In an analysis of data of 15,746 older residents drawn from rural and urban sites in India, China, and 6 countries in Latin America, dementia and dementia severity were associated with lower SBP and, to a lesser extent, with DBP. Heterogeneity across sites was higher for dementia severity than for dementia. The most consistent associations of dementia and CDR score with lower levels of both SBP and DBP were found in Cuba. The Cuban sample was also noted to have the highest mean SBP.
As outlined earlier, the relationship between BP and dementia is complex, with higher BP predicting increased risk of dementia 10 to 20 years later, possibly more so for untreated hypertension,1
but contemporaneous associations between dementia and either lower2
or similar BP.19
These associations tend to be more evident for SBP than DBP and are supported by longitudinal findings of an exaggerated decrease in SBP over 4 to 6 years before the clinical onset of dementia.1
Our findings are consistent in that lower SBP was found for people with dementia and for those with more severe dementia in the combined samples. However, differences between those with and without dementia were not significant and relatively small in most individual sites. Only the dementia-associated SBP difference in Cuba (6.9 mm Hg, ) was comparable to, for example, the 6 mm Hg lower mean SBP in cases of incident dementia compared with survivors without dementia in wave 6 of the Honolulu-Asia Aging Study (Japanese American men living in Hawaii),4
or the 13 mm Hg lower SBP associated with prevalent dementia in the Kungsholmen Study (Swedish older residents).2
Although it is possible that BP decline is purely secondary to the neurodegenerative processes underlying dementia, this does not readily account for the much smaller associations found in these low- and middle-income settings, because the limited neuropathologic research in diverse populations suggests comparable postmortem findings in dementia among Brazil, Germany, and Japan,20
as well as between Indian and North American samples.24
Therefore, there is no reason to suppose that dementia has markedly different somatic manifestations in different countries. Supporting this, weight loss, another somatic correlate of dementia that precedes the clinical onset25
and continues afterward,26
has been consistently found across a range of international settings,27,28
including within the 10/66 study sites.29
A component of the association between dementia and lower BP might reflect a similar underlying process to that resulting in weight loss, because waist circumference was identified as a significant potential mediator, although results were unchanged when we further adjusted for this covariate.
International heterogeneity in associations between dementia and lower BP may have other explanations. As mentioned earlier, SBP decline associated with dementia in the Honolulu-Asia Aging Study was also not homogeneous but was confined to people who had not received antihypertensive treatment.4
In discussing this, the authors proposed that this BP decline might reflect previous hypertensive disease—either because of arterial stiffness causing cognitive decline30
or through watershed ischemia and disturbed cerebral autoregulation, white matter damage, and Alzheimer pathology.31,32
The fact that associations between dementia and BP were relatively small and did not differ by hypertensive history or antihypertensive treatment might reflect that mean BPs in all sites were relatively low compared with what would be expected in higher-income populations.33
Thus, some lack of association between dementia and lower BP may simply reflect populations where hypertension has been uncommon. In keeping with this, the associations that were most prominent and consistent were those in Cuba, where mean BP levels were closest to higher-income setting norms.7
Strengths of this study included the large samples, high response rates, and consistencies in measurement among sites. Resting BP was measured according to a standard protocol and dementia was ascertained in an identical manner following a procedure that had been extensively validated.9
Measurement error (in BP or dementia) cannot be excluded absolutely and may have diluted our results. However, procedures were highly standardized and quality control was thorough, and there have been no difficulties identifying other associations with BP in the same samples.7
Limitations also include the cross-sectional design and the sampling procedure, and missing BP measurements might have altered results in Venezuela and Puerto Rico. However, because dementia prevalence was higher among those without compared to those with complete data, our results may be an underestimate. Participants' BP measurements before inclusion were not available, and BP levels rather than BP changes were thus analyzed. However, reported clinical diagnosis of hypertension previous to study inception did not significantly modify associations. The 10/66 protocols preserved internal validity so that comparisons among study sites were appropriate.8
Findings were near identical for CDR score analyses, but heterogeneity due to differences in dementia severity cannot be excluded, and wider issues of differential survival might have accounted for differences from higher-income settings, although most international life-expectancy differences are driven by mortality in childhood and survival through mid- and late-life is much less variable.34
The impact of those covariates included in the models was modest, suggesting that confounding was not a major issue. However, residual confounding needs consideration (for example, lifelong diet and physical activity). The nature of the study also precluded measurements such as APOE
genotype and vascular biomarkers, and information on vitamin supplementation was limited (although unlikely to have a substantial influence in these settings). Brain structure is influenced by both genetic and environmental factors,35
and both BP and cerebral pathophysiology have strong genetic influences.36,37
Adjustment for reported family history of dementia made little difference to the associations of interest, but this does not preclude familial influences.
Overall, these findings from large community samples in low- and middle-income settings suggest that contemporaneous associations between dementia and lower BP are not universally strong. Lifetime hypertensive disease may be key to dementia-associated SBP decline and a reason why the latter is more marked in source populations with higher cardiovascular risk. However, LMIC are predicted to experience rapid increments in both dementia6
and hypertension prevalence,5
so closer monitoring of such associations across populations undergoing these epidemiologic transitions is warranted. Clinicians should be aware that BP may be relatively low in patients by the time they develop dementia but this does not rule out effects of earlier hypertensive disease. Whether early antihypertensive use might reduce the extent of this decline remains uncertain, but our data suggest caution in BP lowering, particularly when the disease is more advanced.