneficial; but later on, the vascular changes from long-standing hypertension and its effects on cerebral blood flow autoregulation, endothelial function, etc could lead to impaired cognitive function, especially in the presence of dementia (ie, in the absence of cerebral blood flow autoregulation, lowering the blood pressure leads to more cerebral hypoperfusion and decreased functioning). so, there might be different BP targets in people of the same age group who have normal cognition, MCI, or dementia.

--this study reinforces the utility of ambulatory blood pressure monitoring. I have sent out many blogs over the past 3-4 years with data showing the superiority of ABPM -- for diagnosis (about 30% of those in the mild hypertension range by office-based blood pressure do not have hypertension on ABPM), for cardiovascular clinical outcomes (the correlation between hard clinical cardiovascular endpoints in several studies were only significant for APBM and not for office-based blood pressure), and now this study suggests ABPM is a better predictor of cognitive decline. for more extensive discussion of ABPM, see http://gmodestmedblogs.blogspot.com/2015/01/uspstf-recs-on-ambulatory-blood.html 

--this study also reinforces the significance of the JNC8 targets being increased in elderly to <150/90 (will append below my previous blog on JNC8, since it predated the BMJ on-line blogs)

--and, again, i would like to reinforce that in elderly patients postural blood pressure changes should be assessed pretty regularly. given changes in vasculature as noted above and increases in autonomic neuropathy with aging, it is very common (at least in my practice) to see older patients with even somewhat high SBP but having dramatic BP decline on standing. the immediate concern is falling, but i am also concerned about cardiovascular events (decreased myocardial perfusion) and cerebrovascular effects (hypoperfusion, or more vascular dementia from micro or macro infarcts)

for review of JNC8, see http://gmodestmedblogs.blogspot.com/2013/12/jnc-8.html